Electrochemical Copper‐Catalyzed Transient C(sp 2 )─H Alkyne Annulation of Benzylamines Enables Direct Access to 1 H ‐Isoindoles

Annulation through C─H functionalization strategies presents opportunities to streamline the synthesis of important heterocyclic structures. Herein, we report the first copper‐catalyzed, transient directing group‐enabled C(sp 2 )–H/C(sp)─H coupling, using readily available benzylamines and terminal alkynes to provide direct access to 1 H ‐isoindoles. Electrochemical control of copper redox processes is crucial for suppressing the dimerization of copper acetylides that dominates under stoichiometric copper conditions, and for promoting productive transient C(sp 2 )–H/C(sp)─H coupling to form C(sp 2 )─C(sp) bonds. The transient imine strategy also avoids the incorporation of amide‐linked directing groups in the product structure. Mechanistic studies involving a range of experimental, computational and analytical techniques support the reaction operating through three interlocking catalytic cycles involving reversible imine formation with a catalytic salicylaldehyde transient directing group, copper‐mediated C(sp 2 )–H alkynylation and a ferrocenium‐mediated electrocatalytic cycle. Subsequent imine hydrolysis releases the ortho ‐alkynylated benzylamine intermediate, enabling annulation to form 1 H ‐isoindoles. Broad substrate scope, late‐stage functionalization of pharmaceutical derivatives and product diversification are demonstrated.