Rh-catalyzed asymmetric hydrogenation of α- and β-enamido phosphonates: highly enantioselective access to amino phosphonic acids

Abstract

Catalytic asymmetric hydrogenation of α- and β-enamido phosphonates was developed using a complex formed in situ through a chiral hybrid phosphine-bicyclic bridgehead phosphoramidite ligand and rhodium metal precursor as the catalyst. This strategy afforded a wide variety of substrates in excellent yield (96–99%) and enantiomeric excess (≤99%) with very low catalyst loading (S/C up to 10 000) and relatively mild reaction conditions. Further investigations suggested that the hydrogenation reaction occurred only at the CC bond of the enamido phosphate stage without tautomerization to the imine form. Tandem hydrolysis reactions of hydrogenated products gave the corresponding α- and β-amino phosphonic acids in fairly high yield, which could be multipurpose building blocks for bioorganic chemistry, medicinal chemistry and organic synthesis.