吡咯烷基吲哚啉的不对称合成。在（-）-苯丝氨酸实际全合成中的应用。

Asymmetric synthesis of pyrrolidinoindolines. Application for the practical total synthesis of (-)-phenserine.

作者信息

Huang Audris, Kodanko Jeremy J, Overman Larry E

机构信息

Department of Chemistry, 516 Rowland Hall, University of California, Irvine, California 92697-2025, USA.

出版信息

J Am Chem Soc. 2004 Nov 3;126(43):14043-53. doi: 10.1021/ja046690e.

DOI:10.1021/ja046690e

PMID:15506768

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 sp(3) 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).

摘要

本文描述了一种制备对映体纯的3,3-二取代氧化吲哚和3a-取代吡咯烷并吲哚啉的通用方法，其中对映体纯的双三氟甲磺酸酯10与氧化吲哚烯醇盐的非对映选择性二烷基化是关键步骤。这些反应是手性sp(3)亲电试剂对前手性烯醇盐进行烷基化反应的罕见例子，反应具有很高的面选择性（10-20:1）。我们探索了该方法的适用范围，并提出了一个模型来解释立体选择性的方向。这种二烷基化化学方法被用于从5-甲氧基-1,3-二甲基氧化吲哚（27）出发，通过六步反应以43%的总收率多克规模合成（-）-苯丝氨酸，并完成了（-）-毒扁豆碱（2）的简短形式全合成。