Palladium-Catalyzed Cross-Coupling of Superbase-Generated C(sp3) Nucleophiles

A range of methods has been investigated recently for the arylation of weakly acidic C­(sp3)–H bonds, primarily exploiting directed metalation with a transition metal catalyst or radical formation via hydrogen atom transfer. In this work, a classical base-mediated approach is taken, exploiting the ability of organometallic superbases to metalate very weakly acidic (pK a > 40) C–H bonds. Conditions are developed with either n-BuLi/diamine or n-BuLi/KOtBu superbases to enable metalation to occur with high selectivity. Organolithium nucleophiles can be directly used in cross-coupling, or organozincs can be formed to enable reactions with functional group-dense organohalides.