Solutions to Problems Chapter 1 1-1-8: dipolar resonance stecture has aromatic character in both rings and would be expected to inake a major contribution to the overall structure Od -~ Od 5, The “extra” polarity associated with the second resonance structure woud Soaihate 10 the molecular structure but would not be accounted for by standard group dipoles, © TREE ae thee major Factors contibuing to the overall dipole moments: (1) {he o-bond dipole associated withthe C—O and C—N bonds: (2) the w-bona dipole associated with delocalization of wr electrons from the heteroatom to the direction of the overall dipole moment, The AIM charges have been caleulated. electom ON sacions ay os ¢ i te oe ee ond O>N bona a ae Voce | unshared: 30 7008 aes os Aint chargos a09 2 Savas Pons 13.8 . The nitrogen is the most basic atom, Proven 4 Protonation on oxygen preserves the resonance interaction with the nitrogen unshared electeon pair. oH oH CHC. one! Ney NH Protonation on nitrogen limits conjugation to the diene system, Protonation 62.2) preserves a more polar and more stable conjugated iminium system, Protonation on C(3) gives a less favorable cross-conjugated system, ® —~QoOg oof i 4 Protonation on the ring nitrogen preserves conjugation with the exocyclic nitrogen unshared electrons, t i i Nt 4 ‘charge can be delocalized charge is localized on ‘exocyete nitrogen ‘The dipolar resonance structure containing cyclopentadienide and pyridinium tings would be a major resonance contributor. The dipole moments and bond lengths would be indicative. Also, the inter-ting “double bond” would have a reduced rotational barrier, ‘The dipolar oxyeyclopropenium structure contributes to longer C=O bond and lan increased dipole moment, The C=O vibrational frequency should be shifted toward lower Frequency by the partial single-bond character. The compound should have a larger p&, for the protonated foun, reflecting increased electron density at oxygen and aromaie stabilization of the cation9 ° o A- Pr ph pr Sp © There would be a shift in the UV spectrum, the IR C=O stretch, and NMR ‘chemical shifts, reflecting the contribution from a dipolar resonance structure. i ° oe Coe prefer planar geometry because of the resonance stabilization, The barrier to rotation is associated with MO terminology, the orbital with the orbital provides a stabilized Aslocalized orbital. The nonplanar form leads to isolation of the nitrogen ‘unshared pair from the C=O system, Boom — 85 a ah B09 Non, oe So b. The delocalized form is somewhat more polar and is preferentially stabilized in solution, which is consistent with the higher barrier that is observed © Amide resonance is reduced in the aziridine amide because of the strain associated with sp? hybridization at nitrogen, 2, sen] i ‘The bieyelie compound cannot align the unshared nitrogen electron pair with the carbony! group and therefore is less stable than a normal amide. 1-5. a The site of protonation should be oxygen, since it has the highest negative charge density? ® 4 Soha Pons 16. b The site of reaction of «hard nucleophile should be C(t), the carbonyl carbon, 48 it has the most positive charge © A soft nucleophile should prefer the site with the highest LUMO coefficient, {ns phenyl group decreases the LUMO coefficient, whereas an alkyl group imereases it, Reaction would be anticipated atthe alkyl-substituted carbon ATE 08s differences between the benzofb] and benzole] derivatives pera to all hee heteroatoms. The benzo[b] compounds are more stable, more romatie, and te eae thas the benzoe) isomers. This is reflected in both AH, and the HOMO-LUMO gap. Also the greater uniformity ofthe bond orders (2 the benzo[t) isomers indicates they are more aromatic. Furthermov benzenotd ati I losin the benzofb) adders, whereas it increases inthe Bence] adducts and this i reflected in the TS energy and Ai". The onder of Aff" ia in accord with the observed reactivity trend O > NH > 8. Since these dienes {cas electron donors toward the dienophile, the HOMO would be the frontier Grbital. The HOMO energy order, which is NH > S > O, does not accord with the observed reactvi [The assumption of the CH bond energy of 108kcal/nol, which by coincidence cts fame as the HH bond energy, allows the caledlation of the enthalpy ail ofthe energy diffeence resides in the central bond, rather than in eeu adjustments between the propellanes and bicycloalkanes. Let BE, be the bond ‘energy of the central bond: AH = 2(C-H) ~ BE, ~H—H = 208 ~BE, BE, (2.2. ]propellane = 104—95 = § BE,[2.1.1]propellane = 104-73 = 31 BE,[I.1.1]propellane = 10439 = 65 - 104 = 104 —BE, {iis fest indicates that while rypture of the center bond in [22.1 }propllane is nearly energy neutral, the bond energy increases with the smaller tings. The rngeriying reason is that much more strain is released by the rupture of the [2.2.1}propellane bond than in the [1.1 ]propellane bond. + The various jy values allow assigning observed Affyy and APT, @s inthe chan below. Using the standard value of 27.4keamol for a cis-duble bord allows the calculation of the heats of hydrogenation and gives a value for she ;ruin" associated with each ting, For example, the Aux of cis-eyctoostene is only 23.0keal’mol, indicating an increase of 27.4 ~23.0 = 4:4kcamel of aumin on going (0 cyclooctane, The relatively high AF» for irans-cyclovctene reflects the release of ruin on reduction 10 eyclooctane. The “strin” lor exch Sapound is & combination of tata tain minus any stabilization for conjugation {The contribution of conjugation ean be seen by comparing the conjugated 1.3 ‘isomer with the unconjugated 1, somers of eyelooctadiene and is about dé Tkeal/mol. Since the “srtn” for eyclooctatetraene fs similar to the ‘other systems, there is no evidence of any major stabilization by conjugation,® 19. 1.10, ee () — O ee 22.74 Ne 309, 4-278 C200 3s) 68) 02) j-o80 aA Oe (a9) (ray NA O ea) By subtracting the value for X=H from the other values, one finds the “additional” resonance stabilization associated with the substituent, There is Some stabilization associated with the methyl and ethyl groups and somewhat more for etheny! and ethynyl. This is consistent with the resonance coneept that the unsaturated functional groups would “extend” the conjugation, "The Stabilization for amino is larger than for the hydrocarbons, suggesting additional Stabilization associated with the amino group, The stabilizations calculated are somewhat lower than for the values for groups directly on a double bond. ‘The gas phase AG gives the intrinsic difference in stabilization of the anion, ‘lative to the corresponding acid, The reference compound, CHyCOsH, has the highest value and therefore the smallest intrinsic relative stabilization, ‘The differ, ental solvation ofthe anion and acid can be obtained from p. 5 by subtracting the solvation of the acid from the anion. The numbers are shown below. The {otal stabilization favoring aqueous ionization, relative to acetic acid, is the sum Of the intrinsic stabitization and the solvation stabilization. These tend to be in Opposite directions, with the strongest acids having high intrinsic stabilization, but negative relative solvation, x Ne sotvation| Inuiaic ‘ol a ci, MSM Msai—wTz=me a M249 249-6447 027302 260 cach, 33330 393.5050. 268 ect, 32966 427.65—55.4 403 [HC B41 MUT-os72—077809 LoaWe see thatthe final stabilization relative to acetic acid gives the correct order of pA. Interestingly. the solvation of the stronger acids is less than thet of the weaker acids. This presumably reflects the effect of the stronger intemal Stabilization, These data suggest that intrinsic stabilization dominates the relative Acidity for this series, with solvation differences being in the opposite direction I-11, These observations are the result of hyperconjugation between the nitrogen unshared electron pair and the axial C-H bonds. The chair conformation of the Piperidine ring permits the optimal alignment, The weaker CH bond reflects N= @" delocalizations. The greater shielding ofthe axial hydrogen is also the Fesult of increased electron density in the CH bond. The effect of the axial ‘methyl groups is one of raising the energy of the unshared eleeitons on nitrogen and stabilizing the radical cation. — a" s n OH OH 1-12. a-e, Bach of these substitutions involves extending the conjugated system and results in an MO pattern analogous to allyl for luoroethene and to butadiene for propenal and acrylonitie, respectively, @ © @ 8 cach cxofgg 4. The addition of the methyl group permits «+ * and m+ «interactions that can be depicted by the n-type methyl orbitals. The o orbitals can be depicted as the symmerry-acapred pairs shown, As a first approximation, one of each pair will be unperturbed by interaction of the adjacent m orbital because of the requirement that interacting orbitals have the same symmetry Roa moOFT ay LAGE ef The substituents add an additional p orbital converting the conjugated system to a benzyllke system. Inthe benzyl cation, the i, orbital is empty, ‘resulting in a positive charge. In fuorobenzene, the p, orbital on fluorineQoQ wil we cnste with he sem a wl lo is ets ’ in cece foe eon dey Yon hoa cksheegane carat Moone wl ps he obec aga ane itn a omc ove ergy Wane cea oa fest A a peti he he a met Gi wit etn ogee wi. ee i ih — we wa Comment, With the availability of suitable programs, these orbitals could be calculated, Siena Pris 1.13. a. The resonance interactions involve a -> 1° hyperconjugation in the case of ‘methyl and —+ 1° conjugation in the case of NH, OH, and F, as depicted beiow. K \ He. Ho we Tw eee Q # 7 H XH CHpsCH-x: —~ cH, VB description of interaction with donor substivsnis, ome Bi MO cesciption of interaction win donor substtuents >. There are two major stabilizing factors at work. One is the 1 delocalization depicted for both the methyl group and heteroatoms, The order of this effect should be NH, > OH » CH, which is in accord with the observed order of the inevease in stability. The other factor is the incremental polarity of the bonds, where an increment in stability owing to the electronegativity difference should occur. This should be in the order F > OH > NH, but this ‘onder seems to be outweighed by the effect of the ar-electran delocalization, “ws% ? The NPA charges are in qualitative agreement with the resonance/polar dichotomy. The electron density on the unsubstituted carbon C(2) increases, as predicted by the resonance structures indicating delocalization of the heteroatom unshared electron pair. The charge on the substituted carbon C(1}) increases with the electronegativity of the substituent. As is characteristic (and based on a diflerent definition of atomic charge), the AIM charges are dominated by elecironegativity differences. There is some indication of the st-donor effect in that C(2) is less positive inthe order NH, < OH =F. 1:14 a In the strict HMO approximation, there would be two independent and 4 ‘orbitals, having energies that are unperturbed from the isoleted double bonds, which would be +8 in terms of the HMO parameters b. There would now be four combinations. The geometry of the molecule tilts the orbitals and results in better overtap of the endo lobes. should be stabilized, Whereas Y» will be somewhat destabilized by the antibonding interactions between C(2) and C(6) and C(3) and C(5). Ys should be slightly stabilized by the cross-ring interaction. The pattern would be similar to that of 1,3-butadine, but with smaller splitting of Wy and tly and Hy and ty © The first IP would occur from Ws, since it is the HOMO and the second IP ‘would be from yy. The effect of the donor substituent is to lower both IPs, but |P, is lowered more than IP. The electron-withdrawing substituent increases both IPs by a similar amount, The HOMO in the case of methoxy will be dominated by the substituted double bond, which becomes more electron rich 48 a result of the methoxy substituent. The cyano group reduces the electron density at both double bonds by a polar effect and conjugation, ty fe te OY ay “ ‘The HMO orbitals would each have energy a oe “p — =e 1115: a Since there are four a electrons in the pentadienyl cation, yy will be the HOMO, b. From the coefficients given, the orbitals are identified as and yy, shown below. Ye is a bonding orbital and is antisymmetric. yy is a nonbonding orbital and is symmetric oft> 1-16. The positive charge on the benzylic position increases with the addition of the 9 EWG substituents, which is consistent with the polarity of these groups. There —___) is relatively lite change at the ring positions. All the cations show that q imi Pons substantial part of the overall cationic charge is located on the hydrogens. There is a decrease in the positive charge at the para position, which is consistem: vith delocalization to the substituent, All the structures show very significant bond length alterations that are consistent with the resonance structures for delocalization of the cation charge tothe ring, especially the para position 1.17 a In terms of « the four linear homogeneous equations for butadiene take the Form: axtay ay +ajxtay a tasetay ay tax where x = ~1.62, 0.618, 0.618, and 1,62. For y, x= 1.62, and we obtain =1.62a, +4; =0 4, ~ 1624; +a, =0 4; — 1.024, tay =0 44-1824, =0 ‘The first equation 1.62a, Substitution of this value for ay into the second equation gives 0 4, ~ 1.62(1,62a,) +4; 4; = 1,62, From the last equation, we substitute the a; in terms of a, and obtain 62a, ~ 1.624, =0 We must normalize the eigenfunction: ae tae tagdy 10 ‘Making the appropriate substitutions gives Shei Praena 4? +2.62a7 42.624, 44, and W =0:372p, +0.602p, +0.602p, +0.272p, ‘To obtain the coefficients for Ys we use the value of x, = 0.618, and ‘CAMTY oUt the same procedure that is illustrated above. The tesulis are a; = 06184, 4 =~0618a, and. _ 4,7 40.3824)? +-0,382a,? +a; = @ and 372 an .602p, +0.372p, ~ 0372p, ~0.602p,” a e 118, a, Using the values x = 0.618 and 1.62, we repeat the same procedure for ‘and thy. The four eigenfunctions for butadiene are: 1 =0.372p, +0.602p, —0.602p, -0.372p, 0602p, +0.372p; ~0,372p; ~0.602p, Ys = 0.602p, +0.372p, ~0.372p, -0.602p, = 0372p, +0.602p, ~0.602p; -0.372p, The MO diagram can be constructed using the Frost Circle, The energy of the occupied orbital is «+28, so there isa stabilization of 2B, nominally the same as benzene, suggesting substantial stabilization for this ion, ‘The longest UV-VIS band should correspond to the HOMO-LUMO gap. For 1.3,5,7-octatetraene and 1,3,5-hexatriene the HMO orbitals are as follows 135hoxavione 1,98,7cctteraene 0.445042 0.387298 vel Tm ‘The energy gap decreases with the length of the conjugated system, and therefore the 1,35,7-octatetraene absorption should occur at longer wavelengths. ‘The adcitional strain in spiropentane relative to cyclopropane is due to the fact that there can be no relief of strain by rehybridizaion of the spiro carbon, By symmetry itis tetrahedral and maintains sp° hybridization These values provide further indication of the strain in spiropentane. The intemal angle is close to that of an equilateral triangle (asin eyelopropane), ‘The 137° value indicates considerable strain from the ideal 109° for an sp? carbon. Ths strain induces rehybriization in the C(2) and C(3) carbons Using 0.25 as the 5 character in the spiro carbon, we find the s character in the C(1)—CQ2) bond to be 20.2 = $50(0.25)(x). The s character is 14.5%, For the C(2)—C(3) bond, 7.5 = $50("). The fractional s characteris 11.7% ‘This reaction would be expected to be unfavorable, since cyclopropane is tore acidic than methane. The increased character ofthe cyclopropane C_-H. bond makes it more acidic. A gas phase measurement indicates a difference in AH of about Skeal/mol ‘This comparison relates t0 the issue of whether @ cyano group is stabi- lizing (delocalization) or destabilizing (polar) with respect to a carbocation (see p. 304). The results of a HF/3-21G calculation in the cited reference indicate a net destabilization of about 9kcal/mol, in which ease the reaction will be exothermic inthe direction shown12 Saas 120, 121. 122, 123, The polar effects ofthe fluorine substituents should strongly stabilize negative charge on carbon, suggesting that the reaction will be exothermic Aw MPASDTQU-31+4(d\p) calculation finds a difference of ~ 48 kcal/mol. ‘Because ofthe antiaromaticity of the cyclopentadienyl eaton (p. 31) the first Faction would be expected to be the slower of the two. The reaction has not been observed experimentally, but a timit of < 10°* relative to cyclopentyl iodide has been placed on its rate 5 The exclopropenyl anion is expected 0 be destubilized (anaromatic) ‘Therefore, K should be larger forthe first reaction. An estimate hused on the {ale of deuterium exchange has suggested that the pk difference is at lean 3 fog units © Tie Second reaction will be the fastest. The allylic cation is stabilized by delocalization, but the cyclopentadienyl cation formed in the frst reaction 1G destabilized ‘Tre diminished double-bond character indicates less delocalization by conju gation in the carbene, which may be due to the electrostatic differences. In the cirbocation, delocalization incurs no electrostatic cost, since the net positive charge of | is being delocalized, However in B, any delocalization has an electro, ie energy cost. since the locelized sp" orbital represents a negative charge In the overall neutral carbene. Ze results ae relevant 0 a significant chemical issue, namely the stability of i ines with N-n-donor substituents. such as oximes (OXTHO) and hydrazones (YX = HN), are more stable to hydrolysis than alkyl (YX= HC). The classical explanation is ground state resonance stabilization, Ye-ne=ch, —~ vhen-onye [Tie Sibilzation i greatest for the F > OH > NH series of substituents. The sill sroup (ERG) is destabilizing, and the conjugated EWG groups ere moderately Stabilizing, The most significant structural change isin the bond angle, which implies a change in hybridization at nitrogen. The NPA charges show a buildup of charge on carbon for NH, OH, and F of about the same magnitude for each. This sould result from the 7 delocalization. The charges on N are negative (except {orf where it neu) and seem to be dominated by the elecroncgatvity of {he substituent atom with the order being Si> C > N > O> F. These recalta indicate that as the substituent becomes more electronegative, the unshared pair orbital has more s character. (Results not shown here for X= Li and Ne indicate that the lone pair is p in these compounds.) At least part of the siailization Would then be due t0 the more stable orbital for the unshared electron pei, A second factor in the stabilization may be a bond strength increment from the slectronegativity difference between X and N. The NPA charges indicate thatthe planar (conjugated) structures have charae- leristies associated with amide resonance. The oxygen charge in formamide fs tno Zao inthe planar form and —0.620 in the twisted form. For the NH, uroup, the charge is ~0.080 in the planar form and —0.182 in the twisted form, There differences indicate more N to O charge transfer in the planar form, For 3, aminacrolin, the coresponding numbers at Ona !~0.665, Opn 0.625 and NE! 0.060, NH siusy | ~0-149. These values indicate somewhat{ess Polarization associated with the (vinylic) resonance in this compound. For squaramide, the magnitude of the charges is similar O() jij! 0.655; OM uives ! 0.609 and NHsirigu 0.001, NH:yuinuy : 0.095; The differ. ences in the "0 chemical shifts and the rotational barrier also indicate greater fesonanee interaction in formamide than in 3-aminoacrolein and squaramide ‘The interaction maps show that the nitrogen is repulsive toward a positive charge in the planar forms, but becomes attractive in the (wisted form. The attractive ‘region is associated with the lone pair on the nitrogen atom in the twisted form Chapter 2 2.1. a, diastereomers: £. enantiomers. 22. a. S: CH(C), > CH,CH{C), > CH,CH, > H b. RSi>O>C>H ©. RO >C=0>C(C), >H . RO > C(C), > CH, > H © 5:0 > C(C)sC(C)sH > C(C),C(C)H, > C(C).H £ RIN > C(O), > C(O),H> CCH, & RO >C(C), > CH, > : (electron pair) mers; ¢, enantiomers; d diastereomers; ¢, enantiomers; 23. 24. a Pre ani PB — —— Paco "co. sasition a” Sco racemic (tiso) ——racomie _ Ph, Bee ang ‘con 4 davon racemic (ert) come 13 Bie Pts4 Sia Pons b. er OCH 90H, 2 cama ' : 97% 3% ‘enantiomeric excess = 94% 2.8, The solution to this problem lies in recognizing that there are steric differences for the phenyl group in the axial and equatorial conformations. In the equatorial Position, the phenyl group can adopt an orientation that is more or less “perpen- diculae” to the cyclohexane ring, which minimizes steric interactions with the 2,6-equatorial hydrogens. In the axial conformation, the phenyl group is forced to rotate by about 90°, which adds to the apparent —AG, for the phenyl group. ‘When a I-methy! substituent is present, the favorable “perpendicular” is no longer Available and this destabilizes the equatorial orientation relative to phenyleyclo- hexane, Sp ey prefered confarmation preferred conformation ty group precludes pratered ‘9109 t-phonyleyclohexane of ax tphenyeycherane conformation ane adds a desteizing Iniracton with 26-69 hogan Commen. This i a challenging question but can be approached effectively by MM modeling, 8 was done in the original and subsequent references, As discussed on p. 148, the preferred conformation of acetone is the C-HIC-=0 eclipsed conformation. Tis is stabilized by a ¢ — 1 interaction. For 2-butanone the C(4YC=O eclipsed is prefered, as discussed on p, 148 and illustated by Figure 2.12. For 3-methyl-2-butanone, four distinct conformations aise. The ‘maxima at 60° and 180° represent the CH,/CH, ectipsed conformations, which give tise (0 a barier of about 2.5 keal/mol. This is somewhat less than Tor the CHs/CH, eclipsed conformation of butane and presumably reflects the absence (of additional H/H eclipsing. An analysis of the 3-methyl-2-buianone spectrum is available in Ref. 36, p. 149,Hy cH, CHy__gOHs Ce oss So owt othe W i on, ‘oy 0% 240° CHyC=0 60%, 180", staggered 120%,H1CuO 300, staggered cipeed CHYCHs ecipsed—golpind hiv ecpeod 2.7, The stereochemistry of all of these reactions is governed by steric approach contol +o oy oom = : psc) ad am ye sgt ° 2 : eet « yon in Ry Iyegeraten 7%, oe . reagent spproach (0 ayer soe K Ay CCH aan omy NINO On = seat o meat \ © Zoe non mom ro en a 28. a,b. The conformers of 2-methylbutane differ by one “double” gauche inter- action. The conformation of 2-methylbutane that avoids this interaction is favored by 0.9 kcal. There is good agreement between experimental and ab ‘o results. Surprisingly, the two conformations of 2,3-dimethylbutane are virtually equal in energy, by experimental, MM, and ab initio results. The Qualitative “double” gauche argument fails in this ease. ©. This is an example of the 3-alky! ketone effect (p, 161), by which the conforma tional free energy of a 3-atkyl substituent is smaller than that in cyclohexane. ‘The AG. has been estimated as 0.55 keal/mol Comment. Assuming availability of a suitable program, this question can framed «as an exercise fo calculate and compare the energies of the two conformations of ‘h compound, 2.9. An estimate can be made by assuming additive 4G, and adding an increment (3.7 keal/mot) for |.3-diaxial interactions between methy! groups. The reference takes a somewhat different approach, summing gauche interaction terms 10 stimate the energy differences,> & wad sh = aA Saeegs -AG=9.4-1,7-97 254 H96=3.4-1.7=1.7 8G93.7+3.4-1.7 84 Comment. This problem would be amenable to an MM approach, 2.10. The conformation equilibria shown below have been measured, cH, os, CH, 079 GH, 1.00 HOW, 1.28 ie, 23 yy >100 ‘The wend sa eter modest increase wih size forthe primary groups though isobutyl Ther isa slighly lager change with the scoonduy hoppy eae, 8 followed by avery large factor favoring thesis conformer for poy he very lage Inerease going to buy osur because thee fe Ngee iydrogen tat cn oecpy the postion eclipsed withthe BCH ihe ea conformation omy ox” eR wa 2.11. The product stereochemistry can be predicted on the basis of the Felkin model, ° 5 7 CHy Ph, CH Ph, oh na) aN Wren on 4" Prger ‘threo or syn ° or on os ote myfow mt Po ArH H a ion of Crain's rule and uses an Comment, The reference is an early formula alternative conformation of the reactant.> ‘center. 2.12. The a. B-double bond is held in proximity to the catalyst center by the acetamido Substituent, while the .8-double bond is not brought near the coordination 2.13. cout con go = HORA 00H Hofh = wo K cou bab come c 2nss Gc 250n gout 03H cout = Hoe con HOH W064 ‘cout eae ase ne 2naA CHeCOH 25.5 2M. a ws 108 pos X pos 9 on) i WGC Ta con pee — 3 ent senator th roc wit viene contin iin b. sie vowed fromthe ep 4 i iromine top ©. The reaction proceeds with retention of con! figuration at C(3). Inversion occurs at CQ2). CoH Ch omy cose yy 4 é aN % 4 . mF OS E00 cn SH cg tow ad On We Ron Wy 3828 anas snan 3828 4 mom - Cs, ee ee 7 iain Patens entie 18 2s. 2.16. 2.17. 2.18. ‘An achiral tetramer with a center of symmetry results if the wo enantiomeric mers nonactic acids are combined in a structure that contains a center of symmetry. 4 (@) The cis isomer is achiral while the rans isomer is chiral. The chirality of {he wans-substituted ring system makes the benzyl hydrogens diastereoropic and nonequivalent. This results in the observation of geminal coupling and the appearance of an AB quartet. (b) Hyperconjugation with the nitrogen lone Pair moves axial hydrogens to high field in piperidines. The trans isomer has oe equatorial hydrogen, which appears near 2.8 ppm. Inthe cis isomer, only axial hydrogens are present and they appear upfield of the range shown, b. Isomer A is the cis.cis-2,6-dimethyl isomer, The benzyl singlet indicates that there is no stereogenic center inthe ring and the relatively narrow band at 3.4 icates that there is only eq-ax coupling to the C(I) hydrogen. Isomer B is the trans, trans-2,6-dimethy! isomer. The benzyl singlet indicates an achiral Steueture but now the larger ax-ax coupling that would be present in this isomer is seen, Isomer C isthe chiral cis, rrans-2.6-dimethyl isomer, The AB {quartet pater of the benzyl hydrogens indicates thatthe ring system isthe chiral cis, trans isomer. The splitting of the signal at 3.0 is consistent with ‘one equatorial and one axial coupling, ‘The data allows calculation of ~AG,. The interpretation offered in the reference is that hydrogen-bonding solvents (the lst two entries) increase the effective size of the hydroxy group. The potential donor solvents dimethoxyethane and tetrahydrofuran seem to have ltl effec This result seems to be due to 7 -» 0" and o> 1 hyperconjugation between the oximino and chloro substituents. Since hyperconjugation is also present in the ketone, the issue is rnised a8 to why the oximino ethers are more prone ‘0 the diaxial conformation. The fac thatthe oximino ethers adopt the dial conformation indicates thatthe hyperconjugative stabilization is greater forthe ‘oximes than the Ketones. This implies that the » | @ more polar environment, accounting for the shift toward more of the syn conformation. There does not seem to be stabilization of the 90° conformation, Which would presumably optimize C-X > m hyperconjugation. The anotnalous behavior ofthe nitro group is attributed to the somewhat different spatial orien, tation of the substituent, vty is consistent with a chelated TS. ~ 4 bts ole on Tae OAK —py Rt = ». The observed stereoselectivity is consistent with a Felkin-Ahn model. Siar Pros COCK it 2.24, Application of the oxazaborolidine (p. 196) and (Ipe)sBCI (p. 194) models correctly predict the R configuration of the chiral center. Phs: : p-wrn Ph. OH ; , fe oN CHOC eV’ co,cr 225, ‘The two methyl groups are enantiotopic. Pro-S CHy CH pros ° b. The two methy! groups are enantioto ° post pon cub, €. The metys inthe grpy! group ar dasteretpie as Potts Pro Ne cn & ky pos2.26, 227, 2.28, © diastereotopic, CH pros HNO" por Ky © Both the benzyl and glyeyl methylene hydrogens are diastereotopic. The ethoxy methylenes hydrogens are diastereotopic. The bromomethylene hydrogens are enantiotopic () chiral; (&) chiral, but note that inversion of the configuration of the methyl fsroups on one ring would give a molecule with a center of symmetry; (e) chiral, (@) achiral, plane of symmetry dissecting any ring and a ring junction: (e) achiral, center of symmetry and a plane of symmetry; (f) chiral; (g) chiral by virtue of helicity; (b) chiral; (i) chiral; (j) chiral; (k) chiral; (I) achiral, plane of symmetry aligned with the two C=O bonds; (m) chiral. ‘The following predictions are made by fiting the alkenes to the TS model in Figure 2.27. (a) DHQD (&); DAQ (Ss) (b) DHQD (5); DHQ (R) (e) DHQD (2,8); DHQ (5,5) (@) DHQD (8,8); DHQ (5,5) 4 The TS model on page 196 predicts configuration. Pn meh on ove Ae Sy crc Pn oy 8 b. The TS model on page 194 predicts R configuration, 2 oH oN tpe-200N “Serta,or SS OF> 22 © The empirical predictive scheme on p, 198 predicts thatthe 2R,3S-cpoxide Soe will be formed, *s eS, jour t 2A.35 729, (9) Classical resoltion; (b) kinetic resolution; () chiral chromatography; (4) enantioselective synthesis, 2:30. The original reference analyzed the barrier in terms of o-m hyperconjugation, However, as suggested by the analysis of ethane in Topic 1.1, the rotational barrier is affected by adjustments in molecular geometry, which will lead to changes in all components of the total energy. The analysis ofthe acealdehyde ‘otational barrier given on p. 148 shows that nuclear-nuclear and electron, . The enthalpy of oxidation can be obtained by a simple thermochemical calcu lation, since the 41, for O, the element in its standard state, is 0 PROH=0 + 1120, ——~ Phoo,H SH=-88 sho. SH, = 70.41 = 70.1 ~(-8.8) 61.3 © The difference in 11, between 2-methyl-l-pentene and 2-methylpentane corresponds 0 the heat of hydrogenati imethyleyclohexanol that would be dehydrated to the three alkenes shown, on CHy om ang The formation of a stereoisomeric mixture of 1,2-dimethyleyelohexane from each is in accord with these assignments. The H-catalyzed equilibration would establish the thermodynamic equilibrium so that the structures can be assigned fon the basis of relative stability. The relative stability of the alkenes should be C> B> A, based on the number of double-bond substituents, A plot of In K versus 1/7” gives a good straight line with a slope of 2428. By ‘use of Equation (3.1), this give AW =4,80kcal/mol and AS = —12.2¢u TempC Temp temp Kak AG” a as 728° M02 O.00870-169_aRIaI—1s18@ ~aNOTIey IRIE NS 284.9 Ooms 1.0 2397m8 13527 Lasoned Lis ia0 $81 2912 ooss3 84 ZID8282 “1297.1 Laos _ia 2088 219 3950 ooM0 79 2omoH 23 ond 000331 s—sTia02 2073 4807.64 12.2047 11208 —4su7.68 121921 32 M51 0028 61140828 “Ho924 agones Lise 389 3oRd 000025 5:7 E7404 © —tO614 —aRO7et ~IBLe 32-3103 oom 531647707 mae Dagoes Liat S25 M6 omualT 46 seo oma —worer ietsLnikvs. . fees : 24. —— a Rae 0 ae Oonsr come adm edi aos atm oc Gio " P30, em Baa eeeez~C~CZ~CE___ ime Taek a 250 DRI 0000355136807 —I8aI D008 BBNTT 982 a3 400 313.1 Oousi9e 850807 “13978 23008 22387 Be6s LS 501 3232 o.003094 2728.0 12815 23008 22307 4200 Be 5843319 0.03013 7368-06 “ina 23008 22359 FHI6 ABD Link vs. 177 of fp 3 ye 1620023188 = R= 0.9908 5 | -20 8.003 0.008 0.0081 0.0081 6.0082 0.0082 o0083 0.0083 OoGes o90s4 Ww Fig. 2.Pa, Plot of fa & versus 1/7 for seta of -ehlroheney tosylate, b, B Tempo Temp tks Ink Ea ant sat ast 03.1 o003008boed030—10.1143 27H 26TH asey SDE 70 MBI 0.G02915 ou0097 9.2408 27439 26760 GIT? 3D 25 MB 8002873 ooGOI79 R528 27439 26750 S917 G9 §0 353.4 o.cu2¥92 oun —¥0822 27439 derad S081 997 S03. mon7s4 com0K92 “70229 37439 A6mU AOR OT 2S MB.1_wO2TI7_ov01s90 64490 27439 26710 40979926 iso Plas nk ve. 7 0 2 xt 38683 + 3174 54 ta a3 0.9997 = “10 2 S.on27 0.00275 0.0028 0.90285 0.0029 0.00295 0.003 0.00305, ww Fig Pb, Plotofln vers 1/7 forthrmolyssof3-cloro-33-cloopteny) sine, 3.5. & The reaction profile would show a depression for the diradical intermediate for mechanism (a), but would show only a TS for mechanism (6). . An isotopic labeling study could determine ifthe exoeyclic methylene carbon and the C(3) methylerie had exchanged. Exchange would be expected for the diradical mechanism, but not for the concerted mechanism, Deuterium labeling showed that there was interchange of these carbons on the reaction path, indicating that the two-step mechanism is occurring, Fg. 39.5, Reaction nergy profiles fr dirs! and concerted echanism, 3.6, The reaction can occur by migration of either of the bridgehead carbons, which are in sterically similar environments. The data show that polar EWGs favor migration of the more remote carbon. The same trend is evident, although with ‘alenuated magnitude, in the substituted phenyl derivatives, Thus EWGs disfavor tnigration ofthe adjacent bridgehead carbon, whereas ERGs favor such migration. Migration is facilitated by the group's capacity to donate electrons Io peticipate in the migration process. The cited authors favor hyperconjugation as the cease for the substituent effect, but it could also be formulated in terms of the effect of the bond dipole.7 ac? es a . ype. arog cramieanenie aetna Deller able tomigrate seperated 3.7. & The data and plot show a somewhat higher correlation with « than with a= ‘The p value is +1.23, indicating that EWGs favor the reaction. The magnitude of the p, which is modest, and the poorer of correlation with o~ suggest a relatively early TS, occurring before full conjugation of the phenolate anion leaving group has developed. Group Rate iy Lop kik, « o ry 23 057 ~o2e “097 ~026 cH 24 0682 0192 017 “oy H a4 ' ° ° o Br 95.1 254 ows 023 02s NO, 130 us 161 078 ur Log k/k0 vs. Sigma 12 kiko “04 02002 04 06 084 ‘Sigma Log k/ko ve. Sigma 3 ° 8 7 15 Sigma . The correlation with a” is considerably better and the faily large negative p of $8 is consistent with substantial cationic character atthe teansition state.> 28 Substtent k Key tog ke, ° o Saar a Pons $CHO4RKE-03—Ga2EFO2_———-aDe cH, LOWE—OF — 200B+01 305 ot? “ua 4 SIE—05 ove +09 0 ° ° 41 3I8E-06 — 392E-01 040723 tt NO, M4468 L7RE~03 27st mk Log kiko vs. Sigma 4 3 2 21 #2 2 3 a 46, Log k/to vs. Sigma. Log kiko dobsbosmos 4 5 0 05 1 Sigma+ 6: The correlation is much better with @ than with a. The pis modestly negative (1.14), consistent with the expected qualitative substituent effect, The modest value of p and the lack of correlation with o* indicate that the substituent effect is primarily polar in nature Substivent lop Wop Ky ° ° 2cH,0 932 “099 0a OTe “+CH, 90 “019 017 “on sci, ~905 <00r D1 an 1H 903 00 uo 0 +r ~a98 0.09 0.06 007 40 883 020 023 ou cl ~86r 036 037 on ENO, 819 ost a7 on NO, a x9 on 0799 Log k/ko vs. Sigma 29 7 og 08 go B02 ao 02 4 “04-08 002 oa 08 08 Log k/ko ve. Sigma 1 os 08 204 202 Boo -02 34 28 + “05 ° cr 1 ‘Slgmay 38a. The first step can be treated as an equilibrium and the concentration of the anion expressed in terms of the reactants, How we RN =e senscag. er an [An] = KiBrCH-CHENIRAN) rai {AN = keKIB1CHeCHBH\FAN) "A10 = kp BICH=CHBAAN} > This represents an example ofthe classical Sy reaction Rate = AIR —XI. The ratio of products would be given by ks/ky. k, Ar-H+Bry {_UAHBr*] + Bris rate controlling Steady state approximation for [AcHBr*] leads to Ka(ArH] [Bro] = k_[APHBr”}[Br“]-+-ky[ArHBr*] and Bry = RUAPHIPB | (artery = KIB] +k, The effective [Br] is determined by the tribromide equilibrium = [BHI * BeBe]a 30 39, 3.10. Substituting gives 1 kekyfAPHIIBr) TER Be}* kB] +k, When ky[ArHBr] >> k_[AcHBr this simplifies to [Beslows 1 oe = RSA) a This can be formulated by using a steady state approximation for the enol (Eno! &y[Keto] =k_,[Enol] + 4(Cr]{Enol] __kilKeto] (Eno) = Ae ‘The rate then is Rate = k{Enol]{Cr} = x*lKetollCe} ky FRICH] THe apparent stabilization is given by [Arh (cyclic system)} ~ [Ay (ret)] ‘The following are the apparent stabilizations: ee System Apparent ssblation Cyetopropeny cation 239 Gyetopeopeny anion Cyetobuadiene Cyclopenaieny ation Cyetopentacienyl enon Benzene Cyeobeptaviony eatin ‘Cyeloeptnienyl anion This computation scems to emphasize the antiaromatie character more than the aromatic character. Note, for example, that the cyclopentadiene anion is calculated to be slightly destabilized by conjugation, which runs counter to the Observed relative acidity of the eyclopentadiene cing. The qualitative agreement with Hckel’s rule is exceltent but the agreement with the calculated 8 values is Poor. This treatment makes no explicit separation of stain. For example in the Cr system, the reference point is the allyl system. so the strain associated with losing a three-membered ring is subsumed into the calculated (destabilisation Thclusion of a separate term for strain would increase the apparent stabilization Of the cyclopropenyl cation and decrease the destabilization of the anion by the ‘amount of strain assigned, 4a. The very large heat of hydrogenation ofthe eyclobutadiene reflects the anti present in this molecule. The more or less normal heat of hydrogenation of the second step indicates that tere isnot much change of strain in this step. ‘b. The larger exothermicity of the first sing cleavage is the result of the rehydridization that is possible in the dimethyleyclopropane product. The relief of strain is greater in the first step than in the second because of the ‘adjustment in hybridization© The successive steps reflect: (1) change from di- to tri-substituted double bonds (2) relief of strain resulting from reduction of sp? carbons in the ring from one to two; (3) further relief of strain by removal of the sp carbon from the ring: (4) the final heat of hydrogenation is slightly lower than I-butene, Suggesting a small stabilization of the double bond by the cyclopropyl ring. 3.11, The mechanism is believed to involve rate-determining hydride donation from hydrated benzaldehyde. The lack of exchange with solvent protons indicates that it is the formyl hydrogen that is transferred, Reversible formation of the aldehyde hydrate and its conjugate base accounts for the appearance of "0 in both products. The third-order rate expression is also consistent with involvement of the hydrate, The role of aromatic substituents could be complex. The extent of hydration and the reactivity of the aldehyde to hydride transfer would be favored by EWG substituents. On the other hand, the hydride transfer itself would be retarded by an EWG in the hydrate. The positive p indicates that some combination of the former two factors must be dominant. The inverse and is consistent with 'y of “OD compared to “OH. The observations are Consistent with a mechanism in which the aldehyde hydrate acts as the hydride donor. AcHoO + -on SH AHO bu voy necro som arco aco, EL. ArcHoH + Arcos Nee A 7 312. t step must be rate determining, since the aromatic hydrogens exhibit 4 primary isotope effect, whereas there is no isotope effect for elimination of hydrogen from the styrene reactant, which occurs in Step 3. Step 2 would not be expected to exhibit a primary isotope effect because the aryl hydrogens are not directly involved in the reaction, but should exhibit a secondary isotope effect for styrene-f-ds. 3.13. 1, The larger substituent effect in the gas phase is due to the “leveling effect” in solution. In the gas phase, the adjustments to changes in the electron distribution resulting from ionization must be accommodated internally, so substituent effects are large. In solution, much of the effect of the negative charge is stabilized by solvation, and this reduces the relative importance of the substituent effects, 2. The larger and more polarizable benzoic acid molecule is able to better accommodate the charge of the anion in the gas phase. 3. Stabilization of the anion in solution causes solvent organization, which Appears as an entropy contibution, Substituent effects are translated into differences in solvation. Anions beter stabilized by internal substituent effects resull in somewhat looser solvation, 3:14, The correlation with o~ is marginally better than for @ and both ae significantly better than with o~. This indicates that the chemical shifts result from a mixture of polar and resonance effects that weight resonance slightly higher than for 319 32 Saar Proms the standard ionization of benzoic aci resonance o id. The data were used to assign “pure” flues by using a dual substituent parameter correlation Sutswent ae * 7 © Ma ~one arr 8 CHO “195 § a9 cH, 259 a 205 br -162 cr, 33 cn 3480 CHo.c 42 cco 8 cHso, 464 “on 0.06 017 023 023 ost 0.86 ass 030 on 026 “003 017 ou as 065 oo om oa 1 No, 333 o78 an van a Chemical Shift vs. Sigma i a + do[- = 15 a “5 g oo 1 Sigma Chemical Shift vs. Sigma+ 0 “10 Chemical shin. & 4 a & 15, Chemical shit Sigma315: The correlation with ois somewhat better than with a, although a diet resonance interaction does exist. Both A and AS show good linear correla, tions with AG. indicating that the substituent effect operates by both electroni stabilization and solvati Subsinen pk, K a6 i, cH. 89 68 027-078 cH, a2 6 017 “91 H mas oo 00 cr 3236 023 aur Br sis 02 ous cn ~pka vs. Sigma ° : Pe ] = aston ane as ae : sions Te ° s a: = z . rasan aa Sone ih ee ‘tomes Dt @ve.Deta son [Sara es wo wane eerie ure 33 Bare Pies34 Soha Pons Delta G vs. Delta S Dota s 3416. The absolute (unsigned) deviation fr MM isquitesmall PMG gives sigh high Values forall compounds, especially for nortrieycane and quadieylene- AMT issystematally high exept fornorborane, andisespecally high for novtney. lane and quadricyclane. MNDO is systematically high, excep for norborane and quacricycane, Thus it appears PMB3 gives the best results ofthe semiens, Pirical methods, bt all have some dificult with te stained tiny compounds b. The ab initio results are in quite good agreement with the experimental valoeg although norbornene and norticyelane ate consistently about 3-4 keal/mol less than the experimental value. The B3LYP results ate about IDkealhvol 100 high forthe bicyclic compounds, but somewhat closer although sl for nortcyelane end quackcyelae, The heats of hydrogenation results ffom the semiempirical calculations are similar tothe AH, celulations, withthe AMI results most seriously in eer 37. The order (CH)N > (CiH,),N > (CyH,.,)5N presumably is mainly a sere effect. There is a small variation of the longer-chain compounds inthe onder 4.2 8> 3> 6,for which there is no obvious interpretation. Pyridine i comparable the longer-chain trialkylamines because the sp? trogen is less nucleophilic than the sp? nitrogen. There is further reduction with quinoline, which is probably largely due to the steric effet of the C(8)-H. N.N-Dimethylaniline fs ail ene reactive, The phenyl group would exert both a polar and resonance withdraeeh Of electron density from nitrogen and there is more steve hindrance then pyridine. esse Temp (MeN (EDN (PsN (Bu)sN (Hex),N (OethN PHIM, Pyridine Quinoine co eee 2 ae 502 oe 0 Ler 0.35% 0371 0250 0336 58 30 107 0633 aH 0366 0570 0337 asi @ 451 105 124 0860 0912 os OBI aus 70 149 176 1M LSE 0283 ss w 301322262 27038) 2a ” oe om0 $FTemp KT Me © 9) aH Gas 35 Spry QU 382° “o00038 78009 108] DNTa) aT Sane Fo Zr oo1%66 502 aaosen 759691 torre wat 00399 728 oonors = “a zs21 ta ana Imereept 1464294 slope SU8I4 aH AG ss a M32 wom a9 ‘Temp K vt BAN k 0h) aH ac as 3310003194167 1696-05__ 1.0001 tora) sao) ae 331 00309307 307808 t0.912 todas a B31 ooo se 4 54E05 10 terol) nase 81 aoogsis 7497498 © 949916 taedd ease tek Tmtereept 5.831199 slope SW1I6 aH 8G as fa 4oss392 0725820 ta Temp K we PN x ma) aH aos 3100031960354 3.S4E06 128514 om de166 ae 0.003095 0633 6336-06 003002 105. osE-08 Dooss 176 1.76605 Lho.9e76 yomm2 304 SOMES to Imtereepe 6226278, slope 882.95, Es 689.83 or ro700 1680 toa an 10700 29598 27138 27682 208s ac mm 93, a =394 493 as #3 Temp K it Bun x nak) on Gas 311 G0oni9¢ 0am 47006 _—123658 1074025988 an 3231 0003095 omts Base 6825 333.1 os002 241.2405 “aL 2o7e, M31 002915194 L405 Llo.aso2 35.1 000832322 3maEns _joa3s Imercept 4.26121, slope =317009 0272.97 tox0 10700 eso 10690 an 0700 26464 27018 27595 25044 ac 02s a487 49.1 092 492 as 190 ‘Temp K WT Regn x i) aH aos 331 003d 9.39” 298-06 _—iaas0e Yara ae299) ae 323.1 0003095546 S.66E-06 BB. ono os 8-06, 38.1 omgis isi si-as 3831 one 22 2gE OS Tnx slope Ee 10gat = 11.6637 Host 10.5898 anes w720 10700 180 160 aH 0700 26720 27290, ams 2518 aa ons 495 “98 “97 46 as ~69 36 k me) aH ass Sansa Prone ‘Temp K Wt Onn 3B Oousi9s 0336 3.3606 12a Iona) Reread 321 oomsees as S706 = Liners wana ogete a 381 ooos0: 912 9.1206 1605 to 352 nae AB1 ones 6 aoenmI6 110s Inman ator ak 3u1 om? 2m AMOS §— -02 4 ~04 <= 08, S.002e 0.0028 0.008 0.0037 0.0032 oG0a3 " PhINMe2 Log k vs. 1/7 9 ~o2} 04 = 2048.5x7 6728 Logk 08 og }—— }0027 0.00275 0.0028 0.00885 0.0029 0.60285 0.00 4.00008 ww Pyridine Log k vs. 177 4 ®.c0a7 “0.0088 0002s 0.003 00081 ovoae ww 3.18. The slopes of the line increase with the number of cyano substituents, This indicates there is successively more solvent attenuation, with the increasing stabilization by cyano substituents. This may be because the charge is more localized on the benzylic carbon, permitting more effective solvation39 ov e80- w- ow Lr0~ z0 wo #0 Biorees 900 OD's>¥ os wo Oona ony fo oe sro be 0 Noe 90 390 Now owe io fone aie font aco fone tp 4 o 4 a es aon ‘steuoworeuysaaya ~¢ sag syaorcn eng = sagt 9 40 0 7 Sitar Prag Yet42e0n. 21078 Mo. . yo2.195804 29817 Parets [- Pasar]3:18. There is no corelation with a: The plot has a roughly parabolic shape with the greatest reactivity at the two exitemes. The vinyl group, despite its tow value, is among the strongest rate-enhancing sulstituents, The 4-phenyl and ‘Amethylthio substituents are also rate enhancing. The reaction is believed to Proceed by rearrangement of an intermediate diradical, in which case the radical. stabilizing substituent effect should govern the relative reactivity. Indeed, this reaction was used to establish such a substituent scale, : CHy ee \y r 7 : aon oe a 7 oe ‘e ‘3 a ; a om 7 ‘e oo - Sen" 41 Ri Pros) 42 3.20. These data relate to the general acidifying effect of cyano groups, as manifested in the pK values of the “cyanocarbons.” The referenced papers point to several Properties of the eyano group, which is a strongly polar EWG, combining the clectronegativity of sp carbon and nitrogen, The group is also rather undemanding sterically, allowing several groups to be accommodated without ‘mutual steric repulsions. Richard, Williams, and Giao in the reference cited gue further that the effect is more polar than resonance and cite the relatively high energy of the ketimine resonance form as an explanation. Merrill, Dahlke, ‘and Kass point to hyperconjugation as contributing to the @-stabilization, citing the lengthened C(B)-CN bond. 3.21, The two transition structures shown below ate derived from reactant confor= tations 21-A and 21-B, respectively, As the attacking radical becomes larger, the steric repulsion with the methyl substituent becomes more significant and forces the TS to react through the less favorable reactant conformation 21-B, ‘The product ratios can be used to estimate the difference in the AG? values, as shown in the figure, 3.22. The SAH results show some of the characteristic features of aromat ‘substituents, reflecting the mixture of resonance and polar components. For example, 4-F is less acidie than 3-F and 4-OCH, is less acidic than 3-CHO, reflecting the 7-donor effects ofthe 4-, but not the 3-substituents. The conjugated EWGs 4-CN and 4-NO, are mote strongly acidifying than the corresponding 3-substituents, since they can enhance acidity by resonance. The charge differ. ‘ences that are computed are relatively small. The charge difference on H is a range of 0.007 wnits, about 3% of the charge in the unsubstituted compound. Similarly the ranges of charges on the CO;H and COs groups are about 5 and 3%, respectively. of the charges on the unsubstituted compound. The HOMO ‘energy Of the anion might be expected to be a good indicator of acidity, since it reflects the ability of the stcueture to accommodate the negative charge, Here9 4 the range is about 15% of the unsubstituted compound. The correlation between B44 and the HOMO energy is high. As might have been anticipated for gas phase data all substituents lower the energy of the HOMO relative to hydrogen, but the effect of methyt groups is small. The broad general conclusion that ‘can be drawn is that anion stability, as indicated by the HOMO energy, is the major factor. The rather poor correlation with «, which is derived from aqueous ionization of benzoic acids, indicates that a considerably of substituent effects operates in the gas phase, “Gmp 9 MN Eee Sa gH gO," C0; HOMOGY) Grupa #0000 om) 00803 —1a57 —aasan $F 005 366 02 eons 1329 “dass 3F 038-402 0231 “0041s 1204 3.8487 #Ct 023 3.110239 p0m60 “1397 “aes 31037-3110 0239 0.440 “1326 “aes93 SEN 066-795 0232 “omnes <1215 463 3CN 056-749 0232 00297 “in? “ggasi $NO; 078 =1298 0234 0.0297 “i199 “3108 BNO, 071 has 0385 “aoa? 1207 “Saas 4CHy -017 044 0228 00519 1337 a sea SCH, 007 022 oz 00514 “i237 ass CHO -027 01s 0228 —o0s20 “1257 3000 CHO 012-036 028 00190 13% “43047 GH vs, dottatt a Lr 4 0.226 0228 023 o2a2 0204 026 aH 008 -005 004 003 008 001 0 ‘acozH 43> C02 ve. ea 2 of 7 2 4, is Se ae —— -10 a R07 a4 a S| “124 123-128 4212.10 ‘qco2- HOMOev vs. dotatt 2 ° -2 -4 6 -3 10 “2 a4 2 “04-02 0 02 04 06 08 + sigma OBE 3.23. The reactions are all faster in DMSO than methanol, except for SCN~. This can be the result of @ combination of two factors—less solvation of the anion in DMSO and greater solvation of the transition struture in DMSO. The effect is greatest for CI" and Teast for ~ among the halides, which is consistent with stronger solvation of the harder chloride by methanol. The S* in DMSO becomes mare ‘negative in the order CI” < Br” 46 9 orvoMs0 aaa fm 0548+ 20401 ee 4 crmeoH 5 0.0082 oodses 0.0059 0.00808 O00 odes $$’ Ff Yoon Bata wT NyroMs0 f8 conse aodses O00s9 Ome antsy oedoAE aps 2p 3p 4p yo-97872 20888 wNy7MeOH 1S actee 00025 0609s oat%as ootea onfoss = 1 y=-10960%+ 26.221 “4 ~104 2 wr Brouso 5 0.002 0.00325 0.003 0.00095 0.0084 a0g04s pa COO 0.0099 0.00085 0.0034 0.00 ep a BriMeOH NS 0.0082 a00s25 0.009 0.00805 0.0034 p.odaas +7 pa J J y=—11001% + 27.080 we 47 Sienna PonsYy « ‘SCN7OMSO Salsts 0.002 000325 0.0033 cotess 008 oOgsss S| ee ¥4p—_ : ve-solom + 24109 Pp verrovorn autos -10 “2 - — — SCNMeOH 07 0.04815 0.0082 0.00325 0.0083 0.00985 p.onse oodos ya10280x + 22.698 rouso ° 0.04805 0.0081 0.00815 0.0082 0.00825 0.0083 o.daa5, ———$__$_— 2 2 | -4| 6 { 2-6 [yeaa 7586‘ oofers 0.0082 codees 0.005 cadees oovas nods 2s wr 3.24. a. Cyclooetatetraene is strained by 14.5 kcal/mol, relative to butadiene. on ~908.96208 4x ~78.41192 «-913.64708 iyelo[1.1.0] is strained by 66.1 keal/mo © + sey — aononoy «enn ~195.62205 5.x-70.62661 =~ 998,19208 2x-116.85022 = -297-70044 2 18807751 = -216.15500 © 0.10594 = -66.1 kealino! ©. Quadricyelane is strained by 71.3 keal/mol 2 + TOCHCH, —~ CHCH.CH, + 6 (CHui,CH ~27090520 10%-79.62641= 79626641 ~110.8002 6 x-168.07761 = 048.40506 E=-71.9kealmel = 0.1196 Chapter 4 ‘41. a. The observed order reflects the relative carbocation-stabilizing effect of the Substituent groups: cyclopropyl > phenyl > alkyl. The small differences 49> « Bitar Poems i among the alky! groups correspond to the electron donor capacity 1-C,Hy > E-C\H; > CHy and may also reflect steric acceleration, ‘The increasing magnitude of p reflects increasing electron demand in the TS in the order CH, < CF, GCL —— cronpr—cryen je Ct cy Pcp ——= (CHO},PCHPR bon, These stereospecific rearrangements occur by participation of the C-C bond anti the departing brosylate ion. The rearrangement is driven by relief of strain associated with the four-membered ring oe ohm ot LoS LA ott Bed Hy CH, a - a Bue Cry CH (So Se This reaction occurs by chorine participation resulting in an S-exe cyclization, Followed by ring opening of the chloronium ion at the 5p"! carbon in preference (0 the sp carbon, Heny a) — nok y)-o.00, —- enero I tYY 4. These contrasting rearrangements reflect the relative conformational prefer ences in the diazonium ion intermediates and imply panicipation ‘nthe {Rigration process. The hydroxy groups favor the migration by carbonyl bond formation. tn the conformationally biased r-butyl derivative, preferential ‘migration of the anti hydrogen occurs, wrse- ro © The bridging oxygen can assist a o migration, leading to an oxonium ion, and then to hemiacetal that can open to the observed produet. &.-&- PA 1 F. An achiral aziridi displacement, but thi ium ion can be formed from the endo isomer by back-side pathway is not open to the exo isomer. Alternatively, a the racemization might involv actoy patcplon CH Oy t Ohny yoo oe — dA Boe "x cha Yee te ae 2 ee be 55 Gy achtal &: This rearrangement can occur by pauticipation of one of the imide carbonyl ‘groups, aon, ml wa ata “eb — ae? — oa pbenenc.en ol 43.4, The 2,2.2«rfhioroethy|sulfonate isa somewhat better leaving group and reacts about 175 times faster in the example cited Sl eae Pens9d 52 44, 4S. > fe conor efit ofthe ERG CH favors reaction, whereas the polar effect of TEEN group CF, retards the reaction. The difference is & felon of shove 1000 in the example cited. While ther is some strain atthe 7 postion, the bridgehead position is very the rate scehe fae ratios reported tobe 16:1. According to one analysis (see {he references), the strain associated with ionization of 1-7, ana 2-norborny! Gevivatives are 30. 16.5, and 4 kealimol, respectively. Furthermore mele, ‘philic solvent participation is precluded for the 1 isomer, & Reactant stain (B-stain) increases reactivity in the t-butyl case by @ factor of 39,600 over the CH, compound. & he exo methylene derivative is 8.8 x 10" slower. The double bond is held Perpendicular to the ionizing bond and cannot participate by electron deloc. carbons af a_TS. Additional sain and the unfavorable polar efect of the sp Sarbons of the vinyl group also contribute to the diminished rate {The a-sulfonyl chloride is less than one-twentieth as reactive asthe B-sulfonyl {alle This i de toa steric effect of the branched sulfonyl. perhaps cohaveed by the partial negative charge (repulsive to iodide) associated with ihe sulfonyl oxygens & Je cxclopropyearbiny| structure is about 100 times more reactive asa result ofthe cation-stbilizing effect of the eyetopropyl group. bye unsalurated compound is nearly 100 times more reactive andthe products inate Favorable geometry for neighboring-group participation, 4 The onto isomer is more than 150 times ‘more reactive because of intramolecular neighboring-group participation ion. The rate of exchange measures the rate of internal teture of sulfonate with scrambling of the tosylate oxygens. The rate shone « slight Frere ( Fetum of the original oxygen (k, > h.,), which may be dneere CAtfrential solvation ofthe oxygens. Conversion tothe final racemic produ by Fenuion of the eation with acetic acid occurs at about one-fifth the vate of ie, formation, that is, about four out of five ofthe phenonium ion pass saten reactant, oro v a SEH Aon, OW ‘a Sco, b,com 05 The nonpolar solvent and use of «soluble azide salt promote an $y? mechanism ‘over ionization, as demonstrated by the inversion of conti Sisenoe of any rearrangement, The reduced rate relative to eyclohenyl brosylate ‘iso implies that there is no kinetic entancement from or patcipation aqw oF ake endo and 80% of the exo isomer reacts via a back-side displacement. ‘The nortricyclane must be formed by ‘concerted attack of azide on the exo Ci AS Ny 46, 4 bimolecular process as well, perhaps a (6) hydrogen, m= — cs Fos = He, " = = Pt s oN ais Dog ae Odom es | ray mo, = PA Ci on ‘The results are consistent with the formation of a Z-allylic cation from both eactants, followed by isomerization ‘The normal deuterium isotope effect to the E-cation and product formation, for the diene indicates rate-determining Protonation, whereas the inverse isotope effect for the alcohol results from the higher extent of proton: step is the ionization of the protonat mn in the deuterated solvent. The rate-determining ted alcohol. The £, values refer to the fate-determining step and indicate that the isomerization must occur with a lower energy requirement. The barrier to isomerization would be expected to be significantly reduced, as observed, by the presence of the phenyl group, which brovides alternative (benzylic) stabilization of the carbocation. An approximate reaction energy profile is sketched in Figure 4.6P on page 54. 47. Le oni or Deprotonati sesulting di ~@ of the phenol group permits effective aryl participation and the none has moderate stability Comment. The authors remark on the very surprising chemical shift equivalence of the a and B-cyclohexadienone proions in the 60 MHz spectrum. So far as can be determined, hhas not been pursued is aspect of the propenties of spiro{2.S]octa-d,7-dien-6-one ‘48, The syn isomer can ionize with « participation that leads to analy ion, 0. 2 ~ & = & 5354 Free energy lrans-alcohol Feaction coordinate Fig. 4.6%. Approximate reaction energy profile for fomerzation reactions. Reproduced from J. Am. Chem. Soc. 93, 69 (1971), by Fermission ofthe American Chemie Society 4.9. The following ions are the most stable structures that are isomeric with the initial carbocation that would be formed. See pp. 436-438 for discussion of carbocation structures under stable ion conditions. "By "Opes *Opaee 4 ob oS ‘cs 4-10. The ratios of solvolysis to exchange are 4.55, 4.47, 0.83, and very large, respec- Lively, The relatively unhindered secondary systems represented by i-propyl and cyclopentyl indicate only about 20% internal ion retum, This presumably results from major solvent participation. Note tht the ratio is virtually unchanged, even though the absolute rates differ by a factor of 100. The extent of ion pair rlumn becomes larger in the more hindered 2-adamantyl system, where nucleophil Solvent participation is decreased by sterie factors. The 3,3-dimethy!-2-bity] system rearranges to a tertiary carbocation faster than internal return oceurs. Thes Suggests the possiblity of concerted ionization and rearrangement. ‘411, The smaller p and r values inthe Yukawa-Tsuno equation forthe I-arylpropeny! cation indicate a reduced electron demand, which must be due to the electros- releasing character of the methy! group, OR, — Ox, — OR, 4:12 a. The dependence on [Nj] withthe EWGs reflects a shit from an wacoupled ‘© coupled mechanism in response to lower carhcation stability.3 4d ‘is result is consistent with little direct nucleophilic participation in the reactions that proceed through discrete carbocations TRS test indicates greater selectivity for Ni by more stable (longerlived) carbocations, Less stable carbocations may collapse so rapidly that solvent Geplure is more favorable in competition with the anionic nucleophile ‘This tesult is as atcipated, since the Ny is acting directly asa mucleophii participant ‘The retention of configuration in both cases indicates participation. The Stealer rate enhaneement in 13-A. indicates that the isolated double bond is imore effective at stabilizing the TS than an aryl ring. This can be explained in terms of the -bond order of the participating bonds, which is 1.0 im 13-A 8s opposed (0 0.5 for 13-B. This implies higher electron density to the back side of the bromine in 13-A, The aromatic 7 electrons are also “harder: The cyclopropylearbinyl character of 13-D reduces the electron demand. ‘The product array from reactant 13-E is consistent with formation of the cyclopropylcarbiny! carbocation 13-G. kk 136 1346 Reactant F evidently has a more favorable pathway tothe stabilized ion 13-H, ‘hich ean also account for the observed stereaspecificty. LA. — EA — wt TEPC tae [Js suggested that the ring expansion preference is related to reactant confor- ‘mation, Reactants 13-1 and 13:f have configurations that permit formation of eyclo- Propylearbinyl cation 13-L, On the other hand, the syn relationship of the leaving group to the double bond in reactant 13-K precludes participation 134 Thess results illuswate the effect of remote substituents on adamantyl solvolysis, The EWG fluoro substituent promotes retention inthe sym isornee, whereas the ERG substituent (CH,),Sn leads to retention in the ant! isomer Hess felts have been explained in terms of preferential ¢ bridging of the most electronich C—C bonds. The rate retardation for the anti fear derivative is consistent with this explanation. The nearly complete racen tation forthe ant isomer indicates nearly asymmetsc solvation, Both sana derivatives are much more reactive, which is consistent with the ERG character of the stannyl group, but there is litle rate difference between the two stereoisomers. The extensive inversion with the sym isomer must 55 Sire Pros4.14, 4.15, 4.16, 47, ons ors =o & ant on Dost bridging for best bridging for ERG substituent ERG substivent Ton 1 is an aromatic cyclopropenium ion, Jon 2 is allylic and can also be considered to be the homoaromatic analog of cyclopropenium ion, Jon 3 can be stabilized by conjugation withthe adjacent double bond, fons 4 and $ are isomeric rrepabilic cations that benefit from resonance stabilization. Theie relatively high energy is rather surprising. No conventional stabilization is evident for icy 6, which is a vinyl cation, ‘The highly reactive endo-anti isomer benefits from optimal alignment of the ¢yclopropy! orbitals and can lead to a bridged ion A. This structure also accounts {or the stereospecifiity of the reaction. The exo-syn isomer can benefit Irene ‘Eearrangement to a eyclopropylcarbiny! cation B. The exo-anti and eno-syn ers rem aligned wal fo eyclopops pepe a be = Ay w a> ptm eyclon earangementisaas io ® ‘cyclopropyl ortitats = = a ‘The first two cations benefit only from direct aromatic stabilization, This stabi- lization increases with the donor cha in the thitd cation, the most effective stabilization is from the 2.3-double bond, as can be seen from the very large upfield shifts. This stabilization becomes Zelatively less important, as the aryl substituent becomes more stabilizing, This {Gan be seen in the case of the 4-methoxy substituent, where the chemical shift iS now similar o the other two cations. The strongly bridged carbocation might be formulated as m complexes, as forthe norbornyl cation (ee Section 4.4.5) Ar Zhe T-norbory! system suffers angle stain on ionization and o participation is ‘minimized by the strain involved. The exdo-2 isomer can be taken on ihe “norial” rate forthe system, The exo-2-system benelits from C(5)—C(6) Participation to give the bridged norbornyl cation. The «nti-7-norborn4.18, 49, 420, 4a 422. 423, ‘ystems benefits from 7 participation. The two tricyelic systems benefit from cyelopropy! participation, with additional relief of strain in the ease of the bieyelo[3.2.0.0 }heptan-3-y! system, Ute first-order reaction represents rate-limiting Sy 1 ionization, As substituents become less electron donating, the first-order process becomes negligible in comparison with the second-order reaction. This is consistent with the need for Sarbocation siabilization in the ionization reaction, The curvature in the Yukawe, ‘Tauno plot forthe second-order reaction suggests continuous change inthe “exwfa” resonance component. As the aryl group becomes less able to sablize Poriave charge, the TS becomes more concerted and tighter, with less charge buildup and therefore less substituent sensitivity he 7 values suggest increasing “extra” resonance in the order (CH, CH.) < CH,,H The second set of reactions pertains to aryL-assisted processes, The resonance component is now somewhat smaller, but in the same direction, since the CF, sroup will sgn increase the need for resonance pacicipation, ‘his is considered to be a ease of opposing resonance and polar effects. While the eyano group is a strong polar EWG in both the a- and postions, the substituent ean also provide esonance stabilization. This stabilization is qual Latively similar to propargyl resonance, but less favorable because of the more electronegative character of nitrogen, don 37Yy 58 Bai Proms For the branched system, the potential for forma by rearrangement favors migration, The donor cap ‘migration of the sily-substituted methylene in prefere n of a tertiary carbocation Of the silyl group favors, nce (0 the methyl groups, gs P, sory west Ep oTes OP oo PL cad ae [ites Eonons oH ony body, foes a 10 —~ Compound 25-€ is well alig nortricyclane is observed. rehome a Compound 25-D may ret by an nvamolcuar ennaion reaction - Aeon a are HO "CH, ned for concerted participation and a high yield of FerpPoun 25-8 shows 1 evidence of panicipation and gives only a very low Zicld of apparent oxidation products, Evidently, the primaty toryte sence only by direct displacement.4.26. Compound 25-F is favorably aligned for fragmentation of the“ eyelopropane formation. ro btw ats a ots oak. G probably lies in steric interactions between the ring and the methyl ide” conformation in 25-G, Note, however, that the Participation does retain its stereospecificity, dae ono von, ‘oncHy Gram rgemaniion | famaabymigaten tomes by tagraniaton wah Sens awit serecspecte sftmd ogre sing. tipeas sat ‘Sylpropanetomatan expanse 4 The viny! cations are less stable than the ethyl and thus benefit more from electron donation by substituenis, 5 The sp carbon in vinyl cations is more electronegative than the sp? carbon in chy! cations. This results in a more unfavorable polar interaction with the iMate Clestronegatve substituents, which pantaly cancels the stabilization by sm donation, © The vinyl cations would be expected to be more electronegative than the cyt cations and therefore would lose less eletron density to polar EWG substituents, such as cyano and wifluoromethyl, 4: The order of stabilization is OH > Br > C1» F> CF, > CN, which, except for OH. is inthe order of the potariy ofthe subsiens, indicating that « polar effect is dominant, All the CH,-X groups except CH, CN remain sabi izing, although less so than methyl. This suggests that the dominant effec ie alkyl Group hyperconjugation, attenuated, but not dominated, bythe polar effect ot the substituent group, © These m-donor substituents are all strongly stabilizing in both ethyl and funy! cations. The order is NHy > OH ~ SH for ethyl and NH, > SH OH for vinyl. These substituents presumably have opposing resonance and polar compounds, 59 Iry 60 4.27, Sitoar a Frain Hy om, Invasion aon ce) sf f ance) s +6 seat oy pectin we josesto forte becouse tin mona ‘stoebunon 5) ° oo fo tetorton 316) = | | Chapter 5 51.4 THe dub stew i soit 90 tn re reaive bese of he unui ces of te cleste-dnatng yt pte se > ‘Table 52, whch weld ast omer aera se b Be i home, heh ha the CBr tea win het ah in ons (Cre Forge poner dis-isoner trans-isomor The EWG carboxy group destabilizes the carbocation intermediate and the Bat sited compound is about 100 times more reactive in 20% H,S0,. & Roth alkenes will give the same carbocation, which is tertiary od Siso benefits from cyclopropylcarbinyl stabilization, Under these circumstances, seaman eperBy should determine the relative, and the less stable exocyelic compound is about 23 times more reactive, © The sulfonyl isa much poorer teaving group than the sulfonate and is substan- tially less reactive, f, The EWG methyl stabilizes the B-chlorovinyl carbocation intermediate and is about 65 times more reactive, 8 The bridgehead structure prevents the oxygen from providing any stabilization '0 the carbocation intermediate. Under these circumstances, the polar EWcharacter of the oxygen is dominant and the bridgehead compound is about 61 10 tes reactive, Normally the strain assoiated with the bridgehead dole bond would lead wo enhanced resctivity, so the electronic factor is greater than the observed difference of 10°, 4 This alkene would be expected to give an S-exo cyclization product as a result of intramolecular nucleophilic participation. The preference between the two alternative cyclization TSs is small and a 2:1 mixture of products is formed, ocr ZOX.chete HOH HOGtH, HOCH, a4 HOCH M2 OO ue a “oles °° b. The regiochemisty is controlled by the stability ofthe cyclopropylearbinyh cation, The addition is syn, reflecting involvement of a relatively stable carbocation, There is a modest preference for attack ant o the eyclopropy!- ‘methylene group, which can be attributed to a steric effect. o2 @. & §. fe © This action would be expected to proceed by removal of the acidic proton ‘(0 the carbonyl group. Elimination to the less sterically congested E-nomer is expected and observed. e CM whew whe ao == HOO HO 47 geen peter ested ere aan us i Hy L7H ¢: The product composition corresponds to net substitution, suggesting a carbo- «cation process. The observed product can be accounted for by terminal allone62 Siar Patios 53. 54, Feaation. wih the regiochemistry governed by the eyelopropyl group followed by ring opening and deprotonation, co, oo, oo ° ong oe Oe, 5 MCh os EP BRE — op one Ey cn ie oy? 0 Yo bm F The highly hindered base leads to &3:1 preference for the exocycle alkene OF st O- Qe 2 "minor & These reaction conditions lead to the isolation of the methoxymercuration Product as the chloride, The methoxy group is located atthe benzylic postion 1) Hg(OAC)y CHOH Cty cH=cH SO oy, CHCH Hct 2) Nach i och, 1 Because the reaction can proceed through « phenyl-sabilized vinyl eaton, A rinture of anti and syn addition is expected. Both the dichloride and the solvent incorporation products are nearly a 1:1 mixture of syn and ant addition Fr phat ScleAt incorporation product regiochemistry is controled by the phenyl substituent Pho Pr Cay Pri Ph Gly oot * a? * ancora * anoor™e, The trans isomer can attain art alignment ofa B-hydrogen only in adaxial chai Sintra Conformation, thus disfworing the elimination. Evidently the sym elimination mechanism is also strongly disfavored, because this would inewecge torsional strain, N(CH as (OC LF —N CH, os ‘rane Ihe elatvely large postive p valves are consistent with an Elebstike TS for the quater Holope effects, suggesting more synchronous ‘Ss, None of the eliminations ‘ppear to be El-ike, since the p would be expected to be negative for an Bl-tke ans ietope effect near 7 forthe bromide suggests an TS near he midhoina Sisal ond breaking. An ineresting point is thatthe tosylate sroup, nhroin a Beuter leaving group in Sy2 reactions than bromide. seems to be a soma Poorer leaving group by these criteria$5. In the erythro isomer, the deuterium is ant tothe bromine in the conformation that gives rise to E-2-butene. The primary isotope effect should increme the ‘amount of Z-2-butene and I-butene at the expense of E-2-butene 56. The order of reactivity is expected to be governed by carbocation stability and therefore is in the order shovn, The reported second-order rate constant, (M~'S"") are given with the structures, og Se an > cHy0" 75x10? 20x10 37x10 495x40% 61x10 517. a. The observed regiochemisty isthe result of phenyl stabilization ofthe carbo- ation intermediate, The syn addition is also consistent with the involvement of a stabilized carbocation with rapid nucleophilic capture. The protonation ‘cccurs from an axial direction to maximize the overlap with thew electron density. The reactant conformation is controlled by the #-buty! substituent D ° Dear — Ne BA) wath ie Wor ra '. The regiochemisty is controlted by phenyl stabilization of the carbocation intermediate, The preferred syn addition isthe result of phenyl stabilization ot the ion pair, which collapses faster than dissociation or stereorandomization ‘There is a larger driving force for rotation to relieve strain in the Z-isomen, 4nd this results in a higher degree of stereorandomization © This reaction proceeds from the sterically preferred exo direction, with Markovnikov regioseletivty, There is no need to invoke a bridging carbo. Galion, because ter-earbocations are of suftcient stability to avoid bridging, 4 The stereochemistry results om diaxial addition, with the t-butyl grove Sontoling reactant and product conformation. Although reglochemisty not an issue with the symmetrical reagent, the nucleophilic attack would be ‘expected to occur at the more-substituted end of the bromonium ion 8 HL on, 6364 58 4 The p value is positive, which indicates a net negative charge buildup. ihe formation of 8-B evidently involves an E2 mechanism with some Ele character. similar mechanism should occur in formation of 8C bu the ay ‘group is {00 remote from the site of charge buildup to influence the rate, by The repiochemisty is controled by the influence of the methyl gioup, which teas to a 1.3-dimethylliyl cation (pent-3-en-2-ylium) [as opposed to a pent, 2-en-L-ylium cation that would result from C(4) protonation} The obseced produets are the result of 1,2- and 1,4-addition tothe 1,3-dimethylaliy cation, ‘The lack of equal distribution ofthe two products rules out a dissoctated ton Pain, where any distinction between C(2) and C(4) would be lost Rather, the results indicate a tendency to capture the cation site closest to the site of Protonation. This is consistent with formation and rapid collapse of am ion pair, OF pox CHO CA OM Ohh x 0H:D hay — Mrs AHO > Syn = a a The EWG carbonyl destabilizes carbocation character at C(3), requiring the Slereospecific anti addition mechanism. The regiockemisiry of addition of Br {Ct indicates that the benzylic sie i the point of nucleophilic ting opening Of the bromonium ion, of — of 4. This is an example of the preferred terminal protonation of allen. Internal protonation does not lead to an allylic cation for sterecelectronic Feasons (p, 545), mT Oty-gn — chy-pm0% _ ory-e-y bs 3 c=: The results are consistent with the lesser stability of the cyclohexyl cation and the resulting involvement of an Ad,3 mechanism. The rate acceleration is Presumably due to chloride-assisted protonation (see p. 479), The more stable benzylic cation can be formed without any chloride participation cr a O=- OD character at the TS, and shows that the addition of each fluorine makes it ‘more difficult 10 break a C—F bond,59. a. The stereochemistry is consistent with anti add induced anti elimination, b. The stereochemistry indicates syn elimination, which is likely to occur via intramolecular formation of a oxasilacyclobutane intermediate, ©. Reversible formation of the achiral bromoni ium ion ean account for the racem= zation while retaining anti stereochemistry : X~ Che “er er xtcaly achiral {. Double-bond participation in the bromine attack (or bromonium ion opening) can account for the formation of the product. The ring geometry favers this participation by shielding the back side of both double bonds, Br. Cy a “Ady 5:10. The bridged bromonium ion benefits from both substituent in the disubst derivative, whereas the more localized vinyl cation that isthe inermedinas hydration is primarily stabilized by only one substituent ted, S11. The first two produets are anti audition products thal can be formed through bromonium ions, The major isomer isthe diaxial addition product,66 former taneauatorial aroyloxy substituent. The third and fourth products ean be ‘ormed by intramolecular participation ofthe aroyloxy group, 5:12. This corelation is consistent with a rate-determining formation of a benzyl cation having direct resonance interaction withthe Ar ring. The effect ofthe saeco coer SO trOng, as indicated by the 0.23 factor and the normal «substituent Shenant, 2m Particular, these results are not consistent with direct formation of pphenonium ion by Ar’ participation in the ionization, 5:13: An Ade3 mechanism invelving nucleophilic capture ofan alkene-HCL complex Ould appear to be ruled out by the observed rate decrease in the presence of aries ahloride ion, since added chloride should accelerate the rate of capture sm that would exhibit third-order jinctcs is HClassisted formation of the carbocation. Added chloride cecry inhibit the reaction by complexing with HCI, The lck of deuterium incoxporstion {nto the reactant indicates fast capture of the carbocation by chloride CH= CHR + Ho! cr Her fast ACH=CHR SO". RCHCH A REHCHA a S14. These results are consistent with a change of mechanism from a bridged tyomonium jon for EWG substituents to an open carbocation for ERGs re 515, Consistent with other alkene hydration, the reaction is expected to proceed seegnth & carbocation intermediwe. The observation of both 1-2 and 1a {xidition products is consistent with this expectation, The normal value ar Alki cece tsinent with rate-determining protonation The substituent effects ithe gtder ethoxy > eyclepropy! > methy! > chloro are also consistent wih mace determining formation of a carbocation intermediate) 5.17. 518, 5.19. x. t Rp RoH-kcH cco a crycos ith the stronger acd, a carbocation can be formed and there is some reversal jexling to both deuterium incorporation and react isomerization, The addin is also somewhat less stereoselective. This result indicates that CF,S0,H can ‘fect protonation without solvent participation, RCH=CHA + CF,S0H —== ACHCHAA + CFySO,- RGHCHR + CHyCOH —~ AoHoHAA ,0cH, Zee following tends are apparent in the daa: (1) The ratio of elimination to fubstitution increases with base concentration. The trend is gradual in methanol reid ana the extent of elimination increases. Since the teactant i tetany halide, the competition is expected to be among El. Sy 1, and E2 mechanisne ae very slight inctease in rate with [OMe] in methanol suggests tha fe from increasing deprotonation of the carbocation intermediate with increasing (OMe). The enhanced basicity of MeO in DMSO, along with the semen ‘starded ionization rate can account both for the increased tolal rate and the increased extent of elimination in the DMSO mixtures, 4 Bach of these cations benefis fom the delocalization by the aryl substituent, (Tie onder of the r~ values suggests that this is of inereasing importance in he order tert sp®< sp < sec sp?. >. The energy profile suggests that TS! is close in structure and energy tothe Fyoduet ation H,O complex. There ismore charge on the phenyl ring (0.369) ‘han in the case of the alkene protonation TS (40.196). ‘The alkene proto. nation TS is much closer to the reactanis than to the product. By the Hammond Postulate, it has an “early” transition state, This is consistent with the reduced extra resonance stabilization, as measured by the Yukawa-Tsuno r- ‘These catalysts are believed to function by complexation of the halogen, with release of halide, probably as trihalide anion. The enhanced sucleophilicity of the halide (or wihalide) and diminished eletrophiicty are responsible forthe japon Serie contol of regicsclectvity. The thiowren derivative may be a ‘avoruble catalyst by enhancing the atraction forthe polavizabe hatopene> 68 5.20, 5.21 o — etn ZThe mechanism of oxymercuration is believed t involve nucleophile ‘capture of senotn en, formed mercurinium ion or complex. Markovnikov oriemation Sepealy observed for unsymmetrical alkenes. In conformational pissed eyclo- -butyleyclohexene, there tenis nr Preference for atick away from the ‘-butyl group, as a recul ot SSUE ifelding of the position adjacent co the substituent. This effect i slog pred, pmethyleyclohexene, although the exient is reduced. About 10% of he Droduct from 3-methylcyctohexene results in introduction of equtoria! hydroxy, Timer dee atee conformational bias, compared to the ‘butyl system, limethy|-4-r-bayleyclobexene, the repiochemisty is controlled ty she ‘methyl sipaltuent, but the addition of hydrony is entirely from the axel dnceton Link toapelvlyelohexene, 4-methyleyelohexene shows no regioreleciviy, bar he {odroxylation is axial at both ends of the double bond. These resuve wee Sat ae ith reversible mercuraion followed by product determining nosis ophilic capture. of configuration leads to the desi 5. The stereochemistry and regiochemistry of the solvobrominaion are. as expected, with the nucleophile attacking the more substituted (cationic) Sarhony! group in displacement of the bromide and hydrolysis lends to the more hindered cis-diol chen, Phgooo, Mo Hy os “Br oS, Ho, 5 ony Hy hy cy oH Oe © Narious reagents have been used to achieve chemoselective fanctionaliztfon go polyenss. based on diferential reactivity, This example is reported setlists All the double bonds are tisubstiited suggesting shales The def rcnnoueh asmall polar EWG elect may deactivate the allylic thes deelfeentation between the remaining terminal and interna cosine sabe fowvition effect. The smaller eyctopentadienide ion is more strongly 7 mabitzed in solution, in the gas phase, the size of the molecaks slightly increase the acidity of the fused-ring systems, ‘The Cs" compound shouldbe the most foie and dissociated. The considerably lower rotational barrier for Li” indicates some participation igre rotation abil erat ivolve partial covalent bonding a the TS, which casos ibilize the localized charge associated with the bent anion. $4: a. The additional ring strain imposed by ichybridhenny ‘accounts For the slow reaction of bicyclo[2.1.Ihexan-2-one, eutration cycle will cause exchange al all te postions tha ae part of the cyclopropyl ring in the homoenolate 8 om oe 4 Hh — Ko, — 65. =21 + fog [RH] 226=21 tog log Ra ha q [RH] IR] = 19 og H> R 66, This result is in agreement withthe importance of a stercoclectronic factor arising from better aligniment ofthe axial C—H bond with the carbonyl 7 orbital, 6:7. There is an excellent correlation between the p&’ and the rte of exchange Compound kek pk — 9-Prenyiaorene 1.762 ins Inéene 2301 199 ( SetBerzoflarene 2044 lox ( 1.2 erzeuorene 2.496 203 Fhiorsne 303 2 23-Bonzofeorene 668 as Exchange rate vs. pk Exchange rate 68. The correlation is best with er, This is consistent with the absence of direct Conjugation of the negative charge with a ring substituent, The o~ correlation is the poorest. This confirms that lack of direct conjugation and enhanced resonence stabilization between the negative charge and the ting substituents. $a eRa» ie - 7 3B tag Saga Sa Fr i oe oe a. |... (ot a : ‘ ’ ° (ae i can ae os ts fom ase _ oan tas -— |. owe teste ' sigma ve, pKipKo = eee sie sigma + ve pK/pKo aa oa aa 7 gos fecane aa : cee 18 RS PES SRSA RT EEE NRO ena> 4 69.4, Saar rar » : 4, Pm —— mora —— ec 6 Sen crates ra “h [w {re Prac Proton ne PhsC” anion. I is suggested thatthe use of pyridine fara this process by coordination of Li* and AL?* centers, which could oesene stabilize the alkoxide, b: This rection is thought to proceed by hemiaeetl ting opening, followed by the ization snd elimination of an enedil. The later species cra eves for © This tereoequiibration ean occur via reversible ting ‘opening, which is facil- ‘ated by the stabilization ofthe anion provided by the phenyt ting, 4. The opening of the cyclic hemiacetal generates an aldehyde with a single chiral center that can be racemized via the coresponding achiral enolate, CH oes ons 0 . 0 a oNo : x ‘oNo H i — oh on "0G = o=ow » o=ow © Fe prolates can equilibrate, perhaps trough a 1,5-hydrogen shift The more highly substituted one is more stable. } | SRT eatensame relaxed as the ring size increases, may increate the energy of the lactone and inns dectease the enctay required for deprotonation, Ie observed that the configure ations of eters are about 3kealmol less stable hase sis configurations and this has been attributed toa steroslerue ¢ effect involving ‘he sp" oxygen pair withthe o* orbital ofthe earbony) group. Ayo Ao x wd (or, Iiracon”? —— ebliing O11, DMSO-alkoxide systems are characterized by a bigh degree of internal return, DI ‘This may be due to the proximity of « relive seule coordinated alcoho! Rens te one pee, Ro” Row Row MFos(Crildy —M—108(CH LI} Ih —IosiCHyhy [OS(CHa1, 6-12. a This is due to the somewhat greater stability of endocyctie double bonds in Tha peered rings as compared to fivesmembered rings & he eto forms of ethyl acetate and acelamide are siatilized by resonance reeling the oxygen or nitvogen substituents, respectively, ‘hat is not available to acetone, & Suvetually, this may be due tothe extended conjugation inthe enol of 2- indanone. The hydroxy group is conjugated withthe womete ring. In the eno! OF L-indanone, there is no such conjugation. & The ring favors coplanarty of the conjugned enolate and reduces nonbonded repulsions. 6.13. a, CQ LA ertcorc.a, 5 Phe acidity ofboth the Keto and enol forms of 9formyifiuorene is enhanced by ‘he aromaticty associated withthe common enolate anion and dn increases 18 ins Pron,Dp 6 ie Sit ofthe carbonyl form by an especially large factor. The pK ofthe 3 a keto form is 6.2. whereas i is 7.4 forthe enol form. The K for eetionien ene can be calculated by using the relationship PK octution = PRent ~ PKay = 146.2 = 1.2 © The combined acidifying effect ofthe cyano and ester substituents, along with an intramolecular hydrogen bond, provides a stabilized enol, 6.14. a. The enhanced acidity of 2-indanone can be attributed to greater stability ofthe rere ari from increased planarity and reduction of nonbonded repusions felative to the noncyclic model. ' Jn addition to planarity and reduced steric repulsions, the enolate inthis case benefits from aromatcity of the indole ring & The eyelic enolate benefits feom planarity and reduction of nonbonded ‘repulsion relative to the acyclic model sing sft nach ema honerey a eae nde incite one bi the Ucar on rae Q Te ton can hn be aslo te la sean aaa te he agp TS A or a aN i Re fs en nied Nh ton, ‘a 4 FO Yl e ‘Con, on ar ® Moerttaieed deonstciont testineet —catroecyns saci, SESS teem santo Reon ge explanation iain santo Rt via TSB CH Hop <3997 RE direct alia va TS 8 CH npr 20:20 "Pr directs alton via TS A Se ae easier a SURES reasremmndiomanmn) 6.16. Chelation by the metal ion increases the effective electronegativity of the carbonyl oxygen and promotes base-catalyzed deprotonation. ws 6.17. The steteoselectivity of the deprotonation and protonation implies a stereoelec- MO eset that strongly favors an equatorial orientation of the tarkantee In MO ‘terminology this can be attributed to a combination of destabilizing inter- inter the sulfur unshared electrons inthe axial carbanion and » ac ing thar non wth the C-S o* forthe equatorial carbanion. The resulta se, imply ‘hat the earbanion is pyramidal rather than planar. : ; mph 3 oH G cH 6.18 a The HOMO orbitals shown below for the butadiene dianion and the ‘rimethylemethane dianion indicate that the later would be more sable, = an78 ota — 4 062s i) + +e wroezs jf av1629 . Ht aesz98 Fas da 3.249 408.409 © On the basis of the calculated total HOMO energies, the anion E is the (roconnable, The authors of the referenced paper also calculated the REP {Gesonance energy per atom) basis. On this basis, ion F was most sable et Jom iment! observation is that ion F increases at the expense of the eves fons, implying that it is the most stable, ce ° e F Tiss tho equvalent | Thisisavimethyons- Ths oF wo tated ally anions methane daria pus oy an iclsied dove bond mM 804567 asa aaeo.e7 Basen hoxationy! This a branched Imotyenepantadeny anon 6-19, The second stricture, which provides a relatively acidie enol moiety having 5 > 6 > 7 relationships for most ring closures involving 79 a Pens€ > 80 Bair Palen ‘The dominant produet from 1, result can be explained in terms of ring size preference, ‘ibromopropane is an O-alkylation product. This in this case 6 > 4. The absence of product with the endocyelie double bond is aitibued c equilibration oF he endocyclic and exocyclcenoiaes wih more rapid eyeliaticg ae tater, Ga ee : Ca) mtibromobutane, the product is the result of a spiro dialkylation a SO) ecause the formation of «five-membered ring is prefered te ye sevens ‘membered ring formed by O-alkylation. Again, onl e CH, Hy I een ce ° ° = _ 623, The retention observed with the cyano compound indicates that the proton st exclusively by internal return, whereas the ketone {nr (22) carbanions, which typically have signiticam inversion beri 624, Let the two product ratios be X/Y and X'7Y, where ¥ ie he unchanged rate of reaction at the methyl group. Then: Foe ma X= Mp5 are & ng ya 2X! a 0 6X 20x! 34 gO 480X = 1880x! x _ 1880 x) 480 625. 4 Tis rut can be inetd in terms of Hee shicng by te vere a Raa ete butyldiphenylsiloxy substituent. ‘The use of two equivalents of LDA means that the hydroxy group will be deprotonated and available to participate in coordination nile ee The prepired conformation of the enolate has the smallest group (H) eclipsed Wipe enolate oxygen, Tt has been suggested thatthe solvent melee an mide ions associated withthe Li? conubute the steric bul the fs ‘attack from the opposite face through a TS such as shown Belews© This reaction isan $.2' alkylation. The observed. stereoselectivty is consistent Wit a chicike conformation forthe TS forthe intramolecular alkyaten a Lo- ry 6:26. The computational structres reveal, as expected, that there is significant coordi- havin of Li” to all the oxygens in the dianion, Also, as expected, he deproto- aio atthe CH group, not the CHO” group. The sructurs alse indica ng Sroun f less sterically encumbered tha any ofthe enolates having t-butyl Broups, because the i-propyl group assumes conformations with she hydrogen, cee ing ard the enolate. In the t-butyl esters, a methyl is placed proce near the enolse. Comparing 4 to 1, there is an enhanced preference re hoe eg vlna ta Reece epteduced from Helv. Chin. Acta, 88, 4216 (2002) by permission of Wiley. VCH. Chapter 7 (anomeric effect) c is further enhanced ‘Teena receeesee rem 8 Sinan Pens St82 Bie Pens 72a. The more favorable K for addition, despite the adjacent ‘butyl substituent, reflects the stabilization ofthe carbonyl form of acetophenone resulting from conjugation with the benzene ring, +. The hydrate of the aldehyde group can reset by intramolecular nucleophilic catalysis, °. HO. on on pr cocn, to cn, oe ee ~ 88. a8 & i teslt reflects the greater stabilization of the TS for elimination from Ae terasubtiuted carton inthe former case. The stability of the enone Ss should be in the same order as the products 4 These Keioes have aromatic character, whereas the letrahedral addition inter Feta aaaa xchange donot. This loss of aromatcty contibutes toa higher E, for addition and results in a slower exchange rate, 73a The onder is CHyCH=CHCH(OGH,), CHCH(OGH), > CICH,CH(OC,H,),. ii oer canbe predicted onthe basis ofthe ate-dtermining cleavage ofan Qprotonated acta. Cleavage will be accelerated by the conlugaed docs fond in the but-2-enal acca. The polar effect ofthe chloro substuen ang both decrease the basicity ofthe acetal toward protonation and destailine he oxoniumn ion intermediate The ord is (CH)xC(OC\H,), > CHCH(OCyH,). > CH(OC\H)y. This order reflects the stabi rallels the position of the equilibrium constant for rable for the more-substituted acetals, © Th order is camphor ~ eyclopentanone > cyclohexanone. The order reflects {Preference for sp» sp? hybridization change for five-membered rings Zhe tate of camphor, which also involves a fiveemembered rng, is slightly greater than for cyclopentanone, 4. The order is 3,3-dimethyl-2-butanone > 4,4-dimeth {loser to a stepwise reaction as the alcohol becomes mre basic neds poorer leaving group. The fat thatthe a values are relatively la rae Suggests that proton transfer is advanced.SEE men R09" He nro dod 75: & Intramolecular general base catalysis of water attack fs the most likely possi Pity. Inamolecular nucleophilic catalysis is less likely because of sary Intramolecular general base catalysis is evident as the upward bend in the pH profile corresponding to deprotonation ofthe quinoline nitrogen in the region PIT = 2-4. This pH-ndependent mechanism is dominant inthe pH range 4-8, ‘her which unassisted hydroxide ion attack is the principal reation, Intramolecular goneral ‘base catalysis of wator attack Intramolecular Pueleophile catalysis ® Direct nucleophilic catalysis, general base catalysis of water attack, o intramolecular O-protonation all might be feasible. Ether the carboxylave or the phenol is deprotonated. The increasing rate between pH = sponds to ionization of the carboxy group with a pk’ ~ 3, This mechan and 5 cort gominant inthe pH range 6-8. The second upward bend between pH 8 and 9 is consistent with engagement of the phenol anion, 83 Saas res( > 84 0. = o: ‘OH, Sis Fons — s ~° _ was ooh oo Sok, on Ci on On ks t 2 Initamolecolar lnramoleutar genera invameocuar Frclecphiiccataysis bata caayelofmataretace (Nomoto By carbonate soup by pheno grou ays ion can provide general acidasisted water addition. The upward bend at pH d te consistent with pendent attack ty the deproionated imidazole ring, untich is pH independent and dominates for pH 6-8. Av neve basic pH, itimolecular nucleophilic catalysis by the Imidazole sane is possible, ston wa toed ar ke caren sion at = 3 7 é 3 red nw? Ww 5 3 a cro! cnyo*Brf oe An My Wn Greatactetewee —sunmcncurwt whence @ of water attack ‘base assistance of water catalysis tack 4: Intramolecular general base catalysis by the amino Broup is possible. The PH-rate profile shows an upward bend corresponding to deprotonation of the ‘amino group with a pk ~ 10, 76, The rate depends on the concentration ofthe monoanion (HA), which is much talons are ela te neural species HA or the dianion A2."These comet ‘ratlons are related by the two acid dissociation constants K.» and Ka. (ayer) (aye) | fo Ga) iM ke SO Rate, (HA) 4 hy(Ha) ‘The (HA) and (HyA) terms can be expressed on the basis of Ky and Ky Ka, Ko (H) "(Hy RN acmeWissen wi K, = cha) [iy Ka, : vay[ow a = (Hy) EH KK ary +l+ds]= $0 (tiA,.) = (Ha) [4 a] = (HA) eet Substituting into the equation forthe rate yields a ately) AH) + K (HY) Ky PPE GK EK Ky CHCH), CHC), HICH ‘oxazolinone ‘achiral anion + a: The ‘bridgehead nature of the amide in structure 8A precludes @ normal tree gbe esonance. This means that addition tothe eetbony! {group to forin the tetrahedral intermediate is more facile. b. The geometry of structure 8 precludes part The alkyl group is added entirely trams to the fused cyclopropane ring, This ‘ppears 1 be cue primarily tothe steric effect ofthe axial methyl sutetive No (orc NU (oH0H, ‘cH, '. The phenyl group is added entirely syn to the fused beno ring. On the basis agri considerations the Nat benzene ring provides a somes ‘more open a mot aA aa 85 hao a Pres> 86 © The stereoisomer predicted by the Felkin transition structure model accounts for 95-96% of the product. cH, cH, OH —eX- Pn — mon ¥ CHICHsle Hy oH 7110. Because this is entirely a thermodynamic relationship, neither the structure of the TAL 712. 113, Ta tothe meckanism of hydrolysis is relevant In making these comparisons Pihich are relative to methyl acetate, one has 1o consider two structural factors, (1) the (e)stabitization by resonance or polar effects ofthe carbonyl ‘groups, and @) the stability of the displaced group, which should correlate with ie leaving group ability and basicity. 4 The methylthio ester is more negative (7.7 kcal/mol) than the methylester ($1 keal/mol) because of both diminished resonance stabilization of the ‘eactant and the weaker basicity of the CH,S~ leaving group, >. The EWG character of the phosphate results in reduced resonance stabi- lization and a mich more stable leaving group. The reported velues of cy Fe, 0.Skeal/mol for the phosphate and ~5.1keal mol for the methy! ester © Zhe amino group is protonated at this pH and introduces polar dest ‘eation of the substituted reactant. The AG is ~8.4kcal/mol, compared to =S.1 kcal/mol for methyl acetate. ‘he acetyl group introduces a polar destabilization ofthe reactant, resulting in an increase of AG to —10.Skcal/mol compared 10 5.1 keal/mol for the ‘reference methyl acetate. © The imidazole ring, lacking conjugative stabilization because ofits aromatic Sale, together with the relative weakly basic imidazole ring as a leaving group (PK ~ 7), results in a considerably more favorable hydrolysis (AG = = 13.3 keal/mol versus 5,1 kcal/mol for methyl acetate.) The conjugation of the amide results in reactant stabilization and the secondary amine is more basie than an alcohol, Both factors make the hydrolysis of the ‘amide less favorable than that of the ester: ‘This result can be ascribed to electrostatic stabilization of the anionic transition structure leading to the tetrahedral intermediate, CNR, a 4niogPao” ‘o;0cH, Tre second amino group can provide intramolecular general base catalysis ‘There is a good comelation of the log/og plot with a slope of about 0. "The ‘esulls are consistent with general acid catalysis, maium fon qcbends on the Lewis acid character of the Hg" to generate 87 qeatiom Hon that can capture F-. Nal would not havea sina effect. The | dissociation is an Sy1 process ofthe Hg” complex. The F substituent does not Provide sufficient stabilization to promete ionization of the second thiophenyt Pr, 7S. At the lower range of the acid concentration the ‘neutral tetrahedral interme- alate ves phenylacetanilide by eliminalion of HS. Aa net extent of proto- enn Of the tetrahedral intermediate increases with cid concentration, the intermedia inated by elimination of aniline from the N-protemten (etrahedral intermediate, 8 sH 3H i, Heo i a Wea Poor, ES pmeidon, the Posto, A- ca.csoHn + snsph On 716. ‘The tle ott le, we esd o The coseneg a of hye ‘chars. about 7 anes sone or erminady the magnide torso be pyraane ante han os fandineroteraton esata enced by K, iineemgarmnn te me cltoyee ‘eae 9 ere of excangy {Rikcodtencty ete eusreara ne ate yar, lorba trcroony seated antes g a Z : 2 g 8 RCH ARAMA ———meetin transfer increases, Agi XA CH cH, Exton of protonation decreases vith extent of EAG electron donation because of increased ccarocaton stay AeH-o'CH, SAPO" srk RO groups n acm Ts towel bes compat Detonator 88 fhe Bhetoxy substituents, the tend is in the other direction, with e increas for ERG. because as the leaving group becomes poorer, the exe or proton X—Ar9" Armo-H Extent of protonation increases nth extent of ERG electron donation because of poorer feaving group ably. deca tweet Ra groups aranin 7 {nad mae completa ron Yanan 718, The maximum in the pH-ate profile near 3.8 suggests that the monoanion is the ‘88 was the case for aspirin (see p. 670). The observation of 2chvdronyphthalc anhydride as an intermediate indicalesintramolecalg coche philic atack, followed by panicipation ofthe second carboxy group. « a Se Ct Slt Os Sie % oH on CH 7.19. The kinetic results are consistent with an acet Mechanism at the acidic and basic extremes a Gialyzed and specific base-catalyzed hydrolysis, espectively. At ack this can occur by inital protonation of the methoxy group and ie eng tation, heres the hydroxide reaction presumably oecuts by “OH atack on the enone carbonyl, followed by concerted breakdown of the adduct. Emenee apt SAP So cor ouomoro, — GLE en ae es j Ke = Cpe OS — Op — mad 'C—Ph-3.NOp cH0/ PHENO, OHO” ‘pnano, —_-Pho-NO, HO"m ano, 4 oo Son 00, 0 ™ 0 _ aK CHy0/ Ph3.NO, PO, e 3NOy Speci hone myers chang, 720, Separate plots ofthe rates versus ¢ for CHJOH and CHjOD both show curvature, wing, Ber value for EWG substituents. The isoiope effec is inverce hae ENOu but gradually becomes normal for more ERG substituents, wiih in te ora iZ5 f0F PCH. The curved Hammett plat and the change {fansfer for ERG substituents. For EWG substituents the proton tame, may fe [es Important, with the nature ofthe leaving group becoming the de ie re Cent thon Gototme t CHO Cy CHO Gry Proton transfor is rato- Leaving group abit is ‘storming for X = ERG, ‘more important forX = EWA, {eot0peoffct is normal, ‘Thare ls more CN cleavage at There i eave ile GN {ho transition state and higher eavage al the tansiion sate Sensitivity to the eubstiven 721. Are lative reactivity ofthese acetals can be explained on the basis of stereo: electronic effects involving the orientation of unshared electrons onthe adjacent TFL Ba (anomeric effect). The antiperiplanar alignment in 21-C is optimel [221-B. the aryl-substituted O is poorly atigned with respect tothe alkyl oxygen, 21-A, the bridgehead structure essentially precludes participation ef tine alkyl oxygen. 3 SRRAcaRapera er sanmeen 89 Sinner Fens10. 03 “0F0 001 WS 08 OT Fig. 7720. Hammet plot tor mehovide-caayzed methsnaysis of tifuoroscetarilides in normal and deuterated methtnn, Reprotarsd on Z dim Chem. Soe. 9, 3095 (1972), by permission of the Amerione Chemical Soci. 3 Oat Ae ey aa 8 ae ae maees om p wae 4 f pro sto dt onn, a had - , oN ae - 1 2a 28 inrmolocatar Intamoleclr generat HHtondng astance paulo b Theve are [H"]-dependent regions at pl < 1 and 3-4. Above pl, the reaction i1PH independent. The reaction in the strongly acide region ig presumably B*-catalyzed cyclization (Region A). The inflection near pH 2 corresponds. to neutral water-assisted rate-determining eye (Region B). In the pH region 2-4, acid-catalyzed breakdovrn of the intermediate is vate determining (Region C). Above pHi 4 the ra f HO+0H HO, +HyO- Ye EN oS HOWE) & ey pit nagon A oiiRepen® Ragin Ragen Ma hdrogen-bonded complex) which is dominant in the pH range 6-10, Jnvamolecular nucleophilic atack by phenonide would tlse be corner a Ihe PH profile, although disfavored by the somewhat strained nature of ‘he intermediate, Above pH 10, hydroxide fon attack becomnes destiny On, O20, on, oe COR. “oh. i aH 4 An inamolecolar general seid catalysis ean account for the platens from PH 2-5, which isin the region corresponding to ionization of ihe carboxy Ga92 Sansa Proens group. Consistent with the base stability of acctal, there is no evidence for base-catalyzed hydrolysis 0 “¢ Ho OCH 723, Both the 2- and d-crboxy derivatives show a linear dependence on [8] atthe iG end ofthe PH range, but the d-somer is somewhat more rapidly hydrolyzed in this cange. This results from the formation of the isolated phthalide interne, sha, which undergoes hydrolysis somewhat more slowly than the stating sect in the acidic pH range, The hydrolysis rate of the 2-isomer shows a plaeas from pH 3 to 6, and becomes faser than the 4-isomer in this range. This is due re intramolecular general acid catalysis by the carboxy group. For the 2lsomer the mechanism changes to “OH attack on the oxonium ion intermediate in the BH range 7-8. Above pH &, the ate is [H"] dependent. In this pit range, the ate-determining step is protonation of the anion of the reactant. sate \ my, ZO a X ce sO gHe0 7 Ce to Ne ee Sen — OO sate 7% vo 7-8 recto OH stich on anion ‘xonlimion nemnadate 7724, There are two opposing factors in the rte of addition. Because, as indicated in Section 7.2 the reaction is acid catalyzed, the basicity ofthe carbonyl group influences the extent of protonation, ERGs should favor protonation, On the nthe, band, ERG substituents will stabilize the C=O, which works in the opposite direction, For the reverse hydrolysis reaction, decomposition ofthe protemnd cet should be favored by ERG by the stabilization of the cationic intermediate. are eter! K should be favored by EWGs, because they cannot effectively abilize the aldehyde, The observed rates of hydrolysis, as measured by Aci are favored by ERGs, as shown by the data below. The rates of formation are in the Same direction, although somewhat less sensitive io the substituents, presumablySuing fo the competing basicityreactivty trends. The overall K's are somewhat 93 ‘more favorable for EWGs, as expected, —— ela rans ee ee ery Peers CHO 200 162 20x10" PCH oa M3 Tax 4" m9 asta eB ons 193 MSxi0 ecu 2380x108 the metal aspects ofthe TS. 1 is interesting thatthe effets are observed despite the presumably planar double bond, i W009 nf 04 7.26, The mechanism given on p. 647 indicates that both water and hydroxide ion attack on the protonated imine contribute to the observed rate. ky (iit) ¢ HO ee ns ang + on meng tii) + oF Ee ony oy —2 Products ar) Rate = where (Li,,) isthe sum of neutral and protonated forms of the imine. The steady stale approximation can be applied to (Int) ‘Sa earcreae94 4) (Im) + (mH) (OF) = (Ind fk_ (HY) +45 +4) £, +43(-OH)(Im,,, (H™) (H* DIR (A>) +k +h) Alki (H*) +k] IK HOI) +h] Saeed hydroxide term becomes negligible andthe ky and k» terms drop Out and kip, simplifies to lin) = Fg Rate = ky (lM) = ky (Lat) = ky = bth) TER) fefause the various imines have diferent p& values, the relative magnitude of pe cGrm change with pH. For the most acidic region at pH < 2, kas beeones A:/4-s(H") and is pH dependent. Inthe plateau region a pH 4-5, fy roduecs weed the strongly basic region at pH > 8, hi, is given by gk/R, and i DH independent, + The Product composition indicates that aldol condensation has occured, hich would be consistent withthe celatvely high temperature. Although nor Gctermined, the major stereoisomer is probably E 10 maximize conjugation with the formyl group. 721, oo b. This reactant can undergo intramolecular aldol condensation, ° Co © This reaction should give the kinetically controlled adduct, As discussed see ose the main enolate is Z (98:2) and the major product is the spr stereoisomer (~ 9:1), cH Ph 4. The composition of the praduet under alkaline conditions indicates aldo! auittion. These conditions are not expected to result in high stereoselon, Listy. The composition under acidic conditions indicates that dehydration has Gerurred. Because of the acidic conditions, the branched-chain product would pe Toned. It would be expected to have the E configuration of the doctle bond,° o gH cr ongconjon, MOH guid pratt? A Roun, SoH,cH, arene 9 io. = a bow cn,écH,cH, crd=cron, POO chy — ‘major enet cH, = 728, Thioester 28-A shows a linear dependence on hydroxide ion, indicating a normal 729. 7.30, Bac? mechanism, Thio ester 28D also shows linear dependence on hydroxide, Wilh @ Slight rte acceleration relative to 28-A. This indicates a By-2 mechanism, With possible electrostatic stabilization of the anionic tetrahedral intermediate Thio esters 28-B and 28C show pH-independent regions corresponding 10 ihe ionization ofthe carboxylate and tertiary amino groups, espectively. This result is consistent with an intramolecular general base catalysis for these tw ‘compounds, 9 i i ay, iM or nN grb on PH hy tod Core (CHa)N' ae ane! In the ["OH-dependent range at pH > 10, te nitro compound is more reactive, fonsisient with the EWG effect making the amide carbonyl more reactive ta hydroxide ion auack. In the plateau region, the nitro compound is less reactive ham the unsubstiuied compound. This favors mechanism A over mechaning B. since the nitro group would decrease basicity but should enhance hhydrogen- bonding ability. ‘he reaction ean proceed by participation of the hydrate of the aldehyde. The rapid exchange with water would incorporate "0, which would be transfered to the carboxy group. 95 Winans Paton> % 731, The rate remains constant between pH 4 and 9, at which point increases with (OH), The most likely mechanism for a pH-independent mechanisms wena te intramolecular general base catalysis. The direct involvement ofa water molecule {consistent with the observed solvent isotope effect. OPh-4-NO, ‘The rate expression is Rate = kgs (Ama) where (Am) i the total concent tration of all amine species—(Am) and (AmB the neutral and protonated forms, MAtry) de ote(AM) ‘The term ky, consists of two contributions, one involving intramolecular ‘catalysis and the other the (~OH) reaction ‘ess = [y+ kou(“OH)](Am) ‘The term (Am is @ function of the pH and can be obtained from the acid dissociation constant K,, (Am) (mB) +4, (Am) + (Am) = GEEK amy (Attia Ky (Aan) = Ae Thus, aut K ay lees> Chapter 8 97 Siar Prato 81. rectangular siracture for the cyclobutadene ring implies tat there would be thoy aoanetic L2-dipheny! isomers, and ifthe barter to bond migration is lowe they would be in equilibrium, Ph, Ph, =) Phy 1D +e For steric reasons, isomer 1-D should be more react Peale explanation for the resuits is that the reaction of pubenvoguinone Gand maleimide) ate slow eelatve to this equilibrium. and, as a resol ait at we Faaction Proceeds through 1-D to give product of structure I-A. On the other hand, if the Diels-Alder reaction of tetracyanoethylene and dicyanomaleiae ae fester than the equilibrium, the product ratio of 1:7 favoring 1-C wont Siresoond to the 1-D:1-E ratio. The reactions with the less reactive dienoptiles intemeambles of the Curtin-Hammett principle, withthe bond shift asthe rapid interconversion mechanism, 52. a. A dipolar resonance structure having benzenold character forthe pyridinium Fing and an aromatic cyclopentadienide ring would stabilize this siractune, cyt b The aromatic eyclopentadienide character of the following resonance structure would stabilize this diazo compound, N i N © There is a resonance structure having charged aromatic rings that would be stabilizing, Po Ir» oe « @. Among many dipolar resonance structures are several that depict the fives epnbered ring as cyclopentadienide and the seven-membered ring as cyclo. heplaienylium, These structures should stbilize this compound although ne of the rings must have quinoid character. So far, the compound hes sen been synthesized and its physical properties are unknown, OO hy BEES ASAE rone‘> 98 Sant Pras Se ee emacs aaa -" fe och, Hg orcs oro On > OL OF. ». If the enol were an intermediate the reaction would incorporate deuterium in ‘deuterated solvent, That is not observed, ruling out an enol intermediate, Ph, Ph, ee o sop 7 oft = Jl ol ‘o oon § H 8.4. a This is a 4ntrelectron system analogous to the cyclopentadienylium cation and should be antiaromatic, b, The -electron system perpendicular tothe ring contains 14 electrons (two {or each triple bond) and should be aromatic. There are no serious geomet (or steric constraints to planarity, This is 10n-electron system has the potential to be homoaromatic. However, in view of the lack of evidence of strong stabilization of anions by homoaro. ‘maticity, coupled with the fact that it is a dianion, suggests that this structure ‘would be nonaromatic. 4. This six-electron system has the potential to be bis-homoaromatic, ¢ This compound is isoelectronic with the phenalenyl anion and according to the phenaleny! MO pattern (p. 757), it should be aromatic, F- Ifthe S is considered to be a C=C replacement, this isan azulene anslog. As ‘such it should have aromatic stabilization, and the NMR spectrum is consistent with a diamagnetic ring current. 8. This structure is isoelectronic with the tropylium ion. Although the more electronegative nitrogen would be expected to somewhat destabilize the structure, it should be aromatic. CAS-SCF calculations indicate a planar, delocalized structure, 4h This structure is isoelectronic with the acepentalene dianion, which is calculated to have aromatic properties, including a negative NICS (sce Probiem 8.17). |, This structure is isoelectronic withthe phenaleny! anion and should be aromatic (p. 757). 5:5. a. The structure shows a cyclobitadiene ving, Attaining an aromatic number in both rings would require the transfer of two electrons from the four-membered to the eight-membered ring or vice versa. Such a large charge transfer would be destabilizing.5 Am altemative resonance structure might be construed as petipheral 10 ‘electron system, provided thatthe structure maintained planarity -Ca © The major erteria of aromaticity would apply: (a) stabilization or destabi- {ration energy determined by experiment (eg, heat of hydrogenation) or Computation: (b) bond length altemation as determined by experiment or computation; and (c) magnetic criteria such as evidence from NMR for a diamagnetic ring current or calculation of the NICS. The experimental and \necrtial evidence curently available suggests only weak stailization (eee P. 753), 8.6. The HMO and calculated energies are as follows: HMO energy — Hess-Schaad reference energy = Stabilizati 8 HMO energy = 8a + 10.3812 ~ 10.5628 = ~0.1818 (destabilized), Hess Schaad reference eneray 72 S(HC-C)= 5x06 52180 10302 b. HMO energy 100+ 13.36358 — 13.1328 = +0.2318 (stabilized, Hevw-Schand reference enenpy: 3 (HC=CH) = 3207 =6.210 2 (C=C) =2.32.108 3 (HCmCH) = 3 0.466, 2MC—c) = 20436 § EMO energy = 10a + 12,79938 ~ 13.1228 B= ~0.3298 (destabilized) &: HMO energy = 10c + 13.6832B - 13.128 B = 40,555 (stabilized). & HMO energy = 12a + 16.23138 ~ 16.120 = 40.111 (stabilized). Frese Fesulls are in good accord with the properties of these hydrocarbons, Benzocyclobutadiene and fulvene are distincly destabilized. Naphthalene and, to a lesser extent, azutene exhibit aromatic stabilization, s-Indacene has at most small stabilization. 87. a. There is a substantial ditference in basicity in the order eyclopropenone * {yeloheptattienone > cyclopentadienone, This suggests that the dipolar ‘esonance form, which puts a positive charge on the polyene cing, is of decreasing importance for 3 >7 > 5. A positively charged ring should be ‘abilizing for three~ and seven-membered rings, but destabilizing Tor the five-membered ring, ° o 0-9 ° 99 Siar Pos( ) 100 Boat Paton These resulis indicate tha the dipolar stabilizing structure is more important forthe eyclopropene system thaa for the tropone system, This a leary part, may be a refletion of the ability of tropone to adopts nonplanar crust 8.8, The calculations are as follows: Pecno 4 chycrmcr, [Deore ocnsceo & teaoy — =i “arses “trons “136698 sonsee Deeno + orscnecs, Oao cheno +41 = 70715 190.7592 2043807 ~ra0eu4a Cre cH 5 Crone mene on eee -sor sees senaies ihe negative charge would be favorable in a five-membered rng. 59. The isomer shown on the left appears to be “more” aromati since there is affect the diamagnetic anisotropy $10.4 The anion of 10-4 has an identical resonance structure, and both are [xclopentadienie-like, suggesting good stabilization of the anion. The faced ruucture in each case isa [10}annulene. On the other hand, delocalized struce see Ore anion of 1048 do not indicate as complete a delocalization of charge. The fused structures are of the heptafulvene type 3 — 6-09 0g BO - 20 —ao 5 Both the dication and diunion comespond to phenalenyl strucres, The The nations and monoanions correspond to phenalenyl sirictures in one of the rings and can be delocalized over both rings.bis phenaeny cen !e-phenaiony/canion mongeaton or menoarion can bo doicentzed aver wo penalonyt ing sysoms © AGipolar structure having both phenolate and tropylium conjugation decreases the bond order of the inter-ring bond. 4: peripheral 14-electron system with an isolated charge on the center Euon would correspond o an aromatic system. A downfield shift ofthe ring tpogens would then indicate a diamagnetic ring current. The large pele because of the negative charge on the center carbon, 8:11 a The bond lengths and alteration inthe sit-membered rings of aenaphthene Frag hlts similar to those of naphthalene. The C(2)—C(2a) bonds are longer {han aromatic bonds, suggesting that acenaphthene can be regarded. ae ‘naphthalene, with a fused cyclopentene ring having minimal delocalization, >. I the anion, the bonds ofthe five-membered ring become more uniform. The pzphihalene ring bond lengths change quite substantially, with the C(3)-C(4) bond being particularly short. The uniformity of the bond lengths in the fine tpembered ring suggests that it might have cyclopentadienide character If so, the Zemaining system could be considered to be a delocalized heptasenyl radical ¢ The 'H positions are shifted substantially upfield, consistent with increased Sheeran density associated with the two negative charges. Positions C4) And C(7) are shifted somewhat less than the others. The ""C shifts are alse tess at C(4) and C(1), and C(Se) and C(&b) shift downfield. These shits we in reasonably good correlation with the HOMO coefficients for the ani henens: A eyclopentadienide anion inthe five-membered ring and a noneyclic {ePtatreny! anion encompassing C(3)—C(). In particular this woul explain the shortening of the C(3)-C(4) bond DRAM emene> 102 Bio Pons 8:14. The cation might have cyclopropyicarbinyl (14-B), bis-cyctopropylearbinyl, ise homoaromatic, (14-D), or allylic (14-B) character, The =Vp(r) shows. no the orn between C(2) and C{9) indicating the absence of a fornel teeny in the Piscycloprepylearbiny! structure 14.C, The bond feng altar” in the interaction, (Seep. 744 for examples of eleciton demsly prefte k homoconju- ated cations), SALA SS. * 48 140 classical cyciopropyi-_biseyotos bishomo- alive cabocaton cary pupycatin’ aromas SA cerbocation carbocation” ——_carbucation LESSS45, a. The stabilization can be calculated by comparing the 44,0 a per CH basis, 103 Benzene: 781 +36 = 817 = 136.2 /CH Sines bios Cyclooctatetraene: 1086-4. ([16Jannulene: 2182 +S 16(136.2); SE = 3 keal/mol b. The thermodynamic eycte is [Cyl [Cubh SS tel Cit Gallss #2 NOOK > INCH 420, Ao [Cll th Cth, 356 “280 2Nag) +IHO 4) > INOH gy + Hy 82-82 INay) HICH, 2Na GH 805 1053 ‘Rie loner heat of reaction of (CygHy°~ with water indicates that the anion is omewhat less reactive toward protonation, which may be due to a somewhae IE eer because of the larger sizeof te dianion in the case of [6lannolons, ae ite-eleetrn reduction is aso somewhat more exothermic tha for eycloes, tatetraene, 8.16, The double-annulene strcture would imply similar bond lengths along the inner shu ler perimeters. lt would also suggest similar properties forall he tings. The Phenanthrene-Hike structure implies significant differences between the lke eline {angular fusion) and benzenoid (linear fusion) rings. The H-NMR cheriact Shift values are somewhat more downfield than observed for phenanthrene, Pantculary the inner hydrogen, which would be in the deshielding region ofthe benzenoid-like rings in the phenanthrene-lke strture, The bond lengths shone a Phenanthrene-like patie. The rings depicted with delocalized electrons are ail close to 1.39 A. Inthe other rings, the double bond is dstinelly shorter than the adjacent single bonds. These structural features are in good nceord with ne Phenanthrene-like structure, The substantial NICS difference is also in second With this structure, since the double-annulene structure would not sceousy he. large differences between the two rings. S17. a The danion ad, to somewhat lesser degree, the dcaion exhibit magnetic Properties suggestive of aromaticity, The bond length patiern for the dignion indicales ¢ symmetrical structure with shortened (aromatic) bond lengths Particularly for the C(1)—C(2) and the bonds to the central carbon. One pither hand, the neutral molecule has strong bond alternation, consistent with sain at the central carbon, which is reduced by pyramidalization The HMO patter, white strictly applicable only tothe planar structure, offers ‘A cationale for the observed aromaticty of the dianion and the dlication Bolh the anion and cation would have a fully paired electonie configuration, {Rib all electrons in bonding orbitals. On the other hand, the diagram showy degenerate orbitals that would be hall-filed in the neutral molecule, 8.18, The reduced rate might reflect arene oxide stabilization and/or instability in the YASS a remmemenmee erence“> 104 19. The da permit comparison of chloride transfer rections that should be Eimanrma —_indcave of lative ewtocuton anny oy a Ka Ae A. i+ 27 teal! 7 ‘or cr cl a a Cle et ees aera cr ‘cl or ‘cr Acporaing to this Comparison, the chlorines are weakly destabilizing, bu never: theless the trichloroeyclopropenium ion is more stable than the e-buty! carbo- 520, The fact thatthe three successive Af are very similar indicates there is {ite homoaromatic stabilization. Any stabil Chapter 9 9-1 «The polar effect ofthe single fluorine decreases the op preference of the alkyl SrouP, but the o,p products remain dominant, The reported product ratio a 28% ortho, 18% meta, and 54% para, 5 The wifluoromethyl group is strongly mera directing. According to the data in Table 9.3, 91% of the product is mera © The single methoxy group is not sufficiently electron withdrawing 10 fo he dae fe Rormal ov-ditecing effect ofan alkyl substituent. According {0 the data in Table 9.3, 93 % of the produet is arto and para, The quaternary nitrogen is strongly meta directing. According o the data in Table 9.3, 89% of the product is neta, © As indicated on p. 780, fluorine is an o,p-directi for the para isomer, bate Stlfony group is an EWG substituent The reported product is 89% met, 9.2, Ortho-alky! substituents force the rotation ofthe dimethylanine, group by a steric ‘group, with a preference 1; p = 43.7. The largest difference is at the onto ropy! group leads to a reduced reactivity relative o methyl methyl group is slightly more activating at the ns. The overall reduetion in rate for isopropylbenzene is ‘meta and para posit leaely atibutable 10 a steric factor that decreases the rescivty of the seh position, SER9 Group top rte ogo © 5571 ° Cy wt ars ty CHO 399936 OD oH 46 tot ag (CHW aa Lag 9.5. The appearance of the I bration by alkyl ‘and competing isome dealkytation, - a Slama vs.log k/ko ° 0m “078 ~092 07 1053 106 CHEE © Ae, =a eHCHler wre, —afem over ened MAP me (OH,CH Arc, on | i CH, Hy ° res oe Oe eH oHacH, HY MOH, cy Hy 7 n EHC 0.105 007% 021 Gos 82h ost ‘The reactivity patter is consistent with electrophilic aromatic substitution, The slight para activation of Br and fairly strong ‘meta-directing and deactivating stieetof the CHyO,C group are consistent with the normal pater ae the strong ee ang gn ofthe methony group. The cited reerence reports conelaten oe these and other rates with @* with p = 4.4. This would piece the reaction in ihe relatively nonselective group, suggesting an early TS. The electrophilicity of ‘he reagent derives from the weak O-O bond, A0.s0--% OF = HE — 0) caw b. The reaction feads to desulfonation, 1 on- I> Br ~ Cl, which must be the result of two or mote opposing trends. Resonance stabilization should be in the order F > Cl > Br > T because of the importance of orbital overlap. (On the other hand, the polar and polarization effects are in the opposite order I> Br > Cl > F. Resonance effects are dominant for F, For Cl and Br, the resonanee and polarization effects are less important than the destabilizing polar effect. Reactivity is low, but the resonance effect does lead to 0,p orientation. For I, the polar effect is smallest and polarization provides stabilization of the intermediate. A special feature of the data for F is the high paracortho ratio. This is believed to be due to the strong polar effect of the F, which destabil ortho transition state CHOLE ONE (CHS (CHS, ‘2. A methoxy or similar group should be slightly destabilizing by the polar effect, assuming that E is more electronegative than carbon. There could be 4 stabilizing anomeric interaction with the unshated electrons of the methoxy ‘group and the o* orbital of the CE bond, ». Anitro or cyano group should be destabilizing by polar interactions but could be stabilized by an anomeric effect only if E were a potential « donor such as a halogen. ¢. A group such as trimethylammonio should be destabilizing on the basis of polar effects. Anomeric stabilization would be possible for electrophiles that are 6 donors, d. A group such as silyl would have a small polar stabilization and a strong. hyperconjugative stabilization effect. 9.18. The decrease in the amount of 18-C when deuterium is incorporated indicates that the deprotonation step is at least partially rate limiting. If the assumption is made that the rate of formation of 18-A and 18B from their respective a- ‘complex precursors is unaffected by the isotopic substitution, the relative rates ccan be ealeulated, 9.7. (ose. (yO Lees CHE A exc Berk, Gor), Gre 109> 0 11K, and ky are assumed to be constant, the value of ky ean be calculated from Saw the product ratios: bon 87 foe BT % agg 7046 ai 5g 72 ‘The two independent calculations give the same value of 3.4. This is in the range that is consistent with a primary isotope effect. 9.19, a. These three examples indicate a preference for formation of six-membered tings relative to Seven-membered rings. The second two cases involve endocr- Bonic rearrangement of a tertiary cation toa secondary cation. The carbocation rearrangement must be faster than cyclization. b. These cases suggest a strong preference for formation of six-membered rings over five-membered rings. There is no cyclization in reactions 1 oF 4, where five-membered rings could be formed at primary ot secondary carbons, Entry 2 Suggests a “gem-diakyl” effect favoring cyclization. However, the cyclization product is still a minor product. Entry 3 indicates facile formation of a six- membered ring ata primary carbon, Entry $ suggests that a combination of favorable factors—a stable tertiary cation, an activating methyl group, and em disubsttution—can lead to cyclization forming a five-membered ring. «. These reactions involve Lewis acid-medinted opening of epoxides to generate clectrophilic intermediates. The first entry fails to Form a five-membered ring by eyclization at an unsubstituted epoxide methylene group. The second entry fails to form a six-membered ring at an unsubstituted epoxide or a five- snembered ring tthe monosubstituted carbon, The third entry shows effective formation of a six-membered ring by attack at a monosubstituted epoxide carbon. In Entry 4, both si: and seven-member rings are formed, the former requiring a hydride shift, Taken together these results suggest 6 > 7 > 5 as the order of preference for ring formation by intramolecular Friedel-Crafts reactions. Moreover, there are no endo cyclization produets formed, even in Case 2, where a six-membered ring could be formed. 9.20. a, These reactions can be formulated as nucleophilic aromatic substitutions in which the 4-carbon of the 2,6-di-(r-buty)jphenoxide acts as the nucleophile, ‘owing tothe ster bulk around oxygen. The reactions might also be formulated 8 involving an electron transfer step. STO tyr O- 6 (on sora (or '. This result is best explained by intervention of a benzyne intermediate, The Fegioselectivity of the addition step is contrary to the EWG effect of the oxazoline ring and could be due to a chelation effect.> Ga on hen, “ho “het Tots ot ie ony os ¢. This is vicarious nucleophilic substitution involving reaction at both the = and position. ] _ yr ‘NO, ae o. —O . {ond sina rtrmedates Sorcgen HEN cHCN 4. This product can be formed by two successive benzyne additions, Q 5 o-0-03 & . This reaction illustrates that a secondary carbocation cannot easily be formed from 3,3,3-trifluoropropene. Although the product might be formulated as fan anti-Markovnikov protonation, it is likely that the mechanism is more complex. It has been suggested that most acid-catalyzed reactions of 3,33- Urifluoropropene proceed through the I,1-difluoroallyl cation generated by acid-catalyzed ionization. These reactions imply carbocation stabilization by the remaining fluorine substituents Oyo oO ‘These results indicate that formation of six-membered rings is preferred to Formation of five-membered rings, as is the case for Friedel-Crafts alkylation, ‘The success ofthe acid chloride but not the carboxylic acid in the five-membered suggests that a more reactive intermediate is available 1 the chloride. This could be a mixed anhydride with the Nafion-H sulfonic acid group. 9.21. These reactions are believed to proceed through an aryne intermediate, presumably Lpenerated as the solution warms, The o-cyano product can be generated by an intramolecular addition tothe eyano group, followed by a cleavage reactionChapter 10 10.1, a, Both the basis set orbital array and orbital symmetry correlation diagrams indicate that a disrotatory eyclization is not allowed. The disrotatory orbital array is a Hiickel system with no nodes and four a electrons and is entiaro- matic. For the distoiatory mode, a plane of symmeity is maintained. The yy orbital of the pentadienyl cation does not correlate with an occupied orbitals Of the cyclopent-2-enyl cation, The reaction is forbidden, m & ae — Ma--Eh apy en ee > Ht Bp Ns = WS eee », For the peniadienyl anion the number of 7 electrons is six. This means the disrotatory orbital array is aromatic. Furthermore, in the orbital symmetry Giagram, jy is now filled and all filled orbitals correlate with ground state ‘orbitals in the product. The reaction is allowed, e . oa ws — vA ws eS the hve Vek eS wis eM ih os © For the heptatrieny! cation there are six m electrons and no nodes, so the Uisrotatory orbital array is aromatic, The disrotatory mode maintains a plane of symmetry. The orbital symmetry diagram also shows correlation of the filled reactant orbitals with product orbitals, so this reaction is allowed.k, This reaction corresponds to a [6-44] cycloaddition. The stereochemistry 125 indicates an endo transition structure. The final position of the double bonds is established by a [1,5]-sigmatropic hydrogen shit. ohpacy agai |. This reaction occurs by (2.3]-sigmatropic shift ofthe selenoxide intermediate, followed by solvolysis of the selenenate. Note the retention of « stereochem= istry that oceurs as the result of the suprafacial nature of the reaction, ER ZR ER ERP 'm, The reaction occurs by a [2,3}-sigmatropic shift of a sulfonium ylide. i igen w & nv ot, Oh. FE RE 1, This is an intramolecular [2 +2} cycloaddition. DT esas am ge - ow ° CH ° 10.20, The planar all-Z cation, having eight electrons, would be expected to be antiaro- atic. The large positive NICS valve isin accord with this expectation, Structure 3, with an E selationship can accommodate a Mobius twist, in whieh case the eight-electron system would be aromatic. The NICS value, which is in the strongly aromatic range, supports this. In order for scrambling of all atoms 10 ‘a indicated by the labeling data, the E relationship must not be fixed be available to each pair of carbons, by circulation around the ring.i) 126 ‘The cation 8, which gives rise to product, can be formed by a six-electron electrocyclization, which should be distotatory. CP (A-ce 10.21, a, Ie is clear that the reaction is Kinetically controlled. The (2-+4] adduct is substantially more stable than the observed [2+ 2] adduct 2. However the E, for forming 2 is much lower. The same conclusion holds with the isomeric [242] adduct 3. Lis only slightly less stable than 2, but the E, is substantially higher. Fans Pr — TSA 36.88 kealimol = 84 95.75 kealimo! — TSH 28.95 kcabat 3-22.75 keatimo! = 2225508 heat! od = tana! b. The transition structure shows considerable charge transfer, consistent with the description of the ketene (2-+2} cycloaddition given on p. 889. The TS leading to 2 delocalizes this positive charge over an allylic system, whereas it is more localized in 3. on, 7 ore Tem , The TS I leading to Lis very similar to Diels-Alder TS. The bond formation is quite asynchronous. The initial bonding takes place primarily between the cyclopentadiene LUMO and the ketene HOMO, judging from the orbital separations shown in Figure 21Pe. The C=O 1” bond is nota direct participant in the [2+4] TS. In the [2+2] TS there is considerable charge transfer from the diene HOMO to the C=O m" orbital, This orbital interaction has a smaller gap than the corresponding [2-4] gap and, therefore, according to FMO theory, leads to greater TS stabilization.9 Chapter 11 127 11.1. a, anti-Markoynikov addition oceurs in 93% yield, ° : (CH-CH-CH,Br ‘cH, 99% b. Radical addition of the 2-hydroxy-2-propyl radical is accompanied by lactonization and esterification, e ° ‘0 ° (cH,00H + — (CH) a Le Os ‘co,n oH CHICHa)e ¢, Intramolecular hydrogen abstraction leads to a y-chloroalcohol that eyclizes to a tetrahydrofuran on treatment with base CHyorcHoH, CHICHEHEH, — CHGHICH) FHCHS de 5 bs eHEHNEHE + CIYEHRIO—=cENEMAPION OYREHEN, ot ba $e ° CHJCHICH, eCHH, ase Ln Go ORONO on 4, Radical chain addition of the aldehyde occurs. i CH,CCH,CH,CH(OCH)» 70% 6. This react O-a- Cf CQ” eo Q- eo, : Oxive detonation ad dimeratin curs in 42-56% yield coe oH Osnticrin Nog Tey 9-808 1m results in a transannular cyclization,9 128 hh A radical chain addition of carbon tetrachloride occurs in 70% yield CROCHACHEICH ae oH 70% i, The product is the resull of an Spy substitution. i SH,CCHs 7 08% jj. Anti-Markovnikov addition of the thiol occurs (OHy(CH)9S(CHaliCHs 68% 11.2. The cited source gives the pri-sec:tert selectivity for chlorination and bror nation as 1:4.6:6 and 1:250:6300, respectively. The calculation of the ratio at positions a, b, ¢, and d, is as follows: Chlorination: (6)1 + (3)1 + (4)4.6 + (1)6 = 33.4: 18%, 9.0%, 55%, 18%. Bromination: (6)| + (3)1 + (4)250 + 1(6300) = 7309: 0.08%, 0.04%, 13.7%, 86.2%. 11.3. The formation of 2-hexene can be accounted for by reversible H atom abstraction at the allylic position, The extent of reversible H atom abstraction in competition ‘with addition increases with temperature. The radical chain addition of HBr to ‘2-exene is not regioselective, as would be expected. Cr_= CHEN, ACH, + Br cracHonicnsyscr HEE cH,cHecH(cn)cHy BrCH,CHCHCHy CHpHEHYOHDIOH, + CHYOHLENCHCH, Be be 114. Both the 2- and 4-dioxolanyl radicals are expected to be nucleophilic in character because oF the donor effect of the oxygens. The high-temperature conditions reduce the selectivity for the 2-position and increase the extent of fragmentation. ‘The 2-substituted radical is more susceptible to fragmentation, since it leads (0 an ester. ° ° o iL Q CHecHe ilotctauz & — (Sn ee Hbocer yon e9 11.5. a. The retention of optical activity under these conditions is consistent with inyolvement of a bridged bromine radical, There would be no corresponding bridged intermediate in the case of fluorine. An alternative formulation based ‘on recent computational work attributes this result to a lack of stereospeci- ficity in the Muoro-substituted case (see p. 1028). —~ ots 8 ph Gs ad Grongerycr, —- chzdorych, —- BrHCCHJCH, FOHCCHCH.CH, 8 ‘ero & no bigng su in ‘etenion of rapid version and fentiguaion facamzaton ‘This stereoisomerization can result from reversible addition of bromine atom, which permits ring opening and stereoequilibration to the more stable exo cosets 00,0, wT — DP cosa, aX Pco.0, — wKI corer, ‘The stereoelectronic effect for interaction of the oxygen unshared electrons is more favorable in the case of the equatorial CH, group. This has the effect ‘of weakening the axial CH bond and results ina faster reaction. orga ohh on 8 Hy ‘There are six possible sites of reaction, including the two sites d and e at C(3), which are diastereotopic by virtue of the adjacent stereocenter. The product of chlorination at a should retain chirality. The products of chlorination at € will be achiral because of the identity with the existing chloromethyl group. Products from reaetion at d, e, and f do not involve the stereocenter and should retain the chirality in the reactant, The stereochemistry of the product at b will be dependent on the mechanism, Racemization at this site would indicate loss of stereochemistry in the presumed radical intermediate, and this is the outcome that is observed experimentally af 1 os ct 6—o-oHy At 129 Siar ProneQ 130 €. The radical resulting from hydrogen abstraction at the allylic position can sive the 2-phenylethy] radical by a cyclopropylcarbinyl-type ring openit 0 — Ot — Qnves £, The formation of saturated products indicates that 5-exo cyclization follows the initial addition of the perfluoropropyl radical. The cis and trans isomers resulting From cyclization will give the same exoeyclic elimination product AN BAY — Grote Crate = aot eee pon oo a. These results can be accommodated by an intramolecular shift of an H atom. between the two rings. The resulting isomer can give rise to the cyclization product 5-D and can form $-B and $-F by intermolecular iodine atom transfer. hi, Product $-H can be formed by cage recombination without rearrangement. Products $1 and 5-J result from an acyl group migration. Note that the ‘acyl group migration occurs in preference to aryl group migration, whi ‘consistent with the relative rate data given in Section 11.7. ee Siig i (CH,EECHECOOCICHS)s — cnyegct CHsCCHCHCHs ty ee s foe | crnloadory + crcorie= 6, ° onklocoonens ys ho, “Prstratasom ancron, Hacer h ow 11.6. a. The eyclie product 6B arises by addition to the benzene ring. The unrearranged product 6-C results from decarbonylation and hydrogen atomQ abswaction. The rearanged product 6D can be formed via a spiro inerme- sine ° r pn (ountoncnyen-0 — roryshonengao — sani ra GH gy | cece p See” pengyeonscry 9 saree a craton — 2>S0 a (on,cncn,cPh eo bb. This cyclization can occur by a chain sequence involving selective abstraction of a benzylic hydrogen and exo-6 cyclization ROO. a — ecincnncry 2% mrdncwabrc— CY ‘m Oy chy Ce + PRCH,}CH=CHp, —~ [ee 1+ PRCHICH,),CH= CH, Pn Pn cc. This reduction, occurs by a mechanism related to the Sqy1 mechanism. A tri-n-butylstannyt radical reduces the nitro compound to a radical anion that decomposes with loss of nitrite rs sf pewoin nebo, + aye ae tana ot Hy wm Ar—C(CHy)p + 84;8NH —= Ar—CHICHy), + BuySer 4. This reaction involves addition of the ethyl carbamyl radical and is initiated by one-electron reduction. CMHco.e., + crt) = HNCO.CH, + Gr + Cx) tiation CHYCHCH=Cihy + HNCOAGM, ——~ CHYCHL).CHCH.MNCO,C.H, CHYCHACHCHNHCO,CH, + CINHCO.CM, SHY NEHOH HCO. hs wnconc Hy,132 DB __—sican yu etn ining pest on a he melo Sekai Peer ‘The electron-acvepting capacity of the pyridine ring is important to the effectiveness of the coupling between the radical and the anion, eifo-ofs— offo. of On Ope — OFT OT, £. This is an electrolytic oxidation in which the initia alkoxy radi ‘The 2-propyl radical is oxidized to a carbocation, wh acetonitrile to generate the amide (Ritter reaction). fragments. then reacts with the _ : pono, Ze mews — mow + cto, nom he be 0 a sewou, + neoas — crncwacer, “2 ensonnbon ‘g This reaction involves cleavage of the strained ring to a diradical that reeyelizes to the more stable disubstituted exocyclic double bond. CH CH fr chs open a on ae y f Pn P th. The reaction begins by attack of the phenylthiyl radical atthe least hindered alkene carbon, The resulting intermediate is trapped by oxygen to give a peroxyl radical, which then adds at the second double bond by an S-exo ‘addition, The resulting radical is again captured by oxygen. The cycle is repeated by abstraction of hydrogen from the thiol Pus 6 Hy HOH,CH=C{CHly —PRSCH CHEN cic PrsccHencrmcnctry O MECHAEHCHACHEy —= MELON c bo Ps Y-SHy OF Pe YClere PM Bg YEE 5 Sag Se meg a hs )11.7. The equilibrium between the eyelopropylcarbiny! and 3-butenty! radicals can 133 account for the label distribution (see p. 974, Figure 11.3 and Table 11.3, Entry 30). The equilibration of the Z and E labels involves rotation in the cyclopropylearbinyl radical, The unequal deuterium distribution favoring that in the initial reactant at high concentration indicates that hydrogen abstraction is slightly Faster than equilibration at the higher concentration. (CH-CHCH,CO;CH-O cscHenicDsge0 ——— OvscHotsode cHecHOHCOg) eee ne~ 5> 3, which indicates that there is no aromatic/antiaromati relationship for te conjugated cyclic radials. According to HMO orbitals, the SOMO orbital is antibonding for the seven- and three-membered rings, but slightly bonding for the five-membered ring, The apparent stabilization order is consistent with HMO calculations, which give 1.OB, 1.858, and 2.548 as the delocalization eneray or the eyclopropenyl eyclopentadienyl, and eycloheptatrienyl radical, respectively BOE ASE PhcHe—H e488 O- 74 218 d Ou we as Dx wos 198 CH=CHCH,-H 904186 Dee tose 14 4-74 11.19, a, This reaction ean occur by thiy! radical addition, cyclopropylearbinyl radical opening, addition to methyl acrylate, a 5-exo cyclization and elimination of the thiyl radical. ms + POR ATOM pas’ on | Hro=conco,cHy nm — Team — Pascr Hexen! 137eG Sihaaar te Prins b. The addition of a dimethyl malonyl radical to the double bond is followed by a rearrangement via a cyclopropyloxy radical (acy! group migration) g (CHOCICH 2 (0H,0,C410H, 9 RQ + soHCOH), —_— 2X 2 ° | sms pomneie_ eva ie Ae — & By 11.20, According to the computations the fragmentation of the 1~4 bond is favored for the bieyclo(2.10jpent-2-yl radical 1. I is thermodynamically favorable and has alow activation energy. Rupture ofthe 14 bond relieves the strain in both rings. The resction isa eyclopropylearbinyl ring opening, ¥—& [None of the fragmentations of the bicyclo{2.1.O]pent-I-yl radical 2 are computed to be favorable in terms of AH?, There is poor alignment of all three B, y bonds. y Fragmentation ofthe bicyclo[2. 1 O]pent-S-yl radical 3 is calculated to be thermo- dynamically and kinetically favorable. It relieves the strain in both rings. eg There is poor overlap with the B.y bonds in both the I and 2 bicyelo[1-L)pentyl radicals 4 and § and although the ring openings ae thermo dynamically favorable, they have significant kinetic barriers. The later (1995) ‘compilations indicate a destabilization of the fragmentation transition state by antibonding interaetions in these radicals. oe9 ee itadical must have a sufficiently long lifetime to permit bond rotation. Cleavage Sewn ent ‘of the C(i)—C(4) bond would generate a diracical that ean fragment 10 the 1 dione product. The bieyclo[3.2.0]heptane derivatives must form by hydrogen abstraction. The fact that there is no intermolecular deuterium scrambling means that the reaction must occur by an intramolecular process. This indicates that the 1,4-diradical has a finite lifetime. oo. a (CHa}sPn {CH,sPh — intremolecuar "CH,CH,CHPR ——_ wane Inteamolecuitar | ‘ragreiain | [eoitee Hy oi toh é x cR Sen 1 Pon iran maser Chapter 12 12.1, This issue could be approached by isotopic labeling in the side chain to determine if the two methylene groups become equivalent, as required by the intermediate, ‘Use of "1C labeling indicated no interchange of the (wo carbons, ruling out the symmetrical bridged radical 12.2. a. Orbital symmetry considerations prediet @ conrotatory ring opening and this is observed. oH aC 5 bb Photolysis would be expected to lead to photocyclization of the two vinyl substituents, Two modes are possible and the head-to-tail mode predominates by I hoadttonhead 3140 ‘Sa Praions 123, . The product results from disrotatory electrocyclization. - 4 H, XH - d. The product results from conrotatory opening of the eyclohexadiene ring. OM. lic Hy PPS Cle GES tS ‘ ceaf. The reactions ate disrotatory electrocyelizations. G2 - 4 GD — FO ‘a, This result indicates that there isa triplet state accessible by photosensitization tnd that, as with simple alkenes, rotation can take place at onc of the double bonds, leading to formation of the enantiomer. b.3C is the product of disrotatory electrocyclization, whereas 3-B results irom the conrotatory diene —> triene interconversion. The triene absorbs much more strongly than the diene at 300nm and therefore is a minor ‘component of the photostationary state, allowing the reaction to proceed to the eleetrocyclization product. c, The reaction is proposed to accur by photocyclization of a quinodimethane intermediate generated by acid-catalyzed opening of the dioxolane ring, This intermediate can undergo an electroeyclization. After ketonization, & new {quinodimethane intermediate is formed, which can lead to reclosure of the dioxolane ring.9 124. a, The initial step is e-cleavage. The products are then formed by intramolecular 141 hydrogen atom abstraction, leading to the conjugated dienal, and a 3,5-pairing that gives rise 10 @ ketene intermediate that is trapped as the ester. ale b. This is an intramolecular addition of the alkene to the aromatic ring wit 2,6-pairing, (CH,,CH=CHCH, HCH ce. This product results from intermolecular hydrogen atom abstraction, followed by radical recombination. Speven dpe yn + CHICHHON — tonne quo 4. This rearrangement can occur by 5,6-cleavage followed by 3,6-coupling. ‘The distribution of the trideutero methyl groups indicates that the react proceeds through a diradical intermediate that is sufficiently long-lived for free rotation of the isopropyl group. 7 _ chy 8 Oy Hy C0, “he ye dS™ psa t wh c. This ring expansion and nucleophilic addition can be formulated as occurring through an oxacarbene species. HoH OH ch,3 142 . The altered course of the reaction i i This idic solution indicates thatthe reaction may proceed through a protonated intermediate. In neutral solution the reuction results from a (2+2] electrocyelization, on" “ B, on SE cry A “Coes a Con on, Kany my penta osence of ‘This rearrangement reaction has been proposed to occur via an initial bonding between the aromatic ring and the terminal carbon of one of the ethylene groups oe :- CBs - Komen, “The product results from 1.5:2.6-paiing in the inital trene system. I is an intramolecular example of the bicyclo[3.1,0]hex-2-ene ring closure seen in acyclic analogs. O-B-YB-G an oxa-di-r-methane rearrangement. b-b—b-b-6 ‘This is an oxa-di-m-methane rearrangement. 3 CHIChHat PROM, PUGH ale pOMCHae = * Shoes aos AS HS ‘ers cry “Pn ‘This transformation occurs by intramolecular hydrogen stom transfer and 1 4-diradical cleavage. Although the oxygen appears 10 be in close proximity {0 the hydrogen, the alignment is not ideal and the reaction has a relatively ow quantum yield. # 1 gu.cen1. This reaction can occur by a six electron electrocyclic ring opening, 143 followed by addition of water to the ketene that is produced. It is not clear from the original report if the Z-configuration of the 34-double bond is retained. 1m. This reaction involves a-cleavage, followed by decarbonylation and fragmentation of a cyclopropyl diradical om He om oy os Sm cop? 2 int oo Wn gen by GACH), CCH CH(CHle 1. This product can be formed by a [2+2] addition of dimethyl acetylenedi- carboxylate to the benzene followed by an electrocyclic opening of the cyclobutene ring. The ring opening must be disrotatory and can be regarded asa thermal opening of the eyclohexadiene ring or a photochemical opening of the cyclobutene ring, This facet of the reaction does not seem to have been established, +) r™ Ge co.chs, CO,CHs Ot oe coer, _. 'c0,0Hy 4 ‘0. This reaction is believed to occur through an oxetene intermediate formed by ‘a Paterno-Buchi reaction with the alkyne. The ring opening, which is highly favored thermodynamically, is probably a thermal reaction, 12.5 These reactions ean be expected to proveed by protonation of the strained E-eyclohexene structure, The authors suggest intramolecular participation in this process, leading to the observed stereoselectivity. The regiochemistry can also be interpreted in terms of ring opening of an oxonium ion intermediate. ‘The major product is the 4-acetoxy isomer, which corresponds to the favored iaxial opening of a three-memibered ring, The original formulation involved5 144 ‘Simao Poem 122, participation by the methoxy oxygen, but a similar mechanism involving the carbonyl oxygen might also be feasible. fons fe» Sif of” oH 00,” cn400: CrC0= peal appeteh uno aporoach “The product can be formed by an a-cleavage, followed by an intramolecular hydrogen atom transfer, The isotope effect is 1.07, which is quite small for 4 primary effect. The low value indicates a very early wansition state, which ‘would be expected for a reaction involving the weak C-H(D) bond 8 to @ radical, P cy. CH;CH=O oth - Se — GP o. H o. H HO) 483% 51.7% ‘The contrast between the direct and photosensitized reactions suggests that the di-t-methane rearrangement in this case involves the triplet state, The transformation to benzocyclooctatetraene occurs via bridging between the aryl and vinyl groups, The minor route leading to 3,8-di-labeling proceeds by vinyl- vinyl bridging, The di-r-methane rearrangement could proceed by vinyl-vinyl co vinyl-benzo bridging, The isotopic labeling shows that the former is preferred. Benzocyclooctatetraene formation: = Oa -OD 3 of —- ah -ob OS Sw - 0% —O@ 1 | 5050 | o® - 0%12.8, The {otal quantum yields, 1,04 and 0.99, account for all the photochemistry, 145 ‘The racemization provides a measure of the extent of back transfer of hydrogen —§ ————___— from the intermediate diradical. The alcohol evidently extends the lifetime of the radical, perhaps by solvation, so that fragmentation becomes dominant, ny Mornay wh * 2 hice oH 2 he on gg ol CoH racemization ged mK 129. As shown in Figure 12.P9, the 7; state is generally lower in energy than the 5; state and relaxes to a higher-energy point on the S, surface. As a result, the shift is greater For phosphorescence than for fluorescence. —————————E Fig. 12.9, Diagram showing the relationship between Maorescence and phospho- 12.10. This difference ci be accounted for by the differing orientation of the side chain in the two stereoisomers. Assuming an m—" transition, the electron Ueficieney is in the plane of the carbonyl bond. ‘The cis side chain is favorably oriented toward the oxygen for facile hydrogen transfer and fragmentation, ‘The trans isomer is less favorably oriented, The racemization presumably eccurs by( > 146 ‘a-cleavage and recombination, unless there is a nonphotochemical enolization ‘mechanism operating, cone oe a 2 he ‘ragmontaton = Aud 4 poor atgnment or (oye — Fiseai an ‘0 ‘Saar roo 12.11, This example provides a good illustration that the reaction does not proceed through a thermally equilibrated excited state, since both isomers would give rise to the same 90° minimum energy structure. The results are consistent with the ideas discussed in connection with the butadiene energy surface (p. 1140), which indicate that conical intersections determine efficiency of product formation. ‘There should be more of the s-cis conformation present for the E-isomer, since the methyl group causes sterie interactions in the s-cis conformation of the Z-isomer, The s-cis conformation is required for cyclization, Formation of the tdimethyleyclopropene product requires 2,4-bridging and a hydrogen shift. The 2,4-distance is not as sensitive to the rotational change. 12.12, The frst step is an internal [2-+2] cycloaddition. The second step can occur by 4 reaction sequence tha inially resembles a d-r-methane rearrangement bul then undergoes an acyl shift prior to cyclopropyl diradical fragmentation, The aecid-catalyzed step is a reverse aldol addition triggered by protonation of the enol ether,9 a1 9 147 op 98 om rr ue esr tga FON 0 Sa teat : wen deepen 1, comm | cue pom 8 — with — wD er ‘reverse aldol ee See ee Grea ager ct emuee ns re a ed ee reac omnes oe ee ee | See a ee eee aceite pees A ee le a oeipucae eee ee ETO) A. cyclohexauiene > hexatriene conversionfreversion accounts for the photochromic behavior. Although the product is enolic, and could conceivably revert to a less conjugated dione, the f-carbonyl group is presumably effective al stabilizing the enol form. 9 Ho Opn on Ch ov ¥ Pn on a tes oN en ote en i Pa Ne 12.16, These results ave consistent with conformational control of the reactivity of the excited state and diradical intermediates. The two t-butyl derivatives will be overwhelmingly in the conformations shown, The axial benzoyl group is 3148, Sanwa Poin 12.17, 1218, favorably disposed for hydrogen abstraction and recombination to a eyclobu- tanol, The equatorial benzoyl group is less well positioned for hydrogen abstraction and reacts by a-cleavage and partial recombination, The unsubsti- tuted system has both conformers present and can follow both reaction pathways. Hyéregen-abstracton/recombination pathway for axial benzoyl. Ph to Ho—éPn abrow — aProe AT «Cleavage and recombination pathway for equatorial benzoyl we ar ro oe ‘The azo compounds have a concerted mechanism available for formation of the barrelene structures 17-C and 17-B, Thus they are not necessarily good models for a singlet diradical. The photosensitization results indicate that the T excited state provides access only to the semibullvalenes 17-D and 17-F, ‘The direct photolysis results might suggest that the S state could give rise to both products or that there is $—> T' intersystem crossing. These issues have not been definitively established, but in the original paper the authors comment on the “tight” and “loose” character of the S and T excited states, respectively. ‘The S structure can be depicted as a singlet cyclopropyl diradical and the triplet as an allylic radical ‘The difference between the direct and photosensitized reactions suggest that 18-A and 18-C are triplet products, whereas 18-B isa singlet product. Products 18-A and 18-C can be accounted for by the di-t-methane mechanism, with 18-C being formed by fragmentation rather than recombination, Product 18-B ‘can result from a phenyl migration resulting from vinyk-phenyl bridging. An alternative di-r-methane product, 18D, is missing, presumably because of the preference for formation of the aryl stabilized diradical,7 mw pape 149 emnenongonony pee ont toe AR oor ae Im * : SO Tm Be NS hte HN leg 12,19, These products can all be accounted for by an initial 6-hydrogen abstraction, followed by alternative rebonding patterns. myo Sob as 21% id ssnaa a 12.20, Although the difference in composition is not extreme, the results suggest that the sensitized triplet reaction gives more of the more stable exo product. This could be described in terms of a tighter excited state (or conical intersection) leading to a dominance of the endo isomer, whereas a looser more flexible (and Tonger-lived) wiplet state adopts a geometry influence by the relative stability (strain) of the two structures. 12.21, These data show some very strong directive effects for quite similar substituents. ‘The guiding principle for regioselectivity in the di-m-methane rearrangement is the radicul-stabilizing effect of the substituents. Beyond that, it has been suggested that there is a polar effect as well, indicating that there is some increase of electron density in the cyclopropyl diradical intermediate, in which case EWG > ERG. For the wo monosubslittted cases, the radical-stabilizing and EWG effects would be synergistic and complete selectivity is observed. ‘The CO,CH, > CON(CH,), and CSOCH, > CO,CH, selectivities can be ratio- nalized by the greater EWG effect of the amide and the greater radical sta lizing effect of CSOCH,, The radical-stabilizing effect of phenyl is evident in150 the last entry. The very high regioselectivities are quite impressive, especially considering that they are directing the reactivity of highly reactive species. yy Go ds ia te Pons ‘go — oo Ge 12,22, This reaetion has been shown to be quite general for enynes and is not restricted to the eyclic example shown. It has been suggested that it might proceed through cycloaddition to a cyclobuta-1.2-diene. O-ca—o oe Baal pion cn vole or svat om (Thi ede 2yatudaal ig Teves evsl to he mannged pod ° o 98 had Lyn — BL m — ED pn — rbodononcnaom 3