Manganese-Catalyzed Chemoselective Direct Hydrogenation of α,β-Epoxy Ketones and α-Ketoamides at Room Temperature

Chemoselective hydrogenation of alpha,beta-epoxy ketones and alpha-ketoamides is achieved at room temperature (25 degrees C) using 2.0 bar H-2 and a pincer-ligated Mn(I) catalyst that provides synthetically valuable alpha-hydroxy epoxides and alpha-hydroxy amides. This protocol applies to a wide range of alkyl- and aryl-substituted alpha,beta-epoxy ketones, including terpenes (alpha-ionone, nootkatone, and R-carvone)- and steroids (testosterone and progesterone)-derived epoxy ketones, and tolerates H-2 sensitive functionalities, such as halides, acetyl, nitrile, nitro, epoxide, alkenyl and alkynyl groups. Additionally, alpha-ketoamides bearing reducible functional groups, including acetyl and diazo benzene, were untouched under this protocol and selectively converted to alpha-hydroxy amides. A preliminary mechanistic study highlighted the metal-ligand cooperative H-2 activation process.