Cage-confined photocatalysis for wide-scope unusually selective [2 + 2] cycloaddition through visible-light triplet sensitization

Light-induced [2 + 2] cycloaddition is the most straightforward way to generate cyclobutanes, which are core structures of many natural products, drugs and bioactive compounds. Despite continuous advances in selective [2 + 2] cycloaddition research, general method for intermolecular photocatalysis of acyclic olefins with specific regio- and diastereoselectivity, for example, syn -head-to-head ( syn -HH) cyclobutane derivatives, is still lack of development but highly desired. Herein, we report a cage-confined photocatalytic protocol to enable unusual intermolecular [2 + 2] cycloaddition for α,β -unsaturated carbonyl compounds. The syn -HH diastereomers are readily generated with diastereoselectivity up to 99%. The cage-catalyst is highly efficient and robust, covering a diverse substrate range with excellent substituent tolerance. The mimic-enzyme catalysis is proposed through a host-guest mediated procedure expedited by aqueous phase transition of reactant and product, where the supramolecular cage effect plays an important role to facilitate substrates inclusion and pre-orientation, offering a promising avenue for general and eco-friendly cycloaddition photocatalysis with special diastereoselectivity. Light-induced [2 + 2] cycloaddition is the most efficient way to generate cyclobutanes, while suffering from limitations of specific selectivity. Here the authors report a cage-confined photocatalytic [2 + 2] cycloaddition to enable the unusual production of syn -head-to-head cyclobutane derivatives selectively.