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

Catalytic asymmetric hydrogenation of alpha- and beta-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 C = C bond of the enamido phosphate stage without tautomerization to the imine form. Tandem hydrolysis reactions of hydrogenated products gave the corresponding alpha- and beta-amino phosphonic acids in fairly high yield, which could be multipurpose building blocks for bioorganic chemistry, medicinal chemistry and organic synthesis.

Automated summary

Catalytic asymmetric hydrogenation of alpha- and beta-enamido phosphonates was achieved using a chiral hybrid phosphine-bicyclic bridgehead phosphoramidite ligand and rhodium metal precursor as the catalyst. The reaction showed high yields (96-99%) and high enantiomeric excess (<= 99%) with low catalyst loading (S/C up to 10,000) and mild reaction conditions. The hydrogenation reaction selectively occurred at the C = C bond of the enamido phosphate stage without tautomerization to the imine form. Tandem hydrolysis reactions of the hydrogenated products provided alpha- and beta-amino phosphonic acids in high yield, which can serve as versatile building blocks for bioorganic chemistry, medicinal chemistry, and organic synthesis.