Synthesis of Arynes via Formal Dehydrogenation of Arenes

Arynes offer immense potential for diversification of benzenoid rings, which occur in pharmaceuticals, agrochemicals, and liquid crystals. However, accessing these high-energy intermediates requires synthetic precursors, which involve either harsh conditions or multistep syntheses. The development of alternative methods to access arynes using simpler substrates and milder conditions is necessary for a more streamlined approach. Here, we describe a two-step formal dehydrogenation of simple arenes to generate arynes at a remote position relative to traditionally reactive groups, e.g., halides. This approach is enabled by regioselective installation and ejection of an "onium" leaving group, and we demonstrate the compatibility of simple arenes (20 examples) and arynophiles (8 examples). Moreover, through direct comparison, we show that our formal dehydrogenation method is both more functional group tolerant and efficient in generating arynes than the current state-of-the-art aryne precursors. Finally, we show that aryne intermediates offer opportunities for regioselective C-H amination that are distinct from other methods.