Organocatalytic enantioselective epoxidation of some aryl-substituted vinylidenebisphosphonate esters: On the way to chiral anti-osteoporosis drugs

Abstract

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 activators having a basic character, with the best results being observed using quinine and sparteine. These activators 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.