Migratory Aryl Cross-Coupling.

J Am Chem Soc

Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford St., Cambridge, Massachusetts 02138, United States.

Published: December 2024

A fundamental property of cross-coupling reactions is regiospecificity, meaning that the site of bond formation is determined by the leaving group's location on the electrophile. Typically, achieving a different substitution pattern requires the synthesis of a new, corresponding starting-material isomer. As an alternative, we proposed the development of cross-coupling variants that would afford access to multiple structural isomers from the same coupling partners. Here, we first demonstrate that a bulky palladium catalyst can facilitate the efficient, reversible transposition of aryl halides by temporarily forming metal aryne species. Despite the nearly thermoneutral equilibrium governing this process, combining it with the gradual addition of a suitable nucleophile results in dynamic kinetic resolution of the isomeric intermediates and high yields of unconventional product isomers. The method accommodates a range of oxygen- and nitrogen-centered nucleophiles and tolerates numerous common functional groups. A Curtin-Hammett kinetic scheme is supported by computational and experimental data, providing a general mechanistic framework for extending this migratory cross-coupling concept.

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Source
http://dx.doi.org/10.1021/jacs.4c15086DOI Listing

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