Stereodivergent propargylic alkylation of enals via cooperative NHC and copper catalysis

Abstract

Despite that asymmetric stereodivergent synthesis has experienced great success to provide unusual processes for the creation of chirality complexity, concepts appliable to asymmetric stereodivergent catalysis are still limited. The dependence on the unusual capacity of each catalyst to precisely control the reactive site planar in the region poses unparalleled constraints on this field. Here, we first demonstrate that the chiral Cu-allenylidene species can participate in the stereodivergent propargylic alkylation of enals, in concert with chiral N-heterocyclic carbenes (NHCs). Thus, all four stereoisomers were obtained with excellent enantioselectivity and diastereoselectivity (up to >99% e.e. and >95:5 d.r.) from the same starting materials by simply altering chiral Cu-Pybox complex and NHC combinations. The rich chemistry workable in the products enables the structurally diverse synthesis of chiral functional molecules and holds great potential in alkaloid synthesis, as showcased by the preparation of the key building block to access (-)-perophoramidine.

The ability to construct multiple stereocenters in a modular fashion is an important goal of synthetic organic chemistry. Here the authors present a method to construct oxindoles in four stereoisomers with high enantioselectivity and diastereoselectivity from the same starting materials by using cooperative copper- and organocatalysis.