Photochemical Intermolecular [3Σ+2Σ]-Cycloaddition for the Construction of Aminobicyclo[3.1.1]heptanes

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 bicyclo[1.1.1]pentanes (BCPs), bridge-substituted BCPs, and bicyclo[2.1.1]hexanes. However, progress on the synthesis of bicyclo[3.1.1]heptanes, which serve as meta-substituted arene bioisosteres, has not been previously explored. Herein, we disclose the first photoinduced [3 sigma + 2 sigma] cycloaddition for the synthesis of trisubstituted bicyclo[3.1.1]heptanes using bicyclo[1.1.0]butanes 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.

Automated summary

In this study, we have disclosed the first photoinduced [3 sigma + 2 sigma] cycloaddition for the synthesis of trisubstituted bicyclo[3.1.1]heptanes using bicyclo[1.1.0]butanes and cyclopropylamines. This method offers mild and operationally simple conditions, along with unique meta-substituted arene bioisosteres.