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

Abstract

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 π-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.