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Chapter 5 Three and Four-Membered Ring Systems

5.1 Aziridines
H 104.2 H N Aziridine 116 H
H N N CH3 H N

195.5 H 108.4

N 60o 148.2 pm

60

60 149.1 pm
H ∆G* = 70 kJ mol-1 not separable at rt CH3

153

Cl

Cl N CH3

H ∆G* = 112 kJ mol-1 separable at rt CH3

Aziridines are good alkylating agents because of their tendency to undergo ring-opening reaction with nucleophiles。
O O N O 4 5 N O N N N N N N

例如 mitomycin C 具有 antibiotic and antitumor activity 是因含有 aziridine ring。 O O H2N Me O mitomycin C Industrial application: as monomers for polymerization and as components for reactive dyes for cellulose fibres.
05-Three-m Chinpiao Chen 2008/2/23

CH2O OMe N

NH2

N H

30

597. 1998.5. then LiAlH4 or PPh3 I + I N C O + MeOH Gabriel synthesis HN C O OMe Azidines from azides and olefins R N3 1 R R 2 3 R R 4 5 R 1 N N N R 3 4 R N R 2 3 1 R R 5 4 R 2 R R 5-1 R Ph N Ns R 5 Ph R + NsN=lPh Rh O O P Rh O O [N-(arylsulfonyl)imino]phenyliodinane ~50% ee 5-1 J. IN3. J. Can.1.1 Ring Synthesis R HN R 3 R X OSO3H OSO2R OPPh3+BrCl I I 2 1 R 4 R 5 R N R 2 3 1 R R 5 4 X R Method Notes Wenker synthesis aminoalcohol + H2SO4 or ClSO3H aminoalcohol + RSO2Cl aminoalcohol + Ph3PBr2 chloroamine + NaH in DMSO olefin. ROH olefin. 738. Phys. Chem. 1998. INCO. 05-Three-m Chinpiao Chen 2008/2/23 31 . Chem. Org.

4338. Chem. 1998. Et 3N Cl3CCHO Me(CH2) 3Cl. Org. 1998.2 Functionalization at nitrogen N. Chem.Substituent Reagent ClCH2CO2Me. 6839.1.H N H CO2Et R2 J. PhCH2N+Et 3ClCH2=CHCN ClCH=CHCOPh CH2=C=O MeSO2Cl NaOCl CH2CO2Me CH(OH)CCl3 (CH2) 3Me CH2CH2CN CH=CHCOPh COMe SO2Me Cl 05-Three-m Chinpiao Chen 2008/2/23 32 . Org. N Ts H 5. R1 R1 R2 TMS N Ts + BrS OH TMS Cs2CO3 R1 R2 J.Ph N R1 R2 Ph + N2CHCO2Et [(η5-C5H5)Fe(CO)2(THF)]+[BF4].

1. N N MeOH + R R NaOMe(cat. 1998. PhCH=NMe. 29. Ph N Me Tol S H O Ph t. X=Y = MeO2CCH=CHCO2Me. 2855. 2345. Soc. Chem. Ar N MeO2C CO2Me 100 C o Ar H MeO2C N H CO2Me X Y MeO2C Ar N X Y CO2Me The ring-opening of aziridines to azomethine ylides and subsequent cycloaddition.3 Ring-opening reactions H H o + 2 M HClO4. 1974. 1971.) MeO R H N R 05-Three-m Chinpiao Chen 2008/2/23 33 .4 Fragmentation reactions H N Me Me NOCl Me NO N Me Me Me + N2O 2H-Azirine 2H-azirine is thermally unstable and has to be stored at very low temp. Tetrahedron Lett. PhCHO. 5.BuLi Ph N Me Li H Ph ClCO2Et Me EtO C Ph N Ph H O Tetrahedron Lett. norbornene.5 C N Me H2N Me R 58 7 + OH Me R HO 42 93 NH2 R R=H R = Me J. 473.1. Ar = C6H4OMe-4. EtO2CN=NCO2Et. Am.5.

H Z N R 1 O OH + Me2N N R 2 H Z N R 1 O OMe2N H N+ R 2 H Z N R 1 O O H N R2 Z 1 H R N ONH R 2 O H Z N R1 O N H R2 NMe2 O H2O.2 Oxiranes (Epoxides) O CO2H Leukotriene A. is the biosynthetic precursor of the “slow-reacting substance. H+ dipeptide Me2N O Z= O Me2N + cbz 2H-Azirine synthesis R heat -N2 N R vinyl nitrene R Br2 R Br Br N NaN3 R N3 Br NaOH R vinyl azide .+ N N N O R12N R2 COCl2. is an insect pheromone. and implicated in bronchial asthma (支氣管氣喘) H O H C10H21 Me2HC(H2C)4 (+)-Disparlure. NEt3 Cl R12N R2 NaN3 R12N N R2 5. 05-Three-m Chinpiao Chen 2008/2/23 34 . the gypsy moth (鞦韆蛾) sex attractant.

1 Ring Synthesis R O O O H R O O O H Mechanism of epoxidation by peroxy acids.2. Organic Reactions. Chem. H HO H C10H21 t-BuOOH Ti(Oi-Pr)4. Pure & Appl. 1983.5. (-)-diethyl tartrate HO O H H C10H21 Asymmetric epoxidation of an allylic alcohols. 05-Three-m Chinpiao Chen 2008/2/23 35 . 1823. 48. 1996. 1.

R2 O Comprehensive Organic Synthesis. R1 R2 R1 O Ph2S Darzens reaction. p. Chem. Vol. di o OH xa ne O KOt-Bu Br Selectivity of epoxide formation. 641. J. Perkin Trans. 409. 2.CH CO 3 3 H O NB S .a q. 1993. 2. Soc. Corey synthesis 05-Three-m Chinpiao Chen 2008/2/23 36 . 1991.

1998. 4325. Org. O 05-Three-m Chinpiao Chen 2008/2/23 37 .S)-13 Cl O H Cl O t-Bu N N Co O O OAc t-Bu t-Bu t-Bu 13 J. 621. 1998. 6776. Chem.O H3C S CH3 CH3I O H3C +S CH3 CH3 NaH O H3C +S CH2 CH3 O H3C S CH2 CH3 R1 O R2 + H2C S CH3 CH3 O OR1 R2 H3C CH3 S+ O R1 O R2 + O H3C S CH3 H R1 R2 R3 O 10 PhlO R1 R2 R3 O R O O N O Z O Mn N O O 10 R H Tetrahedron Lett. Commun. EtO2C Ph Ph Ph O Ph 19 Oxone Ph Ph N X H 19 Chem. 1998. H (S.

510. Heterocyclic Chem. N OH H TMS OH MeO O R1 Lewis acid R2 OH Tetrahedron Lett. 1998.Ph Me 25 Ph O Me Me OH OH t-BuOOH NO N V O O t-Bu t-Bu 25 Me Tetrahedron Lett. 865. MeO R1 O R2 05-Three-m Chinpiao Chen 2008/2/23 38 . 5. 1998. 7971. 393. TMS NH2 O Synlett.2. 5923. OH O RO BocHN O OH BocHN Et2AlN3 OH OH N3 Tetrahedron Lett. 1998. 1998. 1998.2 Reactions O O - B H E2 elimination and ring opening of oxiranes OBn LAH RO OBn J.

1998. Org. Polymerization initiated by nucleophilic attack.3 Thiiranes S thiirane OO - O S thiirane-1-oxide N- O S O thiirane-1. 2429. 1998.O Ph Ph SiCl4 55 Ph Cl Ph OH Me N O P N N 55 Me J. Tetrahedron Lett. OH Ph H N 63 O PhLi 65 Ph OH N t-Bu H 63 t-Bu N OH OH 65 (-)-sparteine Symlett. 9023. 1998. Chem. 5.1-dioxide O R SCN NCO S SCN R Synthesis of thiiranes from oxiranes S - S SR R R S Y - S Y etc. 1165. 05-Three-m Chinpiao Chen 2008/2/23 39 .

20oC. 63%. 57%. R3 = But. R3 = Net2. hν. Examples of addition reactions to C=N bond of azirines 05-Three-m Chinpiao Chen 2008/2/23 40 . 1 2 3 R3 = (CH2)6. Chim. 946. 2001. 3651. 1999. Chem. R = R2 = Me.ClSCl t-Bu t-Bu CH2Cl2. Me2SO. R2 = Me. R3 = Ph.4 2H-Azirines N Me H + 1 N CO2H C13H27 H CO2Me Me3N N R 3 R H R 2 N3 R 3 R R 1 N t hea O base B hea t/hv A o 2 R C 3 PPh3 1 R 2 R N R 3 1 R 2 1 R A: R = R = H. R2. 4665. 63%. Tetrhedron Lett. pentane. 4017. 1995. 20oC. 100 C o t-Bu Cl S Cl t-Bu Tetrahedron Lett. 93%. R1 = H. B: R1 = H. 5. C: R1 =R2 = H. Soc. NaH. 120oC. S S Ph Ph CHCl3 50% NaOH(aq) Bn(Et)3NCl Ph Ph Cl Cl Helv. J. 1995. R = Ph. Acta. Am. 94%. 110 C.

4001. 6737. c Ph N + SN Me d 5. NH3 NH HN F3C O O Tetrahedron Lett. Soc. Acta. Chim. d. Tetrahedron lett. 1967. Chem. Synthesis of diaziridines 05-Three-m Chinpiao Chen 2008/2/23 41 . EtMgBr Et Ph H Ph a N Ph N Me Me N H Me2SCH2 Ph Py ClO4+ H N Me Me b N Ph Ph N Me2N Me PhNCS Me Me2N Me a.TsO N O F3C O liq. Am. 1969. 4456. b.di az i r i n e O NH3 H2NOSO3H OEt NH NH Ag2O N N OEt p. 160. Soc. Chem. 2000.Azirine N Ph Ph Reagent Product H N Ref. 1979. Helv. 2758. J. Am.5 Diaziridines and 3H-diazirines R R 3 4 1 N N R 2 R 1 N N R 2 R di az i r i di ne 3H. c. 1972. J.

Sci.H NH R NH2 R Cl - N N H Cl R H N NH Cl R N N Cl Synthesis of 3-chlorodiaziridines from amidines O NH NH2 HCl LiCl. 6227. Pure Appl. 1993.959. Acad. 1992. Cl2. Chem. USSR Div. Soc. 793. OMe O O OMe OMe KHMDS Cl Cl N O SO2 OMe OMe O O OMe OH Tetrahedron. As reagent for asymmetric oxygen transfer. O NH2OSO3H O NH Bull. Am. 10481. 1998.6 Oxaziridines R R 1 2 NR 3 ArCO3H R 1 2 O N R 3 R O O R N H OH CO2Me R O N CO2Me Tetrahedron Lett. 5. 1989. 1998. DMSO. 05-Three-m Chinpiao Chen 2008/2/23 42 . Sci. Chem. pentane O N N J. NaCl H2O. 633. Chem.

3562. Chem. Org.7 Azetidines and azetidinones NHTs Br CO2Et PPh3 N CO2Et Ts N HO N J. 1981.5. H O H RC N H S N Me Me CO2H H NH2 HO2C H2N H O H N O H N S CH2OAc CO2H O R = CH2Ph R = Ph HO H H H Me N O S CO2H NH2 O H RC N N O H CO2H OH R 1 H 2 R N O O N SO3 Na + H O N O CO2H OH Ph NH3 H N Me O O CO2 N - + OH H H N O CO2H 43 Cl OMe 05-Three-m Chinpiao Chen 2008/2/23 .

TEA. Et2O HO NHCbz NHCbz O OR CrO3.NHAc 1. NaI 2. Py O O optically active LDA. 1 N HCl.8 Other four-membered heterocycles 5. Me2CO THF. NaBH4 2. TEA. MCPBA 2. Pd/ C OH NHAc N O S O CO2H (.8.CH=CH. MeOH + NHCbz OR OR MeO2C NHR MeO2C HO OH 1. Py OR O N O H O2N OH OR H N N N O O OR N O O ) 2Mg - O N O H CO2PNB N O R = TMS OH 1. TMSCl. TsN3. Ac2O. DMAP O N N2 H OH O Rh2(OAc) 4 CO2PNB benzene OH O CO2PNB N O Cl N O OH NHAc N O S CO2PNB O OP(OPH) 2 CO2PNB OH 1. O N S O CO2PNB NHAc H2. TLC sepn. MeOH O P(OPh) 2. ( E).).AgS.MeO2C Flavobacterium CO2Me buteocens enzyme HO2C NHCbz CO2Me NHCbz 1. Pd/C 2.Carpetimycin A 5.1 Oxetanes 05-Three-m Chinpiao Chen 2008/2/23 44 . -78oC O O H . H2. CH3CN 2.

2-dihydrodiazete1.3-dihydroazete 45 05-Three-m Chinpiao Chen 2008/2/23 .2-dicarboxylate O oxete S thiete N 2.3 Some unsaturated four-membered rings NCO2Me NCO2Me dimethyl 1.2 Thietanes Ph Br Cl (H2N) 2C NaOH S S Ph Ph Ph + MeSO2Cl Et3N Ph R2N SO2 - Ph R2N SO2 Ph S S S + Br Br S 5.H HO OH O N O NO2 O obafluorin conc HCl O Me O N Me O H Ph Ph Me OH (major) Cl + Me OH Cl (minor) MeCOCH2CO2R Ph2C NH ROH O O O R Me O 1 Me2CO 2 2 O O Me Me O Me R C CNR 2 2 1 NR 5.8.8.