Synergistic Pd/Cu-Catalyzed 1,5-Double Chiral Inductions.

Much attention has been focused on the catalytic asymmetric creation of single chiral centers or two adjacent stereocenters. However, the asymmetric construction of two nonadjacent stereocenters is of significant importance but is challenging because of the lack of remote chiral induction models. Herein, based on a C═C bond relay strategy, we report a synergistic Pd/Cu-catalyzed 1,5-double chiral induction model. All four stereoisomers of the target products bearing 1,5-nonadjacent stereocenters involving both allenyl axial and central chirality could be obtained divergently by simply changing the combination of two chiral catalysts with different configurations. Control experiments and DFT calculations reveal a novel mechanism involving 1,5-oxidative addition, contra-thermodynamic η 3 -allyl palladium shift, and conjugate nucleophilic substitution, which play crucial roles in the control of reactivity, regio-, enantio-, and diastereoselectivity. It is expected that this C═C bond relay strategy may provide a general protocol for the asymmetric synthesis of structural motifs bearing two distant stereocenters.