Chapter 5 Three and Four-mbered ing ystems 5.1 Aziridines Aziridines are good alkylating agents because of their tendency to undergo ring-opening reaction with nucleophiles 例 mitomycin C antibiotic and antitumor activity aziridine ring C 2 2 2 mitomycin C 5.1.1 ing ynthesis 4 5 X 4 5 X thod otes 3 2 P + 3 Br - I I aminoalcohol + 2 4 or 3 aminoalcohol + 2 aminoalcohol + 3 PBr 2 chloroamine + a in DM olefin, IC, olefin, I 3, then LiAl 4 or P 3 Wenker synthesis Gabriel synthesis Azidines from azides and olefins 4 3 5 4 5 5 4 05-Three-m Chinpiao Chen 2009/3/20 11:47 23
+ s=l [-(arylsulfonyl)imino]- phenyliodinane 5-1 s ~50% ee h h P 5-1 J. ys. rg. Chem. 1998, 597; Can. J. Chem. 1998, 738. l=ts 2 Ts * 44% ee Chem. Commun. 1998, 1601. + a l 2 (10 mol%) Ts Ts Cu-catalyst, M-5A * a Tetrahedron, 1998, 13485; Tetrahedron Lett. 1998, 309. + 2 CC 2 Et [(η 5 -C 5 5 )Fe(C) 2 (TF)] + [BF 4 ] - C 2 Et J. rg. Chem. 1998, 6839. C + 2 C 2 + 2 CC 2 Et Yb(Tf) 3 Chem. Lett. 1998, 685. C 2 C 2 Et 05-Three-m Chinpiao Chen 2009/3/20 11:47 24
+ 2 CC 2 Et n 4 C 2 Et J. Chem. oc. Perkin Trans. 2, 1998, 1347. Ts TM Br- Cs 2 C 3 + 1 TM J. rg. Chem. 1998, 4338. Ts 5.1.2 Functionalization at nitrogen -ubstituent C 2 C 2 C()C 3 (C 2 ) 3 C 2 C 2 C C=CC C 2 eagent C 2 C 2, Et 3 3 CC (C 2 ) 3, C 2 + Et 3 - C 2 =CC C=CC C 2 =C= 2 a 5.1.3 ing-opening reactions + 2 M 4, 29.5 o C 2 + 2 = = 58 7 J. Am. Chem. oc. 1974, 2855. 42 93 2 C Ar C 2 Ar 100 o C 2 C C 2 X Y 2 C Ar X Y C 2 05-Three-m Chinpiao Chen 2009/3/20 11:47 25
The ring-opening of aziridines to azomethine ylides and subsequent cycloaddition. Ar = C 6 4-4, C; X=Y = 2 CC=CC 2, Et 2 C=C 2 Et, C=, norbornene. Tetrahedron Lett. 1971, 473. Tol t- BuLi Li C 2 Et Et C Tetrahedron Lett. 1998, 2345. K [Bn 2 ] 2 Cu(C)Li 2 Ts Ts aza-payne rearrangement. Chem. oc. ev. 1998, 145. Ts Bn 2 4 c (Tf) 3 + Bn 5 ynlett, 1998, 754. 4 Bn 5 Boc TBDM Boc MgBr 2 TBDM Br Tetrahedron Lett. 1998, 2385. Cu(Tf) 2 J. rg. Chem. 1998, 4568. 05-Three-m Chinpiao Chen 2009/3/20 11:47 26
e e Bu 3 n ynlett, 1998, 981. 5.1.4 Fragmentation reactions + 2 2 40 o C + 150 o C + 2 5.2 xiranes (Epoxides) C 2 2 C(C 2 ) 4 C 10 21 5.2.1 ing ynthesis chanism of epoxidation by peroxy acids. 05-Three-m Chinpiao Chen 2009/3/20 11:47 27
t-bu C 10 21 Ti(i-Pr) 4, (-)-diethyl tartrate C1021 Asymmetric epoxidation of an allylic alcohols. Pure & Appl. Chem. 1983, 1823. rganic eactions, 1996, 48, 1. C 3 C 3 B, aq. dioxane Kt-Bu Br electivity of epoxide formation. J. Chem. oc. Perkin Trans. 2, 1993, 641. 2 Darzens reaction. Comprehensive rganic ynthesis, Vol. 2, 1991, p. 409. C 3 e 3 1 2 2 2 Tetrahedron Lett. 1998, 8521. 2 2 Mn Tetrahedron Lett. 1998, 3221. 05-Three-m Chinpiao Chen 2009/3/20 11:47 28
- = C = - 2 2 J. rg. Chem. 1998, 2564. Chem. Commun. 1998, 429. Mn X X t-bu t-bu J. Am. Chem. oc. 1998, 948. 10 l Z Mn 10 Tetrahedron Lett. 1998, 4325. (,)-13 t-bu Co Ac t-bu t-bu t-bu 13 J. rg. Chem. 1998, 6776. 05-Three-m Chinpiao Chen 2009/3/20 11:47 29
xone J. rg. Chem. 1998, 2810. 4 5 J. rg. Chem. 1998, 8475. 19 xone Et 2 C X 19 Chem. Commun. 1998, 621. 25 t-bu V t-bu t-bu 25 Tetrahedron Lett. 1998, 5923. Bn TE MCPBA Bn TE Tetrahedron Lett. 1998, 4517. 05-Three-m Chinpiao Chen 2009/3/20 11:47 30
35 2 2 + Br- 35 l Chem. Commun. 1998, 1159. Cu(acac) 2 C C 2 DCM J. Am. Chem. oc. 1998, 8328. C 2 Br C a J. rg. chem. 1998, 4532. 5.2.2 eactions - B E2 elimination and ring opening of oxiranes Bn LA J. eterocyclic Chem. 1998, 865. Bn Boc Et 2 Al 3 Boc 3 Tetrahedron Lett. 1998, 7971. 05-Three-m Chinpiao Chen 2009/3/20 11:47 31
TM 2 ynlett, 1998, 510. TM Lewis acid Tetrahedron Lett. 1998, 393. i 4 55 P 55 J. rg. Chem. 1998, 2429. TM TM TM Tetrahedron Lett. 1998, 529. 63 65 Li (-)-sparteine 63 t-bu 65 t-bu ymlett, 1998, 1165. Tetrahedron Lett. 1998, 9023. 05-Three-m Chinpiao Chen 2009/3/20 11:47 32
Li + J. Chem. oc. Perkin 1, 1998, 2151. Bn Bn TE Tf TBDP n-buli 2 Tol Bn J. rg. Chem. 1998, 6200. Bn TBDP 2 Tol LDA J. Am. Chem. oc. 1998, 10760. ' 2 n-buli Li ' Li Li : Li ' ' J. rg. Chem. 1998, 3808. ynlett, 1998, 337. Ar Pd(Ac) 2, PBu 3 C, t-bu Ar C Pd(Ac) 2, PBu 3 3A M, t-bu Tetrahedron, 1998, 1361. Tetrahedron Lett. 1998, 3107. 05-Three-m Chinpiao Chen 2009/3/20 11:47 33
u(lll), cat. acetone yn. Commun. 1998, 3189. 4 C, C 3 C Ti(TFA) 2 yn. Commun. 1998, 3913. X cat. Eu(dpm) 3 X Tetrahedron Lett. 1998, 4559. 2.2 ml 2 = aryl X 2.2 ml 2 = aryl, alkyl ynlett, 1998, 1073. 6 ml 2 Tetrahedron, 1998, 5819. 5.3 Thiiranes thiirane thiirane-1-oxide thiirane-1,1-dioxide - - C - C C - ynthesis of thiiranes from oxiranes 05-Three-m Chinpiao Chen 2009/3/20 11:47 34
Y - - Y Polymerization initiated by nucleophilic attack. etc. t-bu t-bu C 2 2, 100 o C t-bu t-bu Tetrahedron Lett. 2001, 4017. C 3 50% a(aq) Bn(Et) 3 elv. Chim. Acta. 1999, 946. 2 benzene elv. Chim. Acta. 1920, 838. 8 irradiation 5.4 2-Azirines C 2 C 13 27 C 2 05-Three-m Chinpiao Chen 2009/3/20 11:47 35
3 + 3 heat/hv A base B heat C P 3 A: = =, =, 110 o C, 63%. = =, = et 2, 20 o C, 94%, =,, = (C 2 ) 6, hν, pentane, 93%. B: =, =, =, a, 2, 20 o C, 63%. C: = =, = Bu t, 120 o C, 57%. Tetrhedron Lett. 1995, 4665. J. Am. Chem. oc. 1995, 3651. 1 Examples of addition reactions to C= bond of azirines Azirine eagent Product ef. EtMgBr 2 C 2 Et Py + - 4 a b c 2 C + 2 - d a. Tetrahedron lett. 1969, 4001. b. J. Am. Chem. oc. 1967, 4456. c. J. Am. Chem. oc. 1972, 2758. d. elv. Chim. Acta. 1979, 160. 05-Three-m Chinpiao Chen 2009/3/20 11:47 36
X X hν X heat X X X =, 70% X =, 90% X =, 200 o C, 80%. X =, 140 o C, 87%. Thermal and photochemical isomerization of 3-phenylazirines bearing conjugative substituents. Internal addition of nitrile ylides derived from azirines. 5.5 Diaziridines and 3-diazirines 4 diaziridine 3-diazirine 3 2 3 Ag 2 hν heat 05-Three-m Chinpiao Chen 2009/3/20 11:47 37
Et p-ts liq. 3 F 3 C F 3 C Et Tetrahedron Lett. 2000, 6737. ynthesis of diaziridines 2 - ynthesis of 3-chlorodiaziridines from amidines Li, 2, a 2 2, DM, pentane J. Am. Chem. oc, 1992,959. irradiation Tetrahedron lett. 1998, 9381. 5.6 xaziridines ArC 3 C 2 Tetrahedron Lett. 1998, 6227. C 2 05-Three-m Chinpiao Chen 2009/3/20 11:47 38
2 3 Bull. Acad. ci. U Div. Chem. ci. 1989, 793. Et 2 a 2 C 3 Chem.. Ber. 1958, 1057. Et 2 m-cpba, K 2 C 3, 2 2 J. Am. Chem. oc. 1989, 5964. As reagent for asymmetric oxygen transfer, Pure Appl. Chem. 1993, 633. 3 C Boc Boc Tetrahedron Lett. 1998, 8845. KMD 2 Tetrahedron, 1998, 10481. Et 2 C Et 2 C Et 2 C M M Et 2 C Tetrahedron Lett. 1988, 5855. 05-Three-m Chinpiao Chen 2009/3/20 11:47 39
5.7 Azetidines and azetidinones Ts C 2 Et Br C 2 Et Ts P 3 J. rg. Chem. 1981, 3562. C C 2 = C 2 = 2 C 2 C 2 Ac C 2 2 C 2 2 C C 2 2 3 - a + C 2 3 + C 2 - C 2 05-Three-m Chinpiao Chen 2009/3/20 11:47 40
2 C LDA, 2 C TF, -78 o C C 2 Cbz Flavobacterium buteocens enzyme 2 C C 2 Cbz Cbz +, 2 C optically active Cbz 1. 2, Pd/C 1. ab 4 2. TM, TEA, Et 2 2. Ac 2, Py 2 C Cbz Cr 3, Py - ) 2 Mg C 2 PB = TM 2 1. Ts 3, TEA, C 3 C 2. 1, P() 2, DMAP 2 h 2 (Ac) 4 C 2 PB benzene C 2 PB 1. ai P(P) 2 2. (E)- Ag- C=C- Ac C 2 PB C 2 PB Ac 1. MCPBA 2. TLC sepn. C 2 PB Ac 2, Pd/C Ac C 2 (-)-Carpetimycin A 5.8 ther four-membered heterocycles 5.8.1 xetanes 05-Three-m Chinpiao Chen 2009/3/20 11:47 41
obafluorin 2 conc (major) + (minor) 2 C CC 2 C 2 2 C C 2 2 C 5.8.2 Thietanes Br ( 2 ) 2 C a + 2 Et 3 2 2 + Br - Br 05-Three-m Chinpiao Chen 2009/3/20 11:47 42
benzothietane naphtho[1,8-bc]thiete 700 o C C 2 0.05 Torr J. Chem. oc. 1952, 2127. Tetrahedron Lett. 1980, 343. 2 C 2, Pb(Ac) 4 C 2 2, rt... J. Chem. oc. Perkin Trans.1, 1981, 413. 5.8.3 ome unsaturated four-membered rings C 2 C 2 oxete thiete 2,3-dihydroazete dimethyl 1,2-dihydrodiazete- 1,2-dicarboxylate 05-Three-m Chinpiao Chen 2009/3/20 11:47 43