Access to and unexplored reactivity of nickel-bound 5-membered O- and N-heterocyclic arynes via computational insight.

N-Heterocyclic arynes are versatile but underutilized intermediates for rapidly functionalizing N-containing arenes. Part of the reason for the underutilization of N-heterocyclic arynes is that 5-membered N-heterocyclic arynes are inaccessible due to ring strain. In 2024, our group demonstrated that coordinating such strained intermediates to a metal center could stabilize the aryne bond via metal back-donation and thereby enable formation of otherwise inaccessible 5-membered heterocyclic arynes. Interestingly, heterocycles such as 4-azaindole and benzofuran that lacked subtle steric interactions were found to form borate complexes instead of the desired aryne during the key transmetallation step. Herein, we employ a computationally guided ligand approach to overcome this borate complex formation to generate the desired arynes. Using our computational findings, we accessed new previously inaccessible arynes: 4-azaindol-2,3-yne, pyrrolo-2,3-yne pyrazine, and the first ever proposed aryne, benzofuran-2,3-yne, all bound to Ni. Additionally, we report on a novel 5-membered aryne mode of reactivity in the form of a formal inverse-demand Diels-Alder reaction to yield a new class of underexplored heterocycles.