Asymmetric Synthesis of Pyrrolidinoindolines. Application for the Practical Total Synthesis of (-)-Phenserine

J. Am. Chem. Soc., 126 (43), 14043 -14053, 2004. 10.1021/ja046690e S0002-7863(04)06690-9
Web Release Date: October 12, 2004

Asymmetric Synthesis of Pyrrolidinoindolines. Application for the Practical Total Synthesis of (-)-Phenserine

Audris Huang, Jeremy J. Kodanko, and Larry E. Overman*

Contribution from the Department of Chemistry, 516 Rowland Hall, University of California, Irvine, California 92697-2025

leoverma@uci.edu

Received June 5, 2004

Abstract:

A versatile route to enantiopure 3,3-disubstituted oxindoles and 3a-substituted pyrrolidinoindolines is described in which diastereoselective dialkylation of enantiopure ditriflate 10 with oxindole enolates is the central step. These reactions are rare examples of alkylations of prostereogenic enolates with chiral sp³ electrophiles that proceed with high facial selectivity (10-20:1). The scope of this method is explored, and a model to rationalize the sense of stereoselection is advanced. This dialkylation chemistry was used to synthesize (-)-phenserine on a multigram scale in six steps and 43% overall yield from 5-methoxy-1,3-dimethyloxindole (27) and to complete a short formal total synthesis of (-)-physostigmine (2).

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