Catalyst-Controlled Regiodivergent Synthesis of Bicyclo[2.1.1]hexanes via Photochemical Strain-Release Cycloadditions

Bicyclo[2.1.1]hexane is an emerging scaffold in various pharmaceutical settings, but the scarcity of approaches to target different regioisomers from a common starting material prevents targeting a broader range of chemical space. Herein, we demonstrate a new design for the photocatalyst-controlled regiodivergent synthesis of this scaffold. Of particular interest is that the synthesis of two distinct substitution patterns was achieved under photochemical conditions with catalyst control. This was possible due to the activating group, <i>N</i>-methylimidazole, not only playing an important role in guiding divergent pathways but also enabling transformation to various functional groups. Transient absorption spectroscopy discerned between the regiodivergent mechanisms, as assignable bands consistent with electron transfer and energy transfer processes were distinctively observed, depending on the identity of the photocatalyst.