Selective α-Deuteration of Amines and Amino Acids Using D₂O

Abstract

Monohydrido-bridged ruthenium complex [{(η⁶-p-cymene)RuCl}₂(μ-H-μ-Cl)] catalyzes (catalyst load: 0.5-1 mol %) α-selective deuteration of primary and secondary amines, amino acids, and drug molecules using deuterium oxide (D₂O) as a deuterium source. Mechanistic investigations revealed N-H activation of amines, which was also established by single-crystal X-ray analysis of an intermediate. β-Hydride elimination on amide ligand results in formation of imine-ligated ruthenium intermediate and subsequent 1,3-deuteride migrations to imine ligand leading to the selective deuteration at the α-CH₂ protons of amine functionality is proposed.