Stereodivergent Construction of 1,5/1,7‐Nonadjacent Tetrasubstituted Stereocenters Enabled by Pd/Cu‐Cocatalyzed Asymmetric Heck Cascade Reaction

Abstract

AbstractThe construction of chiral motifs containing nonadjacent stereocenters in an enantio‐ and diastereoselective manner has long been a challenging task in synthetic chemistry, especially with respect to their stereodivergent synthesis. Herein, we describe a protocol that enables the enantio‐ and diastereoselective construction of 1,5/1,7‐nonadjacent tetrasubstituted stereocenters through a Pd/Cu‐cocatalyzed Heck cascade reaction. Notably, a C=C bond relay strategy involving the shift of the π‐allyl palladium intermediate was successfully applied in the asymmetric construction of 1,7‐nonadjacent stereocenters. The current method allows for the efficient preparation of chiral molecules bearing two privileged scaffolds, oxindoles and non‐natural α‐amino acids, with good functional group tolerance. The full complement of the four stereoisomers of products bearing 1,5/1,7‐nonadjacent stereocenters could be readily accessed by a simple combination of two chiral metal catalysts with different enantiomers.