Copper-Catalyzed Direct C–H Alkylation of Polyfluoroarenes by Using Hydrocarbons as an Alkylating Source

Construction of carbon–carbon bonds is one of the most important tools in chemical synthesis. In the previously established cross-coupling reactions, prefunctionalized starting materials were usually employed in the form of aryl or alkyl (pseudo)halides or their metalated derivatives. However, the direct use of arenes and alkanes via a 2-fold oxidative C–H bond activation strategy to access chemoselective C(sp2)–C(sp3) cross-couplings is highly challenging due to the low reactivity of carbon–hydrogen (C–H) bonds and the difficulty in suppressing side reactions such as homocouplings. Herein, we present the new development of a copper-catalyzed cross-dehydrogenative coupling of polyfluoroarenes with alkanes under mild conditions. Relatively weak sp3 C–H bonds at the benzylic or allylic positions, and nonactivated hydrocarbons could be alkylated by the newly developed catalyst system. A moderate-to-high site selectivity was observed among various C–H bonds present in hydrocarbon reactants, including gaseous feedstocks and complex molecules. Mechanistic information was obtained by performing combined experimental and computational studies to reveal that the copper catalyst plays a dual role in activating both alkane sp3 C–H bonds and sp2 polyfluoroarene C–H bonds. It was also suggested that the noncovalent π–π interaction and weak hydrogen bonds formed in situ between the optimal ligand and arene substrates are key to facilitating the current coupling reactions.