Nickel‐Catalyzed Enantioselective Reductive Alkyl‐Carbamoylation of Internal Alkenes

Abstract

AbstractHerein, we leverage the Ni‐catalyzed enantioselective reductive dicarbofunctionalization of internal alkenes with alkyl iodides to enable the synthesis of chiral pyrrolidinones bearing vicinal stereogenic centers. The application of newly developed1‐NapQuinim is critical for formation of two contiguous stereocenters in high yield, enantioselectivity, and diastereoselectivity. This catalytic system also improves both the yield and enantioselectivity in the synthesis of α,α‐dialkylated γ‐lactams. Computational studies reveal that the enantiodetermining step proceeds with a carbamoyl‐NiIintermediate that is reduced by the Mn reductant prior to intramolecular migratory insertion. The presence of thet‐butyl group of the Quinim ligand leads to an unfavorable distortion of the substrate in the TS that leads to the minor enantiomer. Calculations also support an improvement in enantioselectivity with1‐NapQuinim compared top‐tolQuinim.