Hydrogen-Bond-Directed Nickel-Catalyzed Allylation of Primary Phosphine Oxides

Abstract

P-Stereogenic secondary phosphine oxides are versatile precursors for the construction of chiral tertiary phosphines. However, catalytic asymmetric methods for the synthesis of such compounds have remained scarce. Herein, we report a nickel/JoSPOphos catalytic system that enables the asymmetric allylation of primary phosphine oxides. Mechanistic studies demonstrate that the intramolecular hydrogen bond between the JoSPOphos ligand and the PPO substrate lowers the energy barriers of both diastereomeric transition states (TS-2-R and TS-2-S). The 1.3 kcal/mol difference in hydrogen-bond interaction energy between the two transition states accounts for more than half of their total energy difference of 2.3 kcal/mol, which also indicates that this noncovalent interaction improves both the reaction rate and enantioselectivity.