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

The functionalization of remote unactivated C-(sp(3))-H and the reaction selectivity are among the core pursuits for transition-metal catalytic system development. Herein, we report Pd-catalyzed gamma-C(sp(3))-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(sp(3))-C(sp(3)) and C(sp(3))-C(sp(2)) bonds. The alkenylation protocol could be further extended to acrylates with natural product units and alpha,beta-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.

Automated summary

The study introduces a new Pd-catalyzed gamma-C(sp(3))-H selective alkylation and alkenylation reaction with removable 7-azaindole as a directing group. Acid and base were found to be decisive regulators for selective alkylation and alkenylation on the same substrate under the same reaction conditions. The results demonstrate the potential of the strategy for structurally diverse aliphatic chain extension and functionalization.