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.

GRAPHICAL ABSTRACT

Keywords:

• Oxaphospholene
• diketophosphonates
• γ-ketophosphonate
• oxaphosphorane
• α-pyrazole phosphonate

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Research Foundation of Korea (NRF-2020R1I1A3064034 to C.-M. P.).