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.

Fig. 1

The conformational changes of diphosphine ligands and their potential roles in promoting enantioselectivity in transition-metal catalysis.

Scheme 1

Pd-catalysed cyclopropanation/carbonylation of 1,6-Enynes.

Scheme 2

Plausible mechanisms of Pd-catalyzed bicyclization/carbonylation of 1,6-enynes.

Scheme 3

Conformations of the ligand-coordinated Pd(0) catalyst 1.

Fig. 2

Free energy profile of the oxidative addition and migratory insertion steps in the Pd-catalyzed bicyclization/carbonylation of 1,6-enynes. The bond lengths are in Å.

Scheme 4

a Surface distance projection maps of Josiphos-coordinated Pd. Distances are given in Å. Negative distance (blue) indicates that the atoms on the ligand are farther away from the substrate; positive distance (red) indicates that the atoms on the ligand are closer to the substrate. b IGM analyses of 6-TS-R and 6’-TS-R.

Fig. 3

Enantioselectivity of the preferred conformers of Josiphos-coordinated Pd(II) in the migratory insertion step.

Fig. 4

Enantioselectivity in the migratory insertion step with half-chair ligand conformer and IGM analyses of 6-TS-R and 6-TS-S. The bond lengths are in Å.

Fig. 5

Free energy profile of the carbonylation, nucleophilic addition, and reduction elimination steps in Pd-catalysed bicyclization/carbonylation of 1,6-enynes.

Fig. 6

Free energy profiles of the cycloaddition step in the Pd-catalyzed bicyclization/carbonylation of 1,6-enynes.