Efficient Cu-catalyzed Asymmetric Alkylation and Application in the Total Synthesis of Phallotoxins and Virotoxins

Abstract

Asymmetric alkylation is one of the most important methods for synthesis of chiral unnatural α-substituted α-amino acids. Herein, we reported the asymmetric alkylation catalyzed by Cu/(4S,2R)-tBu-Phosferrox catalyst. This catalyst exhibits the highest catalytic performance in the asymmetric alkylation at catalyst loading as low as 1.0 mol %, giving the desired products with up to 95% yield and >99% ee, which is the best results to date. Furthermore, this method was successfully applied to the scalable practical synthesize of unnatural amino acid 4,5-OH-Leu, which could be directly used in the total syntheses of phalloidin, phallacidin, other four phallotoxins and six virotoxins.