Newly developed Pd/ZU-Phos/DBN cooperative catalysis enables enantioselective [4 + 2] annulations for efficient synthesis of diverse spirocyclic scaffolds

Chiral ligands are essential for asymmetric catalysis as they greatly improve the chemical selectivity of the catalytic process. The cooperative action of multiple ligands may enhance catalytic efficiency and selectivity by optimizing individual steps within the catalytic cycle. Here, we synthesized a series of novel P-chiral ligands (ZU-Phos) that enabled highly efficient asymmetric [4 + 2] annulations of 1,2-disubstituted allylic carbonates with activated olefins, yielding a variety of optically active and medicinally relevant spirocyclic scaffolds with yields up to 96% and up to 98% ee through a novel dual coordination mechanism. Mechanistic investigations disclosed that DBN served a dual function as a Brønsted base and formed a unique mixed-ligated Pd/ZU-Phos/DBN complex. This study highlighted the distinctive benefits of Pd/ZU-Phos ligand catalysis and underscored the efficacy of the dual ligand system in broadening the scope of palladium-catalyzed reactions. Density functional theory (DFT) calculations showcased that DBN modulated the catalytic activity of palladium catalysts via weak coordination and enhanced product enantioselectivity by stabilizing the chiral environment through weak interactions with phosphorus ligands.