Indole synthesis by radical cyclization of o-alkenylphenyl isocyanides and its application to the total synthesis of natural products

被引:65
作者
Tokuyama, H [1 ]
Fukuyama, T [1 ]
机构
[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan
关键词
radical cyclization; isocyanides; indole synthesis; indole alkaloids;
D O I
10.1002/tcr.10008
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Development of indole synthesis by tin-mediated radical cyclization of o-alkenylphenyl isocyanide is described. Upon heating o-alkenylphenyl isocyanide in the presence of tri-n-butyltin hydride and AIBN, 2-stannyl-3-substituted indole was formed via 5-exo-trig cyclization of the imidoyl radical intermediate. After acidic workup, 3-substituted indoles were isolated. For substrates bearing simple alkyl groups, a substantial amount of tetrahydroquinoline derivatives were generated through 6-endo-trig cyclization. This undesired cyclization was suppressed by using an excess amount (five equivalents based on o-alkenylphenyl isocyanide) of ethanethiol instead of tri-n-butyltin hydride. The 2-stannylindole intermediates proved to be a suitable substrate for Stille coupling, giving 2,3-disubstituted indoles in a one-pot procedure. In addition, the 2-stannylindole intermediates could be converted to 2-iodoindoles by treatment with iodine or N-iodosuccinimide. The 2-iodoindoles thus obtained served as good substrates for Heck reactions, Stille couplings, Suzuki couplings, and palladium-mediated carbonylations, to afford a variety of 2,3-disubstituted indoles. The utility of this protocol was demonstrated by application to synthetic studies on gelsemine and discorhabdin A, and the total synthesis of an aspidosperma alkaloid, (-)-vindoline. (C) 2002 The Japan Chemical Journal Forum and John Wiley Sons, Inc.
引用
收藏
页码:37 / 45
页数:9
相关论文
共 30 条
[1]  
BARTON DHR, 1979, TETRAHEDRON LETT, P2291
[2]   NATURAL AND SYNTHETIC DERIVATIVES OF DISCORHABDIN-C, A CYTOTOXIC PIGMENT FROM THE NEW-ZEALAND SPONGE LATRUNCULIA CF BOCAGEI [J].
COPP, BR ;
FULTON, KF ;
PERRY, NB ;
BLUNT, JW ;
MUNRO, MHG .
JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (26) :8233-8238
[3]  
Curran DP, 1995, ANGEW CHEM INT EDIT, V34, P2683
[4]  
CURRAN DP, 1991, COMPREHENSIVE ORGANI, V4
[5]   RAPID ACCESS TO THE HIGHLY OXYGENATED ASPIDOSPERMA ALKALOIDS VINDOLINE, VINDOROSINE, AND CATHOVALINE [J].
DANIELI, B ;
LESMA, G ;
PALMISANO, G ;
RIVA, R .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1984, (14) :909-911
[6]  
DEWAR MJS, 1975, CHEM BRIT, V11, P97
[7]   Stereocontrolled total synthesis of (+/-)-gelsemine [J].
Fukuyama, T ;
Liu, G .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (31) :7426-7427
[8]   2,4-dinitrobenzenesulfonamides: A simple and practical method for the preparation of a variety of secondary amines and diamines. [J].
Fukuyama, T ;
Cheung, M ;
Jow, CK ;
Hidai, Y ;
Kan, T .
TETRAHEDRON LETTERS, 1997, 38 (33) :5831-5834
[9]   2-NITROBENZENESULFONAMIDES AND 4-NITROBENZENESULFONAMIDES - EXCEPTIONALLY VERSATILE MEANS FOR PREPARATION OF SECONDARY-AMINES AND PROTECTION OF AMINES [J].
FUKUYAMA, T ;
JOW, CK ;
CHEUNG, M .
TETRAHEDRON LETTERS, 1995, 36 (36) :6373-6374
[10]   A NOVEL TIN-MEDIATED INDOLE SYNTHESIS [J].
FUKUYAMA, T ;
CHEN, XQ ;
PENG, G .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (07) :3127-3128