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

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.