Acid- and Base-Switched Palladium-Catalyzed γ‑C(sp3)–H Alkylation and Alkenylation of Neopentylamine

The functionalization of remote unactivated C­(sp3)–H and the reaction selectivity are among the core pursuits for transition-metal catalytic system development. Herein, we report Pd-catalyzed γ-C­(sp3)–H-selective alkylation and alkenylation with removable 7-azaindole as a directing group. Acid and base were found to be the decisive regulators for the selective alkylation and alkenylation, respectively, on the same single substrate under otherwise the same reaction conditions. Various acrylates were compatible for the formation of C­(sp3)–C­(sp3) and C­(sp3)–C­(sp2) bonds. The alkenylation protocol could be further extended to acrylates with natural product units and α,β-unsaturated ketones. The preliminary synthetic manipulation of the alkylation and alkenylation products demonstrates the potential of this strategy for structurally diverse aliphatic chain extension and functionalization. Mechanistic experimental studies showed that the acidic and basic catalytic transformations shared the same six-membered dimer palladacycle.