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

Abstract

This paper summarizes our recent efforts toward the development of tandem reactions utilizing umpolung reactions of α-imino esters. A highly diastereoselective tandem N-alkylation-Mannich reaction of α-imino esters was developed. A tandem N-alkylation-addition reaction of α-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 α-quaternary alkynyl amino esters and allenoates were developed through the use of umpolung N-addition to β,γ-alkynyl α-imino esters, followed by regioselective acylation. In addition, a highly regioselective tandem N-alkylation-vinylogous aldol reaction of β,γ-alkenyl α-imino esters was discovered. N-Alkylation of α-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. α-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.

Keywords: alkylation; amino acids; synthetic methods; tandem reactions; umpolung.