Chemo‐ and Enantioselective Hydrogenation of α‐Formyl Enamides: An Efficient Access to Chiral α‐Amido Aldehydes

In order to effectively synthesize chiral α‐amino aldehydes, which have a wide range of potential applications in organic synthesis and medicinal chemistry, a highly chemo‐ and enantioselective hydrogenation of α‐formyl enamides has been developed, catalyzed by a rhodium complex of a P‐stereogenic bisphosphine ligand. Under different hydrogen pressures, the chiral α‐amido aldehydes and β‐amido alcohols were obtained in high yields (97–99 %) and with excellent chemo‐ and enantioselectivities (up to >99.9 %  ee ). The hydrogenation can be carried out on a gram scale and with a high substrate/catalyst ratio (up to 20 000 S/C), and the hydrogenated products were further converted into several important chiral products. Computations of the catalytic cycle gave a clear description for the R / S pathways, provided a reasonable explanation for the enantioselectivity, and revealed several other specific features.