TiO ₂ -Mediated Enamine Radical Cation Cycloadditions: Divergent [4 + 2] and [2 + 2] Reactivity

Enamine radical cation cycloadditions were developed under TiO2-mediated photochemical conditions to enable net redox-neutral bond formation in nitrogen-involving reaction systems. Substrates were analyzed by subdividing them into two classes based on whether an aryl unit was directly attached to nitrogen (N-aryl vs non-N-aryl enamines). Their oxidizability was quantified by cyclic voltammetry in LiClO4/CH3NO2, which revealed that enamine oxidizability could be tuned cooperatively by aromatic substituents and N-protecting groups. Under TiO2-mediated interfacial photochemical single-electron activation, [4 + 2] cycloadditions with 2,3-dimethyl-1,3-butadiene showed a strong dependence on oxidation potential within the N-aryl class and were also efficient for non-N-aryl enamines. In contrast, [2 + 2] cycloadditions exhibited a narrower reactivity window and were more strongly influenced by partner reactivity and steric and conformational constraints than by oxidation potentials alone. These results establish enamines in both classes as viable platforms for TiO2-enabled radical cation cycloadditions and provide insight into distinct control elements governing [4 + 2] versus [2 + 2] manifolds.