Asymmetric Markovnikov Hydroaminocarbonylation of Alkenes Enabled by Palladium-Monodentate Phosphoramidite Catalysis

A palladium-catalyzed asymmetric Markovnikov hydroaminocarbonylation of alkenes with anilines has been developed for the atom-economical synthesis of 2-substituted propanamides bearing an alpha-stereocenter. A novel phosphoramidite ligand L16 was discovered which exhibited very high reactivity and selectivity in the reaction. This asymmetric Markovnikov hydroaminocarbonylation employs readily available starting materials and tolerates a wide range of functional groups, thus providing a facile and straightforward method for the regio- and enantioselective synthesis of 2-substituted propanamides under ambient conditions. Mechanistic studies revealed that the reaction proceeds through a palladium hydride pathway.

Automated summary

A palladium-catalyzed asymmetric Markovnikov hydroaminocarbonylation reaction has been developed for the synthesis of 2-substituted propanamides with an alpha-stereocenter. The reaction employs a novel phosphoramidite ligand L16, shows high reactivity and selectivity, and operates through a palladium hydride pathway. The method allows for regio- and enantioselective synthesis of propanamides under ambient conditions.