1,2-Difunctionalization of alkenes has been intensively developed utilizing alkene polarization by π-Lewis acid activation of transition metals. In opposition to outstanding advances in 1,2-vicinal difunctionalization, a similar example for 1,1-geminal difunctionalization of unactivated alkenes, while highly appealing, remains elusive.
Herein, we describe a palladium(II)-catalyzed 1,1-difunctionalization of unactivated terminal and internal alkenes using cationic palladium(II) catalysis. After initial addition of a nucleophile to the alkene, the in situ generated stable palladacycle intermediate can be broken by a cationic palladium(II) catalyst to facilitate regioselective β-hydride elimination. Site-selective oxidative 1,1-difunctionalization is achieved with two nucleophilic components, even with challenging internal cyclic and acyclic alkene substrates. Various electron-rich arene nucleophiles, such as indoles and anilines, add to alkene moiety of 3-, or 4-alkenamides to give γ,γ- or δ,δ-di-functionalized products in fully intermolecular systems. Furthermore, employing intramolecular hydroxyl, carboxyl nucleophiles with external carbon nucleophiles, this method is further extended to unsymmetric difunctionalization, offering a powerful platform for making (oxo) quaternary carbon centers. Detailed computational results point to a reaction mechanism in which the cationic palladium(II) catalysis plays an important role in facilitating the key β-H elimination and migratory insertion steps.