Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

TL;DR

A new copper-based method efficiently produces β-ketophosphonates using mild conditions and affordable materials.

Contribution

A cost-effective aerobic copper(II)-mediated phosphorylation method for synthesizing β-ketophosphonates is introduced.

Findings

Copper sulfate pentahydrate is an effective and inexpensive catalyst for phosphorylation under mild conditions.

Anhydrous CuSO4 significantly reduces phosphorylation yields, highlighting the importance of copper's ligand environment.

Common Cu(II) and Cu(I) salts like halides or nitrates are less effective or inert in this reaction.

Abstract

Aerobic copper(II)-mediated phosphorylation of enol acetates with H-phosphonates leading to the formation of β-ketophosphonates was discovered. The proposed method is applicable to a wide range of H-phosphonates or phosphine oxides as PH-reagents and enol acetates. Unlike previous reports, which generally employed stoichiometric amounts of oxidants or more expensive transition metal catalysts, the present protocol employs only cheap copper sulfate pentahydrate as a catalyst under mild reaction conditions. The achieved phosphorylation proceeds via the formation of P-centered radicals produced by the oxidation of PH-reagents by copper(II)-containing species. Employing anhydrous CuSO4 instead of the pentahydrate led to a dramatic phosphorylation yield drop from 70 to <5%. It seems that the ligand environment of copper is very important for the effective reaction: other Cu(II) and Cu(I) salts, including halides, nitrate, tetrafluoroborate, or perchlorate, were much less effective or completely inert.

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