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.
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Data availability
All data are available in the text or Supplementary Information. Crystal structures can be found in the Cambridge Crystallographic Data Centre under accession codes 2410237–2410238. Source data are provided with this paper.
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Acknowledgements
We thank the Hoye group for use of infrared instrumentation and the Gladfelter group for use of UV–vis instrumentation. We thank A. Younis and S. S. Pullarat for help with crystallography. We thank M. Hillmyer, J. Back, M. Hintz and J. R. Lamb for help with thermogravimetric analysis and differential scanning calorimetry. We all thank the University of Minnesota for startup funding. C.C.R. acknowledges the Amgen Young Investigator Award, the BMS Unrestricted Research Grant, the Sloan Fellowship, the Dreyfus Teacher Scholar Award, the McKnight Land-Grant and 3M-Alumni Professorships. S.S.K. and C.M.S. both thank University of Minnesota for Wayland E. Noland Excellence Fellowships and Doctoral Dissertation Fellowships.
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Conceptualization: experimental: C.M.S., S.S.K., C.-L.Y. and C.C.R; computational: J.-N.B. and D.G. Data curation: C.M.S., S.S.K., C.-L.Y. and D.G. Formal analysis: C.M.S., S.S.K., C.-L.Y. and D.G. Funding acquisition: J.-N.B. and C.C.R. Investigation: C.M.S., S.S.K., C.L.Y. and D.G. Methodology: all authors. Project administration: J.-N.B. and C.C.R. Resources: C.M.S., S.S.K. and C.-L.Y. Supervision: J.-N.B. and C.C.R. Validation: C.M.S., S.S.K. and C.-L.Y. Writing—original draft and writing—review and editing: all authors.
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The University of Minnesota has filed a provisional patent on this work under application no. 63/886,266 with C.M.S., S.S.K., C.-L.Y. and C.C.R. as inventors for potential commercialization of reagents.
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Seong, C.M., Kargbo, S.S., Yu, CL. et al. Myriad aryne derivatives from carboxylic acids. Nature 649, 91–97 (2026). https://doi.org/10.1038/s41586-025-09830-1
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DOI: https://doi.org/10.1038/s41586-025-09830-1
