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

• Published in: Angewandte Chemie International Edition p. e202510811
• Main Authors: Chen, Gang, Morais, Gabriel N., Liang, Hui, Zhao, Jing, Wang, Chuanyong, Chen, Shuming, Ma, Jiajia
• Format: Journal Article
• Language: English
• Published: Germany 25.07.2025
• Subjects: Chiral‐at‐metal; Asymmetric aldehyde catalysis; Glycine ester; Unnatural α‐amino acids
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202510811

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.