Effect of Lewis Acids on Photoenolization/Diels–Alder Reactions

Upon photoexcitation, ortho-methyl benzaldehydes and acetophenones undergo photoenolization to form transient ortho-quinonedimethide intermediates that undergo Diels-Alder reactions with suitable dienophiles. While Lewis acids are often used as Diels-Alder catalysts, their influence on the preceding photoenolization step remains poorly understood. Here we combine theory and experiment to elucidate how Lewis acid coordination modulates photoenolization/Diels-Alder (PEDA) reactivity. We show that coordination can red-shift excitation energies, alter triplet-state hydrogen-atom-transfer (HAT) barriers, and shift the equilibrium between reactive <i>syn</i> and unreactive anti conformers. The magnitude and direction of these effects depend on multiple factors, including the relative basicities of the PEDA precursor and dienophile, the stoichiometry and concentration of the Lewis acid, and the coordination environment defined by its size, charge density, and ancillary ligands. Consequently, Li⁺ inhibits photoenolization for substrates capable of chelation through carbonyl and ortho-methoxy groups but promotes it for others; Ca²⁺ shows similarly variable behavior depending on binding mode. Experimental studies of a model system validate these predictions: Li⁺ suppresses photoenolization, whereas Ca²⁺ leaves it largely unaffected. Literature cases involving Ti(Oi-Pr)₄ and Sc(OTf)₃ further illustrate that Lewis acids can promote, inhibit, or have minimal effect on photoenolization, depending on their strength and binding preferences.