Migratory\nAryl Cross-Coupling

A fundamental property of cross-coupling\nreactions is regiospecificity,\nmeaning that the site of bond formation is determined by the leaving\ngroup’s location on the electrophile. Typically, achieving\na different substitution pattern requires the synthesis of a new,\ncorresponding starting-material isomer. As an alternative, we proposed\nthe development of cross-coupling variants that would afford access\nto multiple structural isomers from the same coupling partners. Here,\nwe first demonstrate that a bulky palladium catalyst can facilitate\nthe efficient, reversible transposition of aryl halides by temporarily\nforming metal aryne species. Despite the nearly thermoneutral equilibrium\ngoverning this process, combining it with the gradual addition of\na suitable nucleophile results in dynamic kinetic resolution of the\nisomeric intermediates and high yields of unconventional product isomers.\nThe method accommodates a range of oxygen- and nitrogen-centered nucleophiles\nand tolerates numerous common functional groups. A Curtin–Hammett\nkinetic scheme is supported by computational and experimental data,\nproviding a general mechanistic framework for extending this migratory\ncross-coupling concept.