A practical, multi-gram synthesis of (±)-herbindole A, (±)-herbindole B, and (±)-herbindole C from a common intermediate via 6,7-indole aryne cycloaddition and Pd(0)-catalyzed cross-coupling reactions

TETRAHEDRON LETTERS

卷:56

Article

Chandrasoma, Nalin¹  Pathmanathan, Sivadarshini²  Buszek, Keith R.^1,2 

[1] Univ Missouri, Kenneth A Spencer Chem Labs 205, Dept Chem, Kansas City, MO 64110 USA

[2] Univ Kansas, Ctr Excellence Chem Methodol & Lib Dev KU CMLD, Delbert M Shankel Struct Biol Ctr, Lawrence, KS 66047 USA

关键词: Herbindole;    Trikentrin;    Indole;    Indolyne;    Aryne;    Cycloaddition;   

DOI  :  10.1016/j.tetlet.2015.02.064

来源: Elsevier

【 摘 要 】

A practical, multi-gram 10-step synthesis of racemic herbindole A, B, and C from a common intermediate is described. The key step features a remarkably regioselective C-7 metal halogen exchange and elimination from a Bartoli-generated N-t-butyldimethylsilyl-4,6,7-tribromo-5-methylindole scaffold to afford the 6,7-indole aryne. Cycloaddition with cyclopentadiene, oxidative cleavage, and Fujimoto reduction gave a common intermediate from which all three herbindoles were readily derived. A final Pd(0)-catalyzed Negishi and Stille cross-coupling reaction at the C-4 bromide afforded each of the herbindoles on a multigram scale. (C) 2015 Elsevier Ltd. All rights reserved.

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