Construction of remote cyano-substituted quaternary carbon centers via nickel-catalyzed migratory hydrocyanation of unconjugated dienes

The transition-metal-catalyzed migratory functionalization has emerged as a robust protocol for the building of C-C bonds remote from the "initiation" position. However, a similar strategy for the construction of quaternary carbon centers is still underdeveloped and only a limited number of reports exist. Herein, we report a nickel-catalyzed migratory hydrocyanation of unconjugated dienes to construct remote cyano-substituted quaternary carbon centers. This transformation features exceptional regioselectivity, mild reaction conditions, broad substrate scope and high yields. The synthetic utility of this method has been highlighted by a series of product derivatizations, and the potential of this transformation has been extended to synthesize TRPV1 antagonist and the key intermediate in the total synthesis of quebrachamine. Density functional theory (DFT) studies unveiled that the specific catalytic pocket assumed a significant role in the selective formation of cyano-substituted quaternary carbon centers.