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 used at present 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 that 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 foresee that future development of this precursor platform will allow even more decorated arynes to be accessed, further expanding the reach of aryne chemistry.