Rigid P-Chiral Phosphorus Ligands for Highly Selective Palladium- Catalyzed (4+2) and (4+4) Annulations

We developed novel shackled P-chiral ligands based on 1-phosphanorbornenes and oxazolines. They were subsequently evaluated in palladium-catalyzed (4+2) annulations, producing enantioenriched tetrahydropyran scaffolds in good yields with high site selectivity and enantioselectivity. Moreover, chemoselective (4+4) products were also achieved by using acyclic imines. In addition, density functional theory calculations were performed to afford the energy profile of the Michael addition step and ring formation step. This demonstrated that the enantioselective (4+2) annulations and the chemoselective reaction between (4+2) and (4+4) products were mostly under thermodynamic control.

Automated summary

We developed novel shackled P-chiral ligands for palladium-catalyzed (4+2) annulations, producing enantioenriched tetrahydropyran scaffolds with high site selectivity and enantioselectivity. Moreover, chemoselective (4+4) products were also achieved using acyclic imines. Density functional theory calculations indicated that the reactions were mostly under thermodynamic control.