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

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 o-amino or o-alkyl benzaldehydes/ketones, with asymmetric variants remaining underexplored. o-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 o-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.