Photochemical Intermolecular 3σ + 2σ-Cycloaddition for the Construction of Aminobicyclo3.1.1heptanes

The development of synthetic strategies for the preparation of bioisosteric compounds is a demanding undertaking in medicinal chemistry. Numerous strategies have been developed for the synthesis of bicyclo1.1.1pentanes (BCPs), bridge-substituted BCPs, and bicyclo2.1.1hexanes. However, progress on the synthesis of bicyclo3.1.1heptanes, which serve as meta-substituted arene bioisosteres, has not been previously explored. Herein, we disclose the first photoinduced 3σ + 2σ cycloaddition for the synthesis of trisubstituted bicyclo3.1.1heptanes using bicyclo1.1.0butanes and cyclopropylamines. This transformation not only uses mild and operationally simple conditions but also provides unique meta-substituted arene bioisosteres. The applicability of this method is showcased by simple derivatization reactions.