Direct, enantioselective synthesis of pyrroloindolines and indolines from simple indole derivatives

TETRAHEDRON

卷:69

Article

Ni, Jane¹  Wang, Haoxuan¹  Reisman, Sarah E.¹ 

[1] CALTECH, Div Chem & Chem Engn, Warren & Katharine Schlinger Lab Chem & Chem Engn, Pasadena, CA 91125 USA

关键词: Pyrroloindoline;    (3+2) cycloaddition;    Enantioselective catalysis;   

DOI  :  10.1016/j.tet.2013.04.003

来源: Elsevier

【 摘 要 】

The (R)-BINOL-SnCl4-catalyzed formal (3+2) cydoaddition between 3-substituted indoles and benzyl 2-trifluoroacetamidoacrylate is a direct, enantioselective method to prepare pyrroloindolines from simple starting materials. However, under the originally disclosed conditions, the pyrroloindolines are formed as mixtures of diastereomers, typically in the range of 3:1 to 5:1 favoring the exo-product. The poor diastereoselectivity detracts from the synthetic utility of the reaction. We report here that use of methyl 2-trifluoroacetamidoacrylate in conjunction with (R)-3,3'-dichloro-BINOL-SnCl4 provides the corresponding pyrroloindolines with improved diastereoselectivity (typically >= 10:1). Guided by mechanistic studies, a one-flask synthesis of enantioenriched indolines by in situ reduction of a persistent iminium ion is also described. (C) 2013 Elsevier Ltd. All rights reserved.

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