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.

Publisher

Wiley

Publication Date

9-8-2025

Publication Title

Angewandte Chemie International Edition

Department

Chemistry and Biochemistry

Document Type

Article

DOI

https://doi.org/10.1002/anie.202510811

Notes

Dedicated to the 5th anniversary of the Frontiers Science Center for Transformative Molecules.

Keywords

Asymmetric aldehyde catalysis, Chiral-at-metal, Glycine ester, Unnatural alpha-amino acids

Language

English

Format

text

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