Direct conversion of various phosphate sources to a versatile P-X reagent [TBA][PO₂X₂] via redox-neutral halogenation

Inorganic phosphates hold significant potential as ideal natural building blocks, forming a fundamental basis for organic and biochemical synthesis. However, their limited solubility, inherent chemical stability, and low reactivity pose substantial challenges to converting phosphates into organophosphates under mild conditions. This study introduces an efficient method for the direct conversion of phosphates into P(V)-X reagents, [TBA][PO₂X₂] (X = Cl, F), via a redox-neutral halogenation process. This method utilizes cyanuric chloride (or cyanuric fluoride) as the halogenation reagent, in combination with 1-formylpyrrolidine and tetrabutylammonium chloride (TBAC), under ambient conditions. The approach enables effective halogenation conversion for various P(V) sources, including orthophosphates, pyrophosphoric acid, Na₃P₃O₉ and P₂O₅. Furthermore, we demonstrate the synthetic utility of the P(V)-Cl reagent in the phosphorylation of diverse O-, S-, N- and C-nucleophiles. Key advantages of this conversion process include the use of inexpensive and readily available chemicals, the avoidance of high-energy redox reactions, and the generation of a reactive yet stable P(V)-X reagent.