Ligand Effects on the Mechanism and Regio- and Stereoselectivity of the Pd-Catalyzed Cascade Allylation of ortho-TsNH Arylimines with 2,4-Dienyl Carbonates.

Ligand-controlled regio- and stereoselectivity in transition-metal-catalyzed allylation reactions is often dictated by subtle energetic differences among competing elementary steps, yet the origin of such control remains insufficiently understood. In this work, density functional theory calculations were performed to investigate the mechanism of a Pd-catalyzed cascade reaction between ortho-TsNH arylimine and 2,4-dienyl carbonate, which synergistically combines the classic Tsuji-Trost allylation with π-Lewis base catalysis. Using P-Phos, WingPhos, and a BINOL-derived phosphoramidite as representative ligands, the full catalytic cycle and the origins of the observed stereo- and regioselectivity were systematically analyzed. The reaction proceeds through an initial Tsuji-Trost reaction followed by an intramolecular vinylogous addition and a subsequent N-allylation. With P-Phos, the vinylogous addition step preferentially leads to the cis-fused product, whereas the bulky WingPhos ligand reverses the diastereoselectivity by stabilizing an alternative vinylogous addition transition state through steric confinement and favorable noncovalent interactions within a well-defined chiral pocket. In contrast, the BINOL-derived phosphoramidite ligand alters the relative energetics of competing N-allylation pathways, favoring a distinct regioselective N-allylation that leads to azetidine formation. The ligand-dependent steric effects, dispersion interactions, and electronic factors collectively differentiate the competing pathways, thereby clarifying how distinct chiral ligand environments modulate pathway selection in this Pd-catalyzed cascade reaction.