Steric and dispersion effect of chiral diphosphine ligand on copper-catalyzed enantioselective incorporation of CO₂ with styrene: a computational study

Herein, we report a comprehensive computational study to understand the stereoinduction of (R)-SEGPHOS chiral diphosphine ligand in copper(i) hydride (CuH)-catalyzed enantioselective incorporation of CO2 with styrene. Mechanistic studies disclose that the stereoselectivity of the final reductive hydroxymethylation product is collectively controlled by the steps of 1,2-hydrocupration of styrene and CO2 insertion into the Cu-C bond. The multimodal stereochemical analyses, including the topographic steric mapping of the chiral (R)-SEGPHOS-ligated CuH catalyst, distortion/interaction, and intermolecular non-covalent interaction analysis on the 1,2-hydrocupration transition states, consistently point to the steric shielding from the P-substituents of the (R)-SEGPHOS ligand to the substrate as the origin of & pi;-facial selectivity in the 1,2-hydrocupration step. Both (R)-SEGPHOS ligands bearing the P-DMTB and P-phenyl substituents can provide sufficient steric repulsion for shielding the re-face approach of the substrate to the Cu-H bond, and thus the (S)-alkylcopper(i) intermediates could be yielded with high enantioselectivity. By contrast, the stereoselectivity of CO2 insertion into (S)-alkylcopper(i) intermediate is primarily determined by the ligand-CO2 dispersion stabilizing interaction. Relative to the (R)-SEGPHOS ligand with the P-phenyl substituents, the substantially enhanced dispersion stabilizing interactions from the P-DMTB substituents of (R)-SEGPHOS ligand to CO2 could help raise the favorability of the inner-sphere CO2 insertion into the Cu-C bond, and thus allow the construction of C-CO2 bond with outstanding stereoselectivity.