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Arynes hold immense potential as reactive intermediates in organic synthesis as they engage in a diverse range of mechanistically distinct chemical reactions. However, the poor functional group compatibility of generating arynes or their precursors has stymied their widespread use. Here, we show that generating arynes by deprotonation of an arene and elimination of an “onium” leaving group is mild, efficient and broad in scope. This is achieved by using aryl(TMP)iodonium salts (TMP = 2,4,6-trimethoxyphenyl) as the aryne precursor and potassium phosphate as the base, and a range of arynophiles are compatible. Additionally, we have performed the first quantitative analysis of functional group compatibility for several methods to generate arynes, including the method developed here and the current state of the art. Finally, we show that a range of “sensitive” functional groups such as Lewis and Brønsted acids and electrophiles are compatible under our conditions.
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Harnessing triaryloxonium ions for aryne generation
Abstract Arynes are highly reactive and versatile intermediates for the functionalization of aromatic rings that are often generated using strong bases or fluoride sources, which, in some cases, can limit functional group tolerance. Here we demonstrate that triaryloxonium ions can be transformed into arynes through treatment with solid potassium phosphate at room temperature. A substantial range of functional group-bearing arynes, including 4,5-pyrimidynes, may be generated and trapped using cycloaddition reactions with high yields. Other arynophiles including nitrones, alkenes and azides are compatible with these conditions. Quantum computation in conjunction with an intramolecular kinetic isotope study is consistent with an elimination, unimolecular, conjugate base-like mechanism of elimination to form the aryne. These investigations demonstrate that the oxonium ion is a powerful electron-withdrawing group and a particularly effective leaving group. We anticipate that this study will stimulate further investigations into the synthetic utility of aryl oxonium ions.
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- Award ID(s):
- 1955876
- PAR ID:
- 10537272
- Publisher / Repository:
- Springer Nature
- Date Published:
- Journal Name:
- Nature Synthesis
- Volume:
- 3
- Issue:
- 1
- ISSN:
- 2731-0582
- Page Range / eLocation ID:
- 58 to 66
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s44160-023-00408-1
