Theoretical study on ligand conformational self-adaptation for modulating reactivity

Abstract

The combination of Josiphos-type ligands with Pd catalysts has been instrumental in the rapid development of efficient catalytic processes. We performed density functional theory (DFT) calculations to elucidate the mechanisms and dynamic conformational changes responsible for the reactivity and selectivity observed in Pd-catalysed bicyclization/carbonylation of 1,6-enynes. DFT calculations indicated that the most favourable reaction pathway involves an unusual alkene insertion into the carbon–palladium bond to give high level of enantioselectivity. Here, the reactivity is enhanced by the self-adaptation of the Josiphos-Pd backbone, which allows for two distinct ligand conformations with different steric environments. A half-chair conformation is preferred in migratory insertion, which is both the rate-determining step and the enantioselectivity controlling step. The less hindered steric environment of the half-chair conformation allows for rapid migratory insertion, as confirmed by Surface distance projection maps and IGM analysis. Furthermore, IGM analysis shows that the steric effect between the phenyl group in the ligand and the methyl group on the allene of the substrate is important for enantioselectivity control. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-75141-6.