Alkyl-to-Alkyl Palladium Migration Enables Remote C-C Bond Formation.

Palladium-catalyzed C-H activation reactions are typically viewed as positionally static, with the site of reactivity dictated by the location of the initial metalation event. Herein, we report a strategy that overcomes this constraint by enabling migration of a σ-alkyl palladium intermediate prior to carbon-carbon bond formation via a previously inaccessible through-space alkyl-to-alkyl palladium shift. This two-component annulation of 2-bromoanilines or 2-bromophenols with allylic bromides proceeds through the formation of an alkyl-Pd species that undergoes translocation across the carbon framework via engagement of a distal C(sp3)-H bond. This process enables a cross-dehydrogenative bond formation at a site far from the point of initial catalyst installation and furnishes tricyclic heterocycle products from simple precursors. Our transformation displays a broad substrate scope across both coupling partners and exhibits excellent heteroatom compatibility. Mechanistic studies support a pathway involving reversible C-H activation and migration driven by relief of steric congestion at the palladium center. These findings establish alkyl-to-alkyl palladium migration as a viable mode of reactivity and provide a foundation for reaction design based on catalyst translocation mechanisms.