Enhancing the Tsuji-Trost Reaction via 1,3-Diene Formation

The asymmetric Tsuji-Trost reaction is a basic transformation model in organic synthesis that usually requires the use of special substrates to form terminal or symmetric π-allyl metal species to avoid resolution issues. The fundamental reason lies in the challenging interconversion deracemization mechanism, which requires the transition metal to function as both the catalyst and nucleophile. This study presents a different mechanistic pathway for efficient allylic deracemization transformations using common unsymmetric internal allyl substrates. By breaking the classical deracemization route, which is restricted to the η³-metal center, the proposed 1,3-diene-formation principle enables diverse allyl electrophiles to react with different types of carbon and phosphine nucleophiles with good enantioconvergence efficiency. In addition, the stereoselective migration of the whole allyl unit is established through deracemization, which differs from prior metal walking models that are limited to alkene migration. Convergent synthesis and concise preparations of a couple of natural products highlight the practical value of the method. Mechanistic studies support 1,3-diene formation as the key process for deracemization and that the final allylic substitution is a slow and rate-determining step.