Rapid Access to Spirocyclic Oxindole Alkaloids: Application of the Asymmetric Palladium-catalyzed [3 + 2] Trimethylenemethane Cycloaddition

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2013 Oct 3

PMID 24083654

Citations 12

Authors

Barry M Trost

Dustin A Bringley

Ting Zhang

Nicolai Cramer

Affiliations

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Abstract

The marcfortines are complex secondary metabolites that show potent anthelmintic activity and are characterized by the presence of a bicyclo[2.2.2]diazaoctane fused to a spirooxindole. Herein, we report the synthesis of two members of this family. The synthesis of marcfortine B utilizes a carboxylative TMM cycloaddition to establish the spirocyclic core, followed by an intramolecular Michael addition and oxidative radical cyclization to access the strained bicyclic ring system. In addition, the first asymmetric synthesis of (−)-marcfortine C is described. The key step involves a cyano-substituted TMM cycloaddition, which proceeds in nearly quantitative yield with high diastereo- and enantioselectivity. The resulting chiral center was used to establish all remaining stereocenters in the natural product.

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