Ni‐Catalyzed Regio‐ and Enantioselective Homoallylic Coupling: Synthesis of Chiral Branched 1,5‐Dienes Featuring a Quaternary Stereogenic Center and Mechanistic Analysis

Asymmetric synthesis of small molecules comprising quaternary stereogenic carbon centers represents a challenging objective. Here regio‐ and enantioselective synthesis of chiral 1,5‐dienes featuring quaternary stereocenters is reported via nickel‐promoted reductive homoallylic coupling. The developed methodology features an atypical preference for the formation of unusual branched regioisomers (rr >20:1) in a sterically challenging allylic substitution event and furnishes the products with enantiomeric ratios of up to 94:6 and with high chemo‐ and E‐selectivity. A range of experimental evidences suggest that zinc plays a dual role to generate electrophilic and nucleophilic Ni(II)‐allyl intermediates empowering a unique formal bimetallic cross‐electrophile manifold in two separate kinetic regimes.