Organocatalytic Stereoselective Epoxidation of Aryl-Substituted Vinylidenebisphosphonate Esters: On the Way to Chiral Anti-Osteoporosis Drugs

The synthesis of a new class of epoxide derivatives from prochiral vinylidene bisphosphonate (VBP) precursors is reported using hydrogen peroxide as the terminal oxidant. The reaction is carried out using a series of possible organic catalysts having a basic character, the best results being observed using quinine and sparteine. These catalysts not only provide from good to excellent epoxide yields with a large variety of VBPs but also interesting enantioselectivities in the 67-96% ee range at least in the case of the Ph and m-MeO-Ph VBP derivatives opening the way to a number of chiral anti-osteoporosis potentially active pharmaceutical ingredients.