Polysubstituted Benzene Bioisosteres and Beyond: Photochemical Access to Bicyclo[2.1.1]hexanes

Bicyclo[2.1.1]hexanes are a versatile platform for the exploration of chemical space, with 10 different substituent vectors available. Disubstituted bicyclo[2.1.1]hexanes have been proposed as bioisosteres of ortho- and meta-substituted benzenes, both far less investigated than their para-benzene counterparts, but the bicyclo[2.1.1]hexane platform also provides new exciting opportunities for molecular design. Polysubstituted benzene bioisosteres and structures bearing substituent geometries that are non-existant in aromatic chemical space can be prepared using the bicyclo[2.1.1]hexane platform. We report the development of a photocatalytic intramolecular [2+2] cycloaddition approach to polysubstituted bicyclo[2.1.1]hexanes that provides access to these high-value motifs and enables the investigation of unexplored chemical space.