Regioselective and asymmetric allylic alkylation of vinyl epoxides for the construction of allylic alcohols via synergistic catalysis

A highly efficient asymmetric allylic alkylation of cyclic and acyclic carbon nucleophiles with vinyl epoxides has been developed, which exhibits good functional group compatibility, high atomic and step economy. This protocol utilizes a strategy of synergistic catalysis with a chiral N,N-dioxide/Ni-II complex and an achiral Pd-0 catalyst, generating a series of multi-substituted allylic alcohols with a quaternary carbon stereocenter in high yield and excellent regio-, Z/E- and enantioselectivity under mild conditions. Further transformations of the product demonstrate the potential utility of this protocol in the synthesis of allyl alcohol derivatives and natural product analogues. Experimental studies revealed that the N,N '-dioxide/metal complexes play an important role in controlling the Z/E- and enantioselectivity. The density functional theory (DFT) calculations further demonstrated that multiple C-H center dot center dot center dot pi interactions between the aromatic rings of the two substrates and the amide moiety in the ligand stabilized the dominant transition state.