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DOI: 10.1055/s-0043-1773537
‘Ring-Walking’ Aryl Cross-Coupling Reactions Involving Palladium Aryne Intermediates
This work was supported by the William F. Milton Fund, the Corning Fund for Faculty Development, and a Dean’s Competitive Fund from Harvard University. Y.S. acknowledges the Uehara Memorial Foundation for a postdoctoral fellowship. E.B. is supported by a Graduate Research Fellowship from the National Science Foundation (DGE 2140743).
Abstract
The regiospecificity of conventional cross-coupling reactions, though advantageous for its predictability and retrosynthetic simplicity, constrains chemical-space exploration. Discovery efforts have become biased toward examining substitution patterns for which coupling partners are readily obtainable. To address this problem, we have developed a migratory (‘ring-walking’) cross-coupling approach that integrates the isomerization of arylpalladium(II) intermediates into catalytic cycles. A reversible isomerization was achieved through ligand design and the use of cesium fluoride as the base, and this process was then combined with a dynamic kinetic resolution of the regioisomeric aryl halides with a broad range of oxygen- and nitrogen-centered nucleophiles. The method permits rapid access to meta-substituted arenes from para-substituted electrophiles. This account summarizes the key mechanistic principles established during the development of these reactions.
Key Words
cross-coupling - Curtin–Hammett - isomerization - ring-walking - transition-metal catalysisPublication History
Received: 13 February 2025
Accepted after revision: 11 March 2025
Article published online:
11 April 2025
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