Nickel-Catalyzed Asymmetric Three-Component Reaction of Unactivated Alkyl Halides, 1,3-Enynes and Aldehydes

The π-propargylnickel(II) complexes, or their resonances, the η¹-allenylnickel(II) ones, are typically generated from propargylic derivatives under Ni⁰ catalysis, and act as versatile electrophilic partners in diverse transformations. Here, we demonstrate that η¹-propargylnickel(II) species can alternatively be generated from unactivated alkyl halides and 1,3-enynes via a Ni⁰-mediated radical alkylation of the alkene. Subsequent isomerization to η¹-allenylnickel(II), followed by reduction, affords η¹-allenylnickel(I) intermediates, which serve as reliable nucleophilic species for the stereoselective addition to aldehydes in the presence of benzoic acid. This protocol features broad substrate scope and good functional group tolerance, and nickel plays multiple roles in accomplishing a complicated Ni⁰/Ni^I/Ni^II/Ni^I/Ni⁰ catalytic cycle. A wide range of chiral homopropargylic alcohols, even the ones having a medium-sized ring, are modularly furnished in fair to good yields with moderate to excellent diastereo- and enantioselectivity. A series of control experiments and density functional theory (DFT) calculations are conducted to illuminate the catalytic pathways and the origin of regio- and stereoselectivity.