Organic chemistry

Combinatorial chemistry

Amine gas treating

Enantioselective synthesis

Catalysis

Chemistry

Regioselectivity

Catalytic cycle

Hydroamination

Journal of the American Chemical Society

The asymmetric addition of an N–H bond to various alkenes via a direct catalytic method is a powerful way of synthesizing value-added chiral amines. Therefore, the enantio- and regioselective hydroamination of unactivated alkenes remains an appealing goal. Here, we report the highly enantio- and regioselective Ni-catalyzed hydroamination of readily available unactivated alkenes bearing weakly coordinating native amides or esters. This method succeeds for both terminal and internal unactivated alkenes and has a broad amine coupling partner scope. The mild reaction process is well suited for the late-stage functionalization of complex molecules and has the potential to gain modular access to enantioenriched β- or γ-amino acid derivatives and 1,2- or 1,3-diamines. Mechanistic studies reveal that a chiral bisoxazoline-bound Ni specie effectively leverages carbonyl coordination to achieve enantio- and regioselective NiH insertion into alkenes.

Nickel-Catalyzed Regio- and Enantioselective Hydroamination of Unactivated Alkenes Using Carbonyl Directing Groups