Myriad Aryne Derivatives from Carboxylic Acids

Abstract

Densely substituted aromatic rings are ubiquitous in pharmaceuticals and agrochemicals¹. For making aromatic molecules, aryne intermediates have synthetic potential that rivals most functional groups². They readily react with nucleophiles, participate in pericyclic reactions, and activate inert σ-bonds. Despite their potential, arynes are currently used by a specialized community for mainly niche applications. The lack of widespread adoption of arynes is due to the undesirable means to generate them. Here, we report the design of an aryne precursor to overcome this prohibitive barrier. Readily available carboxylic acids are derivatized in a single step to a make a precursor which is then activated by blue light or by heat. Dozens of previously unknown aminated arynes, including pyridynes, are generated in this work, opening the door to drug discovery using aryne intermediates. We envision that future development of this precursor platform will allow even more decorated arynes to be accessed, further expanding the reach of aryne chemistry.