Rhenium-catalyzed stereoselective hydrocarboxylation of alkynes and olefins: late-stage NSAID drug's diversification

Abstract

A rhenium-catalyzed, highly efficient, regio- and stereoselective hydrocarboxylation of internal alkynes and olefins has been developed. This simple, atom- and step-economic strategy provides facile access to functionalized aryl enol esters in high yields. Notably, several NSAID drug molecules (e.g., oxaprozin, ibuprofen, indomethacin, ketoprofen, naproxen, flurbiprofen, etc.) underwent hydrocarboxylation without the need for pre-functionalization. Deuterium-labeling studies revealed that proton transfer originates from the COOH group, while O–H bond cleavage is unlikely to be involved in the turnover-determining transition state (TDTS) of the catalytic cycle.