Accessing N-Unprotected Unnatural α-Amino Acid Esters by Half-Sandwich Chiral-at-Ruthenium Aldehyde Catalysis: Scope and Mechanistic Study.

Abstract

Chiral aldehyde catalysis has emerged as an efficient and step-economical protocol for constructing unnatural α-amino acids and related esters. Herein, we report the application of a half-sandwich chiral-at-ruthenium complex featuring an aldehyde group as a versatile asymmetric catalyst with remarkably broad scope. Direct asymmetric α-C─H functionalization of N-unprotected glycine esters with four types of electrophiles (51 examples, all >91% ee) has been successfully realized for accessing structurally diverse unnatural α-amino acid esters. Gram-scale synthesis and successful catalyst recovery underscored the practicability and application potential of the present asymmetric aldehyde catalysis.