Nucleophilic Substitution of Alkyl Halides with Secondary Phosphine Oxides under Solvent‐Free Conditions for the Synthesis of Tertiary Phosphine Oxides

The development of a metal‐free Michaelis–Arbuzov reaction for green and efficient construction of CP(V) compounds represents a significant advancement in organophosphorus synthesis. Herein, a nucleophilic substitution strategy between alkyl halides and secondary phosphine oxides under solvent‐ and metal‐free conditions is reported, using sodium iodide as the catalytic promoter. This method provides a facile operation for the synthesis of diverse tertiary phosphine oxides with significant advantages. Firstly, the reaction exhibits broad substrate compatibility, covering a range of aliphatic halides and phosphorus nucleophiles. Secondly, it can be scaled up to the gram level without sacrificing efficiency, and the reaction pathway clearly established through rational studies. Particularly noteworthy is the complete elimination of transition metal catalysts and organic solvents, which aligns with the principles of green chemistry.