Energy Transfer Mediated [2π + 2σ] Photocycloaddition of Bicyclo[1.1.0]butanes with Maleimides: Formation of Potential Bioisotere of Phthalimide

Replacing aromatic rings with 3D sp³-rich cage structures is a promising strategy in medicinal chemistry for improving the physicochemical and pharmacokinetic profiles of drug candidates. This manuscript disclosed the [2π + 2σ] cycloaddition maleimides with bicyclo[1.1.0]butanes for the synthesis of succinimide-fused bicyclo[2.1.1]hexane as the potential bioisostere of phthalimides. The photochemical reaction achieved high yields, broad functional group tolerance, and scalability. Easy derivatization of products enhances its utility for accessing valuable 3D phthalimide mimics. Mechanistic studies (cyclic voltammetry, luminescence quenching, control experiments) support a visible-light energy transfer pathway.