Direct conversion of various phosphate sources to a versatile P-X reagent [TBA][PO<sub>2</sub>X<sub>2</sub>] via redox-neutral halogenation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40011449.
- Also identified by DOI 10.1038/s41467-025-57255-1 and PMC identifier 11865473.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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][PO<sub>2</sub>X<sub>2</sub>] (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, Na<sub>3</sub>P<sub>3</sub>O<sub>9</sub> and P<sub>2</sub>O<sub>5</sub>. 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.