Expanding Access to Previously Inaccessible 5-Membered N-Heteroarynes

We previously reported the synthesis of an inaccessible 7-aza-2,3-indolyne through stabilizing interactions with nickel. This was achieved via intramolecular Suzuki coupling (i.e. oxidative addition and transmetallation) with ortho-borylaryl bromide derivatives of 7-azaindole. Herein, we sought to use this same strategy to expand the scope of previously inaccessible five-membered heteroarynes. Five new classes of heteroarynes derived from indole, pyrrolopyrimidine, and the remaining isomers of azaindole were accessed. Transmetallation studies show that aryne formation depends on the electronics of the heteroarene. A borate complex of 4-azaindole was isolated and characterized via NMR spectroscopy and crystallographically. This hetero-cycle could be promoted to undergo transmetallation through the installation of an electron-donating substituent. Each class of heterocycles require a unique synthetic strategy. Thus, to demonstrate the utility of heteroarynes as a general synthon, a one-pot difunctionalization was achieved across these classes of heterocycles using the newly accessible heteroaryne complexes.