Difluoro-Substituted bicyclo[1.1.1]pentanes as Novel Motifs for Medicinal Chemistry: Design, Synthesis and Characterization

Herein we developed a practical synthetic approach to the previously unknown difluoro-substituted bicyclo[1.1.1]pentanes. The key step was an addition of difluorocarbene to electron-rich bicyclo[1.1.0]butanes by CF₃TMS/NaI system. The obtained difluoro-bicyclo[1.1.1]pentanes are a new generation of saturated bioisosteres of the benzene ring for drug discovery projects.