Resolution of Racemic α-Hydroxyphosphonates: Bi(OTf)₃-Catalyzed Stereoselective Esterification of α-Hydroxyphosphonates with (+)-Dibenzoyl-l-tartaric Anhydride

A practical and efficient method has been developed for the preparation of optically active α-hydroxyphosphonates through resolution of the racemates. Treatment of racemic diethyl 1-hydroxy-1-phenylmethylphosphonate (1) with (+)-dibenzoyl-L-tartaric anhydride gave two diastereomeric esters 2 and 3 in the presence of bismuth triflate (15 mol %) in an 86:14 ratio. The two diastereomeric esters were separated by simple column chromatography, and the structure for the major diastereomer was determined by X-ray crystallographic analysis. Simple hydrolysis of the isolated major diastereomer in the usual manner afforded (R)-O,O-diethyl-1-[hydroxyl(phenyl)methyl] phosphonate 1. The advantages of the present method are that the operation is simple and easy to handle, along with rapid and good yield preparations of both enantiomers of the racemic α-phosphonates 1. Diastereoselective reactions of various racemic α-hydroxyphosphonates with d-Bz-L-TA in the presence of Bi(OTf)3 are also described.