Hydrofluoroarylation of alkynes with fluoroarenes

Abstract

A combination of Ni(cod)₂ and PCyp₃ is found to be an effective catalyst for chemoselective activation of the C–H bond of fluoroarenes over C–F bonds followed by insertion of alkynes to allow direct alkenylation of the electron-deficient arenes. The characteristics of the reactions are: a C–H bond ortho to a fluorine substituent is selectively activated; the reactivity of fluorobenzenes is roughly proportional to the number of fluorine atoms. The reaction conditions tolerate a broad range of both alkynes and fluoroarenes containing both electron-withdrawing and -donating groups, thus allowing efficient synthesis of a variety of substituted ethenes containing a fluoroaryl motif in high regio- and stereoselective manners. Mechanistic studies including both labeling experiments and stoichiometric reactions reveal that oxidative addition of C–H bonds in fluoroarenes to nickel(0) is kinetically highly facile whereas that of C–F bonds is thermodynamically favoured.