Highly enantioselective approach to geminal bisphosphonates by organocatalyzed Michael-type addition of beta-ketoesters.
A valuable organocatalyzed protocol has been developed for the asymmetric synthesis of bisphosphonate derivatives, a class of pharmaceutically important molecules. Cheap and commercially available dihydroquinine effectively catalyzed conjugate additions of cyclic beta-ketoesters to ethylidenebisphosphonate esters, leading to optically active geminal bisphosphonates, bearing an all-carbon substituted quaternary stereocenter, in high yields and enantioselectivities of up to 99 % ee. Further elaborations of Michael adducts to the corresponding bisphosphonic acids or vinyl phosphonates have also been successfully performed, with conservation of optical purity.
Capuzzi
Marinella
M
Department of Chemistry, Danish National Research Foundation: Centre for Catalysis, Aarhus University, 8000 Aarhus C, Denmark.
Perdicchia
Dario
D
Jørgensen
Karl Anker
KA
D002384:Catalysis; D002930:Cinchona Alkaloids / Q000737:chemistry; D018360:Crystallography, X-Ray; D004164:Diphosphonates / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D006868:Hydrolysis; D007659:Ketones / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D063065:Organophosphonates / Q000737:chemistry; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D002930:Cinchona Alkaloids; D004164:Diphosphonates; D004952:Esters; D007659:Ketones; D063065:Organophosphonates