Copper‐Catalyzed Coupling of Alkynylsulfonium Salts With P(O)─OH Compounds to Access Alkynyl Phosphonates and Phosphates

ABSTRACT

An efficient copper‐catalyzed protocol for the construction of C─O─P(O) bonds has been established, employing alkynylsulfonium salts and P(O)─OH nucleophiles as the coupling partners. This catalytic system exhibits broad substrate adaptability, accommodating a diverse array of substituents on both reaction components to afford the targeted S ‐alkynyl functionalized phosphonate and phosphate frameworks in satisfactory to excellent isolated yields. Of particular significance, this approach proves applicable to the efficient derivatization of phenylphosphinic acid, thus opening up a promising strategy for the upgrading of low‐value phosphorus feedstocks. The synthetic utility is further underscored by the successful gram‐scale implementation under optimized parameters. In addition, mechanistic insights derived from systematic control experiments have enabled the proposition of a rational catalytic cycle. Concurrently, preliminary biological evaluation reveals that selected compounds, notably 3c , exhibit significant antiproliferative activity against nasopharyngeal carcinoma cell lines.