Kinetic resolution of amino acids by phosphine oxide catalyzed enantioselective esterification
2026-04-13
Chiral amino acids are essential building blocks in asymmetric synthesis and drug discovery, yet their efficient preparation from racemic mixtures remains challenging. Here we show that a rationally designed phosphine oxide catalyst derived from L -pyroglutaminol enables the highly efficient kinetic resolution of racemic amino acids under mild conditions. Using L -pyroglutaminol as the esterification reagent, this catalytic system delivers a broad range of chiral esters and recovered amino acids with excellent stereoselectivities (s > 1057). Mechanistic studies suggest that the superior stereocontrol arises from a cooperative double hydrogen-bonding interaction between the catalyst and the pyroglutaminol core. This work provides a practical and scalable approach to enantioenriched amino acids, highlighting the potential of dual chiral cooperative catalysis in asymmetric synthesis.