Synthesis of Polyfuctional Methanes Using Highly Reactive N-acylimine

Abstract

Polyfunctional methanes are often found in biomolecules, such as amino acid and lactic acid. Thus, development of their synthetic method is important for exploring medicine and biocompatible materials. In this review, a novel synthetic method of polyfunctional methanes using diethylmesoxalate (DEMO) and N-acylimine as key electrophiles was described. The high electrophilicity of both compounds facilitates addition reaction by versatile nucleophiles. Indeed, DEMO reacted with less nucleophilic acid amide to afford N,O-hemiacetal. N-Acylimine can be generated in situ by O-acylation of the N,O-hemiacetal followed by treatment with base. A reaction of N-acylimine with various kinds of nucleophile such as pyrrole, indole, amine, and acid amide smoothly proceeded. By the sequential reactions, polyfunctional methanes bearing diester moiety, acylamino group, and an additional substituent could be synthesized. Unnatural amino acid derivatives were successfully synthesized by hydrolysis and subsequent decarboxylation of the 1,3-diester moiety.

graphical abstract