Pd(0)-Catalyzed Asymmetric Carbohalogenation: H‑Bonding-Driven C(sp³)–Halogen Reductive Elimination under Mild Conditions

Carbon–halogen reductive elimination is a conceptually novel elementary reaction. Its emergence broadens the horizons of transition-metal catalysis and provides new access to organohalides of versatile synthetic value. However, as the reverse process of facile oxidative addition of Pd(0) to organohalide, carbon–halogen reductive elimination remains elusive and practically difficult. Overcoming the thermodynamic disfavor inherent to such an elementary reaction is frustrated by the high reaction temperature and requirement of distinctive ligands. Here, we report a general strategy that employs [Et₃NH]⁺[BF₄]⁻ as an H-bond donor under a toluene/water/(CH₂OH)₂ biphasic system to efficiently promote C­(sp³)–halogen reductive elimination at low temperature. This enables a series of Pd(0)-catalyzed carbohalogenation reactions, including more challenging and unprecedented asymmetric carbo­bromination with a high level of efficiency and enantioselectivity by using readily available ligands. Mechanistic studies suggest that [Et₃NH]⁺[BF₄]⁻ can facilitate the heterolytic dissociation of halogen–Pd^IIC­(sp³) bonds via a potential H-bonding interaction to reduce the energy barrier of C­(sp³)–halogen reductive elimination, thereby rendering it feasible in an S_N2 manner.