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.