Substrate and Condition-Dependent Palladium-Catalyzed Switchable Alkenylation and Alkylation of Indolizines with...

A substrate- and condition-dependent, switchable palladium-catalyzed strategy for the alkenylation and alkylation of indolizines with allyl alcohols has been developed. The reaction selectivity can be precisely controlled by varying the solvent, temperature, and the nature of the allyl alcohol. Regioselective C3-alkenylation of indolizines is achieved in DMSO at elevated temperatures using primary or secondary allyl alcohols, whereas C3-alkylation preferentially occurs in DCE at room temperature with secondary allyl alcohols. Mechanistic investigations indicate that the alkenylated product may arise from the corresponding alkylated intermediate via Pd/Cu-mediated oxidation. The protocol employs readily available starting materials, demonstrates broad substrate scope, excellent functional-group tolerance, and is scalable to gram quantities, highlighting its synthetic practicality and versatility.