Asymmetric Cascade Photocycloaddition-Acyloin Rearrangement Enabled by Cage-Confined Visible-Light Catalysis

Enzymatic catalysis in biological systems is characterized by the specific pocket confinement imposed by various protein matrixes, enabling the synthesis of a diverse array of functional biomolecules. Development of new catalysts that incorporate multiple catalytic centers within the enzyme-mimic confined spaces presents a meaningful yet challenging project for synthetic chemists. Here, we present our recent achievement in synthesizing a chiral photosensitive metal-organic cage (cPMOC), <i>Δ</i>₄-/<i>Λ</i>₄-MOC-68-Ru₄, which possesses multiple chiral pockets that can facilitate the visible-light-induced asymmetric cascade intermolecular [2 + 2] cycloaddition/acyloin rearrangement for the first time. The current photochemical transformation affords various bicyclo[3.2.1]octanes with opposite regiospecificity in contrast to well-established thermodynamically favored cascade [3 + 2] cycloaddition transformations with similar reaction counterparts. The distinctive pocket size of cage 2 inhibits the dimerization of α,β-unsaturated ketones and promotes the heterocycloaddition between the ketone and smaller cyclic 1,2-dione, underscoring the critical role of the microenvironmental shape and size for guest binding in determining the confined catalytic reactivity.