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 are employed usually in the form of aryl- or alkyl (pseudo)halides or their metallated derivatives. However, direct use of arenes and alkanes via a twofold 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. Not only relatively weak sp3 C-H bonds being at the benzylic or allylic positions but also non-activated hydrocarbons could be alkylated by the newly developed catalyst system. A moderate to high site-selectivity was observed among various C-H bonds in alkanes including gaseous feedstocks and complex molecules. Mechanistic information was obtained by performing combined experimental and computational studies to reveal that copper catalyst plays a dual role in activating both sp3 C-H bonds of alkanes and sp2 polyfluoroarene C-H bonds. It was also suggested that non-covalent pi-pi interaction and weak hydrogen bonds formed in situ between the optimal ligand and arene substrates are key to facilitate the current couplings.