Water enhanced synthesis of gem-bisphosphonates via Rh(i) mediated 1,4-conjugate addition of aryl boronic acids to vinylidenebisphosphonate esters

Abstract

A new synthetic method characterized by low environmental impact for the synthesis of a wide range of gem-bisphosphonates bearing aryl substituents in β position as potential anti-resorption species to contrast osteoporosis is reported. The pivotal role played by water ensures higher yields compared to the organic medium in the rhodium-catalyzed 1,4-conjugate addition of arylboronic acids to vinylidenebisphosphonate tetraethylester, as well as easy product isolation.