Cu-Catalyzed Diastereo- and Enantioselective Synthesis of Borylated Cyclopropanes with Three Contiguous Stereocenters

Abstract

Direct synthesis of enantioenriched scaffolds with multiple adjacent stereocenters remains an important yet challenging task. Herein, we describe a highly diastereo- and enantioselective Cu-catalyzed alkylboration of cyclopropenes, with less reactive alkyl iodides as electrophiles, for the efficient synthesis of tetra-substituted borylated cyclopropanes bearing three consecutive stereocenters. This protocol features mild conditions, a broad substrate scope, and good functional group tolerance, affording an array of chiral borylated cyclopropanes in good to high yields with excellent diastereo- and enantioselectivities. Detailed mechanistic experiments and kinetic studies were conducted to elucidate the reaction pathway and the rate-determining step of the reaction. DFT calculations revealed that the π···π stacking interaction between the phenyl groups on the substrate and the phosphorus ligand, along with the smaller distortion in the CuL-Bpin part, contributed to the high diastereo- and enantioselectivities. The synthetic utility of the protocol was showcased by the facile synthesis of some valuable chiral cyclopropanes with multiple chiral centers.