Regio- and enantioselective nickel-alkyl catalyzed hydroalkylation of alkynes

The migratory insertion of metal-hydride into alkene has allowed regioselective access to organometallics, readily participating in subsequent functionalization as one conventional pathway of hydroalkylation, whereas analogous process with feedstock alkyne is drastically less explored. Among few examples, the regioselectivity of metal-hydride insertion is mostly governed by electronic bias of alkynes. To alter the regioselectivity and drastically expand the intermediate pools that we can access, one aspirational design is through alternative nickel-alkyl insertion, providing opposite regioselectivity induced by steric demand. Leveraging in situ formed nickel-alkyl species, we herein report the regio- and enantioselective hydroalkylation of alkynes with broad functional group tolerance, excellent regio- and enantioselectivity, enabling efficient route to diverse valuable chiral allylic amines motifs. Preliminary mechanistic studies indicate the aminoalkyl radical species can participate in metal-capture and lead to formation of nickel-alkyl, of which the migratory insertion is key to reverse regioselectivity observed in metal-hydride insertion. Although the stereochemistry of nickel hydride addition to alkenes is well-explored, the analogous addition to another feedstock, alkynes, is less studied. Here the authors develop a regio- and enantioselective hydroalkylation of alkynes to produce chiral allylic amines, proceeding via migratory insertion of a nickel-alkyl species into an alkyne pi bond.