Umpolung Reactions of alpha-Imino Esters: Useful Methods for the Preparation of alpha-Amino Acid Frameworks

摘要

This paper summarizes our recent efforts toward the development of tandem reactions utilizing umpolung reactions of alpha-imino esters. A highly diastereoselective tandem N-alkylation-Mannich reaction of alpha-imino esters was developed. A tandem N-alkylation-addition reaction of alpha-imino esters derived from ethyl glyoxylate with various aldehydes proceeded to give 1,2-amino alcohols. The same reaction also proceeded efficiently using a novel flow system comprising two connected microreactors. Novel syntheses of alpha-quaternary alkynyl amino esters and allenoates were developed through the use of umpolung N-addition to beta,gamma-alkynyl alpha-imino esters, followed by regioselective acylation. In addition, a highly regioselective tandem N-alkylation-vinylogous aldol reaction of beta,gamma-alkenyl alpha-imino esters was discovered. N-Alkylation of alpha-iminophosphonates followed by a Horner-Wadsworth-Emmons reaction with aldehydes occurred to afford enamines, which can be used in a four-component coupling reaction with methyl vinyl ketone. alpha-N-Acyloxyimino esters served as highly efficient substrates for the N,N,C-trialkylation reaction to introduce various nucleophiles at the imino nitrogen and carbon atoms.