Photoinitiated Enantioselective Cycloisomerization/Addition Cascades of 2-Acyl Benzaldehydes with α,β-Unsaturated Carbonyl Compounds

Photoenolization is an efficient strategy for generating reactive intermediates to achieve various functionalizations in organic photochemical synthesis. However, the synthons participating in this process are predominantly limited to <i>o</i>-amino or <i>o</i>-alkyl benzaldehydes/ketones, with asymmetric variants remaining underexplored. <i>o</i>-Phthalaldehyde (OPA) as a synthetic precursor demonstrates unique chemical properties, forming a complex architecture of organic small molecules. Photoenolization-driven asymmetric cascade reactions of OPA are crucial for stereoselective construction of chiral lactone architectures. Herein, we report the first direct asymmetric photocycloisomerization of OPA and <i>o</i>-benzoylbenzaldehyde (OBBA), which subsequently undergoes 1,4-conjugate addition with α,β-unsaturated carbonyl compounds, providing various chiral lactones with excellent yields and diastereo-/enantioselectivities (up to 99% yield, >19:1 dr, 99% ee). Notably, trace amounts of carboxylic acids significantly accelerate the reaction by acting as a hydrogen atom shuttle, enabling low catalyst loading (0.5 mol %). Mechanistic studies (spectroscopy, deuterium labeling, EPR, and control experiments) support a catalytic cycle diverged from traditional photoenolization.