Intramolecular β-Alkenylation of Cyclohexanones via Pd-Catalyzed Desaturation-Mediated C(sp³)-H/Alkyne Coupling

Site-selective C-C bond formation through the direct coupling of C(sp³)-H bonds with unsaturated hydrocarbons represents an atom-economical and redox-neutral way to functionalize chemically inert positions, such as those β to a carbonyl group. While most existing β-functionalization methods utilize a directing group (DG) strategy, here we report a Pd-catalyzed intramolecular β-alkenylation of ketones using alkynes as the coupling partner without the aid of DGs. Mediated by a ketone desaturation process, the reaction is redox-neutral and avoids using strong acids or bases. The resulting cis-5,6-fused bicycles can be diversely derivatized with excellent selectivity. Mechanistic studies imply an unusual "hydride-transfer" chain-like pathway, which involves the cyclometalation of an enyne intermediate and protonation of the resulting Pd enolate followed by an intermolecular hydride transfer through the desaturation of another substrate.