Enantioselective hydroamination of unactivated terminal alkenes

Asymmetric alkene hydroamination could be a direct route to valuable chiral amines from abundant feedstocks. However, most asymmetric hydroaminations have limited synthetic value because they require a large excess of alkene, occur with modest enantioselectivity, and proceed with limited tolerance of functional groups. We report an enantioselective, intermolecular hydroamination of unactivated terminal alkenes that occurs with equimolar amounts of alkene and amine, tolerates many functional groups, and occurs in high yield, with high enantioselectivity and turnover numbers. Mechanistic studies revealed factors, including reversibility of the addition, reversible oxidation of the product amine, competing isomerization of the alkene reactant, and unfavorable replacement of sacrificial ligands in standard catalyst precursors by the chiral bisphosphine, that needed to be addressed to achieve enantioselective N-H additions to alkenes.

Automated summary

Asymmetric alkene hydroamination reactions often have limited synthetic value due to the requirement of excess alkene, limited enantioselectivity, and low tolerance towards functional groups. In this study, an enantioselective and intermolecular hydroamination reaction of unactivated terminal alkenes was developed, which occurs with equimolar amounts of alkene and amine, shows high tolerance towards functional groups, and yields products with high enantioselectivity and turnover numbers.