Accessing <i>N</i> ‐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 &gt;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.