Synthesis of Polysubstituted 2-Oxabicyclo[2.1.1]hexanes via Visible- Light-Induced Energy Transfer

Synthesis of bicyclic scaffolds has attracted growing interest because they are of high importance in modern pharmaceutical development. Here we report a strategy to access polysubstituted 2-oxabicyclo[2.1.1]hexanes in a single operation from readily accessible benzoylformate esters and bicyclo[1.1.0]butanes via visible-light-induced triplet energy transfer catalysis. The process is proposed to involve a formal [27r + 2o-] photocycloaddition/backbone C-H abstraction/aryl group migration sequence. A diverse range of (hetero)aryl groups successfully underwent migration to the backbone (C2) position to provide previously inaccessible bicyclic molecules, and the ester group of the product can serve as a handle for downstream manipulation, thus offering opportunities to rapidly build up molecular complexity and access new sp3-rich chemical space.

Automated summary

The synthesis of polysubstituted 2-oxabicyclo[2.1.1]hexanes has been achieved in a single step using visible-light-induced triplet energy transfer catalysis. This method offers significant potential in pharmaceutical development, allowing for the rapid construction of complex molecular structures and access to unexplored chemical space.