Pd-Catalyzed Asymmetric Allylic Substitution Annulation Using Enolizable Ketimines as Nucleophiles: An Alternative Approach to Chiral Tetrahydroindoles

A synthesis of chiral tetrahydroindoles has been developed via a Pd-catalyzed asymmetric allylic substitution annulation using unstable enolizable ketimines as nucleophiles and our previously developed Bu-t-RuPHOX as a chiral ligand. The reaction proceeds via an asymmetric desymmetrization of the meso-diacetatecycloalkenes, providing the desired chiral tetrahydroindoles in moderate to good yields and with up to 96% ee. The annulation reaction could be performed on a gram-scale in high yields and the resulting products can be transformed to several types of N-hetereobicyclic derivatives. In addition, a chiral cis-perhydroindolic acid derivative was also readily synthesized starting from a prepared chiral tetrahydroindole.