Ruthenium-Catalyzed C–H Activation/Cyclization for the Synthesis of Phosphaisocoumarins

Abstract

An efficient and cost-effective ruthenium-catalyzed oxidative cyclization of phosphonic acid monoesters or phosphinic acids with alkynes has been developed for the synthesis of a wide range of phosphaisocoumarins in good to excellent yields under aerobic conditions. A multitude of arylphosphonic acid monoesters and arylphosphinic acids having electron-donating and -withdrawing groups were oxidatively cyclized. Various diarylacetylenes, dialkylacetylenes, and alkylarylacetylenes effectively underwent the ruthenium-catalyzed oxidative cyclization. A substrate possessing benzoic acid as well as a phenylphosphonic monoester moiety was smoothly cyclized with hex-3-yne to afford a compound having both isocoumarin and phosphaisocoumarin moieties. Alkenylphosphonic monoester afforded phosphorus 2-pyrone through oxidative cyclization with alkyne. Competition experiments between diaryl- and dialkylalkynes and between diarylacetylenes having <i>p</i>-methoxy and <i>p</i>-chloro groups gave results which showed that the present oxidative cyclizations were not affected by the electronic effects of alkynes. Mechanistic studies revealed C–H bond metalation to be the rate-limiting step