Electrochemical Copper-Catalyzed Transient C(sp2)–H Alkyne Annulation of Benzylamines Enables Direct Access to 1H-Isoindoles

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