A GENERAL AND FACILE SYNTHESIS OF BETA-HYDROXY AND GAMMA-HYDROXY PHOSPHONATES FROM EPOXIDES

A practical and facile method for the preparation of hydroxy phosphonate esters is described. Regiospecific ring opening of monosubstituted epoxides by phosphorus and carbon nucleophiles, derived from diethyl phosphite and methanephosphonates, in the presence of BF3.OEt2 furnishes the corresponding beta- and gamma-hydroxy phosphonates, respectively. Ketals, bromides, sulfonate esters, and carbamates (compounds 12, 13, 15, 16, and 18) are stable under the reaction conditions, but benzoate esters(14) behave differently. While they survive phosphite nucleophilicity, they are cleaved by phosphonates. Several chirons (2, 28a, 30b, and 31) for the synthesis of phosphonate isosteres of nucleotides and phospholipids are also described.