Kinetic Resolution of Phosphines and Phosphine Oxides with Phosphorus Stereocenters by Hydrolases

Lipase from Candida rugosa (CRL) and cholesterol esterase (CE) catalyzed the enantioselective hydrolysis of pendant acetates in chiral phosphines and phosphine oxides. The enantioselectivity for most substrates was modest (E = 1.5–4.8), but both hydrolases showed high enantioselectivity for one substrate, ArPhMeP═O (Ar =1-(2-acetoxy)naphthyl, 4c), E = 81 (CRL) and 32 (CE). Preparative-scale resolution of (±)-4c (1.0 g) catalyzed by CRL yielded enantiomerically-enriched starting acetate, (S)–(+)-4c, 0.48 g, 90% ee as well as product alcohol, (R)-(–)-4b (Ar = 1-(2-hydroxy)-naphthyl), 0.39 g, 88% ee. Recrystallization of 4b from toluene raised the enantiomeric purity to >95% ee. Standard chemical steps followed by stereospecific reduction gave both enantiomers of phosphine ArPhMeP (Ar = 1-(2-methoxy)naphthyl) with 96–97% ee. This phosphine is an analog of PAMP (Ar = 2-methoxyphenyl), a chiral phosphine used in asymmetric synthesis.