Direct synthesis of γ,γ-diketophosphonates from pentacovalent 1,2λ5-oxaphosphorane

Abstract

Pyrazole phosphonate derivatives are receiving increasing attention in the pharmaceutical field due to their wide range of biological activities. However, the syntheses of diketophosphonates, as precursors of α-pyrazole phosphonates, require high temperatures and excess of reactants to proceed. Therefore, a simple and efficient procedure to prepare γ,γ-diketophosphonates via reactions between 1,2λ⁵-oxaphospholene and aromatic acid chlorides under mild conditions is proposed herein. The formation of the keto phosphonium ion of 1,2λ⁵-oxaphospholenes is favored at −10 °C, and these ions react with aromatic acid chlorides to yield γ,γ-diketophosphonates in 83–89% yields. This reaction may be readily applied for the preparation of γ,γ-derivatives of α-diketophosphonates as precursors of α-pyrazole phosphonates, which are molecules of immense medical significance.