Chem. Rev.

2003, 103, 977−1050


Stereoselective Cyclopropanation Reactions
Helene Lebel,* Jean-Francois Marcoux, Carmela Molinaro, and Andre B. Charette* ´` ¸ ´
Departement de Chimie, Universite de Montreal, Montreal, Quebec, Canada H3C 3J7 ´ ´ ´ ´ ´ Received August 30, 2002

I. Introduction II. Halomethylmetal (Zn, Sm, Al)-Mediated Cyclopropanation Reactions A. Introduction B. Relative Diastereoselection 1. Cyclic Alkenes 2. Acyclic Alkenes C. Chiral Auxiliaries D. Stoichiometric Chiral Ligands E. Chiral Catalysts III. Transition Metal-Catalyzed Decomposition of Diazoalkanes A. Introduction B. Intermolecular Cyclopropanation 1. Diazomethane 2. Diazoalkanes Bearing an Electron-Withdrawing Group (N2CH(EWG)) 3. Diazoalkanes Bearing Two Electron-Withdrawing Groups (N2C(EWG)2) 4. Aryl- and Vinyldiazoester Reagents C. Intramolecular Cyclopropanation 1. Diastereoselective Intramolecular Cyclopropanation of Chiral Substrates 2. Enantioselective Intramolecular Cyclopropanation: Chiral Catalysts IV. Michael-Initiated Ring Closure A. Introduction B. Relative Diastereoselection (Addition to Chiral Substrates) C. Removable Chiral Auxiliaries 1. Chiral Michael Acceptors 2. Chiral Nucleophiles D. Stoichiometric and Catalytic Promoters V. Other Methods A. Enzymatic Methods B. Chiral Stoichiometric Carbenes C. Other Ring-Closing Reactions of Chiral Precursors VI. References 977 977 977 980 980 983 989 992 994 995 995 996 996 997 1006 1006 1008 1008 1011 1016 1016 1018 1026 1026 1031 1036 1036 1036 1037 1039 1041

cyclopropane-containing unnatural products have been prepared to test the bonding features of this class of highly strained cycloalkanes3 and to study enzyme mechanism or inhibition.4 Cyclopropanes have also been used as versatile synthetic intermediates in the synthesis of more functionalized cycloalkanes5,6 and acyclic compounds.7 In recent years, most of the synthetic efforts have focused on the enantioselective synthesis of cyclopropanes.8 This has remained a challenge ever since it was found that the members of the pyrethroid class of compounds were effective insecticides.9 New and more efficient methods for the preparation of these entities in enantiomerically pure form are still evolving, and this review will focus mainly on the new methods that have appeared in the literature since 1989. It will elaborate on only three types of stereoselective cyclopropanation reactions from olefins: the halomethylmetal-mediated cyclopropanation reactions (eq 1), the transition metal-catalyzed decomposition of diazo compounds (eq 2), and the nucleophilic addition-ring closure sequence (eqs 3 and 4). These three processes will be examined in the context of diastereo- and enantiocontrol. In the last section of the review, other methods commonly used to make chiral, nonracemic cyclopropanes will be briefly outlined.

II. Halomethylmetal (Zn, Sm, Al)-Mediated Cyclopropanation Reactions A. Introduction
The observation that diiodomethane reacts with zinc to give an iodomethylzinc species was first reported in 1929 by Emschwiller.10 However, about 30 years later, Simmons and Smith11 were the first

I. Introduction
Organic chemists have always been fascinated by the cyclopropane subunit.1 The smallest cycloalkane is found as a basic structural element in a wide range of naturally occurring compounds.2 Moreover, many

10.1021/cr010007e CCC: $44.00 © 2003 American Chemical Society Published on Web 04/09/2003

978 Chemical Reviews, 2003, Vol. 103, No. 4

Lebel et al.

Helene Lebel received her B.Sc. degree in biochemistry from the Universite ´` ´ Laval in 1993. She performed graduate studies in organic chemistry in the Chemistry Department of the Universite de Montreal under the ´ ´ supervision of Professor Andre B. Charette as a 1967 Science and ´ Engineering NSERC fellow, during which she worked on stereoselective cyclopropanation reactions. In 1998, she joined the research group of Professor Eric Jacobsen at Harvard University as a NSERC postdoctoral fellow, where she completed the total enantioselective synthesis of taurospongin A. She started her academic career in 1999 in the Chemistry Department of the Universite de Montreal as an assistant professor. Her ´ ´ research activities involve the development of new transition metals containing catalysts that mediate fundamentally interesting and useful organic reactions. She recently developed a new olefination reaction via the transition metal-catalyzed synthesis of salt-free phosphorus ylides.

Carmela Molinaro received her B.Sc. degree in biochemistry at the Universite de Montreal in 1996 and stayed to study for her M.Sc. and ´ ´ Ph.D. degree in organic chemistry (2002) with Professor Andre B. Charette. ´ She has worked on the characterization of zinc cyclopropanating reagents and the development of catalysts for the enantioselective cyclopropanation reaction using these reagents. She has since joined the research group of Professor Timothy F. Jamison at the Massachusetts Institute of Technology as a FCAR postdoctoral fellow and is working on nickelcatalyzed coupling reactions.

Jean-Francois Marcoux received a B.Sc. degree in chemistry from ¸ Sherbrooke University, Canada, and went to Universite de Montreal as a ´ ´ NSERC and FCAR predoctoral fellow, where he received his Ph.D. degree in 1996. His graduate work, directed toward the development of chiral auxiliaries and catalysts for the stereoselective Simmons−Smith cyclopropanation of olefins, was carried out under the mentorship of Professor Andre B. Charette. He then joined the laboratory of Professor Stephen ´ Buchwald at MIT, Massachusetts, as a NSERC postdoctoral fellow. There he was involved in the development of practical catalysts for the palladiumand copper-catalyzed formation of aromatic amines and ethers. He currently is a Research Fellow in the department of Process Research at Merck & Co., Inc., Rahway, NJ.

Andre B. Charette received his Ph.D. (1987) from the University of ´ Rochester under the supervision of Robert K. Boeckman, Jr., where he completed the total synthesis of the ionophore calcimycin. He then joined the research group of David A. Evans at Harvard University as a NSERC postdoctoral fellow, where he worked on the total synthesis of bryostatin. Since 1992, he has been professor at the Universite de Montreal, and he ´ ´ is currently the holder of the NSERC/Merck Frosst/Boehringer Ingelheim Research Chair on Stereoselective Drug Synthesis at the Universite de ´ Montreal. He has received a number of awards, including the Eli Lilly ´ Grantee Award, an Alfred P. Sloan Research Fellowship, the Astra Pharma Award, the Merck Frosst Centre for Therapeutic Research Award, a Steacie Fellowship, and the Rutherford Medal. His research interests are in the area of stereoselective synthesis of organic compounds.

were quickly followed by the development of several alternative methods to prepare related ZnCH2X species or to activate the zinc metal.14

to appreciate that this reagent (IZnCH2I) could be used for the stereospecific conversion of alkenes to cyclopropanes (eqs 5 and 6).12 The cyclopropanation reactions using these reagents are characteristically stereospecific, proceeding through a “butterfly-type” transition structure.13 One major advantage of the reaction is its excellent chemoselectivity, since it is applicable to a variety of olefins and compatible with several functional groups such as enamines, enol ethers, esters, ketones, etc. (vide infra). Simmons and Smith’s seminal studies

Stereoselective Cyclopropanation Reactions
Table 1. Important Methods for the Preparation of Cyclopropanating Reagents reactants (ref) reagent Oxidative Addition Zn/activator, XCH2I (14) IZnCH2X (X ) Cl, I) Sm/activator, CH2I2 (28) ISmCH2I Alkyl Exchange Et2Zn, CH2I2 (16) EtZnCH2I or Zn(CH2I)2 EtZnI, CH2I2 (19,22a) IZnCH2I CF3COOH, Et2Zn, CH2I2 (23) CF3COOZnCH2I 2,4,6-Cl3C6H2OH, Et2Zn, CH2I2 (24) 2,4,6-Cl3C6H2OZnCH2I C4F9C(O)OCH2I, Et2Zn, hν (26) C4F9C(O)OCH2ZnEt R3Al, CH2I2 (30) R2AlCH2I Nucleophilic Displacement ZnX2, CH2N2 (15) XZnCH2X ZnX2, CH2N2 (1:2) (15) Zn(CH2I)2

Chemical Reviews, 2003, Vol. 103, No. 4 979

Figure 2. Chem3D representation of the X-ray crystal structure of the benzo-18-crown-6‚IZnCH2I complex.

Figure 3. Chem3D representation of the X-ray crystal structure of the bis(quinoline)‚Zn(CH2I)2 complex.

Figure 1. Chem3D representation of the X-ray crystal structure of the bis(iodomethyl)zinc‚diether complex.

Shortly after Simmons and Smith’s seminal publication, Wittig15 reported that treatment of zinc iodide with either 1 or 2 equiv of diazomethane was an alternative method to prepare IZnCH2I or the analogous bis(iodomethyl)zinc reagent (Zn(CH2I)2). In 1966, Furukawa and co-workers16 found that a similar reactive species could be prepared by substituting a Zn/Cu couple with ZnEt2, to presumably form EtZnCH2I. Denmark has further elaborated on the reactivity profile of Zn(CH2X)2 (X ) I, Cl), prepared from 1 equiv of ZnEt2 and 2 equiv of XCH2I (X ) I, Cl), showing that it is sometimes advantageous to use the more reactive bis(chloromethyl)zinc with deactivated alkenes.17 This procedure was found to be particularly useful in the cyclopropanation of iodo-substituted alkenes.18 Another very good and underused method for preparing IZnCH2I involves treatment of EtZnI with CH2I2.19 This method is particularly suitable for the large-scale preparation of IZnCH2I, since it avoids the use of Et2Zn. These reports were followed by the discovery of several new halomethylmetal reagents that are also very effective cyclopropanating reagents with unique properties and reactivities. Table 1 gives an overview of some preparative methods to generate these reagents. The structures of these halomethylmetal reagents have been the subject of several postulates over the years, but it is only recently that X-ray crystal structures of some of them have become available. The complexes of Zn(CH2I)2, Zn(CH2Cl)2, and IZnCH2I, with several ligands, have been characterized both in solution and in the solid state by Denmark20 and Charette21 (Figures 1-3). Conversely, Furukawa’s reagent, “EtZnCH2I”, has been characterized by solution NMR,22 but its structure has not yet been determined in the solid state. Finally, two very effective reagents were reported recently for the cyclopropanation of unfunctionalized alkenes. Iodomethylzinc trifluoroacetate, which is

prepared by mixing equimolar amounts of trifluoroacetic acid, diethylzinc, and diiodomethane, cyclopropanates alkenes very effectively.23 Substituted iodomethylzinc aryloxides are also very effective reagents for the cyclopropanation of unfunctionalized alkenes.24 Several other structures of zinc carbenoids, such as those of MeOZnCH2I25 and (PhC(O)OCH2)2Zn,26 were recently resolved, but these reagents are quite unreactive toward alkenes unless they are activated (vide infra). In general, the classical Simmons-Smith reagent in ether has been used in 90% of the zinc-mediated cyclopropanation reactions. However, the use of the Furukawa version, involving diethylzinc, is preferred when less nucleophilic alkenes need to be converted to their corresponding cyclopropanes, since noncomplexing solvents are better suited (higher electrophilicity of the reagent in noncomplexing solvents). These conditions are also experimentally quite practical, since both diethylzinc and CH2I2 are commercially available and can be used without purification. The other zinc reagents have been used sporadically in specific cases. Other cyclopropanating reagents of the proposed general structure “MCH2X” have also been prepared, but they have not been characterized as well as their zinc counterparts.27 For example, the use of a samarium/mercury amalgam in conjunction with CH2I2 to generate samarium carbenoids was reported by Molander.28,29 The analogous R2AlCH2I reagent, which displays a unique reactivity that complements that of the zinc- and samarium-mediated cyclopropanation reaction, was discovered by Yamamoto.30 The synthetic utility of these reagents is clearly illustrated by the chemoselectivity observed in the cyclopropanation of geraniol (eq 7). The allylic alcohol group can be cyclopropanated in the presence of an isolated olefin with zinc- or samarium-derived reagents. Conversely, the isolated olefinic group can be converted into the corresponding cyclopropane, with outstanding chemoselectivity, with the aluminum reagent. Optimization of the reaction conditions has shown that zinc-based reagents could also be effectively used to achieve good chemoselectivities in that reaction.31 However, a chemoselective cyclopro-

or nine-membered ring.33 The cyclopropanations of five-. Winstein also observed that proximal hydroxyl groups could “direct” the delivery of the methylene group. Scheme 1. was involved.3) strain and is similar to that proposed for acyclic. entry 5). Prior coordination of the zinc or samarium reagent with the hydroxy group or the corresponding metal alkoxide to direct the addition of methylene to the neighboring alkene. simple cycloalkenols have served as model substrates for kinetic studies. CH2I2 CHCl3.34a An elegant synthesis of (R)-muscone. 4 Lebel et al. CH2I2 (1:2) >99:1 Et2Zn. Table 2.35 A reversal of selectivity is observed with the analogous eight. it has been the main controlling element for the high stereocontrol in these reactions. reasonably good syn selectivities are observed with dihalocarbenes under phase-transfer conditions (Table 2. NaOH 91:9 panation at the allylic ether position is observed with all three types of reagents if the benzyl-protected geraniol is submitted to these conditions. in which the bulky hydroxyl group occupies the equatorial orientation (eq 8). . Diastereoselective Cyclopropanation of Simple 2-Cycloalken-1-ols diastereoselectivity (syn:anti) entry (ref) 1 (34a) 2 (16) 3 (16) 4 (28) 5 (34d) reagent n)1 n)2 n)3 Zn/Cu >99:1 >99:1 90:10 Et2Zn. to enhance the rate of the reaction.36 The hydroxyl-directed cyclopropanation was achieved with complete diastereocontrol to produce the corresponding cyclopropane. BnEt3NCl.11 He suggested that coordination between the ether oxygen and the reagent.32 Since these observations.980 Chemical Reviews. The following sections summarize the recent advances in hetereoatom-directed and nondirected stereoselective cyclopropanation reactions. 2003. 2-Cycloocten-1-ol prefers to adopt a chair-boat conformation. chiral allylic alcohols (vide infra). which is based on the minimization of the A(1. No. This can be explained on the basis of simple conformational analysis of the ground state. Relative Diastereoselection 1. Along with steric effects. The stereochemical outcome of this reaction is best explained by the model shown in Figure 4. and transition-state models have recently been proposed for these directed processes. and sevenmembered-ring 1-cycloalken-3-ols generally produce very good syn:anti ratios with Simmons-Smith’s. that features a diastereoselective cyclopropanation of a macrocyclic (E)-allylic alcohol 10. six-. ClCH2I (1:2) >99:1 >99:1 >97:3 Sm/Hg. was reported by Oppolzer (Scheme 1). 103. and Molander’s reagents (Table 2).34 Sometimes. Oppolzer’s Muscone Synthesis B. Furukawa’s. Cyclic Alkenes Simmons was the first to observe that the cyclopropanation of 1-(o-methoxyphenyl)-1-propene gave a higher yield of the cyclopropane than that of the related meta and para isomers.28. Recent additional examples of stereocontrol in the cyclopropanation of functionalized cycloalkenol de- Figure 4. prior to the methylene delivery. Vol. Transition-state model for the cyclopropanation of the 15-membered-ring alkenol leading to the syn isomer. has been used extensively to control the stereochemical outcome of the cyclopropanation reactions.

More recently. that β-hy- . Selected Examples of Diastereoselective Cyclopropanation of Cyclic Alkenes rivatives are presented in Table 3. No. in his approach to enantiomerically pure cyclopropyl ketones. especially when an alcohol or a basic group is present to direct the methylenation. Much of the early work in this area has involved substrates deprived of functionality that could potentially compete for the reagent complexation. 103.Stereoselective Cyclopropanation Reactions Chemical Reviews. 2003. 4 981 Table 3. Johnson37a has shown. Vol.37 This collection of examples shows the compatibility of a variety of functional groups under the cyclopropanation conditions.

13-double bond of 17 (eq 10). with Furukawa’s reagent (Scheme 3). The directed cyclopropanation has been widely used to introduce angular methyl groups on steroidtype skeletons (Table 3. 4 Lebel et al.40 The selective methylenation of 17 to form 18 is striking. Momose has reported a highly diastereoselective cyclopropanation reaction of silyl enol ether . Scheme 3. with excellent yield and stereocontrol (>15:1). The directed cyclopropanation of functionalized cyclopentenol (Table 3.38 Scheme 2. Some examples of stereocontrol in the cyclopropanation of functionalized cyclohexenol are presented in Table 3 (entries 3-7). The synthesis of cyclopropanated sugars. whereas the anti isomer could be prepared by a multistep sequence involving a phase-transfer dichlorocarbene cyclopropanation (Table 3. It is not clear whether the silyl ether exerts any directing effect in this case. 24. entries 8-14) is also fairly common. in which the cyclopropanation occurs anti to the ester and to the ketone group (eq 11). Schreiber’s Bis-Cyclopropanation The cyclopropanation of 23 leads to only one diastereomer. clearly show that a benzyl ether and a THP group can also be used as a good directing group in these reactions. as a single isomer (eq 9). the protecting groups used had little impact on the level of stereocontrol in that reaction. entries 16-18).41 The cyclopropanation proceeded to produce the syn-dicyclopropane 22.42 In the course of the asymmetric synthesis of (-)pinidine. a key intermediate in the synthesis of (+)-acetoxycrenulide. In the absence of a directing group. entries 1 and 2). with excellent stereocontrol. The cyclopropanation of the fused [5. droxysulfoximines derived from cyclic enones could undergo reaction to produce the cyclopropane syn to the hydroxy group (Table 3.4. this reaction has been cleverly used recently to install the C19 methyl group of taxusin (Scheme 2). the cyclopropanation of cyclic olefins is generally subjected to steric effects. This is one of the first examples in which two relatively basic groups (hydroxyl and sulfoximines) can compete for the group-assisted methylene delivery. No.0] shown in entry 20 (Table 3) produced the cyclopropane syn to the OTBS group. 2003. Introduction of C19 of Taxusin face to produce 16. Vol. 103. and those shown in entries 19 and 21 of Table 3. entries 10-12).982 Chemical Reviews. since the analogous dichlorocarbene reaction also produced the syn isomer. A key building block of 1. was recently reported by two groups. entries 8-9). since the analogous reaction using dibromocarbene adds exclusively to the 12. and the sense can be predicted on the basis of the prevailing ground-state conformation of the starting olefin. The syn isomer was obtained as the major product with halomethylzinc reagents.39 The stereoselective cyclopropanation allowed the introduction of an oxygenated angular methyl group at the C(17) in Corey’s β-amyrin total synthesis. The stereoselective cyclopropanation of 15 is directed to the more accessible β Schreiber and co-workers reported that the bis(trimethylsilyl)enol ether 20 can be efficiently cyclopropanated. These examples. In addition. involving a directed cyclopropanation of glucal derivatives. Interestingly. The stereochemistry of the allylic benzyl ether group was the controlling element in these reactions.25-dihydroxyvitamin D3 was accessible by a stereoselective cyclopropanation of a diol or the corresponding monoprotected diol (Table 3. The level of stereochemical induction is usually very high. Some recent examples are shown in eqs 9 and 10. and similar selectivities were observed if the secondary alcohol was protected as a tert-butylsilyl (TBS) ether.

the use of an excess (5 equiv) of Furukawa’s reagent (EtZnCH2I prepared from a 1:1 mixture of Et2Zn and CH2I2) in CH2Cl2 produced the highest selectivities to date.1-diiodoethane and diethylzinc (eq 12).50 Although the facial selectivity of the attack on the alkene was very high. CH2I2 (1:1). the stereochemistry of the third substituent could not be completely controlled. 103. From these data. The selectivities obtained in the cyclopropanation of other simple (E)-disubstituted chiral allylic alcohols with these various reagents are shown in Table 5.f These trends are also followed with more complex systems that contain other basic groups that could have affected the stereochemical outcome of the reaction. CH2Cl2 Et2Zn. Acyclic Alkenes The stereoselective cyclopropanation of a chiral. the samarium-derived reagent led to the formation of the anti isomer as the major product with this substrate (Table 4. a high syn selectivity was also reported by Schollkopf for the cyclopropanation of the ¨ bislactim ethers 33 with Et2Zn/CH2I2 (eq 14. The choice of Table 4. For example. ether Zn(CH2I)2. 4 983 25 with the reagent derived from 1. For example. CH2Cl2 Sm(Hg). ether Et2Zn. dichlorocarbene also reacts with secondary allylic alcohols. especially with (E)-disubstituted olefins. favoring the syn isomer 31 with this substrate. but the analogous reaction on (E)-disubstituted olefins gave modest ratios (<2:1) (vide infra).47 The cyclopropanation of (E)-3-penten-2-ol. acyclic allylic alcohol using the Simmons-Smith reagent (Zn-Cu. CH2I2) was first reported by Pereyre and co-workers46 in 1978.44 The level of induction was highly dependent on the nature of the nitrogen protecting group. the ratio drops to 2:1 if ether is used as the solvent with Furukawa’s conditions.45 The cyclopropanation of 2-methylenecyclohexanol using 13 CH2I2 in pentane produced the isotopically labeled syn isomer in an 86:14 ratio. CH2I2) or Zn(CH2I)2 generally gave lower diastereomeric ratios. EtZnCH2I clearly appears to be the most general reagent to access the syn isomer with (E)disubstituted olefins. and high syn selectivities are observed (eq 15). Cyclopropanation of (E)-3-Penten-2-ol47 the solvent in these various processes is certainly a very important issue for optimizing the diastereoselectivities. one of the substrate that produces the lowest diastereomeric ratios under Pereyre’s conditions.51 In addition to the iodomethylmetal-derived reagents. 2. No.49 The cyclopropanation of these bislactim ethers was conditions Zn/Cu. Vol. entries 21-26). Charette has shown that the nature of the Zn carbenoid used in these reactions is very important for obtaining high diastereoselectivities. to form a major diastereomeric cyclopropane with cis-alkenes.48e. R ) H). Lautens and Delanghe have shown that this reaction can be extended to silyl-substituted olefins (Table 5. entries 4-10). The classical Simmons-Smith conditions used by Pereyre (IZnCH2I from Zn/Cu. entry 12) by a trifluoromethyl group (Table 5. Interestingly. Ph). The same reaction carried out in ether afforded a 50:50 mixture. entries 1-3) and the samarium-derived reagent (Table 5.48 The general trends described above are maintained with more complex systems. It is also clear that stereoelectronic effects play an important role in these reactions. CH2I2 (1:1). Conversely. R ) Me. the substitution of a methyl group (Table 5. The cyclopropanation of (Z)-disubstituted chiral allylic alcohols is uniformly good. The SimmonsSmith reagent (Table 5. CH2I2. . 2003. CH2I2. entry 5).or aryl-substituted carbenoids of type CHR or CHAr were used (eq 14. An interesting cyclopropanation of an exocyclic olefin was reported by Ronald (eq 13).46 served as a model substrate to highlight the efficiency of each reagent with (E)olefins (Table 4).43. They observed that very high syn selectivities (>200:1) were obtained with (Z)disubstituted olefins.Stereoselective Cyclopropanation Reactions Chemical Reviews. entry 19) with the samarium reagent led to a spectacular increase of the syn selectivity. For example. THF ratio 31:32 56:4446 86:14 67:33 67:33 25:75 also reported to occur when alkyl. entries 11-18) generally give lower diastereoselectivities than the excess EtZnCH2I (Table 5.

f 48e. ClCH2I. ClCH2I. 103. CH2I2. CH2I2. CH2I2. CH2Cl2 Sm(Hg). CH2I2. Cyclopropanation of Chiral. CH2I2. CH2Cl2 Et2Zn. b Formation of the 1. CH2I2. THF Sm(Hg). CH2I2. CH2I2. THF Sm(Hg). (CH2Cl)2 Et2Zn. CH2Cl2 Et2Zn. NaOH BnEt3NCl. THF Sm(Hg). The cyclopropanation of trisubstituted alkenes leads to only one diastereomer when a (Z)-substituent is present at the R2 position. CH2I2. NaOH >98:2 97:3 50:50 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 >98:2 50:50a 96:4 yield (%) 86 95 >95 98 98 75 76 70 63 89 77 81 80 80 67 85 71 92 26 40 53 77 ref 52a 47 47 28 28 48e. THF Sm(Hg).53 It is clear . THF Sm(Hg). THF Sm(Hg). THF Sm(Hg).or samarium-based reagents are used (Table 6). Acyclic Allylic Alcohols: (E)-Disubstituted Alkenes substrate products R1 Me Et t-Bu Me Ph Ph Ph Ph Ph Ph Me Ph Ph Ph Ph t-Bu t-Bu Bu Ph n-C6H13 TMS TMS TMS Bu Bu Bu Me R2 Me Me Me Me Me Et Et Bu i-Pr t-Bu Me Me Bu i-Pr t-Bu Me i-Pr i-Pr CF3 CF3 c-hexyl Pr Me c-hexyl i-Pr Pr Me yield (%) 57:43 63:37 67:33 86:14 88:12 >98:2 >98:2 >98:2 >98:2 >98:2 25:75 14:86 42:58 >98:2 >98:2 15:84 >98:2 83:17 >98:2 >98:2 98:2 43:57 9:91 95:5 85:15 60:40 89:11 nr nr nr 75 86 97 87 98 97 84 >95 98 99 88 76 98 46 93 87 92 81 84 76 73 85 94 68 a Lebel et al. CH2I2. DCE Sm(Hg). CH2I2. CHCl3. THF Sm(Hg). THF Sm(Hg).1-dichlorocyclopropane.984 Chemical Reviews. entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 a conditions Zn/Cu. No. CHCl3. CH2I2. THF Sm(Hg). CH2I2. 4 Table 5. CH2I2.f 48e.f 48e. CH2I2. CH2Cl2 Sm(Hg). THF BnEt3NCl. CH2Cl2 Et2Zn. THF Sm(Hg).f 48e.52 The stereochemical outcome of these reactions can be qualitatively predicted by assuming an oxygen group-assisted delivery of the reagent from a conformation in which the minimization of the A(1. 2003. CHCl3.f 48e.f 48e.f 48e. CH2I2. Vol. THF Sm(Hg). CH2I2. THF Sm(Hg). CH2Cl2 Et2Zn. THF Sm(Hg). NaOH ref 46 46 46 47 47 47 47 47 47 47 47 28 28 28 28 28 28 28 48d 48d 48e. CH2I2. CH2Cl2 Sm(Hg).f 48e.f 34d Not reported. CH2I2. CH2I2. CH2I2. THF Et2Zn. THF Sm(Hg). THF Sm(Hg). ClCH2I. ClCH2I.f 48e. THF Sm(Hg).f 48e. CH2I2. regardless of whether zinc.f 48e. THF Sm(Hg). CH2I2. ClCH2I.3) strain is the predominant controlling element. ClCH2I. CH2I2. CH2I2. CH2I2. CH2I2.f 48e. CH2I2. Cyclopropanation of Chiral. THF Sm(Hg). CH2I2. THF BnEt3NCl. ether Zn/Cu. THF Sm(Hg). THF Sm(Hg). THF Sm(Hg). CH2I2. CH2Cl2 Et2Zn. CH2I2. THF Sm(Hg). ether Et2Zn. THF Sm(Hg). THF Et2Zn. Acyclic Allylic Alcohols: Trisubstituted Alkenes substrate products entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 a R1 Et Ph Ph Me2CdCH(CH2)2s Me Bu3Sn Bu3Sn Bu3Sn Bu Bu Bu Bu TMS TMS TMS TMS SnBu3 SnBu3 SnBu3 TMS H Me R2 I H H Me Me2CdCH(CH2)2s Bu Bu Bu SnBu3 SnBu3 SnBu3 SnBu3 SnBu3 SnBu3 SnBu3 SnBu3 SnBu3 SnBu3 H H H Me R3 H Me Me H H H H H H H H H H H H H H H SnMe3 SnMe3 Me H R4 Me Me Me Me Me c-hexyl Me c-hexyl c-hexyl i-Pr Pr Me c-hexyl c-hexyl Pr Me c-hexyl c-hexyl Me Me Me Me conditions Et2Zn. CH2I2. CH2I2. ether Zn/Cu.1-dichlorocyclopropane. THF Sm(Hg). THF Sm(Hg). CH2I2. THF Sm(Hg). CH2I2.f 48e. CH2I2. THF Sm(Hg).f 48e. CH2Cl2 Et2Zn. CH2I2. CH2I2. CH2I2.f 48e.f 48e.f 48e. Table 6. CH2I2.f 52e 52e 34d 34d Formation of the 1.

Methylene delivery from the face away from the alkyl group would then lead to the anti isomer. 2003. It is possible that the increase of the steric bulk of the alkoxide under certain conditions is a significant feature to increase the energy difference between A and (C. Unfavorable nonbonded interactions.and Stereoselective Cyclopropanation of Allylic Alcohol 37 Figure 5. Lautens and Delanghe have reported a highly regioselective cyclopropanation of R-allenic alcohols using a samarium carbenoid that provided a variety of methylene. the cyclopropanation did not proceed when the SEM protection group at C-5 was replaced by a TBS moiety. depending on the reaction conditions (Table 5. 4 985 Figure 6. entry 2 vs 5). the cyclopropanation is still directed by a zinc alkoxide moiety. These differences are evident in the cyclopropanation of (E)-3-penten2-ol. arising from the bulky zinc alkoxide substituent. The use of the samarium reagent was essential to optimize the regioselectivity of this process and to minimize the formation of spiropentane carbinols. The diastereoselective cyclopropanation of allylic ethers using Furukawa’s reagent has been systematically investigated by Charette with simple systems (Table 8). The nature of the carbenoid reagent used is extremely important. The fact that the samarium reagent leads to the anti isomer as the major adduct with this substrate is an indication that a different conformer is involved in the cyclopropanation reaction.and alkylidenecyclopropane carbinols in good yields (Table 7).Stereoselective Cyclopropanation Reactions Chemical Reviews. that other important factors should be taken into account in order to explain the level of induction. It was shown that. In addition. under Furukawa’s conditions. Regio. depending upon the substitutents on the carbinol side chain and on the substitution of the allene. with large R3 (Figure 7). to maximize the nucleophilicity of the alkene (Figure 6). and D. The acidity and the bulkiness of the reagent (EtZnCH2I vs Zn(CH2I)2 vs IZnCH2I) appear to be very important in some cases. D). In comparison. Vol. B. for which the diastereoselectivities go from 1:3 to 6:1 (syn:anti). Reactive conformers: zinc vs samarium.55 The diastereoselectivities vary from 33:67 to 98:2. No. as shown by Takemoto and co- workers in the asymmetric total synthesis of halicholactone. the methylene delivery occurs from complex 36. The transition-state model A was postulated to be the predominant one. One possible assumption is that the deprotonation does not occur with the samarium reagent and the most reactive conformer is the one in which the C-O(H)Sm is orthogonal to the π-system. Scheme 4.57 Both the steric hindrance of the substituents and the nature of the protecting group were found to be pivotal elements for obtaining high selectivities and for determining the sense of induc- . C. Transition-state models for the cyclopropanation involving zinc reagents. The outside Houk model56 was used by Molander28 and Lautens55 to explain the sense and level of the diastereoselection in the samarium-carbenoid reactions. 103. Even in the presence of other proximal basic groups. are present in three staggered transition structures.54 The regio.and stereoselective cyclopropanation of allylic alcohol 37 produces 38 in 68% yield as a single product in the presence of an equimolar quantity of diiodomethane and diethylzinc (Scheme 4). the corresponding acetonide at C-1 and C-2 was ineffective for the delivery of the methylene. Four possible transition-state models for this reaction are depicted in Figure 5.

The size of the protective group was shown to play a very important role in these reactions. Table 8. Shi’s reagent (CF3COOZnCH2I) had to be used for optimal selectivities . Figure 7. Diastereoselective Cyclopropanation of Allylic Ethers57 R1 H H H H Pr H H H H a R2 H H H H H Me Me OMe OMe R3 t-Bu c-hexyl i-Pr heptyl c-hexyl c-hexyl heptyl c-hexyl heptyl ratio 39:40 98:2 90:10 80:20 46:54 63:37 89:11 33:67 98:2 93:7 yield (%) 57 82a 67 73 70a 66 52 47 59 entry 1 2 3 4 5 6 R1 Me Et i-Pr Me Et i-Pr R2 Bn Bn Bn Me Me Me yield (%) 94 97 82 95 93 94 ratio syn/anti 10:90 33:67 95:5 39:61 77:23 98:2 Table 9. tion. entries 1-3). 2 vs 5. Cyclopropanation of Silyl-Protected Allylic Alcohols58 ClCH2I was used instead of CH2I2. Synthetically useful anti diastereoselectivities were obtained when the benzyl ether was replaced by a more hindered silyl ether (Table 9). 103.3) strain arguments is not sufficient to explain the diastereoselection in these reactions. these data clearly show that the use of simple A(1. Vol.58 However. 4 Table 7. 2003. increasing the steric bulk of the protecting group decreases the syn selectivity (Table 8. entries 1 vs 4. the sense of induction inverts as the steric bulk of the substituent on the carbinol side chain increases (Table 8. First. No. Diastereoselective cyclopropanation of allenic alcohols. Furthermore. in these cases. Second.986 Chemical Reviews. Diastereoselective Cyclopropanation of Allenic Alcohols55 Lebel et al. and 3 vs 6).

CdC) is more highly populated when a bulky protective group is present on the alcohol. The analogous fluoro derivative 45 could also be converted into the corresponding syn cyclopropane 46 (dr >99:1) in 73% yield upon treatment with Et2Zn/ CH2I2 in CH2Cl2. since the reaction of the chlorosubstituted alkene led to the syn diastereomer (eq 16). Kodama independently reported a related reaction in the total synthesis of (+)bicyclohumulenone. Barrett has shown that a double asymmetric Simmons-Smith cyclopropanation of the (E)bis(olefin) 49 could be used to successfully prepare (1S. Transition structures for the cyclopropanation of silyl-protected allylic alcohols. 86 90 ratio syn:anti 68:32 82:18 100:0 Figure 8. but the reaction required 8 days (eq 17).2S)-(E)-1. CH2I2 (10) CH2Cl2 yield (%) quant.67 entry 1 2 3 4 5 H H R conditions Et2Zn (2). since the products are precursors to cyclopropyl carbocyclic nucleosides. 103. A appears to be the most plausible one. on the basis of the work of Gung. 2003. it is expected. which are potential chemotherapeutic agents (Tables 1062 and 1163). 4 987 Table 11. Diastereoselectivity of the Cyclopropanation of 43 as a Function of the Protective Group63 entry 1 2 3 Bn R conditions Et2Zn (5). the nature of the protecting group was found to be extremely imporTable 10. No. Of the two possible transition structures A and B. MOM TBDPS and conversions.Stereoselective Cyclopropanation Reactions Chemical Reviews. Diastereoselectivity of the Cyclopropanation of 41 as a Function of the Protective Group62 In a model study related to the total synthesis of FR-900848.65 The discrepancies between the two results may be a consequence of the difference of solvent (ether vs CH2Cl2) and reagent (IZnCH2I vs EtZnCH2I).59 Furthermore. in which the cyclopropanation of allyl alcohol derivative 47 proceeded with the opposite diastereofacial selectivity (eq 18).2-bis[2-methylcyclopropyl]ethene with excellent stereocontrol (eq 19).64 Quite interestingly. The diastereoselective cyclopropanations of (E)and (Z)-allylic alcohols derived from 2. that the eclipsed conformation will also be the most reactive when the oxygen is complexed with the reagent (Figure 8).61 tant for obtaining high yields and high levels of stereocontrol.60 This elegant use of diastereocontrol led to the efficient synthesis of the chlorocyclopropane unit of callipeltoside A. With both isomers. ClCH2I (4) (CH2Cl)2 Et2Zn (5). on the basis of stereoelectronic arguments. Vol. Furthermore.66 The analogous (Z)bis(olefin) 51 reacted in a similar fashion to produce bis(cyclopropane) 52 as a single diastereomer (eq 20).3-O-isopropylideneglyceraldehyde (41 and 43) have been the subject of several investigations. CH2I2 (10) CH2Cl2 yield (%) 70 61 94 86 84 ratio syn:anti 77:33 58:42 84:16 92:8 100:0 Bn MOM TBDPS . who has established that the eclipsed conformer (CsO. the anti selectivity seems to be quite substrate dependent.

Scheme 5. Table 13. as shown in Figure 9. For example. entry 2). the cyclopropanation of 62 led to the opposite diastereomer (Scheme 5). In both cases.988 Chemical Reviews. rt. Diastereoselective Cyclopropanation of Homoallylic Alcohols69 Lebel et al. 103. 5 h (50%) CHBr3. cyclopropanation of 57 produced a 71:29 mixture of diastereomers under the same conditions (eq 23). 4 Table 12. the cyclopropanation of (Z)-5-hydroxy-2alkenylsilanes 53 occurs with very a high level of stereochemical induction (eq 21). The lower stereoselectivity with 57 was explained by the fact an alkyne. No. Addition of dichlorocarbene to 55 led to the exclusive formation of 56 (eq 22). led to a chiral allylic amine.72 The change to a noncoordinating solvent may be responsible for the participation of the amide butyloxycarbonyl (Boc) group in the delivery of the reagent. reflux. Diastereoselective Cyclopropanation of Chiral Allylic Amine 62 The stereoselective cyclopropanation of homoallylic alcohols has been used with moderate success.2-stereocontrol to produce the anti isomer irrespective of the geometry of the starting olefin (Table 12). CH2I2 Et2O.3) allylic strain). Cyclopropanation of Chiral Allylic Amines71 entry 1 2 3 4 R1 H H n-C5H11 Me R2 Ph n-C5H11 H Ph yield (%) 88 83 71 79 ds 93:7 >98:2 >98:2 >98:2 entry 1 2 conditions Et2Zn.69 A chairlike transition state. which was cyclopropanated to give the anti isomer with outstanding diastereocon- . The that the spacial relationship between the hydroxy group and the alkene is not optimal for a directed reaction.71 The analogous dibromocyclopropanation of tert-butyl-2.73 Hydrozirconation of exclusive formation of 56 can be rationalized by considering that the carbene delivery is hydroxyassisted on the most stable alkene conformation (minimization of the A(1. Vol. has been proposed to explain the high diastereoselectivity of this transformation. Landais has shown that the cyclopropanation of 2-silyl-3-alkenols occurred with very high 1.2-dimethyl-4-(2′-phenylvinyl)-3-oxazolidinecarboxylates afforded good diastereomeric ratios of dibromocyclopropanes (Table 13. An interesting anti-selective cyclopropanation has been reported by Wipf (eq 24). Chairlike transition structure for the cyclopropanation of homoallylic alcohols. The cyclopropanation of chiral protected allylic amine 59 produced the anti isomer 60 with good selectivity (Table 13). followed by the addition of the vinylzinc intermediate to the N-phosphinoylimine. unassisted delivery of the carbene from the least hindered face of the olefin in its most stable ground state conformation can be invoked to predict the stereochemical outcome of these reactions.70 Conversely. 2003. 2 d (87%) ratio 60:61 75:25 (X ) H) 85:15 (X) Br) Figure 9. Quite intriguingly. NaOH TEBAC.68 This is one of the few acyclic homoallylic alcohols in which the cyclopropanation produces a good level of control.

. Chiral Auxiliaries A number of auxiliary-based approaches have been reported.76 Table 15. Chiral allylic ethers (A). A number of acetal-derived auxiliaries have been studied for this reaction (Table 16. The chiral auxiliaries in each class are shown in Table 16.74 Figure 10.3) allylic strain. 2003.78e. the cyclopropanation of 64 led to equal amounts of both diastereomers of 65 and 66 (eq 25). Transition-state model for the cyclopropanation involving the glucose-derived chiral auxiliary. Synthesis of Bis(cyclopropane) Derivatives76 entry 1 2 3 4 5 R Ph Me i-Pr C6H11 TBDPSOCH2 yield (%) 80 68 72 78 72 ratio 70:71 83:17 83:17 86:14 88:12 >95:5 The major products in all the cases presented above can be predicted on the basis of the minimization of the A(1. For example.75 The level of stereochemical induction depends Table 14.and samarium-derived reagents failed to produce the desired product.77 and enamines and enol ethers (D) have been successfully studied for these reactions (Figure 10).2-cyclohexanediol (Table 16. Diisopropyl tartrate has been particularly effective with (E)-disubstituted and -trisubstituted acyclic substrates (Table 16. reasonably good diastereoselectivities can be observed (Table 14). Barrett and Tustin have found that the cyclopropanation of various vinylcyclopropanes 69 produced the anti isomer as the major product (Table 15).β-unsaturated carbonyl derivatives (C). It is interesting to know that both the zinc. The cyclopropanation of (E)-vinylcyclopropane proceeds with surprisingly high induction.78d Cleavage of the chiral auxiliary is then accomplished by a ring contraction reaction (glucosederived auxiliary) or by a three-step sequence involving conversion of the alcohol into an iodide and reductive elimination of the cyclopropylmethanol moiety upon treatment with BuLi. and many of them offer the advantage of producing enantiomerically pure cyclopropyl derivatives after the cleavage of the auxiliary. 4 989 trol.78a-c It is believed that the chiral auxiliary acts as a bidentate ligand to complex to the zinc reagent (Figure 11). Cyclopropanation of Chiral Allylsilanes75 Figure 11. however. in which the basic group that directed the reagent is not on a stereogenic center. R.78 Carbohydrate-derived chiral auxiliaries79 have produced extremely high diastereoselectivities in the cyclopropanation reaction involving substrates of type A (Table 16. entry 1 2 3 4 R H Me Bn H PG H H H TBDPS yield (%) 79 81 67 67 ratio anti:syn 75:25 95:5 86:14 60:40 C.f whereas diO-benzylthreitol undergoes efficient and diastereo- on the nature of the groups on the chain and on the protecting groups. This is the first example that demonstrates that a methylzinc amide can undergo an alkyl exchange reaction with diiodomethane to generate the reactive iodomethylzinc amide. 103. entries 1-3). the stereocenter at the allylic position bears a bulky dimethylphenylsilyl group. This postulate has given rise to the simpler auxiliary derived from 1. entry 5). acetals (B). is usually not very high. Vol. entry 4). Various classes of chiral auxiliaries. entries 5-8). If. The different chiral auxiliaries that have been developed for the reaction with the various halomethylmetal reagents are emcompassed in four general classes. No.Stereoselective Cyclopropanation Reactions Chemical Reviews. The stereocontrol in the cyclopropanation of acyclic alkenes. The most efficient auxiliaries are derived from tartaric acid.

81 The configuration of the cyclopropane can be rationalized by the models shown in Figure 12. 4 Table 16.78g. entry 6). selective cyclopropanation with cyclic substrates (Table 16.990 Chemical Reviews. Vol. In the case of 2-cycloalken-1-ones. 2003.80. 103. Chiral Auxiliaries for Halomethylzinc-Mediated Cyclopropanation Lebel et al. studies support a mechanistic model that involves preferential chelation of the reagent by the least sterically hindered dioxolane oxygen atom proximal to the alkene (Figure 12.h Both auxiliaries are readily cleaved under acidic conditions to produce the corresponding cyclopropyl ketone or aldehyde. model . No.

86 The asymmetric synthesis of (Z)and (E)-disubstituted and -trisubstituted cyclopropanecarboxylic acid derivatives was achieved via a stereoselective electrophilic methylene transfer to R.β-unsaturated acyl ligands bound to the iron chiral auxiliary (Table 16. Precomplexation of the reagent by the dioxolane oxygen and the carboxyl oxygen leads to the model B shown in Figure 12.78°-r The destructive cleavage of the auxiliary produced cyclopropanol derivatives (1.m It was proposed that the olefinic bond adopts a conformation approximately orthogonal to the acyl group. No. K2CO3).and endo3-amino-2-hydroxybornane-derived auxiliaries were also effective only with the hydroxy group protected as a triisopropylsilyl ether (Table 16.82 Mash has also reported that the auxiliary derived from dihydrobenzoin is even superior to the tartrate-derived ligand with cyclic enones. entries 10 and 11).78k but their installation leads to diastereomers that need to be separated.Stereoselective Cyclopropanation Reactions Table 16 (Continued) Chemical Reviews. The last class of auxiliaries is shown in entries 1214 of Table 16. Unfortunately. entry 12). Transition-state model with tartaric acidderived auxiliaries. The exo.β-unsaturated ester. The highly nucleophilic enol ethers derived from ketones react smoothly with bis(iodomethyl)zinc to produce cyclopropyl ethers with outstanding diastereoselectivities (Table 16.78l. 103.85 Other chiral auxiliaries in this class include the one derived from 1-aryl-2. and the selectivities observed are much more modest than those presented above. amide. entry 9).82a but attempts to use it with acyclic systems did not produce high ratios. 4 991 Figure 12.78n Furthermore.84 This is consistent with the fact that bidentate chelation by the chiral auxiliary is not favored in this case. since the electrophilic nature of these reagents often precludes the cyclopropanation reaction with these substrates. 2. PCC. only one example (cinnamic acid) was reported. the addition of diethyl tartrate was necessary to increase the yield of the cyclopropane product. the sense of induction in Yamamoto’s acyclic system is opposite to that found in the cyclic system. A). hexane). or other derivatives is not very common for this reaction. thus increasing its nucleophilicity. This can be accounted for by assuming that the chiral auxiliary acts as a bidentate ligand under Yamamoto’s conditions (Zn(CH2I)2.87 Imai has shown that 1-alkenylboronic esters bearing the tetramethyltartaramide group underwent highly diastereoselective cyclopropanation reactions to produce . These compounds allow preparation of enantiomerically enriched cyclopropyl alcohols and amines. 2003. since the reaction is done in a complexing solvent (ether).2-dimethyl-1. Vol. entry 8). Quite interestingly. entry 7)78j and D-fructose (Table 16. The use of chiral R. The aluminum-derived reagent was superior with this auxiliary.83.3-propanediols (Table 16.

103. One example is 1-cyclohexenylmethanol. such as 3-tributylstannyl-2-propen-1-ol. A major breakthrough in this area occurred when it was found that a simple bifunctional.92 The first practical stoichiometric system for the enantioselective cyclopropanation of allylic alcohol was reported by Fujisawa and co-workers.78t-u This derivative.98 Charette has also shown that the reaction could be used in the case of polyenes.89 Seebach has also used a chiral dihydrooxazole. The reaction proceeds well with cis. to generate the corresponding cyclopropane with perfect stereocontrol (Table 16. which has also been prepared by resolution.and trans-disubstituted allylic alcohols as well as with tetra-disubstituted ones.N′tetramethyltartaric acid diamide and butylboronic acid. The dioxaborolane 75. Inouye and co-workers found that very low yields (e15%) and enantiomeric excesses (e3. No. readily obtained from (S)-serine or (S)-threonine. Since this methodology is one of the most efficient known to date for the preparation of enantiomerically enriched substituted cyclopropylmethanols. Vol.88 The diastereoselective cyclopropanation of chiral 3-vinyl-2-oxazolidinone with zinc monofluorocarbenoid produced the corresponding 2-fluorocyclopropylamine with modest selectivities (Table 16.78v.N. nonracemic ligand containing both acidic (different than zinc) and basic sites would allow simultaneous chelation of the acidic halomethylzinc reagent and the basic zinc alkoxide. chiral. 2003. Stoichiometric Chiral Ligands The first attempts to control the absolute stereochemistry in the cyclopropanation of substrates by adding external chiral ligands were reported in 1968. diethylzinc.95 3-iodo-2-propen1-ol.97 and allenylic alcohols. Enantioselective Cyclopropanation with Dioxaborolane Ligand 7594 R1 H H H H H H H Bu3Sn I Et TBDPSOCH2 BnOCH2 Me H H Me R2 Ph 3-MeOPh Pr PhCH2CH2 BnOCH2 Bu3Sn I H H H H H Me Ph Et Me R3 H H H H H H H H H H H H H Me CH2OTIPS CH2OTIPS yield (%) 95 >98 80 90 87 88 83 73 90 90 93 93 85 96 >98 85 ee (%) 94 93 93 94 94 90 90 90 93 93 91 91 94 85 89 88 D. 4 Lebel et al. KHCO3) (Table 16.96 2-chloro-2-propen-1-ol. They have also shown that this system is slightly more efficient in the cyclopropanation of siliconsubstituted allylic alcohols (eq 28).992 Chemical Reviews. Excellent regioselectivity favoring the allylic alcohol is observed in the . was an efficient chiral controller for that reaction (Table 17). 2-substituted cyclopropanols after oxidation (H2O2.94 The corresponding substituted cyclopropylmethanols of a variety of allylic alcohols are produced with excellent enantioselectivities (85-94% ee) when a mixture of the alcohol and ligand 75 is added to the preformed halomethylzinc reagent.44c Denmark also found that modest enantioselectivities were observed in the enantioselective cyclopropanation of cinnamyl alcohol using (1R. and diiodomethane (eq 27).N′. entry 13). it is not surprising to see that it has been used in the enantioselective cyclopropanation of important chiral building blocks for natural product synthesis. entry 15).w Very little work has been reported on the use of more complex diiodoalkane as precursors to more substituted haloalkylzinc reagents. but others are problematic. is a key intermediate in the synthesis of DU-6859. prepared from the commercially available N.78s.91 Furukawa and co-workers also had very little success when they added L-leucine as a coadditive in the cyclopropanation of vinyl ethers. Some trisubstituted allylic alcohols are converted to the corresponding cyclopropane with high enantiomeric excess. a quinolonecarboxylic acid exhibiting antibacterial activity and little side effects. Sugimura has reported that his chiral auxiliary was effective at producing one major diastereomer from this reaction (eq 26).2S)-N-methylephedrine-modified halomethylzinc reagent.β-unsaturated esters. which is converted to the corresponding cyclopropane in good yield (84%) but with low enantiomeric excess (60%).90 Table 17.93 They showed that moderate levels of enantioselection (7081% ee) were observed if a stoichiometric amount of diethyl tartrate (DET) was added to a mixture of the allylic alcohol. entry 14).4%) were obtained if a mixture of (-)-menthol and IZnCH2I was added to R.

It is not possible to use this reaction to carry out kinetic resolution of chiral. First. the absolute stereochemistry of the cyclopropane is consistent with the model shown in Figure 13. Even though this method can be used to convert an enantiomerically pure chiral allylic alcohol to the anti-cyclopropyl derivative. Transition structure for the cyclopropanation with chiral ligand 75.98 Scheme 6. Accordingly.107 It was also shown that functionalized 1.103 and doliculide.101 U-106305.3-substituted cyclopropanes (Table 18). it has been used to elaborate the chiral cyclopropanes subunits of curacin A. 2003. .1-diiodoalkanes can be used in this reaction (eq 31). For example. 103.Stereoselective Cyclopropanation Reactions Chemical Reviews. the zinc alkoxide reacts with the dioxaborolane ligand in an irrevers- Figure 13. Vol.and diastereoselective cyclopropanation of allenic alcohols.100 FR-900848. it is probably more In all the previous reactions involving the dioxaborolane ligand.3-Substituted Cyclopropanes106 cases where the substrate contains more than one double bond (eq 29). Second. which led to enantiomerically enriched spiropentane derivatives (Scheme 6). the zinc reagent deprotonates the alcohol to generate the zinc alkoxide.3-substituted cyclopropanes using zinc-derived reagents.102 epothilone analogues.104 The same reaction conditions were also applied to the enantio.99 The enantioselective cyclopropanation reaction using the dioxaborolane-derived ligand is quite general and practical. This reaction constitutes the first practical stereoselective synthesis of 1. No. when racemic 76 is cyclopropanated with zinc reagents in the presence of the chiral ligand. Cyclopropanation of Allenic Alcohols practical to simply cyclopropanate its corresponding silyl ether.2.1-diiodoethane and diethylzinc. in which the reaction proceeds via three distinct steps. both enantiomers react at about the same rate.2. which gives also the anti isomer with an excellent anti:syn ratio (vide supra).105 The chiral dioxaborolane-derived ligand was recently used to synthesize 1. 4 993 Table 18. and they both lead mainly to the anti isomers (eq 30). Preparation of 1. racemic allylic alcohols.106 High diastereoselectivities and enantioselectivities were recorded when a variety of allylic alcohols were treated with the reagent formed by mixing 1.2.

4 Table 19. ible fashion to generate the tetracoordinated boron intermediate. product. No. a significantly large excess of diethylzinc is required (enantiomeric excess and yield drop dramatically if less than 6 equiv of diethylzinc is used). Asymmetric Cyclopropanation of Allylic Alcohols with Chiral Disulfonamide Catalysts109-112 ee (%). 75 59. Kobayashi and co-workers109 were the first to report that the Simmons-Smith cyclopropanation reaction could be significantly accelerated by the addition of a chiral Lewis acid. 77 86.1′-bi-2-naphthol-3. Table 20. 93 In situ generation of ZnI2. 103. 83 66. entries 8-11).N′-tetraethyl-1. 82 75. The enantioselective cyclopropanation of tri. 100 36.111 Denmark has published an in-depth study of this reaction and highlighted the effect of the many variables to optimize the enantiomeric excesses of the Figure 14. Consistently high enantioselectivities were obtained with 3-substituted cis. 67 72. Chiral Catalysts A few catalytic systems have been reported for the enantioselective cyclopropanation of allylic alcohols. Transition structure for the cyclopropanation with 83. These optimized conditions. 108 The scope of the reaction seems somewhat limited. Enantioselective Cyclopropanation Mediated by 81108 Lebel et al. led to the formation of the cyclopropanes with consistently higher enantioselectivities (Figure 15). Furthermore.and tetrasubstituted olefins is generally not as effective. E. 86 13. since only (E)-substituted allylic alcohols can be converted into the corresponding cyclopropanes with reasonably good yields and enantioselectivities. Vol. They found that unprecedently good enantioselectivities were observed if the C2symmetric chiral disulfonamide ligand 82 was added in catalytic amounts to the zinc-mediated cyclopropanation of allylic alcohols (Table 20).and trans-allylic alcohols. 81 89. 71 82. 94 81. a ligand that is prepared in four steps from binaphthol. This method has also been extended to the enantioselective cyclopropanation of vinyl silanes and stannanes (Table 20. yield (%) entry 1 2 3 4 5 6 7 8 9 10 11 12 a R1 Ph H PhCH2CH2 BnOCH2 TrOCH2 H H Bu3Sn Me2PhSi H H H R2 H Ph H H H BnOCH2 TrOCH2 H H Bu3Sn Me2PhSi PhCH2CH2 catalyst 82 76. 93 catalyst 83 89. 88a 72. 70 80.994 Chemical Reviews. in which three zinc atoms are involved in the methylene delivery process (Figure 14).3′-dicarboxamide (81).110 Equally high enantioselectivities were obtained if the zinc-derived Lewis acid was replaced by the analogous aluminum catalyst. which was shown to be due to the generation of zinc iodide.112 The independent preformation of the ethylzinc alkoxide and bis(iodomethyl)zinc was found to be crucial. The reaction displayed autocatalytic behavior. using the dimethylsulfonamide ligand 83 derived from trans-cyclohexanediamine. He has shown that the rate and selectivity of the catalytic enantioselective cyclopropanation of cinnamyl alcohol utilizing bis(iodomethyl)zinc and the bis(sulfonamide) 83 are greatly dependent on the order of addition of the reagents.N′. which then undergoes an “amidedirected” cyclopropanation reaction on the most stable conformation of the allylic ether chain. This and other observations have led to the proposed transition-state assembly. can be used for the enantioselective cyclopropanation of allylic alcohols (Table 19).N. 36 65. 92a 81. . 2003. Recently. Katsuki and co-workers have found that N.

Several achiral Lewis acids were effective in inducing the cyclopropanation. as well as the type of the reaction to be carried out (inter. so far. the use of the titanium taddolate produced the corresponding cyclopropane derived from aryl-substituted allylic alcohols in up to 92% ee. In light of this.and intramolecular versions of this reaction have been developed and exploited in synthesis.vs intramolecular). the use of new zinc-based systems for the enantioselective cyclopropanation of unfunctionalized alkenes or those deprived of proximal functionalities that could assist in the reagent delivery is still elusive. 103. However. III. plays a key role in the appropriate selection of the most efficient catalyst for a given transformation. superior with some alkyl-substituted allylic alcohols. Proposed Catalytic Cycle Charette and Brochu have reported an alternative protocol for the Lewis acid-catalyzed cyclopropanation reaction of allylic alcohols. Enantiomeric excesses (yield) for the cyclopropanation with 83. The nature of the starting diazo reagent. asymmetric cyclopropanation using zinc-derived reagents. This substoichiometric system is particularly effective with aryl-substituted allylic alcohols.and intramolecular cyclopropanation reactions. No. Vol. in which the uncatalyzed process is minimized. 4 995 Table 21.Stereoselective Cyclopropanation Reactions Chemical Reviews. the enantioselective cyclopropanation reaction of allylic alcohols using the stoichiometric dioxaborolane chiral ligand is probably still the most reliable method to generate cyclopropylmethanol derivatives in high enantioselectivities.114 but the cyclopropanation of alkyl-substituted allylic alcohols still needs to be improved. At this time. within . However. The Kobayashi/Denmark system is. Finally. Cyclopropanation Catalyzed by Ti-Taddolate 84114 Figure 15. the search for better catalysts to increase the scope of the reaction and to improve the enantioselectivities is still among the top research priorities in this area. Scheme 7. 2003. It is apparent that significant advances have been made toward the development of an efficient catalytic. Introduction The cyclopropanation of olefins using the transition metal-catalyzed decomposition of diazoalkanes is one of the most extensively studied reactions of the organic chemist’s arsenal (eq 32). this section of the review will be divided into inter. and. Transition Metal-Catalyzed Decomposition of Diazoalkanes A.113 The addition of Zn(CH2I)2 (1 equiv) to an allylic alcohol (1 equiv) produced the iodomethylzinc alkoxide (Scheme 7). In addition.115 Both inter. These species are typically not good methylenetransfer agents unless a Lewis acid is added. it is clear from the results presented in this section that a chiral catalyst for the haloalkylzinc-derived cyclopropanation of greater scope and selectivity would still be welcome. namely with regard to the understanding of how to achieve significant ligand-accelerated reaction.

Os). The emphasis will be placed on the most efficient catalyst to use with a given diazo starting material. as shown in Figure 16. because of the large body of data available on this topic. 1. and it will be briefly reviewed below. In the part B of this section. the lactam 91 and lactone 93 produced cyclopropane 92 and 94 in 90:10 and The 1.127 Pd2(dba)3 9 “LnPddCH2” + N2 8 CH2N2 CH2N2 (33) 8 (PPh3)2PdCl2 9 (PPh3)2Pd(CH2Cl)Cl + N2 (34) We have also included in this section the cyclopropanation of alkenes via a 1.3-dipolar cycloaddition. For example.125 B. This reaction has been extensively used in the cyclopropanation of chiral alkenes. with diazomethane produced the corresponding pyrazoline.3-O-isopropylideneglyceraldehyde. For example. only the most effective catalytic systems will be reviewed. Ru. Fe. Diazomethane The simplest diazoalkane. and the scope of the reaction will be presented. derived from 2.117 Although a large number of metal salts interact with diazomethane (Ni. each section.3-dipolar cycloaddition (Scheme 8). The diazo precursors 85-88 will be divided according to their electronic properties. Common diazoalkane precursors.118 palladium salts119 are very effective at decomposing diazomethane in the presence of an alkene to lead to cyclopropane formation. each class of diazo precursor will be reviewed separately. The pyrazolines 89 and 90. treatment of the dehydroaminopentenoate 99.3-Dipolar Cycloaddition of Diazo Compounds Figure 16. are effective catalysts. such as the palladium dibenzylideneacetone complex (Pd2(dba)3).121 A subsequent reaction with diazomethane would generate the palladium carbene (eq 33).130 . but heat or photolysis has also been used to induce N2 extrusion.128 For example. the intramolecular version of the reaction will be reviewed. 103. Zn. No. along with its more stable trimethylsilyl analogue (TMSCHN2)116 and phenyldiazomethane (PhCHN2). The reaction of 95 with diazomethane in the absence of a catalyst leads to only one isomer after nitrogen extrusion (eq 37). upon irradiation. but these species are apparently not good cyclopropanating agents123. 86:14 diastereomeric ratios.3-dipolar cycloaddition of diazomethane to chiral acyclic alkenes has been studied quite extensively. The Pd-catalyzed cyclopropanation of chiral cyclic alkenes usually proceeds with good diastereocontrol when sterically demanding groups are present near the olefin. Co. 2003. Pd.126 The cyclopropanations of chiral acyclic alkenes usually do not proceed with a high level of stereocontrol unless a bulky chiral auxiliary is used (vide infra).122 In some other cases. 4 Lebel et al. respectively (eqs 35 and 36). only the optimal catalysts for a given substrate will be highlighted.124 (eq 34). U. which. Vol. Cu. Intermolecular Cyclopropanation 1. led to cyclopropane 100 as a single isomer (eq 39). diazomethane (CH2N2). the formation of a palladium halomethyl complex has been demonstrated. Again. since some palladium(0) complexes. It is important to emphasize that. It should be pointed out that it is also possible to get similar levels of diastereocontrol by 1.129. has been used in cyclopropanation reactions. are sometimes not stable and decompose directly to the cyclopropane. the cyclopropanation of ricinolic acid derivative 97 does not proceed with an acceptable level of stereocontrol (eq 38). Scheme 8.120 Mechanistically. it is possible that the palladium(II) catalyst precursor is initially reduced to palladium(0) by diazomethane.3-dipolar cycloadition with diazomethane. resulting from the 1.996 Chemical Reviews.

A large number of chiral palladium complexes have been tested by Denmark and co-workers. Chiral Sultam 103 as Chiral Auxiliary133 R Pent Bu t-Bu Ph TIPSO(CH2)3 TBSOCH2 yield (%) 99 98 95 93 89 90 dr 93:7 89:11 87:13 86:14 95:5 70:30 R1 Ph 2-MeOC6H4 3-MeOC6H4 3. no enantioselection was observed. No. Some representative examples are shown in Figure 17. However. The most efficient system known to date uses a copper-based catalyst. Pietruszka has examined the cyclopropanation reaction of vinylboronate esters bearing various chiral auxiliaries.4. Chiral auxiliaries for the 1.4. An attractive approach to enantiomerically pure cyclopropane derivatives would be to introduce chiral ligands on the metal complex (eq 41) in the diazomethane-mediated cyclopropanation of alkenes. in many examples. It was concluded that either partial or complete decomplexation of the ligand was occurring during the course of the reaction. and several derivatives of 105 were cyclopropanated with good diastereoselectivities (Table 23). this auxiliary has been tested only with cinnamaldehyde.137 2.1.5-(MeO)3C6H2 4-NCC6H4 2-MeO-5-FC6H3 2-RC6H4a 2-thienyl 4-Br-2-thienyl 2-furyl ferrocenyl Me decyl a yield (%) 73 73 63 62 29 46 11 71 59 67 76 72 62 dr 93:7 96:4 86:14 83:17 80:20 90:10 81:19 94:6 84:16 88:12 91:9 95:5 92:8 Figure 17. Cleavage of the auxiliary was accomplished with silica gel. although all the catalysts were very active. 4 997 Table 23. 2003.136 but. the formation of the cyclopropylboronic acid could be achieved only through an LAH treatment.134 The most successful auxiliary was that derived from 1.4-tetraphenyl-2.Stereoselective Cyclopropanation Reactions Chemical Reviews.3butanediol. Vol.3-dipolar cycloaddition of diazomethane have also been developed for specific substrates. Cyclopropanation of Vinylboronate Esters 105134 A number of chiral auxiliaries have been developed for the cyclopropanation of acyclic alkenes. but the scope of the reaction has not been described (eq 42).135 The problem with this approach often resides in the stereoselective preparation of the alkene precursor or of the photoinduced nitrogen extrusion. A major advantage of this approach is that diastereomeric products could be separated by chromatography.4-dimethoxy-1.135 R ) 2-methyl-1.133 In an extensive study to generate enantiomerically pure substituted cyclopropylboronic acids that are suitable for palladium-catalyzed cross-coupling. 103.131 Cinnamaldehyde. Although. Unfortunately. produced oxazolidine 101 as a single diastereomer. The cyclopropanation of 101 gave 102 as a single diastereomer. the diastereomeric excesses are quite modest. Oppolzer’s chiral sultam has also been used as a chiral auxiliary for this transformation (Table 22).3-dioxolan-2-yl.3-dipolar cycloaddition of diazomethane. followed by hydrolysis of the resulting borohydride. the diastereomeric products could be recrystallized to remove the minor isomer (96 f 99. upon treatment with ephedrine. which could lead to a diastereomeric mixture under some reaction conditions. An ephedrine-derived auxiliary was shown to be quite effective in these reactions (eq 40). Diazoalkanes Bearing an Electron-Withdrawing Group (N2CH(EWG)) The most exhaustively studied diazo reagents for intermolecular cyclopropanation reactions are the .132 Table 22.134f The cyclopropanations of the corresponding cis isomer of 105 were tested. but the diastereoselectivities were significantly lower (65:35 to 87:13).5% de).134g Chiral auxiliaries that allow control of the facial selectivity of the 1.

R-diazoesters (112.150 have also been carried out on the copper(I)-catalyzed cyclopropanation of propene with Figure 19.145 Porphyrinruthenium carbenes 118 and 119 have been isolated. 2003. Ru. Catalytic Cycle for the Cyclopropanation Lebel et al. 4 Scheme 9. and reacted in situ in the presence of the metal catalyst and the alkene. Most common diazo reagents.998 Chemical Reviews.138 but several others. Nishiyama successfully obtained the X-ray crystal structure of a pybox ruthenium carbene 117 (Figure 19). In most of these cases (Cu. Fe.142 Several stoichiometric carbenes derived from ruthenium143 and osmium144 have been prepared and characterized in solution and were shown to act as efficient catalysts for the cyclopropanation reaction. Rh. Pd.149 and isotope effect and Hammett studies.141 Usually. Rh. and their X-ray crystal structures have been reported. No. . whereas Pd metal carbenes are optimal for electron-deficient alkenes. which was shown to be an active cyclopropanating reagent under drastic conditions. Chem3D representation of several X-ray crystal structures of ruthenium carbenes. and Cu metal carbenes react faster with electron-rich alkenes. Ru. and others have been reported to catalyze the diazo reagent decomposition. Cr.139 have been used to prepare cyclopropanes (Figure 18). 103.140 A wide range of metal catalysts derived from Cu. Co. Vol. Co. Pt. a recent solution-state NMR study of carbene 120147 has been carried out and showed that the mechanistic picture is fully consistent with that proposed by Pfaltz and co-workers (vide infra).146 Although the copper carbenes have never been characterized by X-ray crystallography. Ru. Os). Rh. Y ) OR). all containing one electron-withdrawing group (113116). the mechanism of the transition metal-catalyzed decomposition of R-diazocarbonyl compounds is believed to initially proceed via the formation of a metal carbene complex (Scheme 9). Os. Simple R-diazoesters have been prepared Figure 18.148 Recent calculations.

For this reason. although Cu(II) salts are often used as catalyst precursors. 103.154 The reaction of ethyl diazoacetate with a chiral cyclic alkene usually proceeds well with reactive alkenes. Some examples are shown in Figure 20.159 Figure 20. but these will not be discussed in this review. Vol. Chiral auxiliaries for the intermolecular cyclopropanation of styrene.158 The introduction of a chiral auxiliary on the diazo reagent has not been very successful. represented by the transition structure A (and not metallacyclobutane B in Scheme 9). substituted hydrazine. Although there are some exceptions. the cyclopropanation of acyclic chiral alkenes leads to mixtures of stereoisomers. No. For example. Doyle has shown that the rhodiumcatalyzed decomposition of a very hindered R-diazoester (such as the 2. This section of the review will focus only on the most effective chiral catalysts in terms of both enantio. the diastereoselectivities favoring the trans isomer usually improve when the steric demand of the Y group increases.and diastereomeric ratios.153 An alternative approach to metal carbenes is to substitute the diazo reagent with the corresponding iodonium ylide (PhIdCHCOOR) or sulfonium ylide (Ph2SdCHCOOR). but they generally produce lower enantio. Both studies support the addition of the very reactive metallacarbene intermediate in an early transition state to the substrate alkene in a concerted but strongly asynchronous pathway with substantial cationic character on one alkene carbon.Stereoselective Cyclopropanation Reactions Chemical Reviews.156 125 was treated with ethyl diazoacetate and palladium acetate (eq 45). It is important to point out that.and diastereoselectivity (eq 46). First. the relative stereocontrol for the stereogenic center bearing the ester group is sometimes quite modest (eq 44). the TBS-protected D-glucal could be converted to the cyclopropyl derivative with almost complete stereocontrol when Rh2(OAc)4 was used as the catalyst (eq 43).151 In a seminal work. the most effective catalysts for the preparation of the trans isomer with the widest reaction scope are the copper-based catalysts. along with the diastereoselectivities observed for the cyclopropanation of styrene.157 The decomposition of R-diazoesters by chiral transition metal complexes to cyclopropanate achiral alkenes in an intermolecular fashion is one of the most widely studied asymmetric processes.160 The selection of the appropriate chiral catalyst for a given substrate depends on the nature of the starting alkene and on the appropriate choice of the starting diazoester (generally to maximize the trans: cis ratio). 4 999 diazo compounds. For example. Kochi has shown that CuOTf is one of the most effective catalysts. they have not been .155 Other protected glycals reacted in a similar fashion. Rhodium-based catalysts are very effective.152 Further evidence for the involvement of a Cu(I) species is provided by the observation that Cu(II) salts complexed with chiral ligands need to be preactivated for the reaction to proceed (DIBAL. heat with diazo reagent). a mixture of all four possible diastereomers was obtained when alkene Some general conclusions can be drawn from the experimental data available. As expected from the transition structure A.6-di-tert-butyl-4-methylphenyl ester) led to very high trans:cis ratios with monosubstituted alkenes. it has been demonstrated that Cu(I) salts are the catalytically active species in these reactions. for which an incredibly large number of chiral complexes have been prepared and tested. Although the facial selectivity in the reaction of relatively rigid systems is quite good. 2003.

have also produced some good results in these reactions. Only a sample of the potentially most useful chiral ligands that provide high enantioselectivities will be discussed in the review. The copper(I) complex of bis(oxazoline) 143. used much in enantioselective.182). which displayed unprecedented high enantioselectivities in cyclopropanation reactions. The main discriminating stereochemical element is the steric interaction between the ester group and the semicorrin substituent upon pyramidalization of the carbene center. 4 Lebel et al.149 The calculated relative energies are in good agreement with the experimental enantiomeric excesses as well as with the cis/trans ratio. The reaction proceeds with high yield and enantioselectivities with mono. several hundred chiral ligands have been synthesized and tested in coppercatalyzed processes.175 disclosed by Evans in the early 1990s.165 In 1986. 2003.161 Second.170 146. For example.171 147.153 reduction with LiAlH4 provides the primary alcohol in good yield. Catalyst Cu(I)‚143 had been used quite extensively in cyclopropanation reactions.173 155174). Pfaltz disclosed the novel semicorrin-type ligand 139. this catalyst defined the basis for further ligand optimization.2-disubstituted alkenes. is still a standard to which new bis(oxazoline) ligands are compared. surprisingly.167 141.163 This exercise led to catalyst 135. however. Bipyridine-derived ligands (151. low yields were observed with unactivated alkenes (such as 1-heptene). Many bis(oxazoline) and related bidentate ligands have been reported to be quite effective (140. is not efficient for styrene. which proved to be quite effective in the synthesis of chrysantemate esters (eq 48)164 and the side chain of cilastatin (eq 49).1disubstituted) and cyclic silyl enol ethers (Figure 24). Figure 21.168 142.and 1. suffered from their relatively low Lewis acidity.180 which. The facial selectivity observed is consistent with the model shown in Figure 22.166 These ligands.178 and of vinyl fluorides. even more effective ligands with broader scope. this ligand turned out to be quite good in the Cu(I)‚144-catalyzed cyclopropanation of trisubstituted and unsymmetrically 1. semicorrins.and enantioselectivities are provided for the cyclopropanation of styrene. as well as diamines (148. and others. intermolecular cyclopropanation involving R-diazoesters. and they will be briefly reviewed.and trans-cyclopropanecarboxylates (eq 47).176 of furans (eq 50). and the diastereo.177 of protected allylic alcohols (eq 51). but the ligands are usually structurally quite complex.172 149.162 The copper-catalyzed decomposition of ethyl diazoacetate in the presence of an N-benzylethylamine-based chiral salicylaldimino complex 134 gave about 6% enantiomeric excess of the corresponding cis. 103.1-disubstituted alkenes (Table 24).1000 Chemical Reviews. Although the BHT ester is reluctant to undergo saponification.169 145. cobalt-based catalysts are usually used in cisselective cyclopropanation reactions. Vol.181 152. Some of the structural variations of the ligands include substituted salicylaldimines. Although the enantiomeric ratios were modest. The best chiral ligands for the copper-catalyzed cyclopropanation are shown in Masamune has also developed bis(oxazoline) 144. but the scope is usually a bit narrower than that of the best copper-based ones. No. therefore. bis(oxazolines). Finally. The first example of an enantioselective copperbased intermolecular cyclopropanation reaction was reported by Nozaki in 1966. However. ruthenium-based catalysts are very efficient. Bisazaferrocene ligand 150185 gives very high enantioselectivities not . The stereochemical prediction of the bis(oxazoline) copper(I)-catalyzed cyclopropanation has been rationalized by Salvatella and Garcıa using DFT calcula´ tions (Figure 23).183 154184). Some typical examples are shown in Figure 25. bipyridines. it is quite effective in the cyclopropanation of some acyclic (1.179 In the past four decades. This disclosure was quickly followed by the development of numerous.

The pybox-i-Pr ligand reacts with [RuCl2(p-cymene)]2 to generate a complex that is quite effective in cyclopropanation reactions. The most effective ruthenium-based chiral catalysts are shown in Figure 26.Stereoselective Cyclopropanation Reactions Chemical Reviews.6-di-tert-butyl-4-methylphenyl. it is preferable to . One exception to this is the catalyst generated by mixing the iminodiazaphospholidine ligand 153186 with a stoichiometric amount of CuOTf. ruthenium carbenes bearing chiral ligands are less reactive than those derived from copper and rhodium. However. 103. Vol. including vinyltrimethylsilane (eq 52). Table 24. the enantioand diastereoselectivities observed with ethyl diazoacetate are impressive (Table 25). only with styrene but also with monosubstituted alkenes. Most of them will efficiently convert aryl-substituted alkenes to their corresponding cyclopropane. In general. 4 1001 Figure 21. 2003. but lower yields are observed with alkyl-substituted alkenes. No. The first very effective system was reported in 1994 by Nishiyama. Most previously described catalytic systems require a bulky ester to maximize the trans:cis ratio. Although the scope is limited to 1-aryl-substituted alkenes. Chiral catalysts for the intermolecular Cu-catalyzed cyclopropanation and the diastereoselectivies and enantiomeric excesses observed for the cyclopropanation of styrene.175 R1 Ph PhCH2 Ph Me a R2 H H Ph Me yield (%) 85 70 91 ratio trans:cis 94:6 93:7 ee trans (%) 99 >99 >99 >99 BHT ) 2. Enantioselective Cyclopropanation with 143a.

For example. The sense of induction in these reactions is consistent with the model shown in Figure 27. pybox-Ru 158 catalyzes the reaction quite nicely by producing the cyclopropane not only with high enantioselectivity but also with an improved diastereoselectivity.1002 Chemical Reviews. 4 Lebel et al. Cyclopropanation of Alkenes with Cu(I)‚153186 R1 yield (%) 80 76 71 78 ratio trans:cis 98:2 100:0 98:2 83:17 ee trans (%) 94 95 12 34 Figure 22. 97% ee). which can be purified by silica gel chromatography and is stable in solution.193 produce excellent level of enantio. the trans:cis ratios were not affected by the substituents. It should be pointed out that the use of the L-menthyl diazoacetate produced slightly higher diastereo.188 (Figure 26).and enantioselectivities compare to those observed with ethyl diazoacetate (eq 53). . Cyclopropanation of alkene using Cu(I)‚144. The second interesting observation is that non-C2-symmetric ligands are also quite effective in this reaction. Variable enantioselectivities are observed. 2003. Preferred approach of the alkene for the cyclopropanation with 139. However. a remote stereoelectronic effect has been reported. Two interesting observations have been made. However. depending on the nature of a substituent at the 4-position of the pyridine ring (157).and diastereocontrol. Cyclopropanation of silyl enol ethers catalyzed by Cu(I)‚143. The pybox-Ru catalytic system is probably the most studied Ru-based catalyst for cyclopropanation reactions. and electron-withdrawing groups increase the enantiomeric excess significantly (X ) CO2Me. and many structural variations of the ligand have been tested. 103. in which the alkene attacks in a geometry that puts the phenyl group away from the ester and isopropyl groups.189 Electron-donating substituents decrease the enantiomeric excess (84% ee for the cyclopropanation of styrene if X ) NMe2). Many other chiral ruthenium complexes were disclosed. carry out the reaction under an ethylene atmosphere to generate complex 156187. The cyclopropanation of aryl-substituted alkenes with this catalyst provides the corresponding cyclopropane in enantiomeric excesses ranging from 95 to 98%.191 and the ruthenium chiral Schiff base complexes 162192 and 164.190 It was reasoned that the removal of one of the oxazoline substituents created more space for the ester group in the chiral pocket. Ruthenium porphyrin 159. their synthesis is more tedious than that of the pybox system. and many proved to be very good catalysts. First. Ph 1-naphthyl PhCH2 PhOCH2 Figure 23. Figure 25. Vol. Table 25. No. The proposed metallacyclobutane formed with 143. Figure 24.

78 90. Although the early work in this area established that cobalt(II) complexes were catalytically active.4hexadiene. Among them. the low level of diastereo. Nguyen’s Ruthenium(II)-Catalyzed Cyclopropanation198 Figure 27. 168 95. Transition-state model for the Ru‚pybox cyclopropanation. 103. were shown to give excellent enantiomeric excesses in the cyclopropanation of monoor 1. 168 80. (catalyst) 95. 2003. producing the cis isomer (eq 54). 4 1003 Figure 26.5-dimethyl-2.Stereoselective Cyclopropanation Reactions Chemical Reviews. cis (%) >99 95 89. Mezzetti’s 161195 and Katsuki’s catalyst 163196 provide the highest cis:trans ratios.197 in which two of the free coordinating sites are occupied by a pyridine ligand.1-disubstituted alkenes (Table 26). Cobalt complexes have been shown to be reactive catalysts for the R-diazoester decomposition. Vol. 90 69. 163). A few ruthenium-based systems displayed cis selectivity in the cyclopropanation reaction (160. Mezzetti’s catalyst 165195 is effective for the cyclopropanation of 2. leading to a metal carbene that could convert alkenes to cyclopropanes. 167 97. For example.and enantio- . 166 ratio trans:cis 77:23 >99:1 66:34 80:20 76:24 ee trans. 166 30. Table 26. R3 Ph COOMe MeCHdCH OEt n-Pr R4 H Me H H H yield (%). Ruthenium catalysts for the N2CHCOOR-mediated cyclopropanation of alkenes.194 161. 18 Ruthenium salen complexes 166-168. No.

Excess alkene (5 equiv) was used. but the scope is limited to aryl-substituted alkenes (Table 28).198 Recently. Figure 28202 surveys the wide range of chiral rhodium catalysts that have been prepared so far. the diastereocontrol is not very good. 87 66. a large number of rhodium-based chiral complexes has been synthesized and tested in both inter. even when sterically hindered R-diazoesters are used. the level of diastereocontrol with rhodium carbenes does not match that observed with copper. 76 . As a general guideline.201 Both diastereomeric complexes 171 and 172 were examined and.200 It catalyzed the decomposition of tert-butyl diazoacetate in the presence of styrene to generate the trans-cyclopropane with an excellent diastereomeric ratio (96:4) and enantiomeric excess (93% ee).203 This important drawback has minimized the use of rhodium catalysts in intermolecular processes involving simple R-diazoesters. the level of diastereocontrol observed in intermolecular cyclopropanation reactions with R-diazoesters is problematic.199 The addiTable 27. since most of them are very reactive. although the level of enantioselection is sometimes excellent. Table 28. and 1.1-disubstituted alkenes that are substituted with at least one aryl group are converted to the cyclopropane derivatives with low diastereocontrol. 99 24. Table 29.or cis-selective cyclopropanation reactions. >98 45. Yamada has shown that 3-oxobutylideneaminatocobalt(II) complexes. The following class of the rhodium-based catalysts has been extensively studied for the intermolecular cyclopropanation reaction of alkenes. The optimal trans-selective complex is the cobalt salen 170. Although the reactivity of the rhodium carbene that is generated when the catalyst reacts with an R-diazoester is not an issue. No. Yamada’s Cobalt(II)-Catalyzed Cyclopropanation199 R1 Ph 4-ClC6H4 4-MeOC6H4 2-Naphthyl Ph R2 H H H H Me yield (%)a 89 85 84 94 39 ratio cis:trans 98:2 97:3 97:3 98:2 83:17 ee (%) 98 96 95 97 99 (99) a Based on the diazoester reagent. The reaction proceeded very well in the presence of NMI. Katsuki’s cis-Selective Cyclopropanation200 control limited their use in synthesis. The role of the base is to occupy one additional coordination site on the catalyst.1004 Chemical Reviews. R1 Ph 4-ClC6H4 4-MeOC6H4 2-naphthyl Ph R2 H H H H Me yield (%) 99 93 85 95 47 ratio trans:cis 91:9 90:10 82:18 87:13 47:53 ee (%) 96 96 92 96 99 tion of a catalytic amount of N-methylimidazole (NMI) increases the rate of the reaction as well as the enantioselectivity. The reaction is limited to arylsubstituted alkenes. Some examples provided in Table 29204-208 show that. Rhodium-Catalyzed Enantioselective Cyclopropanation204-208 catalyst 185 202 179 187 202 R Et c-Hex2CH d-Menthyl d-Menthyl Et yield (%) 40 81 100 62 ratio trans:cis 39:61 46:54 37:63 57:43 31:69 ee trans. although similar enantio. There are two general classes: the dirhodium(II) carboxylates (173-186) and carboxamidates (187-208). 103. Katsuki has also designed cis-selective catalysts based on the salen scaffold. The diastereoselectivity in the cyclopropanation of styrene decreases to 83:17 if methyl diazoacetate is used. For this reason. 2003.and intramolecular cyclopropanations (vide infra) as well as in C-H insertion reactions. the rate of the reaction with 171 was significantly faster than that with 172. Vol. cis (%) 75. such as 169. ruthenium. or cobalt carbenes. 4 Lebel et al. 91 52. were quite effective in a trans-selective reaction (Table 27).and diastereoselectivities were observed with both of them. Katsuki has developed a series of new ligands for trans.

Doyle has recently reported that the novel Lmenthyl ester-derived azetidine-ligated dirhodium catalyst 207209 led to good cis diasteroestereocontrol and excellent enantiocontrol in the cyclopropanation of substituted styrenes with tert-butyl diazoacetate (eqs 55 and 56). 4 1005 Figure 28. No. Vol.and intramolecular cyclopropanations. Most common chiral dirhodium catalysts for inter. 103. Very few other diazoalkanes bearing an electronwithdrawing group have been tested in the asym- .Stereoselective Cyclopropanation Reactions Chemical Reviews. the low yield relative to the alkene makes this method not optimal for the cyclopropanation of complex substituted styrenes. 2003. However.

Enantioselective Cyclopropanation with r-Diazophosphonate Reagents The last class of diazo reagents that has been widely used in asymmetric catalysis and in total synthesis is that of the aryl. Diazoalkanes Bearing Two Electron-Withdrawing Groups (N2C(EWG)2) The diazoalkanes bearing two electron-withdrawing groups are substantially less reactive than those described above. For this reason. Furthermore. 103.and Vinyldiazoester Reagents metric catalytic cyclopropanation reactions. 4 Lebel et al.213 R1 Ph Ph Ph Ph 4-MeOC6H4 4-ClC6H4 Ph 1-styryl R2 H H H H H H Me H R Me Et i-Pr i-Pr i-Pr i-Pr i-Pr i-Pr catalyst 143 143 143 156 156 15 156 156 ratio trans:cis 86:14 84:16 90:10 >98:2 >98:2 >98:2 88:12 95:5 ee trans (%) 93 92 92 96 94 98 95 90 Early reports214 established that rhodium complexes were the best catalysts for the decomposition of vinyldiazoesters in the presence of alkenes.1006 Chemical Reviews.211 More reactive and enantiodiscriminating catalysts will have to be developed to increase the usefulness of this class of reagents.212 4. One of them is the R-diazophosphonate reagent. 2003. to lead to the corresponding cyclopropane with a high level of diastereocontrol. which was used to make cyclopropylphosphonate derivatives. Aryl. Vol. styrene reacts with dimethyl diazomalonate (209) in the Ph 4-ClC6H4 4-MeOC6H4 EtO AcO single diastereomeric cyclopropane derivative is formed preferentially over the other three possible diastereomers. A large number of chiral catalysts were screened. presence of Rh2(4S-MEAZ)4 (204) in 97% yield but in only 50% ee. R dr 98:2 >98:2 >98:2 96:4 95:5 yield (%) 84 92 75 71 42 3.210 Table 30. Chiral Auxiliary in the Cyclopropanation of Rhodium-Catalyzed Vinyldiazoester Decomposition As with the corresponding ester reagents.and vinyl-substituted diazoester reagents 211 (eq 57) and 213 (eq 58). and both bis(oxazoline)‚Cu 143 and Nishiyama’s ruthenium catalyst 156 gave satisfactory results (Table 30). styrene reacts with R-nitroester 210 in the presence of 184 in 41% ee (68% yield) and in the presence of 204 in 33% ee (76% yield). The next major finding was the introduction of a simple chiral auxiliary on the ester moiety to generate an enantiomerically enriched product (Table 31). No. more active catalysts are required to generate the corresponding metal carbene intermediate.207 Similarly. For example. the best trans:cis ratios were observed with sterically more hindered phosphonate reagents. cyclopropane diesters are available in enantiomerically enriched form in a two-step process from the vinyl-substituted cyclopropane derivatives described in the following section. .215 It is quite remarkable that a Table 31.

the approach by the alkene occurs on the side of the electron-withdrawing group. Davies has reported216 that rhodium prolinate catalysts (173 and 174)217 in nonpolar solvents were the most active ones for this substrate. Enantioselective. The next major breakthrough in this area was the substitution of a chiral auxiliary by chiral ligands on the catalyst. Presumably. is believed to be the D2symmetric form. (B) top view. since metal carbenes lacking this combination of donor/acceptor functionality lead to much lower diastereoselectivities (Figure 29). In principle. Catalytic Synthesis of Vinylcyclopropanes Chemical Reviews. and applications of this methodology include an approach to cyclopropane R-amino acids.4-cycloheptadienes. A model has been proposed to explain the diastereo. The most reactive flexible ligand arrangement in rhodium prolinate catalysts. Davies has shown that Rh2(DOSP)4 (175) provides the highest enantiocontrol for many alkenes (Table 32).219 Complete diastereocontrol is observed in these transformations. Diastereoselective rhodium-catalyzed cyclopropanation. The Rh-catalyzed cyclopropanation of alkenes using vinyldiazoesters is synthetically quite useful.2.1]octene. Enantioselective cyclopropanation catalyzed by 175. After catalyst optimization.Stereoselective Cyclopropanation Reactions Table 32. No. 216.220 Approach of the alkene from the most accessible trajectories in the orientation shown in Figure 30 correctly predicts the sense of induction in these reactions. it should be pointed out that trans-disubstituted alkenes do not react under these conditions. After an extensive catalyst screening.218 The presence of an electron-withdrawing substituent (ester) and an electron-donating substituent (vinyl group) is crucial for high diastereoselectivity. but catalyst 217 was as effective as 175 (Table 32).225 and to 1. 4 1007 R Ph 4-ClC6H4 4-MeOC6H4 AcO EtO Bu Et i-Pr Ph Ph Ph Ph catalyst 175 175 175 175 175 174 174 174 215 216 217 218 ee (%) 98 >97 90 95 93 >90 >95 95 83 63 98 68 yield (%) 68 70 41 26 65 63 65 58 52 >52 >52 >52 Figure 29. 103.221 Three of them (215. and 218) led to lower enantiomeric excesses than those observed with Rh2(DOSP)4 (175).227 The Rh-catalyzed cyclopropanation of alkenes with aryldiazoester reagents follows the same trends as those found with the vinyl-substituted reagent.224 to 2. responsible for the stereodiscriminating step. which are decomposed nicely with Rh2(DOSP)4 and lead to alkynyl-substituted cyclopropanes with good to excellent enantiomeric excesses. However. Vol.218.226 Davies has also extended this chemistry to alkynyldiazoacetates (Table 33). 2003.3-dihydrofuran. The assumption that the reactive catalyst conformer was that possessing a D2 symmetry led Davies Figure 30.223 to 8-oxabicyclo[3.228 In . (A) Side view.222 to cyclopentenes. to design new rhodium(II) dicarboxylates (215-218) with the prerequisite D2 symmetry. the developing positive charge on the most substituted carbon can be stabilized by the oxygen lone pairs of the carboxyl group.and enantiofacial selectivity using these rhodium catalysts.

1. R1 Ph Et TMS Ph Ph R Ph Ph Ph OBu OAc yield (%) 68 91 84 66 61 dr 92:8 99:1 94:6 >97:3 >97:3 ee (%) 89 56 65 87 95 Table 34. Diazocarbonyl compounds in intramolecular processes can be divided in three major categories: diazoketones. the C-H insertion may become the major pathway. very good enantio. These catalysts are still used today. This reaction has been widely used to synthesize terpenes. As for the intermolecular cyclopropanation with diazo reagents. 103. the cyclopropanation proceeds generally with complete stereocontrol. Quite interestingly. most of the successful systems involve cyclization of either γ. as. 1. Sarkar has described the synthesis of the tricarbocyclic framework of oreodaphnenol using a highly diastereoselective rhodium-catalyzed intramolecular cyclopropanation. the reaction was catalyzed by heterogeneous copper catalysts such as copper powder. However.and diastereoselectivities are usually observed for the Rh2(DOSP)4-catalyzed reaction with styrene or 1. -unsaturated diazocarbonyl systems.1-diphenylethylene (eq 59).237 Initial attempts to induce the . was a useful chiral synthon for the preparation of sesquiterpenes such as thujopsene (223) and mayurone (224). Vol.1. that has been prepared using this strategy in both racemic235 and enantiomerically pure236 forms. 2003. Cyclopropanation Using Phenyldiazoesters appropriate catalyst.δ-unsaturated diazocarbonyl or δ.232 Indeed. Excellent enantio.0] or [4.or six-membered rings. this section is organized to present the best catalytic systems by focusing on the more recent disclosures. Copper and rhodium catalysts are generally suitable. For instance.0] bicyclic systems. will be compared for each class of substrates. Intramolecular Cyclopropanation When both functionalitiessthe diazo unit and the alkenesare in the same molecule. Cyclopropanation with Alkynyldiazoacetate Lebel et al. but the diastereoselectivity becomes an issue.and diastereocontrol is displayed in these reactions (Table 34). this reaction has been extended to a solid-phase cyclopropanation between phenyldiazoacetate and a resin-bound alkene. rather than being an exhaustive review of all the possible methods. leading to the exclusive formation of one stereoisomeric bicyclic product. when diazoketone substrate 219 was cyclized in the presence of a catalytic amount of copper (eq 60). copper bronze. Initially.233 general. and their efficiency. although homogeneous copper and rhodium catalysts are more popular. it is important to consider the chemoselectivity. C. leading to fused [3.1008 Chemical Reviews. It is also possible to form macrocycles using the intramolecular cyclopropanation reaction. 4 Table 33. in some cases. diazoester. and diazoacetamide derivatives. an intramolecular cyclopropanation is possible in the presence of the A variety of intramolecular cyclopropanation reactions of olefin-containing diazoketones have followed this seminal discovery. thus producing bicyclic products. The stereoselectivities are almost identical to those observed in solution. Diastereoselective Intramolecular Cyclopropanation of Chiral Substrates R1 Ph Ph Ph 4-ClC6H4 4-MeOC6H4 Et R2 H Ph Me H H H yield (%) 90 83 88 84 82 86 ratio A:B 98:2 60:40 98:2 98:2 93:7 ee A (%) 87 97 85 (81) 85 88 80 catalyst 175 174 174 174 174 175 The first intramolecular cyclization of an unsaturated diazocarbonyl compound that formed a cyclopropane unit was reported in 1961 by Stork and Ficini. or cupric sulfate. Dihydromayurone 222. No. especially for the enantiocontrol.229 Usually.230 Davies has also extended this chemistry to a wide range of different heteroaryldiazoacetate reagents. the most practical catalyst to use is Rh2(DOSP)4 (175) or Rh2(TBSP)4 (174). only one diastereoisomer is obtained when forming five. the cyclopropanation of diazoketone 221 in the presence of copper or rhodium catalyst led to the formation of bicyclic cyclopropane 222 as a single diastereoisomer (Scheme 10).231 In contrast to the intermolecular reaction.234 With an appropriate chiral substrate.

Stereoselective Cyclopropanation Reactions Scheme 10. lyzed by rhodium(II) octanoate dimer. Scheme 11. Intramolecular Cyclopropanation of 228 en Route to the Synthesis of Oreodaphnenol The stereochemical outcome is consistent with the most favorable transition-state model A. when the silylated protected alcohol 228 and the rhodium catalyst were used. as shown by Taber in the synthesis of prostaglandin derivatives. derived from diazoesters. the intramolecular cyclopropanation of diazoketone 230. The combination of the intramolecular cyclopropanation of dienes with the vinylcyclopropane-cyclopentene rearrangement has been employed as a key . a sesquiterpene that contains two vicinal quaternary carbon atoms and four cis-oriented methyl groups (Scheme 12). favoring 229 (Scheme 11).238 Indeed. The R-ketocyclopropanes could be further manipulated through carbonyl functionalization or cyclopropane ring opening. the diastereoselectivity in the cyclopropanation reaction improved dramatically.240 The selectivity is catalyst However. as the copper catalyst provides an 82:18 mixture of diastereoisomers. Rh2(OAc)4 produced diastereoisomer 235 with a 75:25 selectivity. that minimizes the 1. Ester-substituted diazoketones have also been extensively used in the intramolecular cyclopropanation. No. The presence of the bulky TBDPS group increases the diastereomeric ratios. favoring 234. followed by regioselective cyclopropane cleavage. Systems that are less rigid may afford a mixture of stereoisomers. In contrast. carbocyclic nucleoside precursors have been prepared this way from ribose derivative 233 (eq 63). while Rh2(OAc)4 improved the selectivity to 20: 80 (95%) (eq 61). cyclization of diazoketone 225 with copper catalysts led to formation of a 40:60 mixture of diastereoisomers.242 The key step to construct the bicyclic system was based on the intramolecular cyclopropanation of diazoketone 237. resulting in the introduction of the requisite contiguous four cis-methyl groups to provide the intermediate 239. As an example. 103. they are more reactive and more versatile than the corresponding cyclopropyllactones. Intramolecular Cyclopropanation as a Key Step in the Synthesis of Sesquiterpenes Chemical Reviews. Typically.239 For instance. Vol. Transition-state models for the intramolecular cyclopropanation of 228. 2003. yielded a mixture of diastereoisomers 231 and 232 (eq 62). cata- dependent. thus producing the desired product in 95% yield and with 97:3 diastereoselectivity. 4 1009 Figure 31.241. Srikrishna has recently disclosed the total synthesis of (+)-pinguisenol.3-allylic strain (Figure 31).

1010 Chemical Reviews, 2003, Vol. 103, No. 4 Scheme 12. Total Synthesis of Pinguisenol, Featuring an Intramolecular Cyclopropanation Reaction

Lebel et al.
Table 35. Intramolecular Cyclopropanation of Aromatic Derivatives 246

entry 1 2 3 4 5 6

R Me Et n-Pr n-Bu i-Pr t-Bu

yield (%) 87 80 74 74 70 72

ratio 89:11 96:4 97:3 98:2 >98:2 >98:2

Scheme 14. Buchner Cyclization of Harringtonolide’s Precursor 249 Scheme 13. Corey’s Antheridic Acid Synthesis

step in the total synthesis of triquinanes.5-7 Corey has also used this strategy in the total synthesis of antheridic acid (Scheme 13). The intramolecular cyclopropanation of the diazoacetate 240, catalyzed by copper(II) bis(salicylaldehyde)tert-butylimine catalyst 243, provided the cyclopropyllactone 241, which upon treatment with a Lewis acid afforded the key intermediate 242 en route to antheridic acid. The intramolecular version of the cyclopropanation of aromatic derivatives with diazo reagents, known as the Buchner reaction,243 has also been reported with copper and rhodium catalysts, the latter being the most efficient. Usually the cyclopropanation product 244 is in dynamic equilibrium with the corresponding cycloheptatriene 245, which is the more stable tautomer (eq 64).

Maguire recently investigated the diastereoselectivity in the intramolecular cyclization of chiral R-diazoketone derivatives of general structure 246.244,245 The ratio of diastereoisomers increased as the size of the β-substituent increased from Me to

Et, Pr, and Bu (Table 35). While an 89:11 mixture was obtained with the methyl group, only a single diastereoisomer could be detected with the isopropyland tert-butyl-substituted ketones. In all cases, the formation of the trans diastereoisomer was favored. The two azulenone products, the norcaradienes (247) and the cycloheptatrienes (248), are in rapid equilibrium. The cyclopropane derivative can be trapped as a Diels-Alder adduct when reacted with 4-phenyl1,2,4-triazoline-3,5-dione. Similar trends in the diastereoselectivities were observed with a range of diazoketones bearing methoxy-substituted aryl rings.246 However, a more complex dynamic equilibrium is observed in the cyclization products via rearrangements of the methoxy-substituted norcaradienes. The Buchner cyclization has also been exploited in the context of the synthesis of complex polycyclic natural products.247 For instance, Mander has shown that this strategy was very efficient for the synthesis of 5,7-fused rings of the harringtonolide (Scheme 14).248 The rhodium-catalyzed cyclopropanation of

Stereoselective Cyclopropanation Reactions Scheme 15. Mander’s Gibberellin Derivative Synthesis

Chemical Reviews, 2003, Vol. 103, No. 4 1011
Table 36. Enantioselective Cyclopropanation of 1-Diazo-5-hexen-2-one

entry 1 2 3 4 5 6 7 8

catalyst 258 194 149 139 (P)-185 (P)-185 (P)-186 (P)-186

solvent CH2Cl2 CH2Cl2 CH2Cl2 ClCH2CH2Cl pentane CH2Cl2 pentane CH2Cl2

yield (%) 84 85 50 90 96 96 98

ee (%) 5 23 25 75 74 65 87 64

Table 37. Enantioselective Cyclopropanation of 1-Diazo-5-methyl-5-hepten-2-one

entry 1 2 3 4 5 6 7 8

catalyst 258 191 149 139 (P)-185 (P)-185 (P)-186 (P)-186

solvent CH2Cl2 CH2Cl2 CH2Cl2 ClCH2CH2Cl pentane CH2Cl2 pentane CH2Cl2

yield (%) 91 80 51 58 99 99 99 99

ee (%) 75 27 63 85 80 52 70 58

249 led to the formation of the intermediate 250, which rearranges rapidly to the labile cycloheptatriene 251, which is then converted to the more stable product 252. Furthermore, the same author has described the total synthesis of gibberellin derivatives (256 and 257) using a similar strategy (Scheme 15).249 The cyclopropanation reaction of substrate 253 was best performed in the presence of a copper catalyst that minimizes the formation of byproducts. It was observed that rhodium catalysts led to significant amounts of a C-H insertion product. The cyclopropane adduct 254 was not isolated but reacted with citraconic anhydride to furnish the cycloadduct 255 in 75% yield for the two-step process. Subsequent studies led to the synthesis of gibberellins GA103 (256) and gibberellins GA73 methyl ester (257) in 8 and 12 steps, respectively, from 255. It is also possible to form macrocycles using the transition metal-catalyzed cyclopropanation reaction.250 The diastereoselectivities are usually quite modest when a chiral precursor is cyclized upon treatment with a catalytic amount of Rh2(OAc)4 (eq 65).251

Table 38. Enantioselective Cyclopropanation of 1-Diazo-6-hepten-2-one

entry 1 2 3 4 5 6

catalyst 187 139 (P)-185 (P)-185 (P)-186 (P)-186

solvent CH2Cl2 ClCH2CH2Cl pentane CH2Cl2 pentane CH2Cl2

yield (%) 58 57 96 85 90 92

ee (%) 6 95 90 87 95 89

2. Enantioselective Intramolecular Cyclopropanation: Chiral Catalysts
Chiral catalysts have been studied for the enantioselective intramolecular cyclopropanation of unsaturated diazoketones. Until recently, semicorrin copper complex 139, developed by Pfaltz, was the most efficient catalyst for enantiocontrol.252 Up to 95% ee was obtained, depending on the substrate, although the yields were always modest (<60%) (Tables 36 and 37, entry 4; Table 38, entry 2; Table 39, entry 3). In comparison, rhodium carboxamide catalysts led to a low level of induction (Tables 36 and 37, entry 2; Tables 38 and 39, entry 1).253 Neither the chiral biferrocene-based bis(oxazoline) copper complex 149254 (Tables 37 and 38, entry 3; Table 39, entry 2) nor the ruthenium complex derived from 8-diphenylphosphino-2-oxazolinylquinoline 258255 (Tables 36 and 37, entry 1) provided any significant improvement, the

1012 Chemical Reviews, 2003, Vol. 103, No. 4
Table 39. Enantioselective Cyclopropanation of 1-Diazo-7-methyl-6-octen-2-one

Lebel et al.

entry 1 2 3 4 5 6 7

catalyst 187 149 139 (P)-185 (P)-185 (P)-186 (P)-186

solvent CH2Cl2 CH2Cl2 ClCH2CH2Cl pentane CH2Cl2 pentane CH2Cl2

yield (%) 76 12 50 93 67 69 51

ee (%) 17 64 14 80 63 80 63

former suffering from low reactivity and the latter being less selective.

A major breakthrough came recently from the group of Lahuerta, who disclosed that the use of dirhodium(II) complexes 185 and 186, that contain ortho-metalated aryl phosphine ligands, provide the
Scheme 16. Preparation of Dirhodium Catalysts 185 and 186

desired cyclopropane products in very high yield (>90%) and with enantioselectivities that are comparable to those reported by Pfaltz.256,257 The enantiomeric excesses are significantly dependent on the solvent used, the best being pentane. [3.1.0] Bicyclic systems were best obtained in 9699% yield and with 80-87% ee (Tables 36 and 37). In comparison, the formation of [4.1.0] bicyclic products proceeded in 90-96% yield and with 80-95% ee (Tables 38 and 39). The cyclization of 1-diazo-7-methyl-6-octen-2-one also provided between 7 and 49% of the allylic insertion product, in addition to the cyclopropanation adduct. The amount of the byproduct can be minimized by using catalyst 185 in pentane. Just like most dirhodium carboxylate complexes that are typically prepared from rhodium acetate and carboxylic acids,141 dirhodium complexes derived from ortho-metalated arylphosphines 259 are readily obtained as a racemic mixture by the thermal reaction between rhodium acetate dimer and arylphosphines.258 They were resolved as proline derivatives by column chromatography, and subsequent ligand exchange with trifluoroacetic acid led to the desired catalysts 185 and 186 as pure enantiomers (Scheme 16). Some specific examples of enantioselective intramolecular cyclopropanation of diazoketones have also been disclosed. Shibasaki has described the synthesis of the phorbol CD-ring skeleton through the asymmetric intramolecular cyclopropanation of silyl enol ether 260.259 He found that, after optimization, the desired cyclized product 261 was obtained in 92% ee and 70% yield when 15 mol % of the bis(oxazoline) ligand 262 and 5 mol % of copper triflate were used (eq 66).

Corey has reported a rare example of an intramolecular cyclopropanation involving a γ-diazocarbonyl derivative.260 The cyclization of vinyldiazomethane 263 to bicyclic system 264, a synthetic precursor of sirenin, was studied using various catalysts (Scheme 17). The best-known catalyst produced the desired cyclic compound in 60% ee (copper semicorrin 143). To overcome this problem, Corey designed a novel bis(oxazoline) 265 that yielded the desired cyclopropane 264 with 90% ee. The intramolecular cyclopropanation of diazoacetates bearing an alkene unit is also a very wellknown reaction that has found numerous applications in synthesis. The cyclization of unsaturated diazoacetates can be divided into two types: Type A is the most common one and involves the formation

and ruthenium catalysts have been developed for the intramolecular cyclopropanation of type A. whereas the bis(oxazoline)ligated copper(I) catalysts produce higher yields and enantiomeric excesses in the cyclopropanation. respectively. Katsuki developed a series of salen ruthenium and cobalt catalysts that proved to be very efficient for the intramolecular cyclopropanation of (E)-alkenyl diazoacetate. Corey Sirenin’s Synthesis Chemical Reviews. and very low enantioselectivities were observed with copper catalysts. In addition. were obtained with Rh2(5S-MEPY)4 (187) and Rh2(4S-MEOX)4 (191). The enantioselectivity is dependent on the double bond substitution. None of the other reported catalysts were as effective for the intramolecular cyclopropanation of Z-substituted allyl acetates. using a ruthenium(II) Schiff base complex (162) as catalyst. 103. the best results for the intramolecular cyclopropanation of the simplest case.208 whereas low stereochemical induction was observed with ruthenium146a or copper catalysts. the use of N-acylimidazolidinone-ligated catalysts. but their use is limited to the intramolecular cyclopropanation involving the formation of small rings (five and six members) (vide infra). Vol. rhodium. as illustrated in Table 41. which are obtained consistently with high levels of enantiocontrol. . The effectiveness of each catalyst changes with the substitution262 and the ring size of the fused cyclopropane. cobalt. Type B leads to the formation of a cyclopropanecarboxylate (eq 68). Ruthenium and cobalt catalysts are useful in the synthesis of trisubstituted cyclopropanes. allyl diazoacetate. copper. In general. Enantioselective Intramolecular Cyclopropanation of Phenyl-Substituted Allyl Diazoacetates of a lactone (eq 67). dirhodium(II) carboxamidate catalysts are superior for smallring-fused cyclopropane compounds.263 The dirhodium(II) azetidinonecarboxylates were less selective.0]hexan-2-one with up to 95% yield and 95% ee (Table 40). Enantioselective Intramolecular Cyclopropanation of Allyl Diazoacetate catalyst Rh2(5S-MEPY)4 (187) Rh2(4S-MEOX)4 (191) Rh2(4S-IBAZ)4 (202) Ru(II) porphyrin (159) CuPF6/143 yield (%) 75 95 92 45 61 ee (%) 95 94 80 24 20 Table 41. the cyclopropanation of (E)-(phenyl)allyl diazoacetate proceeded in 97% and 95% ee with catalysts 267 and 268. However. and no chiral catalyst is effective. Excellent enantioselectivities were also observed in the intramolecular cyclopropanation of trisubstituted double bonds. For instance. The cyclopropanation reactions of type B are not common.5R) Isomer was obtained.264 In comparison. produced the desired bicyclic systems with greater than 95% ee.1. No.266 For example. that provided the desired 3-oxabicyclo[3. leading to medium/large rings. 2003. ruthenium catalysts265 furnished the product with 82-89% ee. Rh2(5S-MEPY)4 (187) afforded only 68% ee with the (E)-(phenyl)allyl diazoacetate. the cyclopropanation of geranyl diazoacetate with Rh2(5S-MEPY)4 (187) revealed that γ-lactone formation was exclusive when other double bonds were present in the substrate.267 Similar results were recently obtained by Scott.261 Conversely. Indeed. such as Rh2(4S-MPPIM)4 (200).Stereoselective Cyclopropanation Reactions Scheme 17. 4 1013 Table 40. catalyst Rh2(5S-MEPY)4 (187) Rh2(4S-MPPIM)4 (200) Ru(II) (pybox) (156) Ru(II) (pybox) (157) Ru(II) porphyrin (159) Ru(II) (salen) (266) Co(II) (salen) (267) Co(II) (salen) (268) CuPF6/143 Rh2(5S-MEPY)4 (187) Ru(II) (pybox) (156) Ru(II) porphyrin (159) Ru(II) (salen) (266) Co(II) (salen) (267) Co(II) (salen) (268) a E/Z E E E E E E E E E Z Z Z Z Z Z yield (%) 78 61 83 72 60 54 67 75 77 70 79 24 24 16 24 ee (%) 68 96 86a 89a 85 82 97 95 4 g94 24 53 14 74 68 (1S.

192 A number of 1. In general.2. in addition to minimizing the amount of the undesired dipolar addition reaction. No. for which copper catalysts usually provide higher enantiomeric excesses.268 During the course of this study.272 In addition.271 Indeed. 2003. 4 Lebel et al. as the In all macrocyclic cyclizations.273. although the enantioselectivity was far from practical.270 Similar levels of enantiocontrol were observed with Rh2(4S-MEOX)4 (191).3-trisubstituted cyclopropanes were prepared through the enantioselective Rh2(5SMEPY)4 (187)-catalyzed cyclization of allylic diazoacetates with high enantiomeric excesses and have been studied as conformationally restricted peptide isosteres. whereas Rh2(4S-MPPIM)4 (200) provided lower enantiomeric excesses. provided a better enantiocontrol for homoallylic diazoacetate (42% ee) than for allylic diazoacetate (20% ee). homoallylic diazoacetates afforded the bicyclic products with slightly lower enantiomeric excesses when Rh2(5S-MEPY)4 (187) was used. the CuPF6/143 complex was superior to dirhodium(II) carboxamide catalysts. With substrate 269. favoring exclusively the macrocyclic product over the allylic cyclopropanation product (eq 72). The enantiocontrol for the intramolecular cyclopropanation of allylic and homoallylic diazoacetamides with dirhodium(II) carboxamide catalysts is similar to that found with allylic and homoallylic diazoacetates.and 20-membered ring-fused cyclopropane products. 103. enantiomeric excesses between 93 and 95% could be achieved when Rh2(5S-MEPY)4 (187) or Rh2(4SMPPIM)4 (200) was used (Table 42). It is interesting to note that copper catalysts. such as the CuPF6/143 complex. with the exception that slow addition of the substrate was not required (eq 69).1014 Chemical Reviews. since the formation of a macrocycle is similar to intermolecular cyclopropanation. the enantioselectivity increases significantly with the CuPF6/143 complex. whereas the enantioselectivity decreases with dirhodium(II) carboxamides. However. and the enantioselectivity was not highly dependent on the substitution pattern of the double bond (eq 71). although a mixture of cis and trans isomers was observed (eq 74). This is not too surprising. Martin has reported that prochiral secondary divinyl diazoacetates undergo cyclopropanation with exceptional enantiocontrol and with moderate to high diastereocontrol (eq 70).269 Comparable enantiomeric excesses were obtained for the synthesis of 15.274 The use of a methyl nitrogen substituent favored the desired s-trans conformer. the formation of 10-membered rings in the presence of the CuPF6/143 complex proceeded with 87-90% ee (eqs 72 and 73). the CuPF6/143 complex has a different chemoselectivity than Rh2(5S-MEPY)4 (187). Vol. ring size increases. The homoallylic . Doyle has also proposed that the selectivity for the catalyst reflects the divergent trajectories of the carbon-carbon double bond to the reacting carbene center.

Stereoselective Cyclopropanation Reactions Table 42. followed by a Cope rearrangement of the resulting divinylcyclopropane intermediate. With an unsubstituted allyl group. Vol. the Z isomer as well as the 1. In the case of trisubstituted olefins. Davies has also shown that the intramolecular cyclopropanation of vinyldiazoacetates and dienes. were equally effective. Depending on the electronic nature of the substituents. 4 1015 Table 44. whereas the 1. the desired bicyclic system was isolated with 68% ee. whereas 58 and 59% ee’s were observed when Rh2(4S-IBAZ)4 (202) and Rh2(4SMEAZ)4 (204) were used. 2003. 103. dirhodium(II) carboxamidate systems are still effective at catalyzing the cyclopropanation reaction. with slightly lower enantiomeric excesses. In the case of dirhodium tetracarboxylate catalysts. When the substituent is an alkyl such as methyl. The latter catalysts have not been tested with more substituted Pentane as solvent.277 For instance.5S) Isomer was obtained. leading to the cyclopropane fused-lactone in 4445% ee. The dirhodium(II) azetidinonecarboxylate catalysts [such as Rh2(4S-IBAZ)4 (202) and Rh2(4S-MEAZ)4 (204)] proved to be equally or more effective for the enantioselective cyclization of R-phenyl-R-diazoacetates (Table 45). .and aryl-substituted diazoacetates requires a more reactive catalyst. Enantioselective Intramolecular Cyclopropanation of r-Styryl-r-diazoacetates R1 yield ee (%) (%) 62 20 88 88 93 95 93 75 94 95 92 93 H H H H H H H Me Me Me a R2 H H H Me H H Me H Me Me R3 H H H H Me Et Me H H Me catalyst Rh2(R-DOSP)4 (175) Rh2(4S-IBAZ)4 (202) Rh2(4S-MEAZ)4 (204) Rh2(S-DOSP)4 (175) Rh2(S-DOSP)4 (175) Rh2(S-DOSP)4 (175) Rh2(S-DOSP)4 (175) Rh2(S-DOSP)4 (175) Rh2(S-DOSP)4 (175) Rh2(S-DOSP)4 (175) yield (%) 81 59 56 54 72 56 62 53 68 46 ee (%) 28 58a 59a 25 72 69 74 87 45 60 R 1 R 2 catalyst Rh2(5S-MEPY)4 (187) Rh2(4S-MPPIM)4 (200) Rh2(4S-MPPIM)4 (200) Rh2(4S-MPPIM)4 (200) Rh2(4S-MPPIM)4 (200) Rh2(4S-MPPIM)4 (200) H H Me n-Pr H Me H H Me H n-Pr Me2CdCH(CH2)2s Table 43. both catalysts. Doyle has shown that Rh2(4S-MEOX)4 (191) provided the best enantiocontrol.and aryl-substituted diazoacetates. double bonds. Table 45. rhodium or copper catalysts were used. Doyle has reported that dirhodium(II) azetidinonecarboxylate catalysts [such as Rh2(4S-IBAZ)4 (202) and Rh2(4SMEAZ)4 (204)] enhance the reactivity toward diazo decomposition and are also effective for the intramolecular cyclopropanation of unsaturated vinyl.276 More recently. the cyclization of allyl-R-styryl-R-diazoacetate proceeded in 81% yield and with 28% ee when Rh2(R-DOSP)4 (175) was used. afforded fused cycloheptadienes with good to excellent levels of enantioselectivity. a wide range of substitutions patterns have been examined.1-disubstituted alkene provided a good level of enantiocontrol (69-84% ee) with Rh2(SDOSP)4 (175). leading to the desired cyclopropanes with 71-85% ee for the trans isomers and 43-52% ee for the cis isomers (Table 43). Enantioselective Intramolecular Cyclopropanation of Allylic Diazoacetamides 269 Chemical Reviews.1-disubstituted alkene derivatives afforded the product in 84% ee. Although the E isomer afforded low enantioselectivities (e25% ee). A few unsaturated R-substituted diazoacetates have been tested in intramolecular cyclopropanation reactions. Enantioselective Intramolecular Cyclopropanation of (Phenyl)diazoacetates R1 Me n-Pr Ph H H R2 Me H H n-Pr Ph yield (%) 81 62 65 46 70 ee (%) 71 85 78 52 43 R1 H H H H Me Me Me Me H H H H a R2 H H H H H H H H Me Me Me Me R3 H H H H H H H H Me Me Me Me catalyst Rh2(S-DOSP)4 (175) Rh2(S-DOSP)4 (175)a Rh2(4S-IBAZ)4 (202) Rh2(4S-MEAZ)4 (204) Rh2(S-DOSP)4 (175) Rh2(S-DOSP)4 (175)a Rh2(4S-IBAZ)4 (202) Rh2(4S-MEAZ)4 (204) Rh2(S-DOSP)4 (175) Rh2(S-DOSP)4 (175)a Rh2(4S-IBAZ)4 (202) Rh2(4S-MEAZ)4 (204) yield (%) 92 93 83 80 90 77 80 82 76 85 92 93 ee (%) 28 36 64 68 29 51 68 84 29 44 19 45 diazoacetamide provided the bicyclic product. Davies and Doan made a breakthrough in this area by disclosing that dirhodium tetracarboxylates [such as Rh2(R-DOSP)4 (175)] are effective for the decomposition of these diazoacetate reagents to carbenoid intermediates (Table 44).275 The diazo decomposition of vinyl. respectively. Rh2(S-DOSP)4 (175) and Rh2(4S-MEAZ)4 (204). No. Intramolecular Cyclopropanation of r-Substituted Diazoacetates (1R.

as is usually the case for systems with trans alkenes. arsenium. Intramolecular Cyclopropanations of Diazo 271 Lebel et al. IV. Few examples of enantioselective intramolecular cyclopropanation of the very unreactive diazomalonates have been reported so far. Davies has reported a short asymmetric synthesis of the tremulane skeleton (Scheme 18).284. Two types of substrates/reactants can give rise to MIRC reactions. Conversely. but low enantiomeric excesses were observed. No. thus affording the trans-divinylcyclopropane 275. respectively (eq 75).279 Only copper catalysts are effective for this purpose.and (Z)-olefins give the transcyclopropanes. and both (E).281 Cyclopropanation reactions which involves a conjugate addition to an electrophilic alkene to produce an enolate. 4 Scheme 18. A variety of nucleophiles can be used. In conclusion. which then subsequently undergoes an intramolecular ring closure. presumably through initial equilibration to the cis-divinylcyclopropane 272. but it rearranges on heating.278 The initial attempts in the intramolecular cyclopropanation of E.280 For example. enolates. the formation of a configurationally stable tetrahedral intermediate after the first addition may also lead to a stereospecific process. and telluronium ylides have all been used as cyclopropane precursors. there is still room for improvement with some substituted diazo substrates. are defined as Michaelinitiated ring closure (MIRC) reactions. Michael-Initiated Ring Closure A. in which the leaving group is present on the nucleophile. the enantioselectivity could be enhanced to 93% ee by using the Z. Scheme 19. Introduction Using this strategy. Cyclopropane 275 is stable at room temperature. cyanides. Grignard reagents. However.282 Although there are exceptions. Generally. 103. The first type involves the formation of cyclopropanes by nucleophilic addition to electrophilic substrates containing a leaving group (eq 76). step C) is faster than the rotation around the single bond in the first intermediate formed (Scheme 19. intramolecular cyclopropanation reactions prove to be a very useful transformation for the construction of complex cyclopropane-fused systems. phosphites.and enantiocontrol can be achieved with the appropriate cata- These nucleophiles include the R-halo carbanions. Koskinen has reported that the cyclization of Me and t-Bu allyl diazomalonates in the presence of copper bioxazoline complex 276 afforded the desired cyclopropylactones in 72-73% yield and with 11% and 35% ee. Vol.E-diene 271 with Rh2(S-DOSP)4 (175) proceeded with low enantiocontrol. 2003. However. thiolates. step B). high levels of diastereo.285 but the most effective reagents for methylene transfer to electron-deficient olefins are probably the heteroatom-derived ylides. cyclopropanations via the MIRC reaction of acyclic olefins are usually nonstereospecific. constitute the other class of the MIRC reactions (eq 77). such as alkoxides.E-diene 274 at -78 °C.1016 Chemical Reviews. The desired fused seven-membered ring 273 was isolated in 85% yield with high enantiomeric excess. hydrides. Sulfur. phosphorus.283 Cyclopropane-forming reactions. via a diradical intermediate. Cyclopropanation reactions involving sulfonium salts were first . Stereospecific cyclopropanation reactions using the MIRC reaction are observed only when the ringclosure process (Scheme 19. Michael-Initiated Ring Closure Cyclopropanation Reaction lysts. and phosphonites.

depending on the steric nature of the ylide. Cyclopropanation of 1. In contrast to that of other sulfur ylides (vide supra). in this case.2-dioxine 287.290 The Figure 32.β-unsaturated ketones.288 These studies were quickly followed by the development of several new sulfur ylide reagents that have unique properties as cyclopropanating reagents.287. and aldehydes to provide ester-substituted cyclopropanes.β-unsaturated thioamides has also been recently published. nitriles.2-dioxine 287 by base-induced rearrangement or cobalt-assisted radical rearrangement. Grieco proposed a convenient synthesis of trans-2. No. the ester-substituted ylide 282 reacts readily with R.286 Nevertheless.2-Dioxines 287 with Phosphorus Ylides reported in 1950. Vol. which relies on the use of chiral cobalt β-ketoiminato or cobalt salen complexes. the addition of isopropylidenediphenylsulfurane 281 to conjugated carbonyl compounds (ketones.298 However. Unsaturated aldehydes and ketones react with 279 to give oxirans.296 They showed that. if cis-γ-hydroxy enone 288 is enantiopure. Stabilized arsonium ylides. 4 1017 Scheme 20. then the resultant cyclopropane.β-unsaturated esters (eq 80).294 This reagent also reacts with conjugated ketones to afford the corresponding cyclopropyl derivatives. subsequent capture by an ylide afforded enantioenriched cyclopropanes. via the oxaphospholane intermediate 289. formed on addition of ylide. when Corey reported that the addition of methylenedimethylsulfoxonium to chalcone (277) gave trans-1-benzoyl-2-phenylcyclopropane (278) (eq 78). Since the chemistry of these reagents has been previously reviewed. Subsequent syn 1. are also known to react with conjugated esters and ketones and to lead to cyclopropanes (eq 81).β-unsaturated carbonyl compounds. the reaction of conjugated ketones with the methylenesulfoxonium 280 usually produces cyclopropanes (aldehydes also form oxirans).βunsaturated carboxylic and sulfonic acids. The same research group also established that stabilized phosphonates could be used and represent a viable alternative to ylides in the cyclopropanation reaction involving 1. Until recently. and E-olefins give trans-cyclopropanes). In 1962.295 The reaction has been shown to proceed through the cisγ-hydroxy enone 288 intermediate. the understanding and the synthetic potential of this reaction were appreciated only in the 1960s. which are prepared from bromide 293. it will be only briefly presented in this review (representative examples of the four types of sulfur ylides are shown in Figure 32). The reaction of sulfur ylides with R.4-Michael addition of stabilized ylides to the enone then leads. esters.2-dioxines. 103.4-addition of isopropylidenetriphenylphosphorane to trans-R. have been developed for cyclopropana- . is also enantiopure. Finally. the enantioselectivity ranged from 30 to 78%.2dioxines leads to the formation of diastereomerically pure trisubstituted cyclopropanes (Scheme 20). Recently.297 Conversely. as stabilized phosphorus ylides do not produce cyclopropanes upon addition to R. such as carbomethoxyand benzoylmethylenetriphenylarsorane. esters. which can arise from 1.293. Selected examples of sulfur ylides. silylated telluronium ylides. they performed the first catalytic asymmetric ring opening of meso-1.Stereoselective Cyclopropanation Reactions Chemical Reviews. In contrast. to either cyclopropane isomer 290 or 291. Taylor and co-workers have shown that the reaction of stabilized phosphorus ylides with 1. 2003. the stereochemistry of the alkene is usually maintained with 281 (Z-olefins give cis-cyclopropanes.289. Thus. and amides) leads to gemdimethylcyclopropane derivatives. this approach was limited to unstabilized phosphorus ylides. reactions involving methylenesulfonium 279 are restricted to esters and amides derived from R. Substituted methylene reagents have also been developed. Bestmann and Seng observed that the reaction of methylenetriphenylphosphorane with crotonate ester 283 gave the corresponding cyclopropane 284 (eq 79).2-dimethylcyclopropanecarboxy- lic esters 286 based on the 1.291 The phosphorus ylides were also reported to be effective cyclopropanating reagents.292 Ten years later.299 As an alternative to sulfur and phosphorus ylides.

leading to 302 with excellent diastereoselectivities.301 A catalytic version of this reaction that minimized the amount of tellurium was also developed (eq 82). respectively. The preference for the axial attack may be attributed to stereoelectronic control. esters.302 Figure 33. the stereoselectivity of these reactions changes to give cis-2-vinyl-trans-3-substituted cyclopropyl carboxylates or carboxamides 298 (eq 84). high yields and diastereoselectivities were obtained. and amides.306 Recently. and diesters. whereas an . However. with high selectivity and generally with excellent yields (eq 83). 2003. 103. but in low to moderate yields (Table 46).309. the cyclopropanation of (R)-(-)-carvone (299) with methylenedimethylsulfoxonium provides the desired cyclopropylcarvone 300 in 95% yield.and tetrasubstituted unsaturated aldehydes with methylenedimethylsulfoxonium could be achieved. the use of electrochemical techniques for the activation of various precursors suitable for MIRC reactions and leading to cyclopropanes was described.289a For example. although in some cases. as a single diastereoisomer. in the presence of lithium ion.304 The authors postulated that. Relative Diastereoselection (Addition to Chiral Substrates) The reactions involving sulfur ylides and substituted cyclohexenones are well known to proceed with very high diastereoselectivities under steric control. the same reaction with alkylidene malonic esters was found to be independent of the reaction conditions.307 The absolute stereocontrol for this reaction has not yet been introduced.1018 Chemical Reviews. reacts with R.trans isomers were always obtained.303 The allylic telluronium ylides 295. which results from the attack of the ylide on the less hindered face (eq 85). tion of R.305 Conversely. and the trans. The ratio of the two isomers varies from 99:1 to 1:99. No. esters.β-unsaturated ketones. an axial attack generates the halfchair cyclohexane conformer directly. B. Few asymmetric versions of the Michael-initiated ring closure reactions have been reported.311 The authors have postulated that the addition to cyclohexenal derivatives 301 (which predominantly exist as the diaxial conformer) favors the formation of an axial carbon-carbon bond in the initial nucleophilic attack. such as potassium (Figure 33).trans isomer can be mainly produced in the presence of lithium salts when more than 2 equiv of HMPA was added. Vol.β-unsaturated ketones to yield vinyl- Sterner used a similar reaction with cyclohexenecarboxaldehyde 301 and demonstrated that cyclopropanation of tri.308 The following sections summarize the recent advances in stereoselective cyclopropanation reactions by the nucleophilic addition-ring closure sequence. The stereochemical outcome has been demonstrated to be highly dependent on lithium salts for the cyclopropanation of conjugated ketones. amides.310 of lithium salts.βunsaturated amides or esters to afford trans-2-vinyltrans-3-substituted cyclopropyl carboxamides or carboxylates 297. depending of the reaction conditions. and the main stereocontrolling elements were mostly based on steric and stereoelectronic effects. allylindium reagents have been also added to R. Transition-state models for the diastereoselective cyclopropanation with telluronium ylides. In the transition state. 4 Lebel et al.300 In the case of chalcone (277). in the presence of lithium salts. In the absence cyclopropanes. whereas an open transition state is operative in the presence of a less coordinated species. stereoelectronic arguments could also be invoked. a chelating six-membered-ring transition state is involved. It was also shown that the cis.

the desired bicyclo[3. Figure 34. Stereoselective Cyclopropanation of 5.319 Only one stereoisomer was obtained in good yield for the cyclopropanation of several derivatives of 310. Vol.0]hexane 309 was obtained in a diastereomeric ratio of 94:6. as the bottom face of the enone is blocked by the A ring (Figure 35).3didehydropipecolate 303 and methylenedimethylsulfoxonium (Scheme 21). readily available by enzymatic resolution.8-Cyclopropyltaxol analogues 307 have been shown to be almost as potent as taxol in a number of biological assays.0]hexane derivative 315 could be revealed by a retro- . Krief described a novel and highly convergent synthesis of (()-cis. Cyclopropanation of taxol derivative 306.25-dihydrovitamin D3 and its analogues as potential bioactive compounds.3-methano-6-methoxypipecolate 304. 103. Figure 35. This approach was extended to ethylidenediphenylsulfonium.5-dimethyl-2-cyclopentenones 310 with isopropylidenediphenylsulfonium (Scheme 22). 7.Stereoselective Cyclopropanation Reactions Table 46.6-Disubstituted 1-Cyclohexenecarboxaldehyde Chemical Reviews. which arose from the reaction between 2.313 The cyclopropanation proceeded with an excellent diastereomeric ratio (>98%). but stereoselectivities were much lower when the reaction was carried out under the same conditions.0]hexane derivatives 311.3-methanopipecolic acid 305 was prepared from 2.and (+)-cis-chrysanthemic acid (312) from bicyclo[3. involving the cyclopropanation of suitably 4-functionalized 5. Intermediates formed in the diastereoselective cyclopropanation of cyclohexenal 301. as shown by Moher.1. the starting material could not be prepared in an enantiomerically pure form. affording 314 as a single diastereoisomer.316 The first method involved the stereoselective cyclopropanation of a chiral γ-alkoxy-Rdiazo-β-keto ester.3-Didehydropipecolate 303 During the course of his work on the synthesis of 1R.321 proceeded with high selectivity.317 To circumvent that problem.1.0]hexanes.1. but a low diastereoselectivity was obtained. 4 1019 R1 H CH3 CH3 (CH2)6CH3 R2 Ac Ac TBS TBS yield (%) 24 65 52 29 Steric arguments can be invoked to explain the selectivity. equatorial attack generates the less stable twistboat conformer (Figure 34). Diastereoselective Cyclopropanation of 2. Excellent diastereoselectivities are usually obtained when using a bicyclic template.318 The bicyclo[3.315 Only one diastereoisomer was obtained in 69% yield when methylenedimethylsulfoxonium was used (eq 86).312 Enantioenriched 2. No. Scheme 21. The stereochemical outcome of the reaction is easily explained by assuming that the sulfur ylide attacks the more accessible face of the olefin.314 Wender has disclosed the preparation of such derivatives from enone 306 using sulfur ylide chemistry. however. 2003. Dauben developed methods for the enantioselective synthesis of bicyclo[3.1. he elaborated a diastereoselective intermolecular cyclopropanation reaction involving the addition of methylenedimethylsulfoxonium ylide to chiral cyclopentenone 308 (eq 87).320 The cyclopropanation of (+)-dicyclopentadienone 313.

1020 Chemical Reviews. Diastereoselective Cyclopropanation of Cyclopentenone 310 Lebel et al. However. Total Synthesis of (+)-2-Aminobicyclo[3. reaction of 324 with Me2S(O)dCH2 afforded mainly a dimerization product.0]hexane ring systems that are designed as prolinetemplated amino acids. Both products arise from the cyclopropanation of the less hindered exo face. Synthesis of Cyclopropatryptophane Derivative 322 Table 47.N-acetal 323 and N-BOC-pyrrolinone 324 with isopropylidenediphenylsulfonium smoothly afforded the desired products in 89% and 79% yields. Vol. The asymmetric synthesis of (+)-2-aminobicyclo[3. entry 1 and 4). No.6-dicarboxylic Acid (LY354740) Diels-Alder reaction (Scheme 23). resulting from the ylide addition to the convex face of the tricyclic system 320. Ph(NMe2)S(O)dCH2. with only trace amounts of the desired product (entry 5).0]hexane-2. Cyclopropanation of O. The reaction was attempted with the less basic ylide.N-Acetal 323 and N-BOC-Pyrrolinone 324 with Various Sulfur Ylides Scheme 23. respectively (Table 47. was achieved by Domınguez and co-work´ ers.1. Indeed. the cyclopropane derivatives can be prepared in good yields from 323 and 324 by using a variety of unsymmetrical substituted sulfur ylides.322 The cyclopropanation of the protected dihydroxycyclopentenone 316 with sulfonium bromide 317 and DBU afforded the exo product 318 exclusively. 103. Diastereoselective Cyclopropanation of (+)-Dicyclopentadienone 313 entry 1 2 3 4 5 6 substrate 323 323 323 324 324 324 LnSdCR2 Ph2SdCMe2 Me2S(O)CH2 Ph(NMe2)S(O)dCH2 Ph2SdCMe2 Me2S(O)CH2 Ph(NMe2)S(O)dCH2 yield (%) 89 78 60 79 trace 19 Scheme 24.324 Only one isomer was obtained. LY354740). 2003. Madalengoitia prepared new 3-aza-bicyclo[3. The endo: . but this also resulted in a low yield of cyclopropane (entry 6). 4 Scheme 22. respectively (entry 2 and 3).1. Interestingly. a potent and selective agonist for a glutamate receptor involved in the mammalian central nervous system. in almost quantitative yield (Scheme 24). Scheme 25.0]hexane-2. the acidity of the methine proton was not a problem in the reaction of 324 with other sulfur ylides (Table 48).323 Crich used the sulfur ylide chemistry to prepare the enantiomerically pure cyclopropatryptophane derivative 322 (Scheme 25). The delivery of the methylene group arises from the convex face of the bicyclic system.1. The unsubstituted cyclopropane derived from 323 was successfully prepared from methylenedimethylsulfoxonium and Ph(NMe)2S(O)dCH2 in 76% and 60% yields.6-dicarboxylic acid (319.325 The cyclopropanation of O.

resulting from the delivery of the methylene group on the more accessible face of the dideoxynucleoside.329. the highest selectivities with acyclic systems are observed with conformationally constrained alkenes. Synthesis of Cyclopropyl Nucleoside Derivative 335 Scheme 26.3′-R-methylene[3.N-Acetal 323 and N-BOC-Pyrrolinone 324 with Various Unsymmetrical Substituted Sulfur Ylides Chemical Reviews. It reacted with carbon dinu- Only one isomer was observed for the MIRC reaction of 335. which is a precursor for pentalenene. was reported (Table 49).331 Krief exploited this transformation in the course of a study directed toward the synthesis of chrysanthemic acids.1.328 The 5′-protected R. Although the facial selectivity was excellent. in which the stereochemical induction is based on steric arguments. and both methylene bisdiethyl phosphate and bisphenyl sulfone. As a part of his program related to the discovery of new types of dideoxynucleosides as specific inhibitors of the HIV reverse transcriptase. the diastereomeric ratio at the ester center could not be controlled. MIRC Reaction of Enone 329 exo ratio varies with the substituent on the ylide and the substrate. only one isomer was obtained. Mulzer demonstrated that the addition of isopropylidenetriphenylphosphorane to γ-alkoxy-R.1. acetophenone.3′-deoxy2′. 103.β-unsatured carbonyls. a biological intermediate involved in the biogenesis of the antibiotic pentalenolactone. to give access to 2′.0]nucleosides derivatives (334) in 18-67% yields (eq 88). derived from D-glyceraldehyde using several ylides. and conjugate bases of nitromethane. Cyclopropanation of O.0] bicyclic cyclopropane analogues of 2′. Sanghvi used the Chattopadhyaya’s strategy for the preparation of a new conformationally constrained dimeric building block 337 containing a cyclopropylamide functionality (Scheme 27). In all cases. CH2+-CH2+.3 1:1 1:4 1:1 1:3 1:1 Recently.2-O-isopropylidene-D-glyceraldehyde-derived esters. highly diastereoselective MIRC reactions have been reported for a number of cyclic systems.332 . 4 1021 cleophiles such as sodium malonate. Conversely.Stereoselective Cyclopropanation Reactions Table 48. isobutylcyanoacetate. As illustrated above.3′-dideoxyuridine. and the cyclopropanation was directed to the more accessible face. The vinylcyclopropane 331 can be prepared by the addition of the lithium dienolate anion 330.326 The reagent was added to β.β-ene-3′phenylselenone 333 is a synthetic equivalent of a dication. One wellstudied system involves the use of 1. 2003.β-unsaturated esters derived from D-glyceraldehyde proceeded with good diastereoselectivity and yield.327 Pyrolysis of vinylcyclopropane 331 gave triquinane 332. Chattopadhyaya has developed a new stereospecific synthesis of [3. to the conjugated system 328 (Scheme 26). derived from ethyl 2-bromocrotonate.330 Scheme 27.5 5:1 1:1. Vol. entry 1 2 3 4 5 6 7 8 substrate 323 323 323 323 324 324 324 324 LnSdCHR Ph2SdCHMe Ph2SdCHCHdCH2 Ph2SdCHEt Me2SdCHCO2Me Ph2SdCHMe Ph2SdCHCHdCH2 Ph2SdCHEt Me2SdCHCO2Me yield (%) 84 60 82 78 54 68 62 82 ratio endo:exo 1:2. No. A systematic investigation of cyclopropanation of various γ-alkoxy-R.β-disubstituted enone 329.

2-O-Isopropylidene-D-Glyceraldehyde Ester 346 entry 1 2 3 4 5 6 reagent Ph3PCH3I.3-allylic strain between the ester group and the γ-substituent in the (Z)-series (with all reagents). 103. which now adopt the conformation shown in the model B. the reaction of the sulfur ylide was highly stereoselective.334 He also showed that the cyclopropanation of dimethyl alkylidene malonate 342 with either sulfur or phosphorus ylides afforded dimethyl cyclopropane-1.5 h 0 °C. Conversely.1′S. an isotype-selective agonist of metabotropic glutamate receptors (eq 90).335 Ma used a similar strategy in the synthesis of (2S. It was found that the reactivity and selectivity observed with 2-lithio-2-propyl-N-tosylisopropylsulfoximide are closely related to those obtained with isopropylidenetriphenylphosphorane. 5 h yield (%)‘ 66 0 82 82 80 73 ratio 347:348 57:43 67:33 67:33 80:20 95:5 . both phosphorus and lithium reagents delivered the isopropylidene moiety to the si face. n-BuLi Ph3PCH3I. With (Z)-338. and the tert-butyl ketone.β-Unsaturated Esters Derived from D-Glyceraldehyde with Various Reagents Lebel et al. However.333 He suggested that the conformation shown in model A (Figure 36). Krief reported that the related tertiary amide. L-CCGI). This model is not favored. NaH Me3S(O)I. Vol. Krief proposed two models based on Stork’s work to rationalize these results. while the sulfur ylide attacked the re face of the alkene. 2003. The initial geometry of the double bond has some effect on the sense of induction. Reactive conformers for the diastereoselective cyclopropanation of (E)-338 and (Z)-338. 0. derived from D-glyceraldehyde. leading to the formation of the cis-cyclopropane 342. No. 1 h 20 °C. the behavior of isopropylidenediphenylsulfurane is dramatically different. both the phosphorus and lithium reagents led to the isomerized trans-cyclopropanes 339 and 340. NaH Me3S(O)I.1-dicarboxylate 343 with good yields and very high diastereoselectivities (eq 89).1022 Chemical Reviews. the tert-butyl ester. gave results similar to those shown above (Figure 37).and (Z)-r. NaH Me3S(O)I. NaH conditions 20 °C. Figure 37. Other conjugated systems derived from glyceraldehyde. Cyclopropanation of (E). 5 h 0 °C. However.336 Figure 36. no transition-state model has been proposed to account for the stereochemical outcome of the reaction between the closely related sulfur ylide and (E)-338. Similarly. due to 1. Cyclopropanation of 1. which results from a favorable interaction between the π orbital of the double bond and the electron pair of the γ oxygen. the attack of all three reagents occurred on the re face. With (E)-338. 5 h -30 °C. is operative in the (E)-series of com- Table 50. 4 Table 49. 5 h 55 °C. n-BuLi Me3S(O)I. Nevertheless.2′S)-(carboxycyclopropyl)glycine (344. D- reagent E-338 Ph3PdCMe2 Me2CS(O)(NTs)CLiMe2 Ph2SdCMe2 Ph3PdCMe2 Me2CS(O)(NTs)CLiMe2 Ph2SdCMe2 yield (%) 55 70 92 61 48 84 dr 339:340:341:342 90:10:0:0 93:7:0:0 2:98:0:0 6:94:0:0 39:61:0:0 0:0:2:98 Z-338 pounds with the phosphorus and lithium reagents.

2.and Garner’s Aldehyde-Derived Enones Table 52. 4 1023 Table 51. Synthesis of 1.3-Trisubstituted Cyclopropanes from (S)-Glyceraldehyde Acetonide.Stereoselective Cyclopropanation Reactions Chemical Reviews. While the phosphorus ylide was poorly reactive and diastereoselective. Vol. the desired cyclopropane 347 was prepared from methylenedimethylsulfoxonium at low temperature. Ma also prepared a series of 1.337 . No. with good yield and diastereoselectivity (Table 50).3-trisubstituted cyclopropanes from (S)-glyceraldehyde acetonide.2-O-isopropylidene-Dglyceraldehyde-derived ester 346.and Garner’s aldehyde-derived enones (Table 51). 103. Diastereoselective Cyclopropanation of Bis(Unsaturated Ester) Derived from Tartaric Acid The key stereoselective cyclopropanation involved the ylide reaction of the 1. 2003.2.

Surprising results were obtained in the reaction between the (Z)-bis(conjugated ester) 358 and the phosphorus reagent. However. 103. Diastereoselective Cyclopropanation of (Z)-Bis(conjugated ester) 358 Lebel et al. The cisenone gave better geometry selectivity than the trans-enone. the yields and the selectivities were mediocre. A 83:17 cis:trans ratio was obtained when the reaction was run in hexane. Both phosphorus and sulfur ylides were used with the bis(unsaturated esters) 357 and 358. Vol. both the yield and the diastereoselectivities were poor.2-O-isopropylidene-D-glyceraldehyde 366 has also been reported (eq 92). when methylenediphenylsulfonium was used. but the latter is superior. Conversely. and (d) cyclopropanation of the second carbon-carbon double bond. (c) cyclization of the betaine.3-allylic strain.3-epoxybutylidene)malonate 372 (Scheme 29). The model presented in Figure 36 accounts for the observed sense of induction. 5.3-isopropylideneglyceraldehyde) to produce the corresponding dimethyl-substituted nitrocyclopropanes 370 in good yields and diastereomeric ratios (eq 93). after cyclopropanation and oxidative cleavage. No. (b) the stereoselective isomerization (Z to E) of the remaining olefinic linkage. The cyclopropanation of chiral (Z)-oxazolone derived from 1. and 7). When the (Z)-monoadduct 365 was resubmitted to the same reaction conditions. and the results correlated well with those of the simpler system. the reaction between 358 and only 1 equiv of phosphorus ylide gave a 1:1:1 mixture of 358:362:364.1024 Chemical Reviews. Kasatkin reported the synthesis of cyclopropane dicarboxylates using MIRC reactions with diethyl (2. 4 Scheme 28. These hemicaronaldehydes can be easily transformed into transchrysanthemic acid or its analogues. respectively (entries 2. Krief extended this approach to C2-symmetric bis(unsaturated esters) 357 and 358 (Table 52). and the corresponding isoxazaline N-oxide became an important byproduct. MIRC Reaction with Diethyl (2. Patzel has used the isopropylidenediphenylsulfo¨ nium ylide for the cyclopropanation reactions of various nitroalkenes 369 (derived from (R)-2. leading to a betaine. 2003. 361 (and not 362!) was formed in the process (eq 91). which led to 362 (Scheme 28).341 Scheme 29.3-Epoxybutylidene)malonate 372 The overall stereochemical outcome of the reaction must then be consistent with the following events: (a) the addition of the ylide across one of the (Z)carbon-carbon double bonds. Good yields and diastereoselectivities could usually be obtained with ester-substituted ylides.339 Both methylene- . dimethylsulfoxonium and -(diethylamino)phenylsulfoxonium produced the desired cyclopropanes 367 and 368.340 The sense of induction can be predicted by minimization of the 1. leading mainly to products 351 and 354 from E isomers and Z isomers. These observations led the authors to assume that a Z-to-E isomerization took place via an unknown mechanism on the betaine resulting from the first addition of the ylide. Although the reaction proceeded with amide-substituted ylides.338 These bis(unsaturated esters) are easily prepared from tartaric acid and generate two hemicaronaldehyde units per molecule of bis(adduct).

2003. the best case being the (E)-cis-cyclopropanecarboxylate 380. Arene metal-π complexes and related systems constitute another category of substrates that are suitable for MIRC reactions. Very few diastereoselective MIRC reactions of acyclic precursors. the steric hindrance of the arylsulfonyl group on the aziridine nitrogen atom influences the preferred conformation of the substrate in the transition state. implying a selective approach of the nucleophilic reagent to the other face of the double bond moiety (Figure 38). Zwanenburg has developed an analogous method for the nucleophilic addition/ring-closing tandem process of activated aziridinylmethylenemalonates 377 (eq 94). The Grignard reactions catalyzed by CuCN provide the highest diastereoselectivities. which led to a 75:25 ratio of the bis(cyclopropane) products 381 and 382 (eq 95). 4 1025 Treatment of the epoxide 372 with either a Grignard or an organolithium reagent in ether in the presence of 5 mol % CuI led to cyclopropane-bearing lactones 375 in 38-85% yield and with 60:40 to >95:5 trans: cis selectivities via intermediates 373 and 374. A variety of cis-substituted cyclopropane dicarboxylic ester derivatives 278 could be prepared with a moderate level of diastereoselection (cis:trans ratios ranged from 50:50 to 91:9).344 For cuprate reagents. Reactive conformers for the cyclopropanation of 2. When the enantiomerically pure 2-(trimethylsilyl)styrene complex 385 was submitted to (methoxymethyl)triphenylphosphonium chloride and potassium tert-butoxide. In the favored conformation.348 Accordingly.342 Figure 38. In contrast. Zercher has reported one of these examples with the ylide-mediated bis(cyclopropane) formation.347 The double bond in tricarbonyl(styrene)chromium(0) complexes is polarized such that nucleophilic attack occurred at the β-carbon of the alkene. these substrates are suitable for MIRC reactions. the R-carbanions generated upon nucleophilic attack may be quenched with electrophiles. This syn-directing effect may be the result of an initial ylide coordination to the Cr(CO)3 group. 103.346 In contrast to other nucleophilic additions to arene chromium complexes. For instance. Transition-state models have been proposed on the basis of the work of Yamamoto on the conjugate addition of organocuprate reagents to γ-alkoxy R. the conformer in which the carboncarbon bond of the epoxide is perpendicular to the alkene is favored. it is presumed that the steric factors are more important than the stereoelectronic factors. an 89:11 mixture of two .343. thus.and trans-aziridinylmethylenemalonate. have been reported so far. as shown by Gibson and co-workers. good diastereoselectivities were obtained by using a sulfur ylide.345 Low diastereoselectivities were observed. Vol.β-unsaturated diester derivatives. in which the chiral center does not contain a C-heteroatom bond. No.349 The cyclopropanation of tricarbonyl(styrene)chromium(0) complexes with sulfur and phosphorus ylides proceeded in good yields. The preferred formation of the cis-cyclopropane derivative is opposite to that observed by Kasatkin during the MIRC reaction of the epoxide analogue (vide supra). the cyclopropanation of arene chromiumtricarbonyl complex 383 with trimethyl- sulfoxonium iodide under phase-transfer catalysis conditions yielded the corresponding cyclopropane 384 as a single diastereoisomer (eq 96).Stereoselective Cyclopropanation Reactions Chemical Reviews. In some cases. the product resulting from an endo addition (syn to the chromium) is formed. one face of the Michael acceptor is effectively shielded by the N-arylsulfonyl group.3-epoxybutylidene.

354 Yamazaki also reported the use of menthyl esters as chiral auxiliaries for the diastereoselective cyclopropanation of 1-seleno-2-silylethene 394 with di(-)-menthyl ethene-1. which is stabilized by the selenium atom. Finally. Proposed Reaction Course for the Cyclopropanation with 1-Seleno-2-silylethene The transition-state model shown in Figure 39 illustrates the stereochemical outcome of the reaction.353 Krief reported that the cyclopropanation of bis-(-)-menthyl fumarates 392 with isopropylidenetriphenylphosphorane afforded an 88:12 mixture of stereoisomers (eq 97). The nucleophilic addition of the vinyl selenide 394 to the unsaturated ester. This approach was explored very early.2migration of the silicon atom yields the second zwitterionic species.352 The chiral enantioenriched starting material 389 was prepared from the racemic mixture by resolution.355 Scheme 31. 4 Scheme 30. generates the first zwitterionic species. Synthesis of Chiral Cyclopropanes from Chiral (Pentenediyl)iron Complexes diastereoisomers (out of a possibility of four) was obtained (Scheme 30). which leads to the thermodynamically more stable diastereoisomer. The 1. Diastereoselective Cyclopropanation of Tricarbonyl(styrene)chromium(0) Complexe 385 Lebel et al.1026 Chemical Reviews. leading to a mixture of three diastereoisomers.350. can be also envisioned to account for the observed stereoselectivity.351 The oxidatively induced reductive elimination of 390 proceeds with retention of configuration at the two centers undergoing C-C bond formation. activated by the Lewis acid. The major diastereoisomer 386 was purified and isolated in 66% yield and with a diastereomeric ratio greater than 98%. Removable Chiral Auxiliaries 1.1-dicarboxylates 395 in the presence of zinc halides (eq 98). A synclinal addition involving SesCdO secondary orbital interactions (not shown) has been postulated. Scheme 32. Such a strategy has been used for the synthesis of cyclopropylglycine derivatives. The nucleophilic attacks of R-chloro carbanions were less selective. Vol. 103. Both menthyl groups were fixed by the chelation . The authors have postulated that an equilibration process. No. The ring closure then produces the desired cyclopropane. 2003. could explain the stereochemical outcome. C. The cyclopropyl sulfone 387 was purified and isolated as a single diastereoisomer. but generally low diastereoselectivities were observed. chiral (pentadienyl)iron complexes 389 have also been converted to chiral cyclopropanes under oxidative conditions by using ceric ammonium nitrate (Scheme 31).β-Unsaturated chiral esters constitute the first class of chiral auxiliaries used as Michael acceptors in these reactions. whereas the trisubstituted cyclopropane 388 could be obtained only as a mixture of two unseparable diastereoisomers. a metal-mediated delivery process. However. such as the one described above. Scheme 32 outlines a possible reaction course for the cyclopropanation with 1-seleno-2-silylethene 394. Chiral Michael Acceptors R.

The use of (-)-8-phenylmenthyl-derived 3-aryl-2phosphonoacrylates 403 also afforded a mixture of diastereoisomers upon treatment with methylenedimethylsulfoxonium (eq 100). Stereochemical course for the cyclopropanation using 10-dicyclohexylsulfanoyl-D-isoborneol-derived auxiliary. 2003. Removal of the chiral auxiliary (1. The diastereoselectivity was better for the trans isomers (407/405 ) 85-93%) than for the cis isomers (406/404 ) 70-75%). compound 408 was sterically preferred and formed as the major product.Stereoselective Cyclopropanation Reactions Chemical Reviews. 103.1-dicarboxylate 395 (R group was omitted for clarity). CaCO3) afforded the . cyclopropyl derivative 398 was obtained in ca. The use of (-)menthol and (-)-8-phenylmenthol-derived auxiliary could not produce any stereochemical induction. 4 1027 Figure 39. 10-dicyclohexylsulfanoyl-D-isoborneol. Approach from the re face would have resulted in steric repulsion between the selenium and the isopropyl moiety of the menthyl group.356 After considerable optimization. with poor diastereoselectivities for both isomers. each leading to two opposite enolates. 399 and 400.β-unsaturated ester (Figure 42).and trans-cyclopropanes. The telluronium ylide attacked at C-3 on the re face. One could explain the formation of the minor diastereoisomer with the E isomer here again by a rapid equilibration between s-cis and s-trans conformers. No im- Figure 40. the authors have postulated the contribu- tion of a low-lying conformer. The synclinal addition of vinyl selenide 394 occurred from the si face of di(-)-menthylethene-1. provement in the diastereoselectivity was observed when Oppolzer’s sultam was used. 75% yield with very low diastereoselectivity (eq 99). BF3‚Et2O.358 The phenyl group was proposed to block the si face of the alkene by a π-stacking effect between the phenyl and the dienyl groups of the (-)-8-phenylmenthyl R. The same argument could also be used to account for the lack of selectivity with the Z isomer.β-unsaturated esters could react with silylated allylic telluronium ylide 295 to provide silylvinylcyclopropane derivatives 408 with good diastereoselectivities and yields (Table 53). Synclinal approach of the vinylselenide 394 from the si face of the di-(-)-menthyl ethene-1. The modest diastereoselectivity is imputed to a rapid equilibration between s-cis and s-trans conformers of the substrate in solution. and Oppolzer’s sultam-derived auxiliary has been tested by Little. MeI. with zinc iodide (not shown). 2. The cyclopropanation of the Z isomers gave a nearly equimolar mixture of cis. No. However. in accord with Oppolzer’s original model (Figure 40). thus.359 Isopropylidenetriphenylphosphorane reacted with oxazolidine 410 with excellent π-face selectivity (eq 101). in which the acrylate moiety is twisted out of conjugation and both faces of the double bond are equally opened (Figure 41).357 The reaction of E isomers afforded preferentially the trans isomers 407 (trans:cis ) 67-75:25-33). Scolastico described one example of a chiral auxiliary involving a chiral γ-substituted conjugated ester. HSCH2CH2SH. Tang and co-workers have reported that a variety of (-)-8-phenylmenthyl R.1-dicarboxylate 395. (-)-8-phenylmenthol. The attack of the nucleophile is speculated to occur preferentially from the backside at the β-carbon. H2O. The effectiveness of (-)-menthol. Vol.

Figure 41. using . Vol. such as chrysanthemic acid. the stereoselectivity of the reaction was reversed. Stereoselectivity in Lewis Acid-Mediated Cyclopropanation of N-Enoyl Oxazolidinones entry 1 2 3 4 5 6 7 R Ph H p-ClC6H4 p-FC6H4 p-MeC6H4 p-CF3C6H4 p-MeOC6H4 yield (%) 83 72 94 100 89 94 90 ratio 408:409 92:8 86:14 88:12 90:10 89:11 88:12 86:14 entry 1 2 3 4 5 6 R Me Me Me Ph Ph Ph Lewis acid none Yb(OTf)3 Y(OTf)3 none Yb(OTf)3 Y(OTf)3 yield (%) 79 84 87 75 75 71 ratio 414:415 33:67 91:9 89:11 30:70 93:7 70:30 corresponding hemicaronic aldehyde.360 The proposed transition state involves the conformer 412.363 Cyclopropanations of the unsaturated lactams 416 were performed first. No. Meyers developed a very useful chiral auxiliary based on chiral bicyclic lactams prepared from lvalinol or l-tert-leucinol.362 In the absence of Lewis acids. However. 4 Lebel et al.3) strain is minimized and the most electronegative substituent (oxygen) is perpendicular to the π orbital of the alkene (Figure 43). which is a key intermediate for most syntheses of pyrethroids.1028 Chemical Reviews. Postulated reactive conformer for the cyclopropanation of (-)-8-phenylmenthyl R. It was suggested that the Lewis acids chelates both carbonyl groups of the substrate. Preferred conformer for the diastereoselective cyclopropanation using oxazolidine auxiliary. albeit with a lower selectivity (entries 5 and 6). Figure 42.and (Z)-(-)-8-phenylmenthyl-derived 3-aryl2-phosphonoacrylates.361 Madalengoitia showed that the cyclopropanation of chiral N-enoyl oxazolidinones 413 with isopropylidenediphenylsulfonium in the presence of Lewis acids proceeded with a good level of diastereocontrol to generate 414 (Table 54). the diastereoselectivities were low. The same trend was observed with cinnamoyl oxazolidinone.β-Unsaturated Esters with Silylated Allylic Telluronium Ylides Figure 43. Diastereoselective Cyclopropanation of (-)-8-Phenylmenthyl r. in which the A(1. Table 53. favoring 415 (entries 1 and 4). affording respectively a 10:1 and an 8:1 414: 415 ratio (entries 2 and 3). Table 54. Speculated angle of attack in the cyclopropanation of (E). when 2 equiv of Yb(OTf)3 or Y(OTf)3 was used. 2003. affording a dominant reactive rotamer in which one face of the β-carbon is shielded from attack (Scheme 33).β-unsaturated esters and silylated telluronium ylides. 103.

For example. [(Diethylamino)phenyl]methylenesulfoxonium reacts with the diphenyltetrahydrooxazinone 425. treatment of 419 with isopropylidenediphenylsulfonium afforded the gem-dimethyl cyclopropyl adduct 420 in 94% yield and >99:1 dr (eq 102). whether another stereo or stereoelectronic effect is also operating is still an open question. followed by mild acid hydrolysis. the mode of addition was found to be highly dependent on the angular substituent of the unsaturated lactam. the steric environment in these systems is such that the nucleophiles (sulfur ylides) approach from the most sterically hindered endo face. Lewis Acid-Mediated Cyclopropanation of N-Enoyl Oxazolidinones Chemical Reviews. An alternative way involved reduction of the lactam. Although the Cieplak effect was proposed as a possible explanation for the high facial selectivity observed during cyclopropanations.369 All these cyclic chiral auxiliaries. phenyl-. to give the keto aldehyde. but epimerization occurred in some cases prior to completion of the cleavage.365 Substituted sulfonium ylides were also employed for the cyclopropanation of the unsaturated lactams and led to very high endo:exo selectivities. presented in Table 57. Cyclopropanation of Chiral Unsaturated Lactams with Methylenedimethylsulfoxonium R1 t-Bu t-Bu t-Bu i-Pr R2 Me vinyl Ph Ph yield (%) 95 59 41 47 ratio 422:423 83:17 97:3 88:12 >99:1 Unsymmetrical substituted sulfonium ylides produced very high endo:exo ratios and modest to excellent anti:syn selectivities. are based on a stereoselective cyclopropanation of an exocyclic double bond via an addition/elimination sequence. This method has been used recently for the preparation of a key precursor to (-)-indolizomycin. the predominant mode of cyclopropanation can be predicted simply on the basis of the size of the angular substituent present in the bicyclic lactam. In one procedure. no directing effect was observed during cyclopropanation of the unsaturated lactam substituted in the angular position by a pentafluoroethyl group. Conversely. 4 1029 Table 56. and furnished the desired cyclopropane adduct 417 in good to excellent yields (Table 55). Nevertheless. and a simple change from methyl to hydrogen leads to a complete reversal in endo:exo selectivity (Table 55. Cyclopropanation of Chiral Unsaturated Lactams with Substituted Sulfur Ylides entry 1 2 3 4 Table 55.Stereoselective Cyclopropanation Reactions Scheme 33. No. thus eliminating simple steric arguments. acid hydrolysis led to the corresponding cyclopropylcarboxylate. developed by Wil- . Methyl-. Vol.367 probably as entry 1 2 3 4 5 6 7 8 9 R1 i-Pr i-Pr i-Pr i-Pr i-Pr t-Bu i-Pr i-Pr t-Bu R2 CH3 CH3 CH3 CH3 CH3 CH3 H H H R3 H CO2CH3 Ph SOCH3 SO2CH3 H SOCH3 CO2CH3 H yield (%) 64 65 60 90 70 81 50 50 40 ratio 417:418 98:2 >99:1 >98:2 >95:5 >95:5 95:5 <5:95< <3:97 <5:95< methylenedimethylsulfoxonium ylide.364 In all the cases.368 A number of chiral auxiliaries have been elaborated for the preparation of enantiomerically pure cyclopropyl R-amino acids. entries 1-6 vs 7-9). 2003. and vinylmethylenediphenylsulfonium gave 3:1 to >50:1 syn:anti ratios (Table 56). while the carboxymethylene sulfonium derivative led to the exclusive formation of the anti isomer 424 (eq 103).366 the result of thermodynamic equilibration of the initially formed endo-syn-carboxycyclopropyl adduct. the cyclopropanation proceeded with a high degree of exo:endo (416:417) diastereoselectivity. However. Removal of the chiral auxiliary from the cyclopropyl bicyclic lactam adducts was carried out using two procedures. Actually. 103.

coordination of the Grignard reagent to the oxygen atom of the sulfinyl group was involved. only the coupling product was observed with either methyl Grignard or methyl cuprate reagents. Vol. when applied to the E isomers. Chiral Auxiliaries for Preparation of Cyclopropyl Amino Acids Lebel et al. lower diastereoratios were obtained (from 67:33 to 75:25).4addition proceeds generally with high asymmetric induction. Reductive or oxidative cleavage of the chiral auxiliary liberated the cyclopropyl R-amino acid. the corresponding cis isomers have not been prepared by an analogous method. Conversely. the optically active vinylic sulfoxide 430 was stereoselectively transformed into the chiral cyclopropane 431 by means of a Michael addition reaction with an allyl Grignard reagent (eq 104).375 liams. Chiral vinyl sulfoxides have been used as Michael acceptors with a variety of nucleophiles. with a nonaromatic sulfoxonium ylide such as methylenedimethylsulfoxonium. they were separated by flash chromatography and recrystallization.1030 Chemical Reviews. but the major product was contaminated with the coupling byproduct to the extent of about 10%.β- One diastereoisomer was obtained. The yield of the desired cyclopropane decreases in favor of the coupling byproduct when cuprate reagents are used as the nucleophile or mesylate groups as the leaving group. Moreover. The transition-state model depicted in Figure 44 can rationalize the stereoselectivity. the chiral (Z)-R. However. A pinanone-derived chiral auxiliary 426 was described by Calmes. followed by the preferential delivery from the bottom face through the energetically more favorable conformer A. 4 Table 57. The same reaction. as an equivalent of amino acid olefins (entry 4). and the 1. a 50:50 mixture of diastereoisomers was obtained. Michael addition of methylenedimethylsulfoxonium to optically pure methyl R-(p-tolylsulfinyl) acrylate 432 provided cyclopropylcarboxylic ester 433 in high yield and moderate stereoselectivity (eq 105). Nevertheless.3- . entry 3). didehydroamino acid derivatives 428.371 Nucleophilic attack occurred from the less hindered face opposite to the gem-dimethyl group. The major stereoisomers were isolated in 70% (R ) Me) and 79% (R ) Et) yields.370 π-Stacking between the phenyl group of the ylide and the aryl substituents was proposed to explain the fact that reactions occur on the same face as the diphenyl substituent of the oxazinone. The 1. and elimination occurred prior to bond rotation. led to a mixture of two inseparable diastereoisomers (55:45). Acyclic chiral vinyl sulfoxides have also been converted into cyclopropanes. Najera and co-workers used Seebach’s oxazolidine ´ auxiliary 427 in the cyclopropanation reaction with phosphorus ylide (Table 56. Methylenedimethylsulfoxonium addition afforded only one cyclopropyl derivative in 45-95% yield (Table 56. entry 1). entry 2). The Figure 44. Models for the stereoselective addition of Grignard reagents to chiral sulfoxide 430.374 For example. cleavage of the chiral auxiliary from aryl cyclopropyl derivatives led to the opening of the cyclopropane.372 Unfortunately. The same authors also reported a six-membered-ring version. and both enantiomers were obtained in enantiomerically pure form after acidic cleavage. to give cyclopropyl derivatives with excellent diastereoselectivities (Table 57. 2003. Only the cis isomers were reported. Alkylcyclopropane can be liberated from the chiral auxiliary by acid hydrolysis. only a 24% yield of allonorcoronamic acid in high enantiomerical purity (>98% ee) was isolated after treatment with 3 M hydrochloric acid at 100 °C for 4 days. Only the trans isomers were demonstrated to be accessible using this approach.373 The cyclopropanation with Corey’s dimethylsulfoxonium methylide furnished the corresponding spiro compounds as 92:8 (R ) Me) and 96:4 (R ) Et) mixtures of diastereoisomers.376 The proposed transition state involves a nonchelate model in which the dipoles of the p-tolylsulfinyl and the carbonyl group are opposed (Figure 45). Many attempts to hydrolyze the chiral auxiliary afforded decomposed products. No. 103.

Lower yields and diastereomeric ratios were obtained with cyclohexenone derivatives. No. S-benzyl. Pyne found that highly enantioenriched cyclopropanes were produced from lithiated S-allyl. The (S)-(+)-R-(diethoxyphosphoryl)vinyl p-tolyl sulfoxide 436 reacted with deuterated methylenedimethylsulfoxonium and isopropylidenediphenylsulfonium. 2003. Figure 46. to form the corresponding cyclopropane 437 as a single diastereoisomer in good yield (eq 107). Chiral sulfoximide can also be used as a chiral Michael acceptor.(445). The unsubstituted sulfoximine yielded the 1. a constrained analogue of phaclofen. to yield cyclopropanes. were shown to influence both the yield and the selectivity.382 More recently. 2. leading to the formation of the major diastereoisomer. Chiral Nucleophiles A variety of stoichiometric chiral nucleophiles have been developed in recent years to perform enantioand diastereoselective cyclopropanation of alkenes. chiral sulfur. albeit with low enantioselectivities.381 The diastereofacial selectivity in the enolate addition is opposite to that obtained with sulfur ylide (vide supra). using a similar strategy. 4 1031 forded the desired cyclopropane derivatives with diastereomeric ratios ranging from 75:25 to 92:8 (eq 108).(444). Indeed.2-disubstituted cyclopropanes 447 with a diastereomeric ratio of 99:1 and in 99% ee in the presence of chalcone (277) (eq 110).379 Indeed.377 The polarity and complexing ability of the solvent. phosphorus. Johnson was a pioneer in this area.383 The stabilized lithiated sulfoximides undergo highly diastereoselective Michael reactions with the enones at -78 °C. The same research group also reported the synthesis of 2-amino-3-phenyl-1-cyclopropanephosphonic acid. as well as the nature of the base and the counterion. since chelate formation between the carbonyl and sulfoxide oxygen is possible due to the presence of a complexing metal. Hiroy extended this strategy to the addition of the bromomalonate carbanion to chiral R-ketovinylic sulfoxide 434. The initially formed anionic Michael adducts ring-close upon warming to room temperature by an intramolecular displacement of the sulfonimidoyl group with inversion of configuration. An acylcyclopropane derivative 435 was prepared in moderate yields and diastereoselectivities (eq 106). the relative stereochemistry has not been established. The asymmetric cyclopropanation using chiral sulfur ylides was reported as early as the 1960s. 103.β-unsaturated carbonyl derivatives. Model for the diastereoselective cyclopropanation of acyclic chiral vinyl sulfoxide 432. Model for the diastereoselective cyclopropanation of acyclic chiral vinyl sulfoxide 434.380 Reaction between lithiated phenyl phenylthiomethyl sulfone 440 and 1-(phenylthio)vinylsulfoximide 441 produced a mixture of two stereoisomeric cyclopropanes (442 and 443) in a 75: 25 ratio (eq 109). and arsenic ylide derivatives as well as chiral enolates have been added to R. Figure 45. The addition of bromomalonate enolate occurred from the sterically less crowded lone-pair side of the chiral sulfinyl substituent (Figure 46). developing a series of chiral aminosulfoxoniums which produce the optically active disubstituted cyclopropanes with up to 49% ee. Although moderate diastereoselectivities were obtained with the S-allyl derivative (444).378 However. elimination occurred preferentially from the lone pair side of the p-toluenesulfinyl. and S-alkyl-N-tosylsulfoximines (446) and enones (Table 58). Vol. the S-benzyl(445) and S-alkyl-N-tosylsulfoximines (446) provided the corresponding cyclopropane with diastereomeric ratios greater than 96:4.Stereoselective Cyclopropanation Reactions Chemical Reviews. the cyclopropanation of chiral (E)-(S)-(1-dimethoxyphosphoryl-2-phenyl)vinyl p-tolyl sulfoxide 438 with various sulfur ylides af- .

Scheme 34. Vol. in which the largest groups of the sulfoximide (the sulfonimidoyl moiety) and the enone (R2) are anti in order to minimize steric interactions (Scheme 34). this enolate underwent an intramolecular displacement of the sulfonimidoyl moiety upon warming to room temperature. Walker found that the addition of chiral imidazolyl sulfoxide 450 to methyl 4-bromocrotonate produced the cyclopropane 451 as a single diastereoisomer in good yield (Scheme 35). When the reaction was quenched with acetic acid at -78 °C. 4 Table 58. Transition-State Model for the Enantioselective Cyclopropanation of Enones with Chiral Lithiated Sulfoximines The stereochemical outcome of the reaction has been rationalized by the transition state A. In contrast. with inversion of configuration. 103. No. Indeed. Asymmetric Cyclopropanation of Enones with Chiral Lithiated Sulfoximines Lebel et al. 2003. Other types of sulfur reagents were recently tested. the 1.384 Thermolysis of the cyclopropyl sulfoxide gave the vinyl cyclopropane .1032 Chemical Reviews.4-adduct derived from enolate 448 was isolated.

such as phosphazene bases [EtNdP(NMe2)2sNdP(NMe2)3] (460). 103.β-unsaturated carbonyl derivatives (Table 59). while acrolein led mainly to the corresponding epoxide. Excellent diastereo. The substrate reacts with the ylide from the re face to avoid the steric interaction between the R1 group and the methyl substituent of the bicyclic system. 4 1033 Scheme 36. 2003. A single diastereoisomer was also observed in the synthesis of β-(trimethylsilyl)ethyl cyclopropanecarboxylate derivatives from chiral p-tolyl β-(trimethylsilyl)ethyl sulfoxide 454 (Scheme 36). Using a similar strategy. Cyclopropanation Reaction with Chiral Sulfoxide 454 corresponding cyclopropanes with good diastereoselectivities.2. favoring the trans isomers in high diastereomeric ratios and very high enantioselectivities (95-99% ee).385 The cyclopropanecarboxylate 457 was converted into cyclopropanecarboxaldehyde 458. To account for the observed stereochemical outcome. and reacted with ethyl acrylate. Tang and co-workers prepared 1. No. Asymmetric Cyclopropanation of Michael Acceptors with 464 Scheme 37. MIRC Reaction with Chiral Oxathiane 461 452 as a mixture of isomers. The chiral oxathiane 461 could be recovered from the reaction mixture with 80-89% yield. the authors have proposed the transition-state model shown in Figure 47. Cyclopropanation Reaction with Chiral Sulfoxide 450 Chemical Reviews.387 The corresponding chiral sulfonium ylides were generated in situ upon treatment with a strong base. Methylvinyl ketone is compatible with the reaction conditions. whereas low yields were obTable 59. a chrysanthemate precursor. Aggarwal has developed a new and very elegant process for the in situ preparation of sulfur ylides and .388 The chiral sulfonium salt 464 is readily available from the corresponding sulfide 463. Standard transformations afforded dictyopterene A (453) in 50% overall yield.3-trisubstituted vinylcyclopropanes with high enantioselectivities.and enantioselectivities were obtained with (E)-aryl-R.Stereoselective Cyclopropanation Reactions Scheme 35. in which the carbonyl group of the substrate is coordinated to the metal via a six-membered ring. which is easily prepared from D-camphor (eq 111). Vol.386 Chiral sulfonium ylides have been also reported for the asymmetric cyclopropanation of electrophilic alkenes. leading to the served with aliphatic alkenes as well as with Z isomers. The reaction of chiral oxathiane 461 with arylmethyl alcohols in the presence of triflic anhydride produced a series of (arylmethyl)sulfonium salts 462 in 80-85% yield (Scheme 37).

constitutes another improvement in this process. which can be epimerized to the exo.β-unsaturated γ-lactones. and a catalytic amount of rhodium acetate. were developed and were shown to be more efficient for the catalytic version of the reaction. Rhodium-Catalyzed Asymmetric Cyclopropanation of Enones with Phenyldiazomethane and Chiral Sulfide 465 entry 1 2 3 4 5 R Ph Ph Me Me p-BrC6H4 sulfide (equiv) 1. However. while the meso isomer was obtained in about 20%. the use of the cis-chloroallyl phosphonamide reagent under the same conditions led to the exo. 4 Lebel et al. several applications have been reported. Hanessian described an efficient and versatile protocol. In theory.2 1. No. albeit with a moderate diastereoselectivity of 60% (Table 61).0 0. using a phase-transfer catalyst.389 The chiral sulfur ylide is generated catalytically from a metal carbene intermediate which derived from the reaction of a metal complex and a diazo reagent (Scheme 38). reduced yields were obtained when substoichiometric amounts of sulfide 465 were used. the chiral sulfur ylide could be recycled and used in a substoichiometric amount. Although phosphorus ylides are not as commonly used as sulfur ylides. the cyclopropane derived from chalcone was produced in 73% yield and 91% ee using 0. Proposed transition state for the cyclopropanation using 464. Synthesis of Cyclopropyl Amino Acids has used this technology for asymmetric cyclopropanation reactions.endo product. A second generation of chiral sulfides. In the presence of a stoichiometric amount of chiral sulfide 465 and phenyldiazomethane. Cyclopropyl amino acids 470 can also be prepared from amino acrylate derivatives 469 with greater than 90% ee by using this strategy (Table 62). Rhodium-Catalyzed Asymmetric Cyclopropanation of Enones with Chiral Sulfides 466 and 467 Figure 47.endocyclopropane with excellent yields and diastereoselectivities.endo isomer.391 Indeed. involving a chiral phosphonamidederived auxiliary. cinnamate derivatives were transformed to the corresponding cyclopropane products with high enantiomeric excesses and moderate yields and diastereomer excesses (Table 60). Table 61. for the stereoselective synthesis of substituted cyclopropane derivatives. A subsequent ring closure leads to the formation of the corresponding endo.0 yield (%) 60 38 55 14 35 dr 80:20 80:20 80:20 80:20 80:20 ee (%) 97 97 >98 >98 >98 The major diastereoisomer is chiral. The chiral auxiliary was removed by ozonolysis to generate the cyclopropyl aldehyde 474. δ-lac- .1034 Chemical Reviews.0 0. 2003. This method was extended to a variety of Michael acceptors. Catalytic Cycle for the Formation of Sulfur Ylides from Diazo Reagents Table 62.4addition of the anion derived from trans-chloroallyl phosphonamide 471 to conjugated compounds (such as 472) (Scheme 39).390 Table 60. Alternatively.392 The method consists of the highly stereocontrolled conjugate 1. such as R.2 1. Vol. 103. The in situ generation of the diazo reagent from the corresponding tosyl hydrazone derivatives 468. 466 and 467. Scheme 38.2 equiv of chiral sulfide 467.

Stereoselective Cyclopropanation Reactions Scheme 39. Vol. Elimination provided two possible cyclopropyl Figure 48. have been reported. and acyclic esters. re face of the cyclic enone. but low enantioselectivities were typically observed. as outlined below. Again. 2003.393. Other chiral ylides. 103.399 High enantioselectivities (>90% ee) were obtained when cinnamate derivatives were used Figure 49. the preponderant or exclusive products were the endo. Transition-state model for the diastereoselective cyclopropanation using chiral phosphonamide 471.398 The use of lithium anions and enolates as chiral reagents for MIRC reactions have also been described. derivatives. leading to a Li-chelated enolate intermediate.394 Such a strategy was used for the enantioselective and total synthesis of the cytotoxic agent (-)-anthoplalone.401 Reaction between (E)-ethyl-3-(trifluoromethyl) acrylate (476) and R-haloacyloxazolidinone enolate 475 afforded chiral cyclopropanes 477 and 478 as a 67:33 mixture of two out of eight possible stereoisomers (eq 112). such as pyridinium and arsonium ylides.396 It was suggested than the approach of the carbonyl substrate most probably occurs from the more accessible “left cleft” of the reagent. . in 5188% yield. Chiral cyclopropane subunits were also prepared from alkenes via the (-)-sparteine-catalyzed carbolithiation reaction. and a subsequent epimerization at the ester center accounted for the erosion of the diastereoselectivities. Enantioselective Carbolithiation of Alkenes Leading to Chiral Cyclopropanes tones. while vinylcyclopropanes (R1 ) RCHdCH) were produced in 50-83% ee (Scheme 40). which expels chloride to give the observed product. Yamazaki and Kitazume proposed the formation of the anti isomer 479 (Figure 49). as shown in Figure 48.397.395. Proposed mechanism for the stereoselective cyclopropanation. γ-lactams. Hanessian’s Chiral Auxiliary for the MIRC Reaction Chemical Reviews. No.4-addition of the other oxazolidinones to the (E)-ethyl-3-(trifluoromethyl)acrylate (476). 477 and 480. On the basis of the results of 1. Yamazaki and Kitazume explored the use of the enolate derived from Evans’s chiral auxiliary as a chiral nucleophile in the cyclopropanation reaction. 4 1035 Scheme 40. Attack of the γ-chloroallylic anion occurs on the (when R1 ) Ph). The phosphonamide derivatives could be further manipulated by chemoselective reactions to generate functionally diverse cyclopropanes.endo isomers (95:8 to >98:2 diastereoselectivity).400 In the course of studies directed toward the synthesis of trifluoromethylated compounds. as reported by Marek and coworkers.

A number of efficient chiral nucleophiles have recently been developed and are particularly useful for the synthesis of enantioenriched 1.402 The hydrolysis of the adducts afforded the enantiomerically pure R-cyclopropyl-R-amino acids. 4 Lebel et al. which could be separated by flash chromatography (eq 113).4. as illustrated by the two examples below.362 The cyclopropanation of N-enoyloxazolidinones 489 with isopropylidenediphenylsulfonium. entry 1 2 3 4 5 6 7 8 R Me Me Me Me Me Me Ph Ph Lewis acid Zn(OTf)2 (1 equiv) Mg(OTf)2 (1 equiv) ZnBr2 (1 equiv) ZnCl2 (1 equiv) Zn(OTf)2 (0. highly versatile chiral nucleophile systems are now available. Other Methods A. few promoters have been reported for enantioselective MIRC reactions. Enzymatic Methods Other methods have been developed over the years to access chiral enantioenriched cyclopropanes.6-trimethylphenyl 4-bromo-4.403 It is apparent that a number of Lewis acids afforded the desired cyclopropane in good yields and excellent levels of enantioselection (entries 1-4). Stoichiometric and Catalytic Promoters Until now. as shown in Table 63. Chiral Lewis Acid-Mediated Enantioselective Cyclopropanation of N-Enoyloxazolidinones Stoichiometric chiral nucleophiles that are added to electrophilic substrates containing a leaving group have been also developed. Shioiri reported the use of phase-transfer catalysts (PTCs) for the synthesis of 1. a loss of stereoselectivity was observed with less than 1 equiv of Lewis acid (entries 5 and 6). No. 103. The use of chiral auxiliaries or stoichiometric promoters is still the best choice to produce enantioenriched cyclopropanes with ylide chemistry. modest enantioselectivities (49-83% ee) were typically obtained with chiral PTCs.5 equiv) Zn(OTf)2 (1 equiv) MgI2 (1 equiv) yield (%) 63 57 60 53 65 63 69 70 ee (%) 95 92 93 92 82 55 36 14 The synthesis of trans-gem-difluorocyclopropanecarboxylates 488 was achieved with good diastereoselectivities via the Michael addition of the lithium enolate of homochiral N-acylimidazolidinone 487 to 2.75 equiv) Zn(OTf)2 (0.2. the course of the reaction is dependent on Lewis acid stoichiometry.2. Madalengoitia reported the first examples of chiral Lewis acidmediated asymmetric cyclopropanations of a Michael acceptor with a sulfur ylide. thus.406 In conclusion. proceeded with high enantioselectivities. The alkylation of lithiated bislactim ethers 482 with racemic 4-alkyl-4-bromobut-2-enoates 483 led to a 50:50 mixture of the corresponding diastereoisomers.3-trisubstituted cyclopropanes. chiral Lewis acids have been tested in the cycloaddition reactions of 1-seleno-2-silylethene. However. Although chiral acceptors were first introduced. Table 63. Good yields and moderate to high diastereoselectivities were observed. D.4-difluorocrotonate (486). Interestingly. This .1036 Chemical Reviews.405 Finally. but low yields (33-41%) and enantioselectivities (4347%) have been observed.3-trisubstituted cyclopropanes 493 from R-halocycloalkenones 492 and stabilized carbanions (eq 115). Vol. mediated by Lewis acids complexed to chiral bis(oxazoline) 490 (1 equiv).404 The examples above have illustrated that research toward the development of efficient chiral auxiliaries for MIRC reactions has been very active. Unfortunately. 2003. V. followed by a triethylborane-mediated intramolecular substitution reaction (eq 114). the asymmetric reaction of the cinnamate derivatives proceeded in low enantiomeric excess (entries 7 and 8) and appears to parallel the trends observed with the chiral auxiliary (see Table 54). a practical level of enantioselectivity has yet to be achieved in catalytic MIRC reactions.

when the substituent was aliphatic (Table 64). nonracemic R-substituted zinc homoenolate. the hydrolytic kinetic resolution of trans2-arylcyclopropanecarbonitriles 497 using a microbial cell.411 Seebach has reported the use Ti-taddolates as an alternative to hydrolytic enzymes for the ring opening of cyclic meso-anhydrides. Rhodococcus sp AJ270. B. has been also described. 2003. leading to enantiomerically pure γ-lactones in a convenient one-step route. Selectivity factors (e) greater than 40 are rarely observed. Many processes were reported in the 1980s and early 1990s for the desymmetrization of diester cyclopropanes such as 494. have been frequently used in the synthesis of chiral cyclopropanes.415 Recently. The lipase-catalyzed kinetic resolution of cyclopropyl acetals 500 was recently disclosed (Scheme 42). the starting material could be recovered with greater than 99% ee when Candida antarctica was used. including cyclopropane derivatives.407 Among them. chloro. Dordick disclosed the use of chloroperoxidase as a catalyst for the oxidation of cyclopropylmethanols.2-cyclopropylcarbinols produces enantioenriched cyclopropylmethanol units with up to 99% ee. Vol. the reaction with 2-(4-methoxyphenyl)cyclopropanecarbonitrile proceeded with a poor selectivity. Pseudomonas cepacia. Chloroperoxidase-Catalyzed Kinetic Resolution of Cyclopropylmethanol aldehyde entry 1 2 3 4 5 6 7 8 9 10 11 R Ph ArOCH2 BrCH2CH2 Br(CH2)3 Ph C6H4CH3 CH3 CH3CH2 n-Pr ArOCH2 BrCH2CH2 E Isomer 34 3 39 48 18 33 31 7 32 37 30 44 40 35 Z Isomer 65 66 90 89 82 92 91 alcohol e 1. such as lipases and esterases. thus producing enantioenriched building blocks. the kinetic resolution of cyclopropanes using hydrolases provides modest selectivities compared to those observed in the desymmetrization of meso compounds.3 6. we discussed the transition metal-catalyzed cyclopropanation of olefins with . such as methyl. providing a simple technique for the separation of the starting material and the product. The enantiomeric excess ranges from 20 to 100%. Indeed. leading to the desired aldehyde with 82-92% ee. was described (eq 116).417 After the reaction.412 In general. Subsequent opening of the cyclopropyl acetals with ZnCl2 leads to chiral. the hydrolases. No.419 Although the selectivity of the enzyme with the trans isomer of the cyclopropylmethanols was very low.408 Lipases409 are the other category of hydrolases that have been extensively studied.2 1. Jones showed that enzymes that catalyze oxidation reactions could be successfully used for the desymmetrization of meso diols. In contrast. by enantiotopic group differentiation. using tert-butyl hydroperoxide as the terminal oxidant.414 The kinetic resolution of racemic substituted cyclopropanyl carboxylic acids.6 1. A different enzyme. a practical level of selectivity was observed with the cis isomer. 103. the hydrolysis of cis-diacetoxy-1. was used to isolate the other enantiomer of the starting material with 96-98% ee. 4 1037 Scheme 42. Chiral Stoichiometric Carbenes The corresponding amides 498 were recovered with good to excellent enantioselectivities for a variety of Previously in this review. Lipase-Catalyzed Kinetic Resolution of Cyclopropyl Acetals section will briefly outline some of these methods by focusing on the most recent examples. anchored on a solid support with lipase.0 35 27 30 34 44 60 yield (%) ee (%) yield (%) ee (%) 60 31 31 46 >90 45 60 57 42 57 50 15 20 21 22 18 95 37 57 93 57 83 aryl substrates bearing para substituents. and fluoro.413 Sometimes.7 2. better selectivities are observed with substituted substrates or substrates containing chiral centers other than the cyclopropane moiety. Enzymes and microorganisms have been extensively used for the resolution of racemates and the desymmetrization of meso compounds.418 Very recently. Enzymatic Desymmetrization of Meso Diesters Chemical Reviews.Stereoselective Cyclopropanation Reactions Scheme 41. depending on the substituents and the esterase source (Scheme 41).416 Table 64.410 Such a strategy was used for the preparation of chiral fluorocyclopropanes with greater than 90% ee.

425 However. although no enantiomeric excesses were disclosed. not determined. . and isopropenyl acetate with enantiomerically pure or enriched cationic iron carbene complexes 503 yielded the corresponding methylcyclopropanes with moderate to good enantioselectivities (Table 65). efficient method to generate electrophilic iron carbenes from diversely substituted aldehydes. The reactions of these chiral iron carbene complexes with olefins. low enantiomeric excesses (40% ee) were observed for the methylene transfer.426 In this case. 2003. Hossain has investigated the origin of diastereoselectivitity and found that the carbene 514 is quite stable and less reactive.428 Upon reaction with gem-disubstituted olefins. Table 66.5:1 1. Scheme 43. favoring the trans isomer.9:1 1:1. Subsequent treatment with trimethylsilyltriflate produced the chiral carbene 514.6:1 1. the formation of the cis isomer was predominant with vinyl acetate.0 ee (%) product E/Z 73/51 64/41 83/69 92/74 43/36 47/35 R ) (S)-CH2CH(CH3)CH2CH3.0 1:4. 103. thought to involve the intermediacy of metal carbene complexes. Ethylidene Transfer from Chiral Cationic Iron-Carbene Complexes 503 to Alkenes Lebel et al.0 1:4.8:1 ee (%) product E/Z 88/84 83/77 72/64 92/86 95/83 70/70 71/68 76/76 75/73 R3 Ph2Ra Ph2Ra Ph2Ra Ph2Ra Et3 Et3 chirality ee olefin yield at Fe (%) R1 (%) S R S R R S 96 90 96 90 nd nd CH3 CH3 OAc OAc OAc OAc ndb nd 30 30 24 21 ratio E:Z 1. vinyl. Hossain reported a simple. It was also reported that alkyl-substituted alkenes gave predominantly the trans isomers. mainly the cis isomer was obtained. Vol. the trans:cis ratio was typically below 4:1. he could easily prepare chiral iron carbenes from chiral aldehydes. followed by the decomplexation reaction with iodine or photolysis.3 2. the development of chiral stoichiometric metal carbene systems as cyclopropanating reagents has also been disclosed in the literature. Preparation of Chiral Carbene 511 diazo reagents.3:1 1. carbene 514 produced the desired cyclopropanes with excellent enantioselectivity. success has been achieved with iron-421 and chromium-derived carbene systems. R ) (S)-CH2CH(CH3)CH2CH3.423 however. provided the corresponding cyclopropanes in high yield (Table 67). Indeed.0 1:4.0:1 1. In the presence of styrene derivatives.427 For instance.5:1 4. 4 Table 65.424 Brookhart demonstrated later that much higher enantioselectivities could be achived when the carbene carbon was prochiral. the cyclopropanation reaction of styrene. but with moderate to low enantioselectivities.422 The introduction of chiral iron complexes in the stereoselective synthesis of cyclopropanes appeared as early as 1974.420 Although they have not been used extensively. the reaction of the [CpFe(CO)2] anion 511 with chiral (+) or (-)-o-anisaldehyde(tricarbonyl)chromium 512 in the presence of chlorotrimethylsilane produced the optically pure (+) or (-) bimetallic complex 513 (Scheme 43). Brookhart also described the benzylidene transfer from iron complexes 507 (Table 66). In parallel to these processes.6:1 1. b nd. resulting in a late transition state.1038 Chemical Reviews. which accounts for the trans selectivity observed with nonaromatic alkenes. Indeed. Benzylidene Transfer from Chiral Cationic Iron-Carbene Complexes 507 to Alkenes cyclopropane carbene complex entry 1 2 3 4 5 6 7 8 9 a cyclopropane carbene complex entry 1 2 3 4 5 6 a R3 Ph2Ra Ph2Ra Ph2Ra Ph2Ra Ph3 Me3 Et3 Me3 Et3 chirality ee at Fe (%) S R S S S R R S S 98 92 96 98 100 77 76 87 77 alkene R1 R2 H H H OAc H H H H H Ph Ph OAc Me OAc OAc OAc OAc OAc yield (%) 75 75 33 40 30 50 35 59 27 ratio E:Z 3.429 The formation of the cis isomer with aromatic alkenes may be explained by a strong π-stacking effect.8:1 1. No.5:1 1:4.

2-sulfates433 are very popular. Enantioselective Carbene Transfer Reactions from 514 to Alkenes Chemical Reviews.4% ee (eq 118).448 Bis-(-)-8-phenylmenthyl malonates were also used to prepare enantioenriched cyclopropanes by a double alkylation procedure using 1.or epibromohydrins. However. sulfone-. Otera and Furukawa showed that the yield could be slightly improved by using glycidyl 3-nitrobenzenesulfonate (nosylate) and cesium fluoride.2-electrophile for double displacement with malonate anions.2-electrophiles. better yields are obtained with cyclic sulfates compared to epoxide derivatives. 2003. the use of chiral 1.430 This approach has been particularly useful for the synthesis of alkoxy-substituted cyclopropanes. were studied.Stereoselective Cyclopropanation Reactions Table 67.439 The reaction proceeded with good diastereocontrol and high enantiomeric excesses (70-99% ee).2-electrophiles has found many applications in the synthesis of aminocyclopropanecarboxylic acids from masked glycine nucleophiles. 103. Burgess disclosed that the reaction of glycidyl triflate 527 (92% ee) and sodium di-tertbutylmalonate led to the formation of the lactone 526 with the opposite configuration in 48% yield and 91% ee (eq 119). glycidol derivatives. No.445 Such a strategy was used for the synthesis of enantioenriched methylenecyclopropanes.441. β-phosphonate-.or epibromohydrins and the glycidol derivatives. Among them. A variety of nucleophiles. Vol.437 In path a. The importance of controlling the two pathways is instrumental. Barluenga reported that chiral oxazolines 516 could be used as chiral auxiliaries for the cyclopropanation with chromium complex 517 (eq 117). respectively. Synthesis of Chiral Cyclopropanes from Chiral Epoxides entry 1 2 3 4 5 6 R1 Me Ph Ph p-MeC6H4 p-ClC6H4 p-CF3C6H4 R2 Me Ph H H H H yield (%) 90 85 93 90 60 45 ratio Z:E ee (%) Z/E >95 92 60/55/46/53 30/72 10:1 7:1 6:1 3:1 A variety of substituted cyclopropanes have been synthesized from chromium carbenes and alkenes. the chiral auxiliary cannot be removed without destroying the cyclopropyl moiety. thus producing cyclopropane derivatives in good yields and with complete inversion of configuration (Scheme 45).431 Recently.434-436 Two pathways are possible for the double displacement of epichloro.432 whereas the ring opening of the epoxide is the first step in path b. Pirrung first observed that the reaction with sodium dimethylmalonate and optically pure epichlorohydrin (525) proceeded through path b and the corresponding bicyclic lactone 526 was isolated in 36% yield and 93. has yet to be described. mainly chiral 1.438 Conversely.or phenylsulfonylacetonitrile and epichlorohydrin in 67% and 82% yield and with 96% and 98% ee.440 More recently. including malonate-. each of them gives access to the opposite enantiomer. which are dependent on the nature of the leaving group (Scheme 44). Shuto and co-workers reported the synthesis of substituted chiral cyclopropane lactones from phenyl.444. Other Ring-Closing Reactions of Chiral Precursors Chiral cyclopropanes have been also elaborated from chiral building blocks.4-dibromo-2-butene (531) . ketone-.447.443 In general. and cyclic 1. and then cyclization. epichloro. C. followed by the Payne rearrangement to generate a new epoxide. Although the diastereoselectivity of this reaction has been investigated considerably. 4 1039 Scheme 44. an enantioselective version. as they are readily available. and nitrile-derived carbanions. the direct displacement of the leaving group is followed by the ring opening of the epoxide.442 Sharpless demonstrated that cyclic sulfates of vicinal diols such as 528 could serve as 1. with chiral metal complexes.446 In addition.

455 The intramolecular opening of epoxides was also reported. that produces fused vinylcyclopropanes with excellent .457 More recently.3-elimination leads to chiral cyclopropanes if the leaving group or the anion is a stereocenter. All attempts to induce the enantioselectivity using a chiral titanium complex failed.458 Taguchi disclosed the diastereoselective iodocarbocyclization of 8-phenylmenthyl allylmalonate.1040 Chemical Reviews. Cheng also reported a tandem lithium-ene cyclization. a chiral 1. with an enolate. leading to the same product. such as halides or sulfonates. Vol. more recently. No.456 Furthermore. This method was used in the total synthesis of ambruticin by Kende451 and. followed by a thiophenoxide expulsion. in which the allyl bromide moiety is opposite to the bulky substitutent of the chiral auxiliary (eq 120).454 This 1.2-nucleophile. It is Scheme 47.449 The desired vinylcyclopropane 532 was obtained in 96% de.450 Scheme 46. thus producing the desired (E)-dimenthyl cyclopropanedicarboxylate 535 with very high diastereoselectivity (Scheme 46). Many examples of intramolecular ring closure reactions. 103. leading to the racemic product.461 Yamamoto showed that the dianion of (-)-dimenthyl succinate (533).453 believed that one of the enantiomers of the benzylic anion 540 cyclizes with retention of configuration and the other with inversion.459.462 The intramolecular rearrangement of (allyloxy)dimesitylsilyllithium led to cyclopropylsilanes as a single diastereoisomer. were reported. and the stereochemical outcome results from transition state A. Cyclopropanation Reaction with the Dianion of (-)-Dimenthyl Succinate Other anionic cyclizations with alkenes producing cyclopropanes were reported. could be added to bromochloromethane. Traditionally. Formation of Cyclopropanes from Vicinal Diol Cyclic Sulfates Lebel et al.2. as electrophile.6tetramethylpiperidide as a base in tetrahydrofuran. the use of unstabilized carbanions. Intramolecular Rearrangement of (Allyloxy)dimesitylsilyl Lithium The best results were obtained with lithium 2. the reaction involves the intramolecular displacement of a leaving group.460 The corresponding cyclopropylmethyl iodide 537 was isolated in 89% yield and with 93% ee when titanium tetra(tert-butoxide) and pyridine were used to efficiently trap the HI generated during the reaction (eq 122). by Trost452 for the total synthesis of Callipeltoside A. it was shown that the treatment of γ-hydroxystannanes with a Lewis acid yielded cyclopropane derivatives in good yields.463 Both isomers of the olefin provided the same diastereoisomeric cyclopropane 541 (Scheme 47). was studied. and complete chirality transfer is generally observed (eq 121).6. forming cyclopropanes. although more limited. 4 Scheme 45. 2003.

.. Germany. Nakamura. C. Yip. 1994. Eds. 1.. 2251. Ed. Chem. M. 971. (c) Houblen-Weyl Methods of Organic Chemistry. 1. 2. M. R. J. followed by nucleophilic opening. The Chemistry of the Cyclopropyl Group. T. trans-cyclopropane 546. React. 1. D. VCH: Weinheim. Org. L.468 In this case. M.. (b) de Meijere. W. 1988.. 1247. Int. leading to a vinylcyclopropane. N.3-trisubstituted cyclopropanes (Schemes 48 and 49). 1990. 1995. Kutchan. Angew. B. Chem. 1987.-W. VI. 20. Int. p 63. 1989. Wang. C. Adv. No. E. Tech. Chapter 16. A. (d) Salaun. J. p 899. Reed. 4 1041 yields.. Klute. S. Lohrenz. Regitz. K.. Chem. Mulzer. 49. 154. M.. 1958. 2001. Chem. Curr.. 809. via the formation of silyloxycycloheptene by ring-closing metathesis. E. E 17c.. Eds. Perkin Trans. Chem. Org. Koch. due to the difficulty in controlling the behavior of the C4H9 cation.. ¨ Med. T. (c) Salaun. Chem. D. v. E. H. Tetrahedron 1986. 1984. N.. (12) (a) Simmons. K. A. Chem. 57.. (d) Wong. 4109. React. Ed. 83. M. C. T. M. Nutley. 96.. Chem.. (b) Simmons. (b) Doyle.-L. I. Thieme: Stuttgart. in which the 1. (d) Charette. S. Thieme: Stuttgart. Rev. (c) Piers. R. Soc.. S. M. 1995. Chem. A. 2001. J. 1988. D. In Comprehensive Organic Synthesis. Angew.. 1995.. Methods of Organic Chemistry (Houben-Weyl). T.-Y. Kobayashi. In Catalytic Asymmetric Synthesis. B. 713. J. W. leading to the corresponding cyclopropanes with 61-93% yield. Contemp. New J. Tse.. 1979. 2002. Synlett 1990. Li.. 2001. Angew. A.. Trost. A similar approach was disclosed by Taylor and coworkers. Chem. Chem. W. the addition of a base allowed the elimination reaction.. see: (a) Fang. Chem.. 1997. This strategy was applied for the synthesis of 1. Beauchemin. 67. (i) Hartley.. (e) Faust.-H. G. 5. K. J.3-allylic strain is minimized for the -CH2SiMe2X substituent. Ed. 103. Rev. U. 347. Ed. Rev. J. 35. Clark. Chem. J. C. Pure Appl.. Cationic cyclizations that lead to cyclopropanes are scarce. 5203. (b) Goldschmidt. Jautelat. (g) Denmark. Ed. 247.... 1959... S. Tam. 188. 927.. Gadamasetti. p 3179. J.. 2000.-C. 42. A. Organomet. Soc. Springer: Berlin. Cyclization of Homoallylic Alcohol 544 Scheme 49.-U. J. Org. (2) (a) Lin. T. C. (c) Boersma. Soc.. 80.. ¨ Nakamura. Band E 19b. 207. Rev. 1988. H...... Vol.. (c) Salaun.. Int. 1998. Org. (10) Emschwiller. C.. as the trisubstituted cyclopropanes 543 was obtained with greater than 99% ee when starting from the enantiopure homoallylic alcohol 542 (eq 123). the use of a β-silyl group to stabilize the cation allowed the formation of the cyclopropane derivatives. 703.. T. G. G. A. Curr. Chem. (b) Furukawa. Chem. 5. H. Eds. Chem. 1996. 4611.-U. Crammer. 1993. K. see: (a) Patai. M.. R. Lab. SpringerVerlag: Heidelberg. In Cycloaddition Reactions in Organic Synthesis.. 1993. 105. H. Ed. Synthetic Pyrethroid Insecticides. p 63. G. 29. 165. Tetrahedron 1993. 17. 537. M. Fan. Cairns.. (c) Hudlicky. N. Smith. Res. 20. Caldwell. B. B.Stereoselective Cyclopropanation Reactions Chemical Reviews. In Methoden der Organischen Chemie (Houben-Weyl). Chem. Hon.. Wiley & Sons: New York. B. H. 1555. T. 12. D. Y. In Comprehensive Organometallic Chemistry. R. Pergamon Press: New York. Chapter 16. p 85. Synthetic Pyrethroid Insecticides: Chemistry and Patents. J. Chem. Schaumann. The anti-propionate subunit 544 provided the Scheme 48. Chem. Am. 2 1996. P. 1929.. 1996. Am. 43. Pergamon Press: Oxford. Kawabata. Doss.. 1989. (c) Wiberg. Synlett 1995. N. 1992.. Haug. (c) Koert. 6997. (8) For recent reviews.467 A variety of nucleophiles were used with homoallylic alcohols. (g) Salaun. W. Rend. Soc.. 1985. 511. Kuhn.. J. H. Rappoport. M. W. 1981... 49. P. Reed. J. H. (j) Donaldson. Y. T. with the tert-cyclopropylmethyl cation being favored. W. Ojima. Ed. 1839. G.2. 1 2000. Angew. Rondan.. (h) Lautens. (d) Dargel. 4256. 20. 1991. Ed. p 971. K. B. Z. E. Smith. see: (a) Davies.. see: (a) Reissig. 435. Soc.. (3) (a) de Meijere. M. A. T. 229. Angew. (f) Charette. 1973. H. 27. 1996. L. G. 2003. Chem.. H. Fleming. Chem. R. Helmchen. H. 877. 2. 89. Acc. Boche. I. Eds. L. Vol. The allyl silane was prepared in two steps from the corresponding homoallylic alcohol. In this case. (13) For recent theoretical studies on the Simmons-Smith reaction. Y.. 1985. Chem. Trost. R. Gugel. Walsh. (e) Mareda. J. In Comprehensive Organic Synthesis.. C.. 1. see: (a) Nonhebel. Curr. Nachr. Vol.-P. 2000. 1197. 8589. R. (e) Motherwell. 1991. 219. The chirality can be transferred in this process. T. C. J.. 1983. Cyclization of Homoallylic Alcohol 547 . Soc. L. S. J. E.. Org. A. Org. T. D. 73. Jorgensen. Vol. 81. In Chemistry of Plant Protection. (b) Djerassi. Naqvi. In ref 1. Compt. 1990. W.-F. W. (c) Hirai. 1. Soc. Lantzsch.. S. Thieme: Stuttgart. J.-Q. H.-U. J. Vol. de Meijere.. Schleyer. J. 58. Vladuchick.. 41. Ed.. Tetrahedron 2000. Beutner. Perkin Trans. Wessjohann.. React. Top. J. 40. Ed. (b) Arlt. (d) Hudlicky. and led to the formation of the desired cyclopropane. 57. (b) Reissig. A and B. 144. Synth. Phillips. Tanko. Hoffmann. Top.. 89. (b) Small Ring Compounds in Organic Synthsis VI. Am. Wiley-VCH: New York. (e) Reissig. Lett. Chem. Hudlicky. Int.. Chem. Chem.. Z. G. Chem. Wilkinson. ¨ 207. H. Vol. G. A.464. whereas the cis-cyclopropane 549 was produced when starting from the diastereomeric syn homoallylic alcohol 547. Marcoux. J. p 195. Rev.-W. C. (7) For reviews on cyclopropane opening reactions. 1974.. K. Tetrahedron 2001. Int. 1. The reverse in the stereochemical outcome between the two diastereoisomers could be explained through the two transition-state models. Curr. M. References (1) For a general review on cyclopropanes. Houk. J. Hoiness. (5) For reviews on the divinylcyclopropane rearrangements. 144. Top. A. (b) Mann. R. 229.. W. ¨ 1988. (b) Hermann. see: (a) Hudlicky.. B. 14. J. 1989.465 Only one diastereosiomer was observed when starting from a chiral allylic alcohol. G. K. React. (6) For reviews on the vinylcyclopropane rearrangements. 5323. (d) Zeller. 18. E. 33... (9) (a) Naumann. (4) Suckling.466 Suzuki showed in 1995 that the installation of two methyl groups altered the situation. 56. R. (11) (a) Simmons. A. (f) Aratani. 5. Vol. A. Pergamon Press: Oxford. 477. In Stereoselective Synthesis of Organic Compounds. E. Hoffmann. D. C.

Tetrahedron Lett. T. 1968. Chem. C. E.. For activation with Lewis acids. 1991. (34) (35) (36) (37) (38) (39) (40) (41) (42) (43) (44) (45) (46) (47) (48) (49) (50) (51) (52) (53) (54) .. Francoeur.. S. E. L. H. Lunetta. Fukutani.. Chem. 2048. Chem. J. 50.. T. 3653. 118. M.-F. J. 52. J. H. J. 24. Tetrahedron 1970. U. 1979. 39.. E.. (b) Takai. p 72. 6585. H. Chem. Soc. Org... Yamashita. Int. Chem. (30) Maruoka. 1996. I. C. 36. see: Hoffmann. 239. 44. 1997. 91. C. J. S. Closs. Y. B. 118. Kim. E. Scott. 6792. Evans. 26. 6078. Soc. J. D. J... 1943. J. 1964. (f) Lautens.. (31) Charette. 468. Org. Chem. 115. Wiley & Sons: New York. G..-Z. Vol. Am. 4539. Iwata. Beauchemin. E. T. Tetrahedron 1968. Domek. 35. E. Hoskin. and the stereochemistry depends on the reaction conditions. 969. Lewis. L. 34. 5994. G. G. J. Chem. T. Tetrahedron Lett.. Am. S. Simmons. (g) Entry 27.-Y. J. L. 34. B. Ratier. (16) (a) Furukawa. Ren. D. M. S. E. Wang. 2647. K. B.. Still. Tetrahedron 1969... Chem. 1995.. 1989. 25. 104. Soc. Ohishi. Kowall. 1987. J. Y. 37. Corey. Wehmeyer. R. C. I. J. J. J. Fleck.. see: (s) Stenstrom. D. 131. M. Chem. J... 490. Nakao. Soc. J. D.. M. Hara. 2001. (e) Entries 19 and 20: Mitchell. C. 66. 2592. 56.. S. (b) Charette. J. J. see also: (m) Scott. 31. Enright. 10: Clive. J. 1985. Rickborn. Iwata. (a) For a good discussion of the various factors involved. Vol. S. J. Chem. 1990. 151. (b) For a review on A(1. T. (q) Entries 19 and 20: Lee. Wilson. P. Commun. Gross.. B. J. S. 112.. Naka.. (o) Drew. Synth. (a) Entry 1: Piers. A. 32. Sonnenberg. Chem. 652. J. 56. J. (m) ´ Friedrich.. Chem. C. Lallemand. 702. This is by no means a general process. Ed. Tetrahedron Lett. Carbohydr.. S. Tetrahedron: Asymmetry 1990. Aldrichimica Acta 1988.. Nishimura. G. Tetrahedron Lett.. Utimoto. Uskokovic. 2139. C. N. Francoeur. Chem. (b) Entries 4-11. 1961.. A. G. A. 6892. M. Simmons. Org. L. L. 4290. J. (f) Entries 21 and 22.. Tetrahedron Lett. Lorenz. Am.. D. 1989. (j) Smith. (24) Charette. 90. 6523. R.. 6406. Chem. Synthesis 1995. K. H.. J. Lee. 54. G. Chem. Hahl. P. Chem. M. J. see: (a) Erdik. (b) Nishimura. Narasaka. Org. B. 2003. Am. p 184... 118. Chem. Closs. 2000. Funahashi. 27. p 30. Horiguchi. B.. Am. (d) Hennion. L. (h) LeGoff. Takemoto. P. 1996. 1959. A. Shechter. Soc.. 9. H. G. Molinaro. (d) Olofson.. Cohen.. 71. D. Edwards.-F. Virgil. B.. 8621. G. H. 410. Belanger-Gariepy. D. D. Org. Angew. W.. Harrison. Paquette. see: (q) Rieke.. Am. E... Organomet. E. 117. J. B. (25) (a) Charette. Chem. (26) Charette.. J. G.. C... Kakiuchi. Am. Charette.. Chem. 893.. see ref 16. Tetrahedron Lett. T. M. Z. Takeda. He.. J.-J. J. 28. Chem. Chem. 3801. 7. 123. Org. (19) Sawada. Chem. Rieke. Nagarajan... 3495.. Schreiber. 6979. A. R. F. 1996. C.. 723. Ottow. 1993.. (c) Seyferth.. H. Kawabata.. Am. O. 798. see ref 28. R. Am. (a) Takemoto.. A. Chem. Chem.. 2001. 114. Chem. Chem. see refs 28. V. (j) Entry 14: Hoberg. 967. R.. H. 92. T. Ramana. E. Shi. Baba. (r) Entry 21: Iwasawa. 103.. Etter. E. Y. L. Bull. Chem.. Y. (20) (a) Denmark. J.. Synlett 1992. 2388. Tetrahedron Lett. Sonnenberg. Pinard. 21. J.. J. Tetrahedron Lett. J. M. R. B. (17) Denmark. (b) Wittig. R. 4412. 1976. 81.. 1987. 3353. R. 59. 1991. 1970. Brochu. B. D. R. (d) Entry 7: Weibel. T. P. A. A. Mott. For related examples. 6615. F. G. A.. 97. Chem. K. J.. (b) Denmark. 39.. see: (a) Chan. 4143. Marquez..3) strain. A. 1990.. A. (c) Dauben. Chem. J. Chem. 9186. A. De Groot.. Castaing. 702. J. Soc. ´ 2343.. 1949. M. M.... R. 1991. ¨ 5293. Chem. G. 1995. (b) Winstein. Chem. H. Harwood. 1963. Rickborn. Ronald. Nicklaus. Chem.. 1969. Brochu.. 117. Wingler. 3525.. P.. D. p 855. R. F. 62. J. 115.. Soc. 1995. P. S. see: (n) Denis. 2669... A. M. Organomet. 1994. 1971. (b) Denmark. R. M. 1987.. J. 1970. 3942. J. 93.. Kuwajima. V. J. Kitazume. Organic Syntheses. J. Organic Syntheses. Y. D. Wilson. Soc. 3023. (c) Ezquerra. K. 1841. C. Kawabata. Y. Saha. S. M. Angew. D. Barbachyn. 54. 1994. Oppolzer. Soc. 8139. Yamamoto.. Saha. 1307. Ogasawara. Tiller. Wijnberg. (21) (a) Charette.. M.. J. 6429. Delanghe. 4539.. Delanghe. Y. P. 1973. Vol. S. (e) Entry 8: Takano. E. J. S. A. N. Ed.. see: (o) Friedrich. Vol. J... Bardenhagen. Chem. Am. J. Soc. 4508. 1993. 61. Martel. P. 60. ¨ 857. 42. E. Collect. Chem. J. Tetrahedron Lett... R. J. M. W. S. J. M.-M. 2146. R. 122. J. Friedrich.. 1964.. Chem. 98. see ref 46.. N. 1986. D. (c) Entries 12-18. C. see: (c) Hoveyda. Lotts. 549. J. O’Connor. Am.-F. Organomet.. (28) (a) Molander. Org. 30. E. see: (a) Winstein. De Vries. C. Org. Thomas. C. 101. 2001.. (p) Friedrich. Chem.. Soc. J. J. Conia. P. For activation by heating.. (f) Entry 9: Rodriguez. see ref 33c. A. 50. G. Organomet. Chem. D. B. Sauer. Chem. 43. Chem. J. K... S. Wiley & Sons: New York. 2311. S.. Am. Francoeur. (b) Molander. Lett. Moher. M. M. Isabel. 85. (d) Entries 19 and 20: Yamazaki... Lebel. Beauchemin. Tetrahedron Lett. (32) For the first reports on the directing ability of hydroxyl groups. 9919. 24. 6831. Am. Kim. J. G. Tetrahedron Lett. D.. L. G. (23) Yang. Furukawa. 4987. U. Chem. Chem. Chem. 1991. Liebigs Ann. Chem. J. Synlett 1994. W. 123. F. (e) Kawabata. Soc. (33) For kinetics studies. 1969. D. Chem.. Macıas-Sanchez. (c) Wittig. Soc.. R. Chem. Chem. Org. No. E. E. (e) Wittig. Synthesis 1972.. R. G. C. Momose. (l) Entries 16 and 17: Murali.. I. 1697. J. Beedle. J.. E. 1309. Wiechert. Tetrahedron 1987. Wiley & Sons: New York. D.. Seeger. for example: (a) Seyferth.. (a) Entries 1 and 2: Johnson.. 1972.. B. 12160. Chem. Commun. chemical reactions. Org. K. A. Schwarzenbach... M... Vogt. see refs 48e. 1989..-Z. Am.. J. Chem.. J. 41. C. Org. (h) Entry 12: Corey. A. 21. Harring. Bozell.. Org. (27) In addition to those presented in this review. Toth. 1996. (k) Entry 15: Grieco. 47. 46. Paquette.. 1998. Uguen. S. Chem. Wiley & Sons: New York. 1995. E. Am. J. 34d. S. M. H. J. For a review on substrate-directable Lebel et al. (b) Entries 2 and 3. J. Am. Jautelat. Lin. ´ ´ R. P. S.. Org. Nishimura. Wilb. (18) Piers. R. 18. R. C. 83. S. Ruder. 1966.. J. T. Belanger´ Gariepy.. Chem. J. Organic Syntheses. H. B. J. J. Heissler.. J. O. 1677. 4230. J. 2001. F. Soc. 1964. T. T. 473. H.. Molinaro. Org.. 1455. S. Li. see ref 34d. 1445. K. 2000. 650. Soc. Y. E. Pong. 1992. D. N... J. J. 1961. B. B.. 41. Soc.. Marcoux. An NMR study of this equilibrium demonstrated that IZnCH2I is the favored species over Zn(CH2I)2. T. Mai.. E. Coish. B. (22) The possible Schlenk equilibrium between these two reagents and ZnI2 is still a matter of discussion. 1969. F. (c) Furukawa. Soc. Takahashi. J. See. Y. 60. Radinov. J. N. L. W. 107. J.. J. T. Am... R. (e) Shank.. Tanaka. Collins. E. Wovkulich. Y. see ref 47. Am.f. 205. Am. 738. (f) Smith. P.. Shechter. Rev. Oh. 1991. 1969. and 48d-f. A.-Y. 1994. (f) Goh. C. Am. Furukawa... Org. (b) Entries 2 and 3.. Cleve. Kawabata.. 2801. 52. For a recent application of this methodology. G. 2491. R. S. Kawabata.. E. 1990. Liebigs Ann. J. J.. S. Soc.. Org. Schollkopf. J. Lillie. Coish. J.. C.. see: (k) Abdulla. 6233. 1992. (29) For a report on the use of TMSCl to activate samarium. J. 1985. J. Commun. Organic Syntheses. M. A.-D. 22. (f) Kawabata. Tiller. see: (n) Hoberg. M. 46. H. 1.. J. H. J.. C. A. W. 2001. F. (b) Paquette. Edwards. Chem. E. See also: (l) Repic.. S. S. M. Chem. 1996. see: (b) Kunzer. 347. 1981. T... Barchi. Jpn. J. 2203.. W. 1967. 1996. 1982. 2002. 62. M. Chem. Angew. 25. Soc. K. Soc. Kiegiel. 56. For preparation of the Zn-Cu couple. (b) Furukawa. (b) Charette. R. M. H. (d) Wittig. J. Soc. Chem. Tetrahedron Lett. Synlett 1992. T. (b) Entry 3: Neef. (b) Baba. 1991. For related examples. J. J. J. J. J. R. J. (a) Entries 1-3. C..1042 Chemical Reviews. V. Soc. 1985. see: (c) Noller.. 89. Fu. R. 617. (a) Entry 1: Poulter. Chem. Vol. A. 1996. related MCH2X cyclopropanating species have been prepared: (a) Seyferth. Chem. J. Chem. J. 19. N. Andrews. M. J. Low diastereoselectivities are usually obtained in the cyclopropanation of cyclic alkenes with CH3CHI2-derived reagents: (a) Rubottom. N. 1995. 3235. Chem. 40. Am. J. Ber. Uhm. T. J. R.. 1993. J. Girard. R. ¨ D. H. 291. 6171. 2000. Chem. 1978. (d) Entry 5: Mohamadi. Soc. 37. 4640. Bittler. Synthesis 1995. Tetrahedron Lett. Y. For selected examples. Kirihara. H.. O. Am. Nishimura. 2671 and references therein. Ibuka. M. A. (a) Wang. T. see ref 34d.. J. G. 1. (e) Entries 21-26: Lautens. Nishio. Org. T. 1989. T. Chem. 54.. P. J. (c) Entries 4 and 5. Marcoux. Chem. Edwards. 1959. Chem. E... Smith. M. Cha. 6974. Yamane. Res. V. Chem.. Chem. A. 1593. S. R. W. N. (d) Entries 6-18. 56. L. 47.. Cha. K. T. 1990. 1995. 18... Schulte.. N.. (M) 1978. (g) Corbin. 47. Justus Liebigs Ann. 57. C. Am. 2966. Soc. Heathcock. Winstein. 1991. (c) Entries 4-6. J. Ibuka.. 217. S. Am.. (g) Entry 11: Corey. J. L. For the Zn-Ag couple. L. D. A. Soc. 29. II. 30. T. J. Sheehan. D. Chem. 31. see ref 47. Wiechert. R. J. Liebigs Ann. 81. H. ´ ´ Chem. see ref 28. G. 1992. J. Naka. J. Soc. see ref 28. 2474. K. 113. A. Collect. 2729. 118.. 1825. Daigneault. ´ 466. E. J. B. R. 1962. (b) Staroscik. 1989. K. Tetrahedron Lett. 23. 115. Jr.. L. Tanaka. 1997. (i) Entry 13: Kabat.. S. (i) Rawson. 1993. B. E. 1982. Kamemura. Beauchemin. G. Chem. Nakao.. Godet. Am. 4323. For preparation by reduction of Zn(II) salts with Li/naphthalene. G. 1964. T.. Inouye. J. Org. N. For a general review on activation with ultrasound. Tetrahedron Lett. M. C. 1961. 44. 8873. J. J. C. T. S. Berezin. H. Org. (c) Jenniskens. Groth. Chem. see: (a) Charette. Soc. R. M. 2210. Rev.. Org.. 1968. Org. F. see: Lautens. Org. P. Res. J. Lewis. Andrews. 2057. Soc. J. J. G. Org... C.. Pinard. S. Fujita. Kawabata. N. S. 2676. U. Org. 2309.. 53. 24. 1993. F. J. C. (p) Entry 18: Boyer. A. 71. 1995. E. Wingler. Am. Pereyre. A. C. B. 3390. Hahn. T. Soc. (r) Zhu. Schwarzenbach. E. 650. 1959. Int. Marcoux. J.. S. 7412. Burns. A.. D. J.. J. 243. Org. (c) Entry 4. (15) (a) Wittig. 35. N. W. Chem... Chem. T. (b) Furukawa. 31. S. Schollkopf.. 4 (14) For an overview of the different methods of zinc activation for the Simmons-Smith reaction and organozinc chemistry. Chem. Beauchemin. 55. Rosenberg. Tetrahedron 1988. Tetrahedron Lett. Org. Chem.

. Chem. Chem. Pharm. Gagnon. T. Chem. J. 55. 1990. Org. I. 1994... Am. D. D. (r) Sugimura. A. Futagawa. 2002.. Newton. J.. T. Gretler. J.. Tetrahedron 1987. Sasaki. (o) Entry 12: Sugimura. A. J.. Burch. 29. A. 7925. Nakatani. Shirai. Hirono. Y. J. Chem. A. W. P. C. Org. E. 1985. S.. 603. 1205. (63) (a) Morikawa. Tai. S. (78) (a) Entries 1 and 2: Charette. A. E. Perkin Trans. Org. 3. 61. M. S. Lee. Org.. P. A. Chem. Soc. K. M. Soc.-F. Kellogg. Tetrahedron Lett. 35. 541. J. Liotta. 1995.. 3. J. L. 60. 1988. Inouye. T. E. Pfammatter.. 1992. 650. K. 1988.. Am. G. J. R. B. J. Angew. T. White. Kamada. T. Y.. Soc.. see: Krysiak... Kim. Soc. Altmann. T. W. Du.. 509. 1992. see: Liu. J. Y.. 2001. 2000. Widenmeyer. T. J. 124... Futagawa.. (79) For a review on carbohydrates as chiral auxiliaries. K.. H. T. Am. Lett. Soc. Bull. G. 3. 1996. M.. Kobayashi. Org.-S. (b) Charette. 2295. E. Kamada. A. Gornitzka. 11030. Ritzen. Am. A.3disubstituted olefins should not proceed efficiently. F. B. Nelson. 1081. Tetrahedron Lett. R. K. S. M. Chem. (b) Ukaji. Williams. A. Yoon. K. 8240. A. T. Hayakawa. King. 1994. A. Jain. Soc. Chem. A. Am. J. Tetrahedron Lett... W. Molinaro. Kim. 40. Ohno.. M. Y. Ruck. T. H.. S. 3905.. Soc. Osuga.. Angew. Cote. 2377. 1 2000. G. Chem. Soc. Y. E. (a) Takahashi.. 64. A. 5236. B.. 123. J. 1995. A. (b) Khan. 32. Chem. N. Chem. A. 1990.. Nagaoka. 1968. Mori. Namoto. Pharm. Soc. P. Kasdorf. Chem. Org. T. 7221. J. M.. Terashima. Chem. 33. Lebel.. White. see: (a) Mash... Soc. H. T. (b) Houk. 3189. 1993. T.. T. H. N. (b) Tamura. Chem. Commun. K. Am. Tai. 1090. P. 1992. 53. S. (k) Entry 8: Kang. S. J. G. Recl. B. H. ˆ ´ Am. Edwards. J. Tetrahedron 1984. Kobayashi. Charette. H. 1996. 552.. Hemperly.. 229. 1996. Jacobsen. 27. Soc. (g) Entry 6: Mash. (75) Panek. J. 32. K..-M.. Tai. see: (a) Pietruszka. E.. Paddon-Row. Koguro. Mekonnen. (f) Arai. T. Bydlinski. R. Soc. Liu. S. J. Chem. 104. Soc. (59) (a) Gung. Chem. K. Nishimura.. B. B. J. Chem. J. (58) Charette. J. K. E... Y... J. H. B. Am. G. J. J. K. 1227. W.. D. Yoshikawa. M. R. A. Chem. Chem. 564.. Chem. 5793. N. Am. Lett..4-di-O-alkylthreitol auxiliary (+)modhephene. Chem. A. Am. Org. Delanghe. Tetrahedron 1986.. M. Chem. See ref 57b. Eur. 1175. Chem. C.. (c) See ref 66a. Org. Gerwick. 6447. Perkin Trans. H. Davies. 55. A.. J. Org. E. R. Chem. Tetrahedron Lett. M. Katoh. A. 1996. Chim. S.. G. Chem. 37. B.. D. Chu.. Chem. H. 55. 8287. B. 1996. 1781. S. and sulfonamides with nucleophilic (phosphino)(silyl) carbenes to produce optically active cyclopropanes. M. Hashimoto. 1995.. Giroux. Bull. S. 2045. G. 8718. Bernabe. (68) Mohr. N. Sugimura. Ito. Hamprecht. 116. Marcoux. Kato. J.. J. K. A.. For a recent improvement of Mash’s auxiliary. (64) Morikawa. Chem.β-unsaturated carbonyl systems. N. Li. Tetrahedron 1996.. 118. Ichihara. W. Yang. H. Tetrahedron 1999. (b) Mash. Kobayashi.. 1994.. M.-Y. M. 109. J. 1995. 16277. (b) Mash. G.. M. 513. Tai. M. C. G.-H. O. Jpn. 113. F. B.. Xu.. M. 11943.. P. M. 1991. Tetrahedron Lett. Am. M. A. Y. J. (77) For additional auxiliaries that are based on an initial 1. Lebel. Ed. Org. H. Tetrahedron Lett. C. T. 2651. S. I. Y. J. 42.. (a) Tamura.. B. 61. Hemperly.. 409. Hanai. J. K. S.. Tetrahedron Lett. Hashimoto. (p) Sugimura. Akiba. Paterson. Chem. Taguchi. Chem. Fujita. 12721. Davies... Lett. Aoki. 2557.. 65. Heidt. (b) Charette. G. Shiro. Int.. 55. S. 167. Angew. Yu. Kasdorf. (a) Charette.. 1986.. J. 5775. S. Chem. Kasdorf. Metz. M. P. 107. Flann.. Davies. A. 33. Inomata. A. Akiba. 3906. J. M. G. 2000. 35. Tustin. (b) Barrett. Soc... (66) (a) Barrett. Taguchi. G. Chem. Chem. (a) Falck. T. B. A. A.... H. Houk. I. J. T... (l) Entry 9: Ambler.. J.. J. Kitajima. 3280. M. J. Chem. A. Stephenson. J. Lett. Giannakakou.. E. 50. O. H. Delanghe. K.. K. see: (i) Yeh. A. 6453. J. E.. S.. Math. This model indicates that cyclopropanation of (Z). 9313. W.Stereoselective Cyclopropanation Reactions (55) (a) Lautens. Chem. 35. T. Melnick. C. 407. 2003.. 1993. Mori.. 1351. K.... J. 2257. M. Iwasaki. J. R. A. Soc. M. 43. (s) Entry 13: Imai.. Lee. 1994. (b) Wipf. Low diastereomeric excesses (44-46%) were observed in the cyclopropanation of a 3-substituted 2-fluoroacrolein bearing the 2.. 1991.D. Inouye. Org. 1968. Arai. Nishida. 59. P. 1988.. (b) Itoh. Perkin Trans. K. G. H. 6277. T. Soc. Hayakawa. A. (w) Seebach.. T.. 34.. M. (d) Entry 4: Charette. 58. A. 5733. J. 36. 595. 73. Chem. Katoh. 37. Yu. Org. Y. (a) Charette. S. (c) Entry 3: Charette. Org. Chem. A. W. Ferna ´ndez. For applications of the Yamamoto’s chiral auxiliary. 33. 8256.. 107.. Rondan. J. A. Takehana. J.. G. S. Nelson. 3189.. Maurer. 40. 1996. 7157. Am. J. 1 2001. 4986. M. Soc. Huang. Tetrahedron 1990. M.. Tetrahedron 1994. 61. D. 1997. Trav. (b) Onoda. 8166. (a) Mash. M. Hashimoto. T. Chem. J. D. K. (57) (a) See ref 47. K. Yoshioka. Stucky. M. D. 3000. R. H. M. M. G.. see refs 66a and 74. (j) Entry 7: Ebens. Nakatani.. M. Chu.. 1995.. Hu. K. Ber. Wu. French.. S. Mori. Nelson.. M. J. R. 2147. (b) Barrett. J. 1189. 1996. Chem. Lebel. J. A.. Mitome. Taguchi. J. J. Cote. Chem. 5955. Soc. S. Chem. N.. W. Tetrahedron: Asymmetry 1994. Garbaccio. 36.. 2001. A... A. F. K. Tetrahedron Lett.. Kodama.. 1998. 7863. Hehre. Org. T. H.. Luh. D. M.4addition on R. ¨ (80) For applications of the 1. 4397. J.. Wolf. Kendall.. E. T. Juteau. B. Tetrahedron Lett. see: Kunz. Sada. J. Chem. Chem. Y.... Turcotte. Soc. Marcoux. M. 1995. Chem. R. Tetrahedron Lett. Chem. A. Chem. 5. 10327... (a) White. G.. T. G. 37. J.-F. Pietruszka. 6979. Synlett 1992. E. K. J. J. Lett. Shirai. Ulven. Jolicoeur. S.. A. Mash. P. Int. K. A. C.. (b) Sawada..-D. Mikolajczyk. 2001. 1996.. Terashima. Saito.. Shoji. D. H. Fujisawa.. 6096. H. (t) Entry 14: Tamura. E. For a recent application of this methodology to the total synthesis of ambruticin. B... 5612. J. H. Suzuki. 1996. 52. Org. Shiro. E. Soc. 3889. G. 2002. Tetrahedron Lett.. Chem. D. Chem. K.... M. 55. (60) Evans. M. B. P... D. Doubleday. Tustin. A. Y. C. Williams.... M. Chem.. 61. 29. Kobayashi. K. (e) Luithle.. Y... Marcoux. Katoh... (c) Hoffmann. 1992. Am. J. (c) Charette.. (71) de Frutos. Org. 60. (b) Nagle. M. 123. 37. 116. D’Amico. Katagiri.. Tetrahedron 1999. 1999. 5037. Chem. A. T. Denmark... Tustin. 3293. Lim. 1988. T... 1995. J. M. 5405. T.. Pietruszka. Falck. P. R. M. Kamada. Yoshioka.. B.. 51. R. 977. (b) Takahashi. Kamada. Iwasaki.. (a) Ukaji. 33. Y. Kawai. 30. Y. M. Charette. 1988. D. (62) (a) Zhao. Kobayashi. Tetrahedron Lett. A. 1995. J. G. 635.. 117. J. (c) Wipf. W. Armstrong. H. see: Sugimura. (b) Luithle...-Y. T. Wartmann. J. Juteau. J. D. S. J. Lett. W. J... J. J... K. (n) Entries 10 and 11: Tanaka. J.-Y. For earlier work concerning enantioselective cyclopropanation with stoichiometric quantities. G.-H. (c) Nelson.. J.-C. T.. Tai. 10772. (76) Barrett. A. 1991.or 3.. 7167. M. D. J. J. 29. S. T.. Ed. 60. 1993. S. Yamada. Futagawa. Katoh. A. Tetrahedron 1994.-S. 118. W. Juteau. 357. K. ˆ Tetrahedron Lett.. 8845. Ed. Vol. K. J. T. 1947. 33. 5654. Stucky. R. Synlett 1997... 97. Chem. 3487. E. 4293. K. C. Chem. Chem. K. see section IV. P. 1993. J. O. Ferna ´ndez-Alvarez. 2001. Katsuki.. H. J. H.. Sasaki. D. 1996.. (b) Charette.. 8254. 1989.. Rondan. Futagawa. E. Masatoshi.. 2575. Tetrahedron Lett. P. A. I.. M.. Tamura. 120. T. (56) (a) Paddon-Row. K.. Chem.. 325. (a) Barrett. A. E. J.. 1996.. M. 367. W. (74) Iguchi. Int. amides. (d) Mash. N. J. 27. Commun. Hayakawa. White. Juteau. Tetrahedron Lett. Commun.. Geralds. 1993.. Yoshikawa. D. Yoo.-F. 1113. Lee.3-butanediol as chiral auxiliary: Morikawa. Lett.. 1992. Chem. A. H. Soc. O. Deschenes.. 40. Baceiredo.. Chem. 46. 1851. J. 118. 60. A. Chem.. 118.. Org.. 1990. (b) Lautens... (u) Akiba. B. T. Am. J.. N. L. G.. (b) Toshima. T.. Emoto. 1992.. Mineta. Chem.. J. Williams. 123. I. Chem. (c) Pietruszka. J. Tetrahedron Lett. Eur... M. (72) Mohapatra. Schinazi. Nambu. N. ´ M. Chem. 6983. Lett. H. 1994. A. 2001. see. 2141. 1994. H. G. T.. D. J.. Hashimoto. Oda. Burch.. R... Chemical Reviews. 4. Am. A. A.. (67) (a) Onoda. Lebel. Lee. 2001. Org. Yamamoto. A.. Chem.... 29. 1441. H. Pietruszka. A. 122. T.. 50. Maru. (c) See also ref 13e.. T.. H. D. Org. (d) Lai. (v) entry 15: Seebach. H. Y. D.... Nambu. 5122. B. 8526. Y.. A. Y. Shibuya. Newton. Am. D. B.. Sasaki. C. Nicolaou.. M. H. 3483.. Tetrahedron 1997. A. Brochu. 1995. J. 1989. (e) Entry 5: Mori.. Tetrahedron Lett. B.. Lett. K. Tetrahedron Lett. C.. (m) Ambler. J. Org. P. 32. Tetrahedron Lett. A. Kasdorf. Soc. T. A. Marquez. Lacasse.. Soc. Mekonnen. Chem. Koberstein.. Nakai. 1992. Kasdorf.. ˆ ´ Am. R. 1994. Van Deusen. 1996. Int. For an alternative application. D. A. 3351. Org. 2001. Org. G. 1779. Tetrahedron Lett. M.. C. J. 117. For a related chiral auxiliaries for the synthesis of cyclopropylboronic acids. A. 2 2000.. Bull. H.. K.. 2002. R. (69) Landais. 61. Chun. M.. R.. J. Ed. Arai. Inoue. Nelson.. 34.. Nakatani.. P.. Koiso. 1986.. 2001. J.. 66. 2055. Uno. Tai... 9194. Parra-Rapado. C. (70) Winkler. S. B. E. Terashima. Bertrand. J. Nakatani. A. (b) Zhao. 13327. H. Lemay. Fryling.. Soc. Witt... (e) See ref 95a. C. 679. 33.. N. Yamamoto. 6556. 109. (h) Mash. 1993. Chem. 40. J.. (b) Charette. 503. K. 1996. Jaeschke. M. (65) Fukuyama.. ´ J. J.. A. (a) Barrett. Chem. (81) (82) (83) (84) (85) (86) (87) (88) (89) (90) (91) (92) (93) (94) (95) (96) (97) (98) (99) (100) (101) (102) (103) (104) (105) (106) (107) (108) (109) . Doubleday.. Lai. Charette. Y. 4 1043 Org. For the use of chiral unsaturated esters. Org. K. Hayakawa.. Pau. 1995.. Tetrahedron Lett. 1995.. K. (d) Barrett.-F. 2000. (b) Charette. 336. A. 34. 3807. A. K. Tetrahedron Lett. No. Angew.. 52. A.. J. 7162. 1985. (q) Sugimura. 1990. 1767. P. for (-)-menthol: (a) Sawada. (73) (a) Wipf. Kim.. 355.. 2721. Chamberlin. 36. Ghosh. 1992. Org. Yang. Commun. Akiba. 1987. Prescott. 8. S. W. Kendall. A. Pays-Bas 1990. G. Tetrahedron Lett. P.. M. K. R. 1995. 1982. D. J. 36. Chem. 103. K. 1987. Tetrahedron Lett. Soc. (d) Luithle. T. Am. Terashima. (61) Evans. B. B. Tetrahedron Lett. Chem. Soc. I. I.

Chem.. P. Alvarez-Larena. B. 1999. 1998. 1553. M. Synthesis 1998. J. Kobayashi.. Y. A.. see: Cativiela. Schneider. S.. Chem. 2002. (a) Charette. N. J. 52. J. 66... 151. D. K. Lenoir. 2557. Chem. 1991. 30. J. 8260. 2533. Eagle. 1996.. 26. 2. (b) Calter. M. Pflatz.. M. W. L. J. G. Witt. Ortuno.. Pfaltz. J. P. Natalini. Prog. 1973. P. Oliva. Nishiyama. M.. Herrero. Gupta. 2000. 1985. 4760.. A. J. Chem.. Xavier.. E. F. J. Lett. 56. N. ´ ´ ˜ J. Am. p 513. 66... Imai. 12168. I. G. 49. J. W.... Yamamoto. J. 2000.. M.. L.. Wagner. H. Rodenhouse. Am. J. Kobayashi. H. Lett. 5033. 1. 123. Jones. The efficiency of the reaction is highly dependent on the stoichiometry Pd/L. Y. 977... N. K. Brochu. H. 7616. J.. Y. 20. 103. Arsenault. ¨ Helv. Suzaki. Z.. M. A. Org. G. A. 110: (d) Sato. C.. H. Lemenovskii.. Pietruszka. 617.. P. Y. Itoh.... Helv. Gulea. E. B. (c) Martın-Vila. 62. Chem. 43. P. Claffey. (140) (a) Wurz. G. S.. M. B.. Straub. Tomilov. S. D. C.. Org. (a) Seitz. Tetrahedron Lett. J. Org. 175. P. Rousseau. E. E. M. 1989. F. B. S. 4.. Escale. J. Chem. Chem. V. P. (c) Alcaraz. G. J. Chem.-S. Tetrahedron Lett. Am.-S.. Jimenez... E. 117. Reynolds. 388. 2001.. Shinozaki. C. 1994. Int.. N. Murray. J. Piers. S. S. Chem.. 82. Tetrahedron 1995. K. Organometallics 1995. Gree. S... Helv. Eur. Soc. I. C.. Y. E. The nature of the protecting group is quite important.. Li. (157) (a) Piers. For a less selective transformation.. O’Connor. Chim. S.. A. (b) Muray. 1994. C. Y. J.. (146) (a) Che. 303. Bosch.. Rife. T. 2001. 37. 947.. R. 8901. 3375. T. H. Sakata. Org. ´ (a) Vallgarda. Chem. P. Krogh-Jespersen. M. C. 37.. See also: (b) Piers. Tohill. M. J. Vol. Soc. 32. 321. Hubert.Y. Fraser-Reid. Tetrahedron Lett. (b) ¨ Muller. Bonnert. E. N. ˜ 2000. L. 2001. (137) Pfaltz. V. 935. A.. S.. M. Curr. 1663.. (b) Werner. J.. J. Jung.-M. Synlett 1997. Org. 2511. Enantiomer 1999. Org. Ohfune. 36. Chem. (d) Denmark. L. 4167. Chim. Dzhemilev. M. J.-Y. 1149. U. Am. W. Nefedov. 1984. (i) O’Bannon. A. 7045. S. A. 3959. R. W. P. (159) For 130 and 131. I. Unpublished results.. Commun. H.. de Vicente. 3581. Tetrahedron Lett. Branchadell. R.... W. Heterocycles 1980.. M. Rev.. 555. (148) Fritschi. Chem. E. Tetrahedron: Asymmetry ´ ´ ˜ 1996. J. Fernandez. B. 112. McAlees. Christenson. Piniella. 123.. Eur. J.. 1987. 37. Daunis. K.. see: Vangveravong. Davies. F.. Chem. (b) Denmark. Lai. Acta 1995. Cowie.. 1997. A. 1996. J. Hossain. Apeloig. P. Appelberg. M. (c) Nishiyama. A. J. 1990. C. 56. Fernandez. E. L... W. 6157. A. H. (b) Hoberg. B. J.. J. 8. M. P.. 123.. J. ˜ R. 35. O. (d) Doyle. Organometallics 2001. E. L. P. R. P.. S.. Valleix. M. Teuben. L. 25. Harn. P.. 2001. D. H. D. Chem. J.. 52. (b) Li. T. 2651. Yoshida. E. 30.. 3685. J. Z... D. K. Rossier. 4293. Eds. 123. Org.. Mirafzal. Nury. D. Wilson. A. Zheng. C. A. 608. Chem. For selected recent reviews. M. J. J. J. Synthesis 1997. Hisamichi. Soc. Chem.. H. 51. Huang. S.. 503. 2001. N. ˜ 1657. (135) 108: (a) Bartels. M. M.. Chem.. Soc. Springer-Verlag: Berlin. L. J. Dalton Trans. Russ..-M.-C. M. (h) O’Bannon. Chim. 139. O’Connor. 7561. Hanafi. M. P. Baibulatova. Tetrahedron Lett. 1135. No. Wandless. ¨ Phys. 2297. 1093. J.. Chem. J. N. Masson. Am.. 65. 3.. see ref 137. 584.. J. PaulRoth. K. P. A. Inukai. Org. Chem. J. Tetrahedron Lett. (139) 113: (a) Dowd.. 3. B. P. Can. J. M.-S.. W.. 82.. Aoki.. L. Ibers. 1988.. P. A. M.. A. 1995. A.. Molinaro. Soc. Chim. M. 12443. D. Tetrahedron Lett. 537. L. Vanboom. 7341. (a) Pietruszka. Liebigs Ann. Tomilov. Moss. R... M. (f) Muller. Tetrahedron: Asymmetry 1991.-Y. A... McAlees. M. ´ Marco.. (e) Simonneaux. Ortuno. K. 2003. (b) Hanafi. A. M. Seitz.. N. (b) Felpin. 78. Brinker. 23. Snyder. Org.. 1972. 1645.. Helv. Dıaz-de-Villegas. Ferguson. Sakamoto. 4843. Org. D. U. 1465. H. P. E. (c) Muller. R. J.. Kurihara. Shinozaki. R. M. 3409. (150) Rasmussen.. T. W./Recl. Bolea.. J. Chem. Ishida. Nury. E. (g) Luithle.. Alvarez´ ´ Larena... (158) (a) Shimamoto. (147) Straub. Marinozzi. H. 4.. Martınez-Merino. P. R.. Woo. Bagheri. J. Shibasaki. Soc. R.. S.. B. (b) Barrett. P. V.. Ph. 20. de Frutos. (a) Denmark. P.. Kobayashi. Soc. F. ´ 13. E. 2002. J. O. Lee. Zablocka. Charette. J. Dyszlewski. Christenson. R. Chem. A. Lee. Teyssie. A. A. ´ ´ 23. M. J. Org. O. Bergstrasser. Soc. Troyanov. Furuya. E. 1995. Soc. S. 1. 137. (b) Luithle.. H. R. 3052... V. Liebscher.. Chem. Tanner. J. 1991. Organometallics 2001. Synlett 1993. J.. Soc. Tetrahe´ ˜ dron: Asymmetry 1999..-W. Yunusov. 111: (e) Alami. (b) Shimamoto.... P. K. Branchadell. A. A. Chem. 35. A. (b) Rovis. Huang. 1999. S. T. Tetrahedron Lett.. 1997. Chem. Wiley & Sons: New York. P. J. 1992. 3802. A. Teng.. Tetrahedron Lett.. R.. O. G.. Hofmann. Tetrahedron Lett. Chem. M. Chem. Chem.. 1988. Chem.. A. A. Chim. N. Lo. Am. Chem. Org. Acta 1988. 197.. J. In Comprehensive Asymmetric Catalysis. D. (142) Many authors have contributed to this proposal. Bernabe. 5171. 5. 177. S. Terpstra. 177. 124.. 6137. (b) Li. Tetrahedron Lett. O’Connor. Takahashi. J. B. 64. N. C. Org. (156) With these substrates.. 1071.. 1969. 9194. Soc.. Motherwell. Wannamaker. Org. Rossier. Protopopova. (b) McCrindle. P. C. A. Fernandez. Chem. Chem.. ¨ 315. J. Braddock. J. U. M.. Norrby.. L. Soc. 5281. 1996. Y.. Jimenez. V. F. 1998. M.. 2001. Dorow. see: (a) See ref 115.. P. Lett. Tetrahedron Lett.. M. Tetrahedron Lett... D. 62. 1997.. R. For recent examples. Chem. Noriaki. J.. (155) (a) Hoberg.. 1991. R. 1 1994. G. 4607. 569. Imogai. Org. (b) Carrie. Tetrahedron Lett. 2001.. (144) Smith. Foces-Foces. R. Forbes. J.. M. J. Org. R. C. Motoyama. See also: (b) Pellicciari. J... Paik. (145) Nishiyama. Chem. A. DattaGupta. J. Chem. (c) Luithle. A. J. Imai. Org.. A. Garcıa. Jennings. R. Che. Eur. Arsenault. Charette. Jacquier. 2735. A. J. Cano. Org. A. 4119. S. 1985.. J. Org. Vol. U. A. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides. N.. A. 36. M. De Montigny. R. (c) Moss.. Tetrahedron Lett.-L. D. A. E. 1997. J. ´ ´ Salvatella. 40. Chem. Kwong. Soc. C. Chem... For an application of this methodology. Ortuno. A. M. Leeuwenburgh.. 1170. Otsuka. J. D.. J. Perkin Trans. (e) Muller. C. C. G. Rev.. 2000. Ohfune. 98. V. E. A. 1998. U. 3390. Chem. N. Ed. P.. (d) Muller. V. C. D. 12013. J.. Perkin Trans.. Jimenez. 1993. V. M. Chem. Jr. J. Tetrahedron Lett. An excess phosphine will inhibit the reaction: (a) Nakamura.. M. Leutenegger. Ortuno. V. G. (e) Denmark. H. B. A. Tetrahedron 1990. Z. For a complete discussion of the early work on the mechanistic issues.. J. J... 7. W. Soc. Chem. Chem. (b) Maas.. Zhou. H... Angew.. S. Ohfune. Christenson.-X. 1998. 461. J. J. J. M. G. Charette. J. It has been shown that Pd(CH2Cl)Cl is formed when palladium chloride is treated with diazomethane: (a) McCrindle. 91. M. 62. 114: (d) Lewis. 2108. J.. 2001. 5625. Inorg. G. (f) Denmark. L.. 8287. O. B. Chem. Org. ´ (a) Abadallah. 1995.. S. Rodrıguez-Garcıa. Chem. 1996... Monahan. S. (d) Luithle. J. M. Widenmeyer. 2258. 2001. (149) Fraile. Imai.. Org.. Ishida. 4843. 115. 1. 2001. J. 50. E. (b) Lebel. 11367. 84.. Ye. Takahashi.1044 Chemical Reviews. 1991. (f) Luithle. Jacobsen. A.. 123. M. A. O.-S. Sekar. G.. H. (138) For reviews on the subject. Edwards. F. Vandermarel. E. 2002. (e) Singh. 2785. (153) Doyle.. 68. J. J. V. F. Kaneko. Tetrahedron: Asymmetry 1994. P. M. J. E. 4167. N. II. Org. Hacksell. S. K. Tetrahedron Lett. Ortuno. Østergaard.. M. Soc. 56. Wolf. J.. R. 1725... P. O’Connor. (c) Hamaker. J. Kaufman. R. Org. M.. Iwamura. 42. Chem. N. R. Alt. Tone..-M... M. J. Rev. J. 1906. O. T. J. 29. Sakata.. Y. 14195. A. B. 65. Russ. (a) Putala. Chem.. R. 1989.. (c) Denmark.. 36... Rh2(OAc)4 appears to be superior to Cu bronze: Henry. J.. K. 116: (g) Pietrusiewicz. M. (b) Charette. 99. J. S.. Acta 2001. (e) Pietruszka. H. 2219. Tetrahedron: Asymmetry 1996.. D. Ortuno. Zhou. Y. A. H. Coe. A. W. Witt. E. 2002. 1985. (136) Denmark. 63. Lett. L. G.. F. J. Brandes. J. Stavenger. J. Sneddon. 60. Chem. Tetrahedron Lett.. Whitesell.. Am. A. C.. see: (a) Doyle. Chem. 1987. A.. Antoulinakis. P. Woo.. 57. K. H. Nefedov. 12160. T. 29. V. D. J... T. T... 50. Dokitchev. Int.. 14. 2001. 71. React. M. S.-S. S. (151) Moser. Am... A.. C.. 123. K.. K.-B. Mayoral.. S. N. 2001. Peng. 4245. 3300. J. 305. Doris. M. C. F. T. 2001. 2283.. (143) Park. I. Am. Bernabe. 1996. see: (a) Rife.. Pure Appl.. Viallefont. Maxwell. Tetrahedron Lett.. Tetrahedron Lett. 1998. Russ. McKervey. S. R. Calmes. D. 123. V. D. Acta 1999. 63. 109: (b) Alcaraz. H.. Roumestant. Evans.. K... 1982. Pietruszka. A. Molinaro.. (d) Aggarwal. F. 2. 11. Dailey. Jensen. Am.. Pietruszka. Tetra´ hedron 1994. K.. Ed. 1529. 26. Sklenak. Chem. R. M. Claffey. M. J. 1994... Faucher. R. Lett. Verheijen. A. Branchadell. C. 4 M. Hacksell. (c) Timmers. 2741. G. Am. F. N. 2001... 1989. 1288. I. A. O’Connor. 761. Ziegler. N. A. 37. Farwaha. S. Chem. 4531. Csoregh. H. O’Connor. Carrie. 62.. Acta 1999.-M. ¨ ¨ Fernandez. Paulissen. M. A. Chem. 6. ´ ´ 33. 1993. M. D.. Nichols.. 799. J. A. Tetrahedron Lett. 2215. as well as the diazoester derived from menthol (up to 13% de). C. 31. Piniella. (154) (a) Muller. 14.. B. 1439. Soc. C. Y. 132: (b) Doyle. Oliva. C.. P. Brochu. Tetrahedron 2000. Ohno. J. 46. 10. Z.. Lahoz.. J. K. 2001. J. 1994.. M. 1977. C. Huang. Y. H. C..-F.. J... 1985. 56. Kochi. Mioskowski. Che. Am. P.. see: Doyle. (b) Vallgarda.. Am. Soc. M.. I. 50. 911.. Moss.. Pietruszka. Mayer.. H. N.-L. S. (a) Shimamoto. Fernandez-Alvarez... Tetrahedron Lett. Marco. 1998. B. Eur. E. F. Chem. J. Pietruszka.-M. J. T. U. B. Org. J. Davletbakova. J. D. 5605. P. (141) For an excellent discussion on the various possible catalysts. 35.. Moss. D. E. P. Zhou. Am. (a) Maas. C. Chem. P. 1997. 115: (f) Padwa.. Huby. M.. (110) (111) (112) (113) (114) (115) (116) (117) (118) (119) (120) (121) (122) (123) (124) (125) (126) (127) (128) (129) (130) (131) (132) (133) (134) . Loh. J. Chem. 2001. 37.. Meetsma. 1990. 1995. 3217 (Additions & Corrections). Dokichev. Lebel et al. (152) Salomon. Brochu. 1995. E. 63. 1987. Maidanova. Soc. see: (a) Davies. 7. Dailey. B. ´ D. 95. (a) Hanessian. 1994. Helv..-C. H. N.-C.. Angew. 1 2000.

901.. 2001.. 48.. Zheng. Lynch. J.. J. 15731.. (b) Nishiyama. (c) Niimi. T. J. 2681. J. M. Motallebi. 10270. J. M. A.. Z. N.. Kitayama.. W. 1571. Fu. 2003. Che.. Synlett 1993. T. Yamada. R. 3443.. H.. Kim.. T. C. Lett.. Chim. Dyatkin. 1997. C.. Scott. 57. 22. 2000. T. G. T. Vol. Soc. N.. see: (a) Li. P.. Park.. Catal. Y. Soc. Kudo. Muller.. 1751. B.. 1541. For the use of a rhodium porphyrin catalyst. J. Lynch. J. Katsuki. I. Hu. C. Lynch. 2002. 2000. the enantioselectivities are usually lower than those observed in solution: (a) Fernandez. Hashimoto.. A. Che. 42. S.-F. 1911. 2865.. 31. 54.. Jpn. Mayoral.. 2001.. Y.. (c) Nakamura. S. 3. A.. (189) (190) (191) (192) (193) (194) (195) (160) (161) (162) (163) (164) (165) (196) (197) (198) (166) (199) (167) (168) (169) (170) (171) (172) (173) (174) (175) (176) (177) (178) (179) (180) (181) (182) (183) (184) (185) (186) (187) (200) (201) (202) (203) (204) (205) (206) (207) (208) (209) (210) (211) (212) (213) (214) (188) . Austin. Tetrahedron Lett. S. 100. L. M. J. G. Chem 2001. S. Chim. Zhou.. D.. Herrerıas. M. Y. Ishitani. Top.. Ene.. 638. Tetrahedron: Asymmetry 2001. Chem. W. M. 1839. Tetrahedron: Asymmetry 1995.-L. A. 1995. Katsuki. Commun. 781. J. 8... A: Chem. P. R. Nakamura. Benaglia. Tetrahedron Lett. T. T... A.. Eur. 4.. Takezawa. S. W.. Gant. 1994.. Harden.. S. Ahn. Ikegami.. H. 5373. ´ S... 825. T. Fu. Org. A. 2459. 459. Chem. H. Y. I. 2000. Chen. G. R. T. Sato... K. W. Z. No. Lett. Matsumoto.. A. (d) Jommi. M.. K.. Tetrahedron 2001. W. T. Y... R.. H.. H. A. M.. Liang. M. Hu. see: (a) Tatsuno. Tetrahedron: Asymmetry 1998. Nagase. Chem. Matsumoto. Adv. H. Acta 1988. Am. 115. J. Keller.. A more extensive discussion on this topic can be found in ref 141. M.. P. H.. C. T. Y. Y. (d) Clarke. Otsuka. S.. Chem. I.. Fraile.. M. Chim.. C. Chem. 38. M. Aoki. J. Iwakura. 2599. W. K. 2000. 1978. Commun.. Zhang. Chem. Chem. Sekino. N. H. A. Reissig. (c) Fraile. Reiser.. Kanemasa. 614. Liras. M.. Garcıa-Verdugo. Y. Y. I. Nguyen. Moriuti. (b) Ebinger.. G. 35. Org. H. M. 3075. (b) Harm.. R. 182: (b) Roos. Many ligands have been synthesized on polymer supports.. Adv.-F. Chem. Galili. Roos. 78.. Tanner. Takaya.. M. H. H. Tetrahedron Lett. Zhou. 377.. H. Tetrahedron: Asymmetry 1996. Catal. J. 2001. P. T.. Itoh.. Soeda. Pfaltz. Schinnerl. C.. 867. M.. Jpn. Brandes. R. W. Tetrahedron Lett. 12.. 67. Tetrahedron Lett. Faul. S. Helv. T. (b) Yamada.-G. Katsuki. Vaultier. (a) Uchida. Synlett 1993. B. L. H. J. D. 18. T. Otsuka. T. For a more exhaustive review... (e) Gross. C. 2487. 72. S.... Tetrahedron Lett. 3063. Ikeda. 7985. 2003. Tetrahedron Lett. Irie. For recent reviews. 35.. 1996. Winchester. Chem. Org. Tatsuno... Dalton Trans. J... T. R. ¨ K. Nishiyama... Lee. Helv. Davies. S. T. T. Garcıa.. 2000. (c) Uchida. Winchester. 18. K. Meyer. Itoh. 1998. 1996. D. Zhang. Ghosh. P. C. T. Mol. Fernandez-Garcia. Hu. B.. W. E.. S. M. G. J. Doyle. A. Irie.. Buono.. Katsuki. P. (a) Lo. (c) Ikeno. J. H. ´ ´ J.. G. 439. H. 7. T. P. Pfaltz. Am. M. 343. 1999..-C... Y. Tetrahedron 1997.. 30. 100. 3326. T. M. Synlett 1999. (b) Davies. Tetrahedron: Asymmetry 1997. 4. J. Dammast. Zhou. J. ¨ Mezzetti.. Acta 1988.. Fluorine Chem. A... 3160. Sugawara. Tetrahedron Lett. T. Protopopova. L.. J. Chen. 1023. Chemical Reviews. H... Achiwa. H. T. (h) Doyle. P. 1990. 1999.. Synlett 1996. 1993. S.. Sanau.. Noyori. Jpn. 79. (a) Ito. Hu. A. 196-201: (g) Doyle. Heinz.. R. J. M. 2002. see: (a) Iwasa. Chim. T. 603. 31. 2151. Zhang. S. Miller. O. D. Catal.. J. T. Gillespie. M. Mezzetti. M. H. B. Nishiyama. Simonsen. Pitillo. 2000. Synth. Doyle. (b) Bohm. Ogawa. Jensen. J. A.. Nishiyama. 2000. G.. M. K. N. Woerpel. Doyle. Matsuda. R. 9968. A. K.. T.. K. Pfaltz. F. 13. Int. Umbricht. 30. Chem. 1990. Lett. A. J. 41.... M. Reiser. Bailey. J. For earlier reports of cobalt(II)-catalyzed cyclopropanations.. O. D. A.. see: (a) Muller. Konishi. ¨ Bernardinelli. Enantiomer 1999. 939. Chem. Furler. H. Chem. 120.. Nishizuka.. Acta 2001. M. V. 74.-L. (b) Nozaki. G. For a series of examples. 1999. Doyle. 1999. 2001. J. W.. 178. Setz. Cho. Tetrahedron 1992. Yamada.. C. Katsuki. 1043.. Otsuka. N. Soc.. 303. Commun. E. Tetrahedron 1968.. Yao. J. 1638. Zabel.. 2002. Y. N. J. Jin. Katsuki. S. S. G. 569. Luis.. N.. Angew. Cheng.. S. 117.. (e) Annunziata. Pays-Bas 1995. 2227. For a water-soluble ligand. Heterocycles 2000. Leutenegger. Helv. Itoh. P. O. R. Perez-Prieto. Tetrahedron Lett. Yamada. B. N. Helv. S. (b) Imai.. W. M. Chem. Ikeda.. H. M.. Iwakura. (b) Ito. J.. H. A: Chem. R. M. E. Chem. 71. B. Luis. A. 163. K. T. (a) Bohm. H. Pfaltz. Burguete.. Nishizuka. D. 38. 1999. (d) Nishiyama.. Woerpel. Leutenegger. P. Bull. Tetrahedron 2000. A.. M. A.. 1989. 65. W. Am. 79. D.. Hu. 114. Lynch. Cozzi.. J. Pieters. Watanabe. B. J. H. Carrie. Protopopova. 406.. W. Org. Pfaltz. Charette. Chem. ´ ´ V. (c) Nishiyama. 1974. Org. 1603.. Soc... Chem. Konishi.. Fraile. Tetrahedron 1998. (a) Ito. 1992. V. H. M. K. S. Chem. Jpn. L. J. 1995. 1993. 1891. A.. 3449. Synlett 1996.. S. S. D. Chen. 21. 430. Uchida. Chem. Tanner. H. Timmons. Synlett 1997. 31. 2143. Itoh. H.. Hinman.... I. Org. 7.-H.... (b) Doyle. S. Commun. C. A... J. Soc. T.. Soc.. 1991. G. M. T.Stereoselective Cyclopropanation Reactions 133: (c) Haddad. (c) Bachmann. Kalinin.. 2953. S. Yabushita.. Irie. 32. 3905. Chem. S. G. 40. A.. M. Tetrahedron Lett. (a) Nishiyama.. 34.. 74... (a) Imai. 2002. 3501... H. 41. 107. Labahn. M. 7373. Angew. T. Commun. Leutenegger. N. 6005. X. Acta 1995. (b) Bachmann. R. H. T. J. X. U. J. J. Shannon. Tetrahedron Lett.-W. L. 1999. 84.. 2002. Tetrahedron Lett. T. Matsumoto. Y. 68. Chem. Knight. M.. G. J. R. Scott. A. 52.. M. J. Ed. Raab. Kishi. Chem. 1157. M. 180. 116. Z. Hashimoto. 1936... Kyota.. H. J. Am. 1997.. V. Cinquini. Tetrahedron: Asymmetry 1997. Nakamura. J. H. I... 66. Umbricht. P.. Masamune. however. Watanabe. H. A. H. Sisti.. Dyatkin. T.. Am. Tetrahedron Lett... Masamune. J. E. Yamamoto. Motoyama. K. Martin. Chem. Park. Soc. Chem. Tuchiya. 2001. Aldrichimica Acta 1997. 2000. J. Stemp. Y. H. A. M. Zheng. Brunel. See also: (b) Rios. 6064. Raab. N.. 35. Zhou. Chem. Rosen. Ed. 3. Org. 85. F.. Commun. 2000. H... Protopopova. J.. Chem. 2045. C. A. (a) Nozaki. V..... C. S. J. Konishi. 517. Miertschin. M. Chem. 1315.. Synth. 20. T. 2002. M. S. N.. 1171. Hayashi. R. K. X. Lynch. Simkhovich. Ghosh.. R. C. Sato. I. T. 1205. Chem. E. 1994. Leutenegger. Y. Davies. J.. 1145. K. Wan. Zheng. 1994. Inorg. Soc. E. H. R. J. A. B.-M. 2001. 599. 697.. A. Lo.. Bull.. 1986. K. R. Wurz. P. 1991. 1997. H. Hamura.. Tetrahedron Lett. (a) Aratani. (a) Stoop. Q. A. 1997. Sato. Ikeno. 74. Chem. 1994. Tetrahedron Lett. 2102.. C.. M. Garcıa.. P. Chem. 719.. R. Soc. Chem. 37. 2001. E. 53. M. S. Chem. see ref 115a. 2001. Barberis. Simkhovich.. G. A. 37.. H. Y. R. P. Pure Appl. Mayoral.. 5173. (b) Aratani.-B. W... B. C. V. T. Synlett 2001. G. J. S. K. Chem. Haufe. L.. S. ´ ´ ´ M. 114. R. O. U.. Synlett 1996... Chem. Soc. Naito. 7187. 184: (c) Hashimoto.. 1345. 57. W. Bull.. Siegmann. M. 1163.. I. (c) Fritschi. R. V. Q. Clark. 2223. 208: (j) Kitagaki. Soc. I. T. R. X. (b) Fukuda. N. Andersson. Trav. T. M. Bull. 1111.. M... (f) Doyle. Noyori. T. Y. Am. Rissanen. 8.. Munslow. Chim. 56. S. Soc.. Yamada. T. Z. I. Acta 1993. Chen.. (b) Uchida.-M. Chem.. T. 183: (a) Pierson. C. Charette. 1966. B. Chem.. T. Lowenthal. Soc.. Chem.. A. Nakatsuji.-C. S. 5057. M. E. M. U. 1985. 1553. D. Commun. Kratky. Hoorn. Ed. G. B. A. Chem. H. A. Weber. Abiko. Z. Catal. F. (b) See ref 146a. Wong. M. Chem. M. 6. 5807. N. Katsuki. Z. 25. B. Lett. Org. M. Lowenthal. (a) Fritschi. R. P. Eur... Katsuki.. Commun. J. P. P... A.. Glos. C. 56... Nishiyama. 3655. 2139. Ng. Simonsen. S. Tetrahedron: Asymmetry 2000. 1992. Li. McKervey.. 6189. 4 1045 2001. 24. (a) Lo. Mak. A. (b) Burguete. Lett.. Kida. Irie. (d) Ikeno... K. (b) Nakamura. 232. Soc. A. P. M. C. E. H. 59.. Chem. see: (d) Gross. A.. H. C. A.. Lahuerta. T. Mezzetti. W. Johansson. Uchida. Z. 5691. Eur. Tetrahedron Lett. von Matt. Helv.. O. Chim. (b) Fritschi. M. R. Mayoral.. H. M. Yoneyoshi.. Roos. (a) Ikeno. Frohlich. 2847. see: (a) Davies. (b) Li. Oalmann.. T.. Y. I. 4. S.. Chem.. C. in press. Kwong. ¨ Parisini. Kida. 4. M. Corey. Org.. A.. Murata. Sekino. S.. Soc.. Lett. Angew. Galili. Dwyer.. Z... 189. T. 43. W. Bubert. Comm. (a) Bedekar. 6083.-U. T. Bauer.... A. H..... 2. Lett. P. M. Organometallics 2001.. Catal. P. M. S. Q. Simonsen. 4073. Aoki. Uozumi. 7201. G.. Nakatsuji. Worle. Legrand. Takaya. 1996. H.. Synlett 1995.. Chim. E. C. Liu.. (d) Niimi. L. Rizzi. Am. Muller.. 343. (b) Niimi. S. Simonsen. 2. Soc. V. Tsujitani... A.. V. McKervey. P.-B. J. 2001.. ¨ C. Katsuki. 1998. (e) Ikeno. Andersson.... H. G. Doyle. P. Winchester.. Umbricht. K. Helv. Ene. Chiu. Reymond. J. 202-207: (i) Doyle. Wong. 1999. G. L. Pagliarin. L. 11. 833... 76. R. 121. Garcıa. P. M. Yang. S. F. 71. A.. S. 10469. 1005... Church.. Recl. Irie. 2955. Uchida. 1978. 9... Simonsen. Am. E. (a) Evans. Østergaard.. 4705. Ohtake. Irie. Lett.. Chem. T. T. See. T. Tetrahedron Lett. F. Haga.. Katsuki.... Fahrni. 1793.. Kwan. Chem. A. M. 697. Int. J. Org.. 1977. C. Park. 5763. (c) Zhang. Q.-T. Synlett 1999.-S. M. Submitted for publication.. 2. (a) Fukuda.. 726. J. D. Deeth. Int. S. Chem. Org. M... 3367. Commun. Tetrahedron 1998. 588. G. Bouchard. 54. J. Pfaltz..-L. Soc. 3647.. Soc. Soc. Synth. Lett. (b) Evans. Itoh.. Soc. Tetrahedron 2000... 165. R. Sato. Synlett 1997. Acta ¨ 1991. J... 1247. U. T. Harmer. S. (a) Schumacher.. Ikegami. Katsuki. N. 191-195: (e) Doyle. J... M. Zheng. 2661. 5239. Harada. (f) Ikeno. ´ Soc. J. I. Baud. I. R. 2001. Mol.. (d) Watanabe. For recent reports of ligands based on this scaffold. Dyatkin. S. F. (c) Li. M. S. Reiser. Tang. M. Garcıa-Verdugo. Soc. Moriuti. 113. Yamada... Lett. Galili. Davies. ¨ Motallebi.. G. Organometallics 1999. H... Z. C. (b) Iwasa. 103.

H. O’Leary. J. 1994. Perez-Prieto. K.. Pereira. C. S. M. F. 60. M. Ahn. K. 2000. Org. Org.. DeLara. B. Med. J. M. 35. Soc. Blake.. S. Roos. S.. R. D. P. G. K. M. Chem. E. 112. L. Chem. ´ Organometallics 1997. 39. Am. D. H. Perkin Trans... A. M. Y. Marnett. Chem. R. G. D. A. K.. T. H. (267) For the cyclopropanation of farnesyl diazoacetate. R. Org. Chem. A. Tetrahedron Lett.. 6509. 115. (233) Stork. 1992. Hartmann. 2040.. Panaro.. Chem. Hillier. F. 2000. 46. (218) Davies. Q. J. J. R.. M. M. J. I. Soc. 3828. Hutcheson. Bull. 1 1998. Chem. Perkin Trans. J. Hornbuckle. M.. J. (266) (a) Saha.. S. D. Gulnik. Jr. Lawrence. J. Rosenberg. G. F. Organometallics 2002. 1980. Condon.. 1998.. M. M.. D.. C. Scholtz. 1998. Russkamp. Kalinin. 3857. 1996. B. 4203. S. Chem. 2371. Chem. Org. L.. 6897.. Dwyer.. (252) Pique. L. Tetrahedron Lett... Topol. M. H. R. see ref 189. 55. Spina. S. R. A. A. G. Martin. Taber. 2929. C. Chem. B. M. Dinesh.. 65. S. see: Doyle. 2000.. M. Tetrahedron Lett. F. Spaller. A. (c) Branca. W.. D.. Perez-Prieto. 2815. Stafford. P. F. Chem. N. Tetrahedron Lett. P. 1305. Soc. Tetrahedron Lett... Kong. M. Liras. Austin. M. A. Phillips. 2000. W. J. Org. 3125. J. Y.. E. M. (c) See also ref 217. III. Cantrell. 120. 260. J. Parker.. (h) Srikrishna. Soc. H. Soc. (f) Davidson. L. Cohen. H. Organometallics 1985... W. Tetrahedron Lett. J.. M. Phytochemistry 1995. 60. (226) Davies. 65. Rusiniak. Chem. Tetrahedron Lett. E. Chem. 955. 1699.. Tetrahedron Lett.. C. P. Am.-G.. (235) (a) Mori. I. 66.. Garcıa. D. J. S. 1995. Zhou. J. H.. M. J.. S. (f) Srikrishna.. D. 3. Tetrahedron Lett. Luzzio. G. Mander.... see: (a) Trost. J. Tetrahedron Lett. 40. 1657. C.. 66. F.. Chem. Commun.. Bailey. Tetrahedron Lett. Cantrell. W. H. M. (230) Nagashima. H. N. C. Cho. J. Chem. 40. C. D. S. (237) Sarkar. E. 1121. M.. 1998. Stiriba. S. Grieco. see: Yoshikawa.-W. Sect. 5763. J. J. Q. F. A. P. Tetrahedron Lett. K.. H.. M. (e) Srikrishna. 6265. (262) Doyle. 49. P. 8839. S. Hu. 7638. Klino.. (250) For an excellent account on this topic. A. J. Zhang. J.. M. A. T.. Cotton. G. Chem. Shibasaki.. J.1046 Chemical Reviews. 37. B 2000. (259) (a) Tokunoh... 39. J. O’Leary. Nandy.. 1999. C. Synlett 1995. B. (b) Mateos. S. 1 1994. 6969. B. 31... Jessop.. N. 9435. McKervey.-L. Soc. McKervey. 57. Eismont. A. Bull. Fall. Soc. H.. Kleinert. (g) Srikrishna. J. A. 1992. E. 2001. 1 2000. V. T. B. (268) (a) Martin. 18. A. (254) Kim. M. K. Munshi. Dwyer. L. Soc. A. B.. R. (b) MoyeSherman. Chem. Lett. Buckley. 6727. 1 1997. M. J. P. K. 2001. T. D.. D.. 41. (b) Doyle. F. 2000.. J.. D. P. L. J. M. B. 5287. Tetrahedron 1970. 116. 114. J. J. 41. P. 10. Vijaykumar. Am. J.. G.. 1993. L. 36.. A... ´ ´ M. Taber. C.-E. M. S.. Tetrahedron 1992. 1997. Wu. Hu. F. (222) (a) Moyesherman. Wells. (b) Estevan. R. T... J. 41. C. Poulter.. 3. J. R. Raab. L. 118. D. A. Chem. R. 1996. X. M. T. 611. Chem. Soc. D. V. 10079. B. see: Rogers. G. Chem. W. S. F. F. 118. M. P. Q. 116.. Hartmann. R. T. 1995. Frey.. T. 42. D. S.. E. Buckley.. Ficini.. E. Lahuerta. (b) Barberis. Vijaykumar. Hendricks. (b) Padwa. H. W. Pieters. Soc. I. 39. A. A.. C. T. P. 2001. 941. 1 2001. 6577. R. H. Indian J. Erickson. N. J. M. Boebel.. J.. Monck. (b) Doyle. J. Curtius. M. (229) For an application of this methodology to the synthesis of a tamoxifen analogue. 123. (b) Doyle. D. (b) McMurry. M. (265) For chiral Ru-pybox catalysts. Koszyk. 4077. 68. see: (a) Fukuyama. S. (c) Lahuerta. J. K.. H. Fahndrich. (248) (a) Zhang. Chem. Commun. N. M. (b) Martin. H.. (b) Frey. (b) Maguire. 1521. 1997. Bull. P. (d) Srikrishna. A. H. ´ ¨ (253) Doyle. D.. 114. Commun. P. D... V.. Soc. M. Dyatkin. P. (245) See also: Sugimura. 3521. Nagaraju.. Am. Synlett 1995.. P.-E. 45.. 455. D. 2000. L. L. (269) Martin. (227) Davies. Barba. Ahmed. A. 26. Soc.... 1995. 1364. T. J.. Pieters. 1992. M. P.. 2001. F. (b) Singh. 441. P. 41. M. ´ Lett. Anebouselvy. Tetrahedron Lett. Koumbis. J. Longoria. .. V. H. (225) Davies. Chem. A. E. M. S. Koftis. J. L. A..... A. R. Chem.. (231) For reviews. Am... N. C... W. J. Rogers.. K. 1992. Lahuerta. 37. F. 211. A. M... (b) Srikrishna. Am... Chen. Bruzinski. 26. Martin. L. A. L. Pandy... M. K. Hoerrner. 109. M.. A. K. Tetrahedron Lett. (263) (a) Doyle.. T. 7166. Chem. B. M. 117. Protopopova. W. Reddy. Am.. M.... S. React. M. Chem.. L. Nagashima. Org. Russ. Am. Nishiyama.. P. (258) Chakravarty. F. B.. R.. H. 6586.. Tocher. Soc. Chem. 2863. P. Chem. 9459.. S. Am..... Saha. L. 3295..... A. ´ Organomet.. S. T. N. 1998. C. Chem. L. 4129.. Spaller. A. Org. 1 1999. ´ S.. M. Mander... K. (264) (a) Doyle. S. 1667.. Perkin Trans. (b) McKervey. K. M. 1976. M. A. P. C. F.. Soc. C. 119. 2001. P. J. Ferguson. Harrington. S. A. M. L. M. 36. Noe. Davies.. Chem. Perez-Prieto. (247) Rogers. M.. H. X. M. G. Shin. 8745. L. Austin. Churchill. Soc. See also: (b) Srikrishna. 3165. (220) For an X-ray crystal structure of Rh2(TBSP)4 and a discussion of solvent effects on the enantioselectivity. Chem. J. L. (c) Ross.. see: (a) Burke. (e) Martin. Lim. Chem. K. Herbst. 1995. M. S. Synth. Chem.. 1997. Hu. L. 41. Kim.. P. J. 42. Chem. Chem. 1998. E. Lebel et al. Ber. M. N. Kanai. Austin. Reddy. P. 1995. Tetrahedron 1999.. S.. Peterson.. M. N. A. 4493. B.. C. D. C. P. Soc. H. B. W. A. J. J. M. McKervey. Tetrahedron Lett. Soc. Chem. Org. Ng. E. 120. P.. Chem. S. 1974. Martin. T. P. S.. Huby. Bhat. Tetrahedron Lett. A. M. Kong.. (272) (a) Doyle. Chem. (221) (a) Davies. 36. Chem. T. M. see: Wynne. Matsui.. S. M. H. J. B. S. (c) Martin. Org. Gane. 7983. B. Org. 2521. 2973. (c) Dauben. 63. 2001.. H. J.. Olive. 2003. (c) Srikrishna.. see: Davies. Chapman. 2001.. G. 29. Chem. B. ´ Tetrahedron Lett. R. Charnsangavej. P. H. 2641. D.. Krumpe. Shibasaki. 2048. P. Peterson. N. J. R. C. Am.. D.. 1997. 1896. Tetrahedron Lett.. Chem. Lett. G. Chem. 7243. J. E.. F.. 7489. R. 1996. (b) Morris. A. Sanau. P. A. (243) (a) Buchner.. 2583. 33. D. N. 2000. M. S. A. 42. 43. Pfaltz. J. Chem. J. Hockless. M. J. 1710. Org. J. K.. Baker.. N. S. 117. 1991. R. M. Am. Martin. 9468. J. Kobayashi.. K. R. D. Commun. T. Protopopova.. (255) Park. J. Russ. (c) Davies. Morris.. Dellios. S. Baur. Calvo. 1996.. J. Kwan. Kim. 16. (b) Buchner. J. Am. 1995.. 63. Tetrahedron Lett. 8826. 64. R... 1998. Tetrahedron Lett... (256) (a) Barberis. S.. 3155. P. C. A. 1987. T. Zaragoza. P. Perkin Trans. Chem. 1751.-E. Hendricks. Perez-Prieto. Chem. Oalmann. S. M... Kong. J. H. E. Oalmann. Welch. Dtsch.. Alper. H. Chem. 39. Fall. R. 2000. 37. (h) Hillier. Ye. Org.. R. 4133. C. J... S. 39. R. S. Am.. Soc. 323. 1 2000.. (b) Doyle. F. Mander. 8189.. G. 1979. A. T. (271) (a) Doyle. Org.. 2385. M. J. J. Peterson. 5020 and references therein.. A. S. 65. Am. A. F. Chem... R. Houser. Kutchan. G. (242) For similar examples. M. H. 1961. Org. ´ S. J. M. Stein. Liras. M. M. Soc.. D. Churchill.. Corey. R. 113. Vijaykumar. J.. (b) Uchida. C. Am. M.. Churchill.. (238) (a) Taber. Chem. Anebouselvy. J. J. Burgess. A. O. Chem. 1977. Churchill. 1903. J. (232) Padwa. No. E. Sheth. J. V. L. 1996. R. 16. (228) (a) Davies. ´ Lahuerta.. Bruzinski. 17.-G. S. 2695. 1999.. Yi. H. Liras. V. M.. F.. J. H. G. Appels. Ruppar. Blaszczak. (270) (a) Martin.. C. Perez-Prieto. G. L. 48. C. 45.. F. (261) See for example: Dauben. Ubeda. N. J.. Commun. Tetrahedron Lett. D. E. M. A. Hu. 3326.-E. Soc... J. M.. Sanau. J. S. Stiriba. B. P. P. J. (236) (a) Lee. 1990. T. J. ´ ´ 840.. Pharm. C. Ohki. P. 10774. J. J. P. (244) (a) Maguire. Massen. 1914. See also: (b) Sato. Perkin Trans. W. (b) Davies. Dwyer. R. R. D.. F. R. Chem. 361... Maguire.. Soc. 6643. Ene... Marın.. C. P.. 2449. Soc.... 4 (215) (a) Davies. D.. K.. (d) Martin. P. Chem. Corey. L.. (b) Taber.. S. Am. J. 4678.. Synlett 2001.. Dinesh. 119. King. Achiwa. Soc. (216) Davies. J. Ges. 1581... 2. S. A. G. Stiriba.. Lake.-E. 32.. F. M. Am. 612. 1885. A. L. 4325 (Additions & Corrections). Katsuki. Ferguson. 361.. (251) Doyle. (c) Barberis. Mueller. O’Leary. 2000. 880. 3580. Chem. L. 1993. P. J. T. Org. ¨ N. I. T. Chem. Marnett. R. A. L. S. Stiriba. J. H. Chem. J. J. Zhou. Sodeoka. Tetrahedron Lett. Davidson. 11021. T. 2411. Smith. 1265. J. J. Oalmann. J.. Kim. Chem. Doyle..-H. Kessler.. K. Zhou. H.. (b) Davies. 1997.. L. Tai. R. Stiriba. 42. (257) See also: (a) Estevan. 1995. M.. Perkin Trans. A. Dyatkin. 1990. R.. C. (b) Gallos. 3317. Am. P. 1874. 39. Tetrahedron 1993. 1998. M. Soc. 34.. Jr. 120.. (234) Hudlicky. (240) (a) Gallos. 7579. Uchida. Bakshi. Son.. Tetrahedron Lett.. F. C. Tetrahedron Lett. A.. Knight. Y. Burgess. B... Chem. Doan. T. (223) Davies. G.. H. M. (246) Maguire.. Soc. A. Tetrahedron Lett. P. 39. 1992. 4. B. Chem.. Soc. M. F. S. 491. 1996.. (b) Doyle. Zhou. R. 8811. Roos.. I. Katsuki. Synlett 2001. Tetrahedron Lett. L. T. Hillier. E.. Jin. 1991. Ubeda. Chem. M. J. Protopopova. M. Bell. (249) (a) King. A. Zhang. C. J. Soc. (224) Davies. L. A. 823. 7102. 122. M. H. D. 1998. S. Dyatkin.. Liras. Chem. (219) For a study of steric and electronic effects of similar catalysts. M. Roden. Med. 1995. R. S. L.. K. A.. F. S... W. Lahuerta. 103. K. Perez-Prieto. Martin. 66. Lynch. 1998.. 8. S. Perkin Trans. 1423. Ruppar. Soc.. J. 2217. 1999. 1994. Oalmann. 1998.. III. Zhou. Matha. Org. (i) Arno.. J... Lock. 1990. 2001. Tetrahedron: Asymmetry 1999. 36. N. Lett. J. 37. H... Ham.. Org.. J.. J.. Commun. J. (c) Srikrishna. Viswajanani. Lahuerta. 1996. 48. F. 38. H. J. 1996. S. Ahn. 515. Reibenspies. Vol. Pure Appl. M. K. Org.. 40. 6187. L. 1999. Soc. Tetrahedron Lett. L. 106. R. (239) For selected examples. 2000. Nagano... Oalmann. 1992. J.. Chem. Chem.. Tocher. (241) (a) Srikrishna. H.. R. Am. 2377. (260) Gant. B. H. C. J. J. (b) Doyle. Soc.. Liras. Koftis. Austin. T. P. Q. Chem. Q. (g) Martin. 5385.. M. 22. Semones. Chem. M. F. Chem. (217) (a) Kennedy. A. Kalinin.. 83. C. Org. T. Olmstead. G. Synthesis 1998. Soc. Morris. 21. Mander.. A.. Liebigs Ann.. 1998. D... 2595. H. 4321.. Tomiyama. H.. 823. F.. 1998. J. 1998.. L.-W. Gonzalez. Ahmed. 2001. Dorsey. Z. Viswajanani. M. Luzzio.

Deng. (c) See ref 250. J. Tetrahedron 2001. 371.. Taylor. 2001. F. Provera. K.. Hoppe.. R. E.. Hoffmann-Roder. 7955. Y. Org.. Tsuji. T. Walsh. D. 1974. Y. 387. Z.. O. 1999. B. see: Takahashi. C. M. Haselgrove. ¨ P. 87... 56. Raman. J.. 74. Kamimura. Russ. R. J. E.. Chem. D. T. Seyden-Penne. 1993. 97.. Adv. Soc. Kim. T. Dugar. E. 56. 50.. Chem. M. Org. L. Pergamon Press: Oxford. Taylor. Chem. 1100. Feducovich. Org. Chi. 1990. Finkelhor. N.. 67. 2001... A. Y. Y. Stephenson. (b) Doyle.. Hendricks. 2002.. Peakman... Org. 84.-X. Org.. Chem. Lett. 58. Commun. Dai. J. Chem.. 5762. D. V. Russ. 152.. Org. Q.. M. A. P. J. M. A. Rose. H. S. P. Lett. W.. Amedio. de O. 8033. J. Res.. L. A.. S. Chemical Reviews.. Taylor. 34. Gonzalez. H. (c) Shen. E.. Synth. E. A.. (d) Shibata. S. Brocksom. III. (c) de Faria. G. A. 43... Chem.. 761. N. Terzis. Y.. M. Taylor. Kirby. D. Huang.. J. B. Greatrex.. Greatrex. R.. Vereshchagin. Murray. Ed. Chem. Hu. 40. Org.. M... Solid-phase-supported reagent: La Porta.-P.. Talib. G.. Synth.-L. Sprott. 31. Commun. Pergamon Press: Oxford. J. 2001.. 6. H. (i) Calo. Tetrahedron 2000. 9423 and references therein. L. P. Y. E. Y. I... J. (295) (273) (274) (296) (297) (298) (299) (275) (276) (277) (278) (279) (280) (300) (301) (302) (303) (304) (305) (306) (281) (282) (283) (284) (307) (308) (285) (286) (287) (288) (309) (289) (310) (311) (312) (313) (314) (315) (316) (290) (291) (292) (293) (294) . A. 1998.. Doan.-Z. Commun... (e) Doyle. Rathbone. M. Chem. (b) Hudlicky. ´ ¨ Loffler. B. 888.. C. 2000. Rev. 4937.. Jenkins. N. Fr. Stentiford. 4093.. Soc. Matsumura.. D.. Melvin. Y. Org. Hartmann. S. Magalhaes. Tetrahedron Lett.. M. Eds. J. 1999. P. Z. J. 227. Viout. D. M. DiMarco. V. Am. Mori. Chem.-F. Huang. SpringerVerlag: Berlin. 893. Chem. Ila.. Kimber. (b) Avery. H. P. Soc. (c) Tomioka. E. L. M. Nesmeyanov.-H. J.. Lloyd-Jones. A.. M. 44.. S... Eur. Synth. 58. 4261. 3302. Dai. E.. 1965. (b) Doyle. Chem. (e) Shen.. F. F. see: (a) Bhattacharjee.. M. C. J... U. H. B.. A. A. Chem. Chem. (b) Rocquet. 1129.. F. T. (S) 1996. Tetrahedron Lett. Slawin. S. Qi. Chem. M. C. H.. 4746.. L... Dai. 867. 2609. A. 1988.. N.. 50. 2000. Soc. 913. Res. 1327. 1 1994. 54... 198. Junjappa. Vol. F. M.. (b) Ahmad. 1998. (S) 1994. Kaji. L. A. M. T. D. p 1105.. P. Z. Chi. Zhou. N. Maki. Y. H. Davies. Chem... Lerario. Chem. 1979. Yong. T. 2002. J. Chem. J. Y. Y. 283... V. S.. Zhong. Huang. Huang..-H.... Diez-Barra. J.. G. see: (a) Taber. Jr.. Nakamura.. Scand. V. T. 2853. 29. J. N. Dai. 66. Angew. Tetrahedron Lett. Silva. (f) Cluet. 1990. (b) Koskinen. Avery. Jubault. Winterfeldt. Org... 328. 4 1047 K. Collignon.. Tang. Gennari. P. M. J.. N. 41. Chem. C. 6257. P.. I. P. Shinozaki. (b) Ono. Ed. Chem. M.. P. D. Dai. J.-J. Z. M. Gorobets. A.-Z. A. T. 1991.-Z. Liao. A. S. Sterner. (b) Corey. 2000. P. 1983.. Chem. S. M.. 4519. R. J. A. 34. Zheng. A. A. 5718. W. D... Z. Jautelat. 51. I. J. Org... 321. 8747. T. A. J. Vitale. Wei. F. R. P. (a) Capps. 37. Soc. M. Castaldi. K. P. Yost.. D. A. B. 48. Zhou... 1997. E. Watson.. Sun. W. Yamamoto. A. Chem. S. Doi. 2000. Vol. 1994. U. M. 2179. Tetrahedron 1998. A. (b) Capps.. (a) See ref 287. B. For an example of a diastereoselective diazoacetamide intramolecular cyclopropanation. Yamamoto. L. D. 1972. Kimber.. S. 2. Palmer. 3363. C. 13. N. Y. Zhou.. 1192. A. I.. H.. J. R. 1992... Chem. 54. W.-G. Nagaoka. (c) Goumain. Organomet. Chem. Tiekink. 2. 127. Angew. Huang. M. Goumain. I. 4619. M. Chem. Adv. K. 1992. Y.. G. P. R. S. Y.-C. Org. Ollis. F. L. 1996. A. Org. Onomura.. L. Tiekink.. Chapman. B.. M.. Chaykovsky.. Q. N. E. Lloyd-Jones. A.. Terstegen. Doweyko. Luna.. 1996. Swingle. J. Brocksom. (a) Trost. J.. T. S. Y. Synthesis 2001.. K. 2643 and references therein... C. F. L.. 37. In ref 1a. 299. E. Samet. 2000. Ren.-C. S. (f) Leonard.. 1997.. Yuan. Walsh. 65. Clarke. Chem. 1. W. M. M.... P. U. Chem. P. 3912. L. Tang. Murray. 1998.. Org. Zhou. Chem. Grieco. Commun. J. M. 1997. (h) Braish. (h) Perlmutter. Moody. Wender. 89.. S. 343. P. J. 2002. (c) Hoppe.. 1993.. Y. E.-Z. E. Organomet. Eismont. Ber... Chem. III. Ngu. M. Y. J. N. L. 154. C. Org. K.. ´ ´ A. A. No. W.. J. Pyke. G.-F. Wu. Ng. K. V.. Tang. R. Contemp. 2806. P. Paio. 1353. (a) Leonel. McKervey.. 115. Piarulli.. 43. 2341. J. 954. Tetrahedron Lett. Tetrahedron Lett. J... K.. F. S. A. R. Raptopoulou. 1999. Wrobleski. Hassila. Tetrahedron Lett. Stereochem. M. 3142. Tetrahedron Lett.. 2000... J. M. 3781. Chem.. Y. Seng. Angew. T. 2000. J. H. Tetrahedron Lett. de Kimpe. Tetrahedron 1994... F. D. J. J. J. Gavin. Jr. J.. C.-L. P.. (d) Avery. Luzzio. Synlett 2000. Leber. 5531. 4049.-L. 3. Chem. B. Tetrahedron 1998. D.. Chem.. 44. Tetrahedron Organic Chemistry Series 9. Z. B. L. 3. J. Doyle. 4520. R. N. M.. Lightfoot.. Quirion. F.. Ohfune. Z. R. Eds. Shen. (i) Rossiter. Adv. 20. R. M. 57. Anderson. Chen. J. P. C. A. A. Bull. Li. Y. J... p 247. T. Nedelec. 57.. 1967. K. X. G.. M. Hamamoto. see: (a) Muller. H. ¨ ¨ ¨ Luning. H. Tetrahedron: Asymmetry 2000. Peterson. Chem. Y.-L.. 39. P.. 31. Gorobets. Y. J. 11-14) for the synthesis of this type of intermediate via the halomethylmetal cyclopropanation reaction. S.. J.. Phillips.. M. 3865. J.. Chaykovsky. D.. M. (d) Duquenne. H. M. See also: (b) Guo. Baba. (c) Guo. Org. Heathcock. S. Y. (j) Oare. Muhlebach. Bull. C. Cardullo. (g) Badiani. A. J.. N. (k) Oare. 171.. A... Q. Bolea. J. Lett. 30. I. Soc. H..-Z. A. B.. K... M. J. 65. E. Y. ¨ Verhe.-Z. Chem. G. Peakman. M. J. Krollpfeiffer... 122.. See also: (b) Davies.. Tetrahedron 1996.... Meynhardt.. Tetrahedron 2000. D. Chem. A. Chem. see: (a) Artaud. In Comprehensive Organic Chemistry. 41.. E.. M. M. 1996. (e) Krause. 1989. J. Pfaltz. E. K. E. K. F. Merino. Tetrahedron Lett. Hu. 4. Kim... For selected examples. Quirion. p 1121. 4273. (j) Escribano.. ` Nacci. 1993. 1998. 2035. H. Lizunova. M. T. 1998. 1975.. Chem. L. Barton. Takeuchi. 771. S. T. J. 453.. Russ. ´ (a) Caine. Conjugate Addition Reactions in Organic Synthesis. Org. C. Feducovich. Tetrahedron: Asymmetry 1995. Soc. E.. S.... D.. D. Shimamoto. 103. N. D. Lopez. L... (b) Yanovskaya.. K. W. W. Chen. Xia. K. Y. Int. Fernandez. J. Seneci. C. N. 2003. See also: (b) Li. M. Acta Chem. 1993. 3275. P.. N. J. (f) Elinson. Soc. Pedregal. Chapter 9. C. (c) Doyle. Chem. A. ´ ´ ´ Y. Perkin Trans. 11. Tang. Condon-Gueugnot.. 2051. N.-C. 8099.. Hassila. 1181. Townsend. 333. V.. Fox. 54. For selected examples. M.. Olessova... Pergamon: Oxford. 50. 1 2000.X. (d) Gololobov. Yamashita. Hu. 31. Fallon. S. M. Taylor. J. 65. Worthington. L. Perkin Trans. C. Matsuda. J. Lysenko.... 1986. Org.. 112. Semenov. J.. E. see: (a) Huang. 47. Pflatz. Org. 1950. Ye.. Commun.. Chem. K.. Lett. E. Taylor. ¨ (b) Sibi. R. Chem. Org. Liao.. J. 1988. 3207.. 61. 15. Chem. F. T. M. 4343... S. A.. For the use of this strategy for the construction of the cyclopropane unit in the synthesis of bicyclohumulenone. K. Chem. K. A. Ceschi. S. (e) Li. Chem. 54. T. Manyem. (b) Moore. Doan. Wick. Hanson.-L. R. Org.. Shi. 2000. K. 1989. O. (g) Leonard. Serafino. 31. Org. 675. M. Phillips.. 7.. Chen.. Soc. J. Tetrahedron 1998. H. D. 1319. 1993. (a) Doyle. Nikishin. S. Y. Bull. 2151. Huang.. P. 1962.. Lloyd-Jones. Med. P. D. Sulfur Ylides. Liu. C.. Paugam. G.. S. Y.. (e) Koskinen. Munoz. C. H. For a review of these reagents. For related examples. S. Heathcock. K. P. Murray. Soc. F. (a) See ref 207. 879. 2001. G. 1975. R. Chem.. 343. P. 61. M. M. D.. 1996. Yu. P. M. Tetrahedron Lett. Farina. Chem. H. Aggarwal. Glass.. N. H. Eur. T. J. Munoz... L. N.. C. Synlett 1994. Synlett 1996.. see: (a) Krause. P. Tetrahedron Lett. Inoue. Starikova. H.. Grazier.. (c) Yamanoi. L. S. Chem. K..Stereoselective Cyclopropanation Reactions C. 154. 1 2000. In Comprehensive Asymmetric Catalysis.. 87. 3063. (b) Valeev.. 43. Chem. Springer-Verlag: Berlin. Sinay. 58. J. 8501. R. 2001. Org. (a) Davies. 1373. Ohfune.. Thielmann. M. M. 90. Chem.. Thielmann. See also: (b) Shen.. S. J. de A. 1962. Sieser. 2000. Yamasaki. Org. P. (b) Shimamoto. 1994. J. W. 30. See also: (c) Koskinen. Org. P. (d) Koskinen. Tiekink. V. Y. Jubault.. Bojilova. Krauss. See also: (d) Doyle. V. A. E. A. Nesterov. Jacobsen. H.. V. 1999. See Table 3 (entries 8. Med. S. see: (a) Huang. In Comprehensive Asymmetric Catalysis.-P. D. C.. 8977. Gustafsson. Perkin Trans. 2000. 1667. 41. E. J. 323. 53. 20. 19. ¨ Peschke. ˜ Matias... Commun. (c) Johnson. Walsh.. D. M. Taylor.. Synth. T. Am. T. J. Chem. Z. Sitter. (a) Corey. 1996. Feasson. Shen. I. Catal.. H. P. S.. 37. Chim. P. Heterocycl.. 3967.. F. Commun. C. Gani. Chem. Kim.. A.. Q.. Z.... Chan. Tetrahedron 2001. Gougoutas. J. Q.-X.. R. J. Y. (a) Dauben. Lett. Nather. G.. X. Nikishin. Top. 1777.. 2002. J. I. Rev.. For similar results with phenyliodonium ylides. Dorso.. 6969. 7662. Eur. Bull. R. V. Stereoelectronic Effects in Organic Chemistry. T.. Chem. 61. 34. Y.. Tetrahedron 1987. H.. J. Chem. Y. Soc. K.. M. T. Feasson. C. K. Churchill. L. N.. Tiekink. Haudrechy.. K. 826.. Russ. 301. Radesca. (c) Corey. 1545. Muller. 375 p. H. Synthesis 1982. (b) Buhl.. see: (a) Lee. M. 2000. M. Tetrahedron 1987. Tetrahedron Lett. A.. (d) Shen. see: (a) Ohfune. A.. 2000. P. Chem. Kierse. Goumain. T. Dombrovskii. Hawkins. Shen. 2157. (b) Tang. Norris. Bioorg. Soc.-X.. Y. J. E. 1985.. E. I. W. 2357. For reviews on stereoselective conjugate addition reactions. C. A. Shi. A.. B.. 64. D. (c) Hakam. S. Atwal. Boldeskul. (b) Jubault. J. (e) Elinson. See also: (a) Valeev. T. Miftakhov. W. T.. E.. C. T... P. V. P. G. 6567. Calvo. 51. (a) Tang. 1999. Chem.. Feasson. 1999. H. D. 46. Eds. Y. D. 1996.... Stanley. 1323.. J. (a) Avery. T. 1998. T. Zhong. Garcia. Sevin. 1993.-Z. P. (e) Rodios. Burton.. A. 9. C. L. D. Stereochem.. Y. L. T. 1. Vol. 1989. Rawlins. Tetrahedron: Asymmetry 1999. Academic Press: New York. Protopopova. Shestopalov. H.. K. F. O. M. V. B. J. 28.. J. R. 52..-C. L. Emerging Synthetic Intermediates. J. Vol. Kalinin. T. 963. (c) Avery. (d) Yamaguchi. N.. 62. V.. Pepper. Huang. F..-X. Y. Top. 1982. A. S.. Watanabe. Am. L. Lan. P. 1990. Keltonic. L. S. Soc. 10. For a review of these reagents.-Z. 83. Synthesis 1980. Am. A. A. H. McGarry. 92. 1993. Rev. 7583. 14767. J. Wee. W.. Peakman. H. K. 4479. Kwan. Huang.. Xia. M. D. Vol. S. M. Catal. Synth. Lupton. B. Org. Int. 2984. Synthesis 1988. M. Shao. Deslongchamps. For other leaving groups. 1. J. Miftakhov. Yanai. J. Tetrahedron Lett. Charmant. Chem. K. T. Jacobsen. M. Ishida. W. Tetrahedron 1995. C. Hu. M. Bestmann. G. Xiang.

12253.. M.. Chem. B.. Org. Tetrahedron Lett. Burgess. Monn. White. W. K. Org. S. 1997. (k) Yamazaki. 41.. Tetrahedron Lett. 1989. Jiang. C. J.. Chim. Cardani. Katekar. 575. 1793.. Shinohara. Lett. W. 1401 and references therein.. 57. E. 6546.. T. 95. 5717. 511. 3727. R. 7418. (b) Garland. Ma. Espada. (344) See also: Mengel. R. S. Soc. Biktimirov. M. Tetrahedron Lett. C. A. Romine. R. Espada. M. G. G. Y.. P. M. 30. 33.. Commun. Williams. Chem. (d) Donaldson... 1993... In Asymmetric Synthesis.-K. Tetrahedron 1990. S. 110. 2385. Yamaguchi. 12.. Org. J. Pedregal.. (332) Krief. 41. J. (341) Kasatkin. 1998. I. Tetrahedron 1989. Soc.. A. B. Chem... Chem. ´ ´ C. 38. M. M. Rogers. D. Wu. 35. 1997.. Inoue. P.. 38. C. 50. Ogasawara. 1976. (b) Williams.. J. 1983. Reischer. A. (319) Krief. 103. C. Jones. Provins. Angew. J. Katoh. 571. 31. Jackson. A. 636. 4589. A. Ueda. W. J. W. C.. 5854. A. A.. Shimizu. see: Meyers. Lewis. 113. J. Commun. Hulce. R. I... (318) Dauben. (b) Entries 4-9: Romo. Nakazawa. 8637. K.. (333) Stork... (b) See also ref 363. 1973. J. C. Synlett 1995. Najera. A. 1968.. (c) Ma. Tetrahedron Lett. Lambertus. Soc. A. Bernardi. 90. J. 4507.. T. C.. Kumar. 2003.. N. 1998.. D. 624.. Wu. Chem. Huizinga.. (d) Johnson. J. Ye. 1339. A. Chapter 7. A. Provins. Pedregal. W. W. 2587. Org. D. M. 39. 63. Najera.... Escale. J. 29. Natchus. (338) (a) Krief. R. see: (b) Pike.. M. S. J. Nakamura. Dumont.. X. Mamai. L. 1993. Calmes.. M. 2001. Devine. (a) Johnson. P. Org. 51. W. (337) (a) Ma. Tetrahedron 1984. 1999. Soc. S. Tsuji. Tetrahedron Lett. 27. A. Tetrahedron Lett. 29.. P. Rev... T. Soc. A.. 1983. S. Galindo. Kahn. (e) Donaldson.. (c) For related examples. Takemoto.. 269. M. G. Chem. 2133. S. L. S.. Org. 1989. see: Romo.. 1989. L. 30. Fegley. Commun. Tetrahedron 2000.. Roel. Morimoto. 3153. F. 92. I.. H. Am. 1983. Tetrahedron 1986.. M.. A. Int. T. S. (g) Johnson. Verbicky. 224. H. (h) Yamazaki. Rev. Org. Am. S. R. 1990. L. I. E.. Yamamoto. Ohkata.... M. A. Synlett 1996. 5891. C. D.. Morrision. 6627. Nower. A.. Kappert.. (a) Entries 1-3: Meyers. Soc. Chem. 3890. P.. J.. Chounan. DC. Tetrahedron Lett. A. Scolastico. B. 23. F. Fleming.. (f) Yamazaki. (d) Hiroi. 2919 and references therein.. Bull. K.. Baker. 3733. N. In ref 1a. 4746. 1970... T. R. R. Yamamoto... Chem. Chem. 7424. Midura. Najera.. Heteroatom. Chem. T. Madalengoitia.. Dai. T. K. I. Schroeck. 45. Y. 1993.. M.. Kumagai. Bernardi. J... W.. 4639. 9009. ´ Chem. Perkin Trans. D.. 4239. D. M. Thomas. R. Chem. ´ ˜ ´ C. Tetrahedron: Asymmetry 1997. A. I. Soc... R. 42. M. Villa.. G. 2002. E. 2509. Chem. 39. H. Schroeck. S. Swenton. 1996. Chinchilla. W.. Chem. Danis. W. Ramaswamy. Fujitomo. C. (e) See also ref 308. S. A. M. L. Soc. 2367. 1983. Theberge. 1990. W. E.. Jefferson. Domınguez. Hubner.. Y. J. P. Pandy. M. Borrelly. J. T. Chem. 130. (339) Cativiela. M.. Dıaz-de-Villegas. M... 2001.. Poli. Ohra. C. Mikolajczyk. R. Tetrahedron Lett. (355) (a) Yamazaki. Chem. Yanase. 7. Romine. Commun. Suppl. Romo. Chem. Chem. ´ A. Chem. J. p 241. A. A. C. Tetrahedron Lett.-C. Arinaga. 43. 4 (317) Dauben. W.. F. Chem. (i) Johnson. Chem. Clardy. K. Takemoto. (b) Domınguez.. 1988... A. Perkin Trans. Soc. Krief... J. 1968. Y. C. Am. 2001. S. Tetrahedron Lett. N. B. Keller... Yamamoto. R. (a) Williams. (g) Yamazaki. M. 65. L. Yamamoto.. Nishida. C. A. R. Tetrahedron Lett... Williams... 24. Lecomte. (326) Hudlicky. Org. 64. 30. Iwata.. Y. (349) (a) Gibson.-C. J. (a) Hiroi.. Weitzberg. Cao. Hamill. J. 30. L. Mandal. J.. Y. Clare. Menendez-Ve´ ´ ´ lazquez. (b) Abellan. (b) Ma. (324) (a) Bruncko. 24. W.. Org. R. Kh. D. S. Ed. S. 21. I. A. 38.. Chem. Chem. 1996. Ed... G. 1992. R. T. C. Chem. Soc. 3025.. H. G.. for example: (a) Semmelhack. L. Chem. A. 1971. S.. Soc. T. (329) Haly. R. R... S. Chem.. Zercher. 1997. 1997. ´ Tetrahedron: Asymmetry 1998. Takahashi. For a review. Jiang. (342) Funaki. C. S.. J. see: (b) Yamazaki. (334) Krief. S. G. Nishii.. Takada. S. C. J. 6594. (h) Johnson. P. M. J. Perkin Trans. J. A. G. Nandi. J. Tetrahedron 1996. C.. Inoue. 1973. Kirchhoff. Kobayashi. R.. Y. Pharm. Ibuka. Prechtl. (350) (a) Yun. Moriguchi. Tetrahedron 1990. 2695. W. Froidbise. K.. 1 2001.. Sinai-Zingde. No. Rev. N. J. E.. T. Peoc’h. 34. 47. (e) Johnson.. H. 1999. 34. G. C. R. 4084. Y. Midura. Org. A. (325) Zhang. 9305. K. T. Janiga. (d) Yamazaki. 1994. (c) Donaldson. Zwanenburg.. Yamabe. Worthington. 1079. Groaning. (336) Ma. (b) Mulzer.. 7652. R. A.. (c) Chinchilla. Tetrahedron Lett. Kumagai. R. Tetrahedron Lett.. Lecomte. R. Tetrahedron Lett. Scolastico. K. R.. Yamabe. J. 1994. J.. J. I. M.. 577. P. 9503. Y. Chakrabarti... (i) Yamazaki. K. 7123. 3951. ¨ ¨ Tetrahedron Lett. Hanna. Slawin. W. J. K. E.. (b) Saberi. A. C. ´ (a) Chinchilla. Soc. R. see: Donaldson. H. T. Coord. Synlett 1991. (322) (a) Domınguez... Arinaga. P... Am. 42. 4915. 7245. Ganesh.. Just. 282.. (354) De Vos. For a review on the use of 1-seleno-2-silylethene. T. S. Soc.. R. S. 1999. 9521. 1. Tetrahedron 1991. Meyers. 3034. J. C. Tetrahedron Lett. G. Chem. A.. Mosher. A.. See refs 9. J. A. S. N. 153. Synlett 1997.. S. S. M. Curr. F. S. J. 2968. J. A. D. M. J. American Chemical Society: Washington. Zwanenburg. W.. Org. Takada. 2000. 164. A. J. 37. 1989.. 378. J. M. Bull. Chem. Tetrahedron Lett. 64. (b) Bruncko. Sugiyama.. 1995. (c) Johnson. 7692. E. R. 1973. Soc. 45. 29. Commun. D. 42. Chem. Chem. W. 2223. Crich. Tetrahedron Lett. 6251. K. M. R. 60. R. Janiga. Ezquerra. J.. K. M. 38. Chem. Sansano. Tetrahedron 1994. T.. 1996. R. C. (b) Hiroi. Crich. Takada. Tetrahedron Lett. J. (348) See. Tetrahedron Lett. Chem. Lockard. M. A. A. Falvello. Hamada. Chem. H. (j) Yamazaki. 1987. A. Suzuri. 1999. (351) For a review on acyclic π-organoiron complexes. 183.. S. 2000. Meyers. D. G.. Chem... W. A.. Miyano. 1986. 95. H. 1995. Org. J. Hamdouchi. 42. (a) Posner... S. (l) Yamazaki. L. 1701. 547. G. Org.. Y. 1936. J. Perkin Trans. M. J. Pasau. Soc.. L. Romo. P. R. W. 36. I. 3061.. J. Chem. K.. 985. R. Chem. (a) Meyers.. Y.. 1999. Chem. Inomota. J. D. 64. M. Tetrahedron: Asymmetry 2000. 1535. Tetrahedron 2001. Chem. Tetrahedron Lett. Jacquier. Chem. Commun.. (356) (357) (358) (359) (360) (361) (362) (363) (364) (365) (366) (367) (368) (369) (370) (371) (372) (373) (374) (375) (376) (377) (378) (379) (380) (381) (382) .. 1745. Org. Sugiyama. Yamabe. J. 1051. I. Chem. 64. M. Seufert. J. D.. (346) Ganesh. S. Yamabe. T.. 141.-X. Hashizume. L. D.. J. (323) Collado. F. Asirvatham.. A. S. (353) For the early work in this area. 1999. 1437. 1995. Tetrahedron Lett. 51.. Ward. Bayley. M.. S.. 2356. Schroeck. A. Matamoros. Tetrahedron Lett. B. 90... (335) (a) Krief. 21. Tetrahedron Lett. 9. S.. S.. Chem.. Chem. 1973. S. C.. Ohkata. M. Doi.. I. Ohra. M. Wieczorek. R.. (327) Hudlicky. M.. Heteroatom. R. Org. Tetrahedron: Asymmetry 1996. (j) Johnson. Soc. 59. Soc. (320) Moher. 56. 1994.. Najera. Krysiak. 1992. Yamabe. Finnegan. Dumont. Tanaka.. A. J. Tetrahedron 1995. M. S.. Organomet. R... Tanigawa. (a) Imanishi. Majzner. Swany. Tolstikov. 1971. Sakamoto. 1992. Fr. 1999. 187. Y. Y. 5303. 1996. 6933.. J. L. W. L. 5041. C.. Org. Am. D. (b) Burgess. W. R.. (a) Kojima. S. Asymmetric Organic Reactions. T. T. Perkin Trans. E. Donaldson. 1991. 5799. 1995. 119. Sarkar. 93. ´ Ezquerra. Tetrahedron Lett. F. Calmes. (e) Yamazaki. Vol. A. see: Morrison. 332. 1988.. G.. Y. Org.. J. B. 46. 8341. M.. 7599. Ramaswamy. J. Zhang. 1988. Chattopadhyaya. 5919. Sanghvi. K.. Yanase. Tetrahedron Lett. (340) Galley... S.. Bull. Soc. 51. Mikolajczyk. C. Y. Falvello. J. A. Yamabe. 63.. 4. Tamura. Luzzio. Chem. M. 285. W. Madalengoitia. Pasau. (352) Godula. 1986.. Little.. 9847. Cao. 4951. see: (a) Alami. 2543. M. Anklam. Tang. T. de Meijere. 11. M. R. Chem. Yamabe. (c) Posner. Radesca. 1973. 1007. A. (b) Posner. G. O. 6265. 1343.. R. J. 99. Tetrahedron Lett.. 2001. Zhou. Tetrahedron Lett. R. P. M. (347) Sarkar. B. C. Shanklin. Chem. Jime ´ ´nez. Prieto. G. 1991. S. J.. Sur. 1 1996. Am. T. Haake. 8796. J. E. Sathe. (c) Takano. A. Org. 33. J. 395.. Dumont. (331) (a) Mulzer. 1983. Frye. Maity. 1996. Cheng. J.. 103. Wallace. J.. 837. (321) (a) Klunder.. L.. S. B. Reiser. Fegley. C. Kitahara. C. C. J. 46. A. Org. Chem. Bharadwaj.. M. 37. 1998... Chem. For reviews of cyclopropyl amino acids. 37.. Meyers. 4. L. 14. K. Es-Sayed. J.. Chem. Z. Chem. Soc.. K. 6584.. Midura.. Soc. Luna... (d) Abellan. M. D. 11. 2000. Chem. W. D.. Ho... 1999. Soc.. 153. S. A.. T. 102. Chem.. H.. H. Daunis. H. M. H. Herr. Mancheno.. S. Meyers. 1992. J. Soc. J. D. Y. S. S. Kojima. 1973.. 1994. J. (b) Johnson. M. Chem.. See also: (b) Krief. T. H. (b) Wu. 2000. Chem. P.. K. and 334. D. Am. Sansano. A.. Swinnen.. (b) Imanishi. Y. 52. P. 687. Moye-Sherman. 95. C. D. For a general review. Garcıa-Granda. Patzel. 1083. Kulak.. 43. M. Mamai. G. 52.. C.1048 Chemical Reviews. Am. Hewkin. Schroeck.. 1 2000. 62. F.. V. J. G. J.. Tetrahedron Lett. 1994. (k) Johnson. Prechtl. Am.... (345) Cebula.. 3039.. D.. 55. 1986. 4641. Am. Chattopadhyaya. 1989. 54. D. H. J. Pharm. Haake. R.. 1993. (343) Yamamoto. Hendricks. J. F. S. P. B. 18. Ramaswamy.. Amputch. J. M.. 95.. 37. C. H. 57. 1343. 114.. (b) Gibson. W. C. Meyers. W. Pireh. J. 40. Z. 6852. Froidbise.. W. Tetrahedron: Asymmetry 2000. (330) See also: Yannopoulos. Chem. Tetrahedron Lett. 7447. Synlett 1994. Am.. Pedregal. (328) (a) Wu. 43... E. Ezquerra. Najera. Soc. Tanaka. R. Chem. D. 5. Kataoka. Org. C. Chem.. J. 22. Tetrahedron 1989. Academic Press: New York. J. Tetrahedron Lett. K. Clegg. Schroeck. Anderson. Imanishi. Cun-Heng. Org. C. J. G. R. O. Am. S. Lebel et al. Chem. 116.. 1998. 1999. Gil.-Q. Donaldson. Galindo. A. E. Kappert. J. (f) Johnson. 1992. R.. C. Am. Iwata. Soc. J. J... P. 5591. A. C.. Chem. Y. Hulshof. J. A. Chem.. Angew... M. P.. K. D.. 1993. T.. Y. Rev. Soc. W. M. R. Prieto. C. L. 857. ´ C. S. 40.. 1 1993. J. Am. Chem. Y. T. 1992. M. See also: (c) Yamazaki. M. A. J. S. 6307. L. 1870. Soc. E. Org. 57. (b) Takagi. 2169. (b) Krief.. J. 1980. 4287. 2 2001. Yang. Sanghvi. J. R.. K.. Y. 66.. 1191. 1109.. G.. K.. 58. Sweigart. Chem.. W. Tetrahedron Lett. J... 1995.. 8. Synlett 1999. 1988.

. 1 1999. S.. Yang. Tetrahedron Lett. R. F. 9. Yang. Hynd. Chem. Williams. Wang. Y. Shimizu. J. Takeda. Jakovac. Tetrahedron Lett.. ´ (e) Barluenga. 777. Santiago-Garcıa. 2001. J.-A. M. Lett. 1570.. ´ ´ ´ S. (e) Walser. Shinohara. Blanco. 6311. Helv. J. Tomas. R. J.. C. R. T. 1785.. 1995. Mikulas. 2537 (Additions & Corrections). 9847. Hassner. (b) Laumen.. Lett. 1997.. T... (c) Barluenga. T. Toru. 1733. J. 1976. H. Pyne.. R. L.. T. R. 3403. 751. Angew. Maiorana. R.. de Meijere. B. (c) Brookhart. D... 7591. G.. 67. Gomtsyan. J.. Org. D.. F. Ed. D. Rev. Jaeschke. K. Chem. Pale. (c) Fruhauf. Synth. W.. D. 961. J.. C. T.. Chem. Flood. Q.. D. (a) Theys. D.. (a) Hanessian.. ´ For the use of other metals. 5260. W. Bull. (a) Guerchais.. Benkouider. B. K. I. 9572. Eur. (d) Barluenga. J. Grubisha. Dai. 6. G.. J.. G. 118. S. J.. R. Golebiowski. T.. (b) Barnier. C. (b) Ruck¨ Braun. Chem.. 47... F. M. 1984. 1371. T. Z. Chem. 1563. 314. N. 939. K. 117. Brown. F. Timmers. Nicolas. 60. 62... J.. Sasaki... ´ (411) (412) (413) (383) (384) (385) (386) (387) (388) (389) (390) (414) (415) (416) (417) (418) (419) (420) (391) (392) (393) (394) (421) (422) (395) (396) (397) (398) (399) (400) (423) (424) (425) (426) (427) (401) (402) (403) (404) (405) (406) (407) (428) (429) (430) (408) (431) (409) (410) (432) . T. Angew. 4893... Ueno. J. Org. D. Morrison. Eur. G. S. (a) Vargas.. 65. M. I.. C. Nakamura. T.... 1987. M. 2000. A.. 65. 1995. 1155. M. 1999. Org. S. Pure Appl.-D. J. 189. Wild.. T. Y. L. P. J. 7.-Q. Amrhein.. 453. Nakayama. 1999. 3819. P.. 1534.. (a) Brookhart. Hossain. 2001. Soc. Am. Tetrahedron Lett. V. A. 111. S. Allen. 1998. R.. Chem. Chem. 5113. Dordick. 60. 72. Hosseinzadeh. Hossain. Reissig. Manzocchi. Shibuya. Soc. For a review on carbolithiation. (c) Du. (a) Aggarwal.. J. R. Lett. J. Commun. B.-X. Chemical Reviews.. S. J.. R. P. 2001. 2. C. Feasson. 8960. Tetrahedron Lett. Durand-Reville. A.. Griffin. Hossain. Endo. S. Witt.. Shiro. J. In Asymmetric Synthesis. T. Gomtsyan. M. M. 9. A. W. Ohkata. J. Rao. M. 131. F. J. Nakamura. Organometallics 1989.U. 1997. Liu.-P. Hossain. M. A.. Ferrara. R. B. Fieldhouse. Marek. 1985. Chem. M. Org. Hossain... Chim.. 1989. Huang. Shioiri. Kitazume. J. 3267... Tetrahedron Lett. 42. J. Theys. Soc... Tetrahedron 1998. Organomet. (b) Majumdar. 41. H. Chem. Husk. Du.. Morikawa. Mori. 271. For selected examples. (e) Itoh. F. 15. 58. ´ Chem. 173. Tamm. S. M.. H. Toru. (d) Yadav. (a) Guibe-Jampel. J. (b) Barluenga. Hossain. Chem. T. M. Fieldhouse. Florez. Bennett. 2000. 4. Q. Takemoto. Phosphorus. J. 1997. Dong. ´ H. 2000. Org. G. J.-W. Andreotti. A... (a) Solladie-Cavallo. (e) Martın-Vaca. M. Soc. F. 1996. M.. Fresse. Pale. 40. 3077. L.. 1995. H. Neil. Blanco.. H. O. D.. C. 10494. Chem. Bennett. M. Schneider. Tetrahedron Lett. J. M. 2000.. Bubert. p 227. (a) Barluenga. Vissiere... Int. (b) Hanessian. Rubio. S. E. 1974. Y. 1994. 1333. 2203. 2000. Tetrahedron 2000. H. S. Synlett 2002. 2. (g) Pietruszka.. Brennan.. 66. Rao.. 701. Perkin Trans.. (b) Solladie-Cavallo. Am. W.. Herse. J. Jones. D. Chem... V. Acta 1994.. ´ Eur. (c) Grandjean. (g) Fujiwara. B.. K. G. 87.. 4 1049 M. S. Williams. T.. Quirion.. Aggarwal. Vol. Acc. A. C. J. No.. J. Normant. G. 4215. Z... see: (a) Herndon.. Am. Sulfur Silicon Relat. Wang. 4. W. M. M.. J. K. B. (b) Kirihara. (d) Herndon. V. Chem. Hossain. 1149.. Soc. Cantin... Vol.. Perkin Trans. Kayo. Chem.. D. P. A. Org. M. T. G. 405. E.. In Advances in Asymmetric Synthesis. 1572. Soc.. Tetrahedron: Asymmetry 1998. K. 113. E. Shibuya. (d) Sabbioni.. 40. Chem... V. (d) Ferreira. (b) Harvey. 119. Y. 54. 1996. (f) Rusconi di Lugano.. A. P. Takeda. 74. 17.. 1991. 3505. Nakamura. 8. Org. 2349. M. Chem... Org. Tetrahedron Lett. Y. K. Smith. 1103. A. Watanabe. GuibeJampel. J... H. DiSanti.. V. 523. Hirokami... J. L.. Thompson. Am. (d) Barloy-Da Silva. 8099. 52.. Am. (d) Soderberg. N. M. 5. T. S. Trabanco. White. Nakayama. (g) Seki. Lopez. R. Soc. Ber. Org. Chim. H. Chem. 1215. Organometallics 1983. 2488. B. D. Chem. 114. 35. S. Jaenicke. 9. Walker. J. E. Chem.. D. Tetrahedron Lett. Engel. J. J. Chem. Am. K. Synthesis 1998. Aggarwal. Goldman. 411. 423. Chem. Eur. Diepvohuule. Marek. V. Uemura. E.. Org. J.. K. K... Renold.. 30.. M. P. J. Tetrahedron Lett..-D. 1985. Am. Chem. J.. H. Inorg.. C. W. Miles. T. T. Trabanco.. C. H. D. Baldoli. 535.. Chem. Grisenti. Bioorg. 8. Chem. Garcia-Granda... 67.. Q. Tetrahedron 1996. P. H. S. Commun. Perkin Trans. Rev. For related examples of the use of chiral phosphonamides under electrochemical conditions. 1071.. Am. Synth. Kawasaki.. 63. 2000. Tomas. Le Goffic.. H.. see: (l) Johnson. (b) Brookhart.. Takuwa. Johnson. Gawronska.-Z. Chuche. Tanaka. V. 223. K. S. Scott.. J. J. D. Am. S.. Soc. P. Boland. J. 122. Vol. Marek.. 61. Jones. B. Michaelson. S. C. Yamazaki. 5223. Tetrahedron Lett. Hammer. Commun. Org. Y.. Barluenga. 1984. R. 2001. T. Tetrahedron: Asymmetry 1992. Mayer. A. W. Yang. E. (b) Wang. R. Chem. (b) Aggarwal. E.. (c) Goumain. 103. 67.. 927.. 36. H. Ngoka. Int. (a) Mohr. T. Hu. H.. Reissig... B. Organomet.. Acta 1991.. Chem. 2001. V. C. 1998. Eds. Tetrahedron Lett. W. Commun. 617. Soc.-C. (e) Hoye.. C. K. Feasson. Spey.. Chem. M... Rev. R.. Chem.Stereoselective Cyclopropanation Reactions For reviews on the use of sulfoximines. 2070. Chem.. 22. Enan´ tiomer 1999. J. F. U. K.. 1973.. 1385. ¨ Coord. Chem. Organometallics 1992. Krusell.. Tetrahedron Lett. Fr. T. See also: (c) Beruben. L. 1190. 803. Heinemann. 124. 124. Chem. F. Rehberg.. C. 665. Barnier. O. Y.. Vielhauer. 1991.. Soc. S. E. Krebs.. W. A. (c) Csuk. 55. Goumain. K. M. J.. ´ ´ Soc. 23. C. 41. Haga. C. H. Jones.. 4046. Chem. Lok. Reiser. Ed. W.. A. D. Chem. I. 41. 1999. Cabrele. Kojima. R. 1941. Durand-Reville. T. J. 2723. R. Med. C. 4659. J. P. 1423. M. 42. 1986. M. Xia. Chem.. P. J. Tumer. Tetrahedron: Asymmetry 1999.. Soc. Tetrahedron 1991. Rev. Chem. H. 1983. V. M... see: (a) Fischer. H. 1995.. 7. (c) Buchert.. W. Schabel.. Organometallics 1990. Fang. M. (a) Itoh. Hofmann. F. 1991. J. 125.. E. J. (d) Theys. Odaira. Rousseau. Liu. Lund. 1992. J. N. L. J. 858.. 4881. 1996. (a) Brookhart. S... A. Goodbrand. 40.. J. Chem. Jubault. 567. von Scholz. R. B. H. R. Andreotti. A. A. M.. Liu.. F. Soc. 5225. Chem. P. J.. (b) Vargas. J. J. J. Elem. Gawronski. Kakuda. Wilhelm. 1990. 38. B.. (b) Brookhart. see: Marinozzi. Andreotti. W. ´ 1989. Soc. Ferraboschi. Q.. S. R.. 10.. (g) Hoye. 2.. 7. F. 7. W. G.. 3... 41. Pedregal.. 1999. Morikawa. Chem. Reddy. Hanessian. Yadav. Synthesis 1999. S.. 2002..-I. V. Oulyadi. S. 52.. E. Y. J. Studabaker. Y. 1981. 2001. Am. 1991.. F. V. 283. D. J. 71. For another use of this methodology. Porcelloni. Tetrahedron Lett. Chem. B. Jones. (i) Miki. Vargas. T. R.. Ed. S. Monteiro. 7749. 4565. Org. Alonso. J. Johnson.. Blanco. see: Marek. 1 2001. S. CT. Hultin.. Licandro. J. 1992. Bidell.. Tang. Soc. S.. 1998. (f) Fujiwara. S. 913. P. J. Shinohara. M. J. H.. 1999. (b) Schneider. G. A. Tetrahedron 1999. 2001. 96. Manzotti. Rev. Braun. M. A. (b) Taguchi. A. Chem. J. Chem. A. Abdelrahman. Gorish. S.. Boland. 2003. T.. P. Org. 1433. Waespesarcevic. 2458. 394. 5. Org. Chem. E. 104. I. Tetrahedron Lett... Roy. J.... V. 1996. Int. 1999. Audouin. N. Reddy. Tetrahedron Lett. Normant. Yamazaki... Florez. Platzer. M.. Commun. 1995. 341. M. 54.-I. Am.. 5905. 8. C. (a) Hanessian. A.-X. Org. 2073. Tetrahedron: Asymmetry 1996.. 32. R. Eur.. C. 1998.. K. J. Soc. Andreotti. Tetrahedron Lett. 1 2000. Chem. Organometallics 1990. see: (a) Goumain. Tetrahedron 1998. 206-207.. Timmers. Sasaki. Furutani. 4363. 1910. (f) Tsuji. G. Tetrahedron: Asymmetry 1994. Organometallics 1998. J. 1994. 1997. J.. K. 2000. Synlett 1999.. Wang. Suarez-Sobrino. Kondo. 727. Hynd. Chem. Onishi.. (b) Santaniello. D. Pietzsch. Org.. ´ ´ Rudler. V. 10393. S. 26. M. D. L. Hegedus. T. 3113. D.. A. R. 3971. J. 1689. Chim. D. 2001. Chem... J. Rudler. Lopez. Nanda. J. Honicke. H.. R. Vyvyan. 3769. D. Chim. ¨ ¨ Chem. Jones. Emoto. 113. 4771 (b) Wienand. Riguet... Mazon. J. S. A. Hossain. K. 783. T.. (a) Santaniello. S. 1998. A. A. (b) Barnier. Organometallics 1989. Chem. V. Feasson. R.. Grubisha. H. K. P. Blanco. F. M. (f) Seki.. K. G.. Brunner. B. (h) Papagni. P. 2001. (d) Martın-Vaca. 41.. W. A. B.. S. Chem. Isarno.. Chem. A. Org. 3. C.. Odaira. Rev. K. 903... M. J. R. B. Mori. 1997. C. J. 42. 8145. Chem. J.. (c) Harvey. Chem. Chem.. Shioiri. F. 56.. 27. F. D. 1997. Soc. Fujitomo. 1995. 1999.. Fernan´ dez-Acebes.. Chem. 26. 370. Morisson. 1 1999. Tetrahedron Lett. 1992. 2055.. Res. (h) Beumer. A.. ´ ` Organomet.. H. (a) Norsikian.. M. Tamm. 237. Arai. Academic Press: New York. (m) Barbachyn. 10. Suriano. Arai. Fliche. Ohe. 2337.. G. Lett. Inorg. P. Mitsukura. 32. Synlett 1997. S. Jai Press Inc. Helv. Sakata. J. M.. (a) Brookhart. M. A.. I. 6501. G. Buck... B.. C. R. Y. L. F. 2291. M. Jubault... Trabanco. (e) Guerchais. Takahata. 40.: Greenwich. J. Soc. Quirion. Audouin. 1995. J. Perkin Trans. 105. 64.-C. J... C.. Organomet. 3133. Tetrahedron: Asymmetry 1999. A. 30. 2432. Fernandez-Acebes. Volle. R. Prowse. Westermann. 9125. 1992. 2002. Yamabe. J.. Tetrahedron Lett. (b) Harvey. Chem.. R. J. S... Cantin. 2002. A. F. Skelton. M.. Jubault. J. 97..-C. P. A. D. Ishida. Feng. (a) Morisson.. 3119. S. S. 1997. I. A. S. Nishino.. W. (c) Wang. A. L. J. P. 2000. Chem. H. Tetrahedron Lett. 1987. 159. Seebach. Tucker. 2000. D. Hatano. Lopez-Pelegrin. T... Davison. Commun. B. Chem. F. 449. M. 2002.. (a) Kasel.U. Klein. J. A. 95. 119. Ferraboschi. 2001. 60.. Am. T. A.. Theil.. 1994. Florez. S. K. (e) Hertweck. 3797... M. 1989. 2000. I... 1982.. Normant. D. T. Jones.. C.. R. A. 37. 5131. D. Tetrahedron: Asymmetry 1997. (b) Duquenne. Chem. (c) Schoffers.. J. 1993... M. 7057... Gomtsyan. L. Rousseau. Chem. Quirion. Devasthale. (f) Hoye. Sigano.. 1107. 2357. M. T.. (b) Hanessian. M. ´ (a) Taguchi. Acta 1983. Poisson. J. Ye. 11. Inorg. 2044. G. 4184. Ed. A. 95-6. 92. M. Chem.. Tetrahedron Lett. Chem. Mattison. 4723. Soc. 123. J. Soc. S. Pellicciari. Lett. J. 6721. P. C. S. Angew. 63. J. K.. 3369. (c) Schotten.. L. 2501. Chem. Smith. Soc.

. 54. Ed.. E.. T. H. Tetrahedron: Asymmetry 1995. T. Org. 290. 3369. Fujii. H. Mittra. W. J. J.. Handa. T. 123. M.. 1999. (e) Krief. H. L.. Hell. K. 11213. D. see: (a) Toke. Ohba. 653. Funaki. Synlett 1994. (446) (a) Ramaswamy. 67. (d) Fujiwara. (c) Taylor. U. D.. Tsuchida. C. (455) (a) Barnes. (g) Paetow. Org. 3425. J.. Evrard. Am. H. Ono. J. Iwayama.. 39. Aitken. A. Tsujino. R. Pedersoli. Grandl.. 1999. S. D. Freifeld. 56. 2923. H... M... 1999. Takacs. T... 3143. Schmitt... D.. (i) Abe. A. Petneha ´ ´zy. 33. Minami... Hughes.. de Meijere. Y. 2002...1050 Chemical Reviews. A. (s) Aoyama. (b) Furuta. T. Synlett 1995. 599. V. Hobe. Doi. Am. Chem. T. D. (b) Pajouhesh. T. Y. E. Vol... Furuta.. 1023. M.. Org. R.. F.. H. Tetrahedron Lett. Surleraux. 12. 41. R. Y. (b) Wells. Tanaka. J.. (d) Zindel. S. Matsuura. 197. T. W. Org. Y. Knox. Carboni. J. Kawasaki.. D. 38. 1.. 9645. C.. Med. 641. (b) Chu-Moyer. Yoshioka. Fujiwara. R.. L. 61. Nakai. K.. 3233. Tetrahedron: ´ ´ ´ ´ ´ Asymmetry 2001. 1991.... B. 11. Jin. 7123. Husson. V. S. A. T.. N. see: Guijarro. J. 31.. J.. J. 6. Aoki. Y. C.. Collet. Badaoui. Matveeva. Konig. A. 57. Bauchat.. Commun. P. Schomenauer.. (438) Pirrung. Iwanaga.. 1996. Lett. B. Suzuki. 2001. 116.. W. S. 753. No. Chem.. Tetrahedron Lett... Arison. N. Y.. (b) Lambs. J. T. H. 3381.. C. Tetrahedron 1993. For related examples.. Chem.. Funaki. (n) Nelson. Kovesdi. Danion.. J. Dirat. (c) Onishi. Y. Fujii. S. Hobe. J.. M. 1034. Furukawa. C. Chem. 1993.. Takeda. D. 34.. S.. J.-C. (a) Krief. Imoto. Chen. 6344. see: Cativiela. S... Y. M. K. 3343. 4088. J. J. 1998.. 415. J. 2157. Davidson. Koroleva. J. K.. P. L. (b) Lim.. Cativiela.. ¨ C. L. S. 47.. Pon. D. D. T.. Baldwin. Y. Chem. (b) Sugawara. 9435. Chem. 1993. Adlington. Le Corre.. L. Provins. 1015. Org. N. 34. F. 2814. J. J. W. H. M. O. J.. (b) Langer. Matsumoto.. (c) Fujiwara. M. J. Schwartz. D. 51. Hedrick. (d) Krief. J.. Chem. M. S. Hanzawa. see: (a) Chu-Moyer. 644. 2583. Tsuji. D. A. Perkin Trans. T. G. S. Chem. De Kimpe. Suzuki. Stark. 2964. Tetrahedron: Asymmetry 1995. Synlett 1999. (d) Sato. A. Org.. Tsubouchi. (a) Taylor. Yoshimoto. Vereczkey. G. For a related example. Scholtz. 65. W. Jaszay... J. (e) Gooding. 1994. Synlett 1998.. P. N. S. Soc. 2001. 48. 33. 1981. Taguchi. 8015. 1191 and references therein. Commun.. 2000. 66.. P. Grehl. N. Heterocycles 1998. Yoshida.. T.. Levizzani.. S. Tetrahedron: Asymmetry ´ ´ 2000. (p) Boger. ¨ Hoppe. (a) Tanaka. Chem. Tabuchi.. 3149. 691.... Dumont. 2001.. Soc. J.. 2000. 3387. (d) Shuto. K. Y. 36.. Am. C. Bittman. Chim. C. 1994. For a related example. 1993. R. T.. H. H. Gentile. R. Wanner. E. (d) Benedetti. 1999. G. Tetrahedron Lett. Hedrick. M. P... K. Bonnaud. E. Ed. T.. (c) Sagnard. 1301 and references therein. J.. Carboni. (c) Achmatowicz. N. Russell. E. S.. Mendoza. 1145. 1 1999.. 9715. M. Chem. M. I. K.. D.. Tamao.. (b) Aitken. J. see: (a) Miyaoka. 391. J. K. K. 1996. Kuzuhara. N. 7006.. (q) Boger. 3. Eur. (d) Achatz. 2002. 22. H. Danishefsky. 1990.. Chem. K. Yamamoto. Handa. 5931. Chem. L. Komine. Synthesis 1978. Hase. J. 4 (433) For reviews. M. H. Chem. P. (b) Byun. K. 8333. (a) Nagasawa. 9382. (442) For a related example. 1993. M. Sharpless. D. O. (435) For selected total synthesis using such a strategy. Soc. L. K.. L.. 69.. J.. 8845. A. 1257.. P. O.. 66.. N. Tamao. Chem. Org.. Bull... Int. (b) Taylor. A. 1982. Chem. D.. Commun. (e) Debache... 39. U.. 619.. K. Mioskowski. A. M. H. R. O.. (444) (a) Burgess.. Ho. Chen. 1717. Mikami.. Stambach. V. Tetrahedron Lett. Ham.. see: Harada.. see: (a) Guillaume. ´ Brunette. L. K. 2000. 1249. Soc. Coll.. Yan. (c) Shuto.. R. Saski. E. Kitagawa.. I.. Chiaroni. Org. Tetrahedron Lett. Zeeck. D. T. (449) Quinkert. 544. K. T. D. Chem. 34. Gotoh. 110. L. A... 278. J. 121. K. A. Chem. M.. Org. C.. 3903. M. M. M. Yuan. Kitagawa. S. S. Am.. H.. 1967. (b) Burgess.. 33. D. Maeda.. R..3-diols. 9167.. (b) Shuto. S. H. K. Onoguchi. Adam. E.. Araki. Z.. Yus. J. ¨ 1994. Hill. 1992... 48. K.. Otera. (c) Krief. (436) For the hydrozirconation of vinyl epoxides. Jiang.. Klyuev. F. R. Chem. Hase.. Soc.. 41. I. 1990.. Engelhardt. Chem. M. 1988. A.. Angew. Provins. Swinnen. Angew. Rockenbauer. Maeda. J. Brumbousquet. Bull. Hercouet. H. Hitzemann. 2000. S. Synth. P. ¨ A. 1999. M. G. K... Higashi. T. (b) Krief. Tetrahedron Lett. 2001. 32. C. ´ Z. Searcey. 4537. Vol. Evano.. 1992. Chem. K. Okunishi. Chim. J. M. E. (b) Kende. Ollivier. (j) Donate. ¨ (450) (a) Misumi. (451) (a) Kende. A. Nakagawa. 57.. N. (452) Trost.. Am.. 2000. 56. J. O... A. R. S. 1995. Eur. M. Q. Ho. R.. 1216. 6443. S. 3604. 58. T. L. 50. Kamiyama. J. Berti. K. Soc. 1984. F. G. Suzuki. K.. Sawada. Wicha. T. 7185. Ohta. 7405. 4.. Chem. Chen... Engelhardt. 8301. M. R. Matsuda. K. S. J. J. J. Guittet. Shigemoto. D. (f) ¨ Krief. Heterocycles 2002. Cheng. M. Tetrahedron: Asymmetry 1993..-I. Yuan. Wicha. W. L. M. Org. J. 6807.. Reinhold. Soc.. (c) Tanaka. Tetrahedron 1992. 57. J. Kowase. H. 1946. W. Hatsuyama. Clementis. K. Dıaz-de-Villegas.. M. A. Tetrahedron Lett. Takeuchi. Tetrahedron Lett. VIII. (a) Majewski. (434) (a) Mouzin. 499. N. Guillaume. Chem.. G. J. H.. 1999.. Bessieres. A. 1992.. Weber.. J.. Tetrahedron Lett. 35. C. (e) Hanessian. Royer. K.. Sekiyama. M. 101. 1992. Y. 761. (441) (a) Shuto. 1669. 841.. P. Tetrahedron Lett. M. S. J.. 1999. E. 49. Chem. G. J. (d) Baldwin. Synthesis 1993. M. Chem. J. Wolkenberg. Chem. T.. 915. (448) For selected examples. Bui... Kabat.... Minami. H. J. (g) Krief. Boyce. S. J. Pajouhesh. H. N. 11. D. K. 116.-P. Jin. A. 2001. H.. Chem. A. 12. 1995. 1988. J. K. 40.. Chem. Int. Iwanaga. (f) Corey. 8731. Grishakov. Chem.. Yoshii. Y.. N. 304. 645. followed by ring formation leading to cyclopropylmethanol derivatives. T. Kanai. Ho. H. Jung. G. 683 (g) Yamashita. Yuan. 1. C. Med. 5131.. J. 531. B. Mendoza. T. 40. B.. Soc. P. Y. (b) Kawachi. Galvez. 739. Eur. G.. (e) Militzer.-I. B.. 29. 1999.. H. Ueno. A. M. T. (b) Nagasawa. Toke. Hain.. Zhdanova. 239. Euzenat. A. Hoffmann. Kaji. Suzuki. Y. Tsuji. Chem. Tetrahedron: Asymmetry 1999.. 4101. Matsuzawa. J. 103. M. (a) Kawachi. Am. Biellmann.. p 141. G. T. M.. K. S.-D. 112. D. (f) Hanessian. Soc. Phimmanao. Dobashi. Bebbington. 289.. 1998. 10201. K. M. M. A. 4107.. N. Perkin Trans.... 2001. Z.. R.. H. M. Synthesis 1995.. Matsuda. Husson.. 2002. Chem. Nakazawa. Tetrahedron: Asymmetry 2000. Q. S. J. J... Chem. H. F.. Chem. Chem. Hughes.. G. Chem.. M... A. Dıaz-de-Villegas. 503. C. Nakamura. Org. J. J. Gueck. 123. T. Burgess. 2002. F. 1992. T. E. H.. K.. 3423. F.. 1996. Schulte.. Tetrahedron Lett. Jr. J.. E. Kotthaus.. Liebigs Ann. P. 1992. Am. C. 1993. J. 2001. 1992. F. 1996.. A. A. 72. Parkanyi. Tetrahedron Lett. 2003. Y... Soc. Taguchi. Doris. Chem.. (h) Agami. Lett. L.. M. Tetrahedron Lett. L. Krajewski. R. K. M..-S.. (b) Finta.. N... C. G. Risaliti. M. J. 43. Ohmura.. Chem. 1992. (b) Tanaka.. K. L. (440) Kitaori. I. H.. T. Vergne. Storer.. A. Acta 1989. Huybrechts. 2727. D... L. 3767. Noguchi. (e) Kazuta. W. A. (454) For selected examples.. Soc. Dumont. 55.. (c) Gaucher. Harayama. 49. Am. T. Inoue. Repic. M. S. 107. 1057. Taguchi.. Y.. 2001. A. K.. D. Tetrahedron Lett. J.. Y. R. Chem. Uneyama. Tetrahedron Lett. Tetrahedron Lett. Org.. Tetrahedron 1995. Soc. Declercq. Y. Am.. A. see: (a) Aitken. Procter. Ghelfi. G. Int. 5677. J. Burgess. Tehrani. Org. 62. J. Balint. Org... 2000. Hase. A.. H. Yamamoto. K. Am. (447) For a review.. 131. 42.. Matsuda. Dobashi. Singh. F. M. Soc.. T. see: (a) Sugawara. Cohen. Wiley & Sons: New York. T. C. G. Onoguchi. 11445. 49. 41. K. W.. S. D. Tetrahedron Lett. Odaira. Tetrahedron Lett. Yamada.. L. Y. B. A. Org. see: (a) Taber. 31. 1994. (h) Dechoux. Org. V. 2000. Chem. Yoshii. (456) (457) (458) (459) (460) (461) (462) (463) (464) (465) (466) (467) (468) CR010007E .. Bull. 110. M.. Tetrahedron Lett. F. Tetrahedron 2000. Ke. A. Constantino. Soc... see: (a) Singh. (c) Moye-Sherman.. 1997. Shuto... B. Otte. 122. A. (d) Hercouet. S. K. K. L. Chem. Matsuda. Ono. Chem. (o) Badorrey.. M.. M. Synlett 1995. 412. Soc. 1996. Agami. Chem.. Brase. Chem.. 6. Am. (c) Dechoux.. B. B.. Med. A. Santillan. S. Synlett 1995. See also: (b) Kabar. Chem. 65.. ¨ Lebel et al... Angew.. Frohlich. 11.. T. J.. Stiasny. Husson. 1891. 1 1994. 67. I.. F... Org. Synlett 1998. Prasad. Ebel. Murai. 2682. Y. Organic Syntheses. J. V. T. Bui. Yamasihita. T. Durner.. (c) Nagasawa. Dunlap. Lett. H. 1917. 1991. B. 4844. Russ. J. 51. Funaki. Odaira. 1997. Snieckus. M. 7538. (k) Forti. J. Soc. De Meijere. Soc. J. Tourwe. Sasaki. R. Puls. H. Z. Ono. Y. Chem. 1984. I. S. Am. Jpn. Lett. Mukai.. Soc. J. Org. Schmitt. Danishefsky. Tetrahedron 1998. Suzuki. Kovats... Ropson. Coppens. Y.. Roberts. K.. K. 1287 and references therein. (t) Krasnov. J. Ono. S.. Y. (453) For other examples. Baier. A. M. 40. A. Synlett 1995. H. 39. A. (f) Le Corre. Org. Tetrahedron Lett. Nagatsuka. R. Ochiai.. A. J. O. H. Matsuda. J. Chem. T. Plouvier. M. A. 1998.. Takeda.. 2. T. Paquette. Synlett 2001. 42. P. Irie.. Bayrakdarian.. Warren. 3507. 1998. (m) Katagiri. (b) Taber.. A. H... S. Tetrahedron Lett. Kamiyama... (r) Boger.. Lim. Lett... 998.. S. 2327. D. 1452... 35. (443) Gao. U. K. Nishi. Tetrahedron 1995. 6527. 1979. A. 41. D. 1990. A. Onoguchi. Chem. Takada. T. S. 6301. Gunzner. J. 151. (e) Takeda.. (439) (a) Burgess. Fr. Synlett 1991.. 1985. S. H. Frank. A. Helv. Dumont. Tetrahedron Lett. J.. E. Couty... T. I. Heterocycles 1998. T. Potier. 37. Synlett 1993. A.. T. (b) Onishi.... S.. (i) Kawana.. Konoike. 120. W. F.. Chem. I. 122. L. 2017. Shimizu. 114. Yoshida. 37..-P. J. S. 36. Riche. (h) Knolker.. Trinks. Chem. Tetra´ hedron: Asymmetry 2000. Eur. Salaun. 1994.. Ono. Hercouet. Y. 2207.. 3666. A. (l) Aelterman. H. 1881. see: Tomooka. 1751. 2000. 601.. Tetrahedron Lett.. H. Suzuki. Cousse. G. ´ 1999. Kashino. Soc. Provins. 2000. S. D.. (437) McClure. Lown. U. A. 2001. I. 10.. S. Chem. Rajcoomar... J. Am... K. Ed. G. Buckle. Pagnoni. Org. J. M. Org. da Silva. (445) For substituted cyclopropanes from 1. Shimane. He. A.. J. 7051. Tetrahedron: Asymmetry 2001.... J.

Sign up to vote on this title
UsefulNot useful