Site-Selective Deuteration of α-Amino Esters with 2-Hydroxynicotinaldehyde as a Catalyst.

Abstract

An efficient method has been developed for the synthesis of α-deuterated α-amino esters via hydrogen isotope exchange of α-amino esters in D2O with 2-hydroxynicotinaldehyde as a catalyst under mild conditions. This methodology exhibits a wide range of substrate scopes, remarkable functional group tolerance, and affording the desired products in good yields with excellent deuterium incorporation. Notably, the ortho-hydroxyl group and the pyridine ring of the catalyst play a crucial role in the catalytic activity, which not only stabilizes the carbon-anion intermediates but also enhances the acidity of the amino esters' α-C-H bond.