Syntheses of Methylphosphinic Acids using Tandem Pudovik/Abramov-Barton/McCombie Reactions

Abstract

Methylphosphinic acids are very effective and potent carboxylic acid bioisosteres. We have developed a novel mild and eficient method for the syntheses of (sec-alky1)methylphosphinic acids based on tandem Abramov addition of readily available ethyl methylphosphinate, 2, to a ketone, la-lg, followed by a modified Barton-McCombie deoxygenation procedure. The resulting esters, 4a-4g. are readily hydrolyzed. The method gives high yields even for sterically demanding ketones. Using this method we have synthesized several new biologically interesting methylphosphinic acids.