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.