Sequential Organic/Metal Relay Catalysis Enabling the Regioselective Synthesis of Functionalized α-Carbolines from Alkynyl Ketimines.

Herein, we report an efficient organo/silver relay catalytic system that enables the sequential Mannich/6-endo-dig cyclization/aromatization cascade of β,γ-alkynyl-α-ketimino esters with indolin-2-imines, which exhibits remarkable substrate generality and affords a broad range of α-carboline derivatives in good to excellent yields. Mechanistic studies confirm a stepwise relay catalytic pathway, and the practical utility of this protocol is verified by late-stage functionalization, gram-scale synthesis, and facile synthetic transformations of the resulting α-carboline products for accessing more elaborate N-heterocyclic derivatives.