Mechanism and Origins of Enantioselectivity in the Rh(I)-Catalyzed Pauson–Khand Reaction: Comparison of Bidentate and Monodentate Chiral Ligands

The narrow substrate scope of the asymmetric Pauson–Khand reaction (PKR) presently limits its synthetic utility. We recently reported an example of an enantioselective PKR with a precursor not comprising a 1,6-enyne by using a cationic Rh­(I) catalyst and a chiral monodentate phosphorous ligand. Herein, the mechanisms and ligand effects on the reactivity and selectivity of enyne PKRs using Rh­(I) metal complexes with three different ligands ((R)-BINAP, (S)-MonoPhos, or CO) are examined experimentally and computationally. A correlation between experiments and DFT calculations is demonstrated. The PKR with the bidentate ligand (R)-BINAP is fast and shows a low calculated Gibbs free energy of activation (ΔG ‡) for the oxidative cyclization step; the monodentate ligand, (S)-MonoPhos, affords a much slower reaction with a higher ΔG ‡; and using the CO-only Rh complex, the reaction is very slow with a high ΔG ‡. A linear relationship between the enantiomeric excess of (S)-MonoPhos and the PKR product suggests that the active Rh catalyst involves a single ligand. The absolute configuration of the product afforded by each of these ligand-bound catalysts is determined by DFT calculations and confirmed by vibrational circular dichroism spectroscopy. Transition-state structures for the oxidative cyclization step show that the chiral induction is controlled by steric interactions between the phenyl groups of the (R)-BINAP ligand or the methyl groups of the (S)-MonoPhos ligand and an alkenyl hydrogen of the enyne. DFT calculations revealed two competing oxidative cyclization pathways involving either four- or five-coordinated Rh­(I) species. The preferred mechanism and the enantioselectivity are affected by the ligand, the substrate, and CO concentration. Incorporating experimental temperature and CO concentration into the Gibbs free-energy calculations proved crucial for obtaining agreement with experimental results.