Mild and General Conditions for Negishi Cross-Coupling Enabled by the Use of Palladacycle Precatalysts

摘要

Biaryls, particularly those containing one or more heterocyclic components, are ubiquitous among pharmaceutically active compounds, natural products, and agrochemicals. For their preparation, palladium-catalyzed cross-coupling reactions have been extensively studied and practiced in both academic and industrial settings. Although various palladium-catalyzed cross-coupling methods to form C_(sp~2)-C_(sp~2) bonds have been developed, the Negishi coupling is one of the most frequently utilized. The utility of Negishi couplings is partially due to the fact that organozinc reagents, despite their considerable basicity, are compatible with a large number of sensitive functional groups. Equally important is that a wide array of highly functionalized organozinc reagents can be readily accessed. Additionally, the recent development of solid salt-stabilized organozinc reagents, which are much less sensitive towards air and moisture, has also rendered the Negishi coupling a more practical and user-friendly technique for synthetic organic chemists.