Synergistic catalytic allenylic alkylation for stereodivergent construction of allenes bearing 1,3-axial and central chirality

Abstract

A highly efficient asymmetric allenylic alkylation for the construction of allenes bearing allenyl axial and central chirality through synergistic Ni/Pd catalysis has been developed. This catalytic protocol operates smoothly under one-pot, additive-free conditions, offering exceptional step efficiency and high atom economy. A wide range of chiral two- or three-substituted allenes bearing multisubstituted acyclic or cyclic carbonyl moieties were obtained with excellent reactivity and stereoselectivity using this dual catalytic system. The stereodivergent synthesis was successfully realized, delivering all stereoisomers in high yields. Diastereoselectivity reversal manifested that the chiral Lewis acid catalyst could effectively override the stereocontrol capability of the chiral palladium catalyst itself, enabling access to dynamically disfavored diastereomers with high enantiocontrol. Gram-scale synthesis and further transformation experiments demonstrate the potential utility of this method.