Difluoro-Substituted Bicyclo[1.1.1]pentanes for Medicinal Chemistry: Design, Synthesis, and Characterization

A practical synthetic approach to the difluoro-substituted bicyclo[1.1.1]pentanes was developed. The key step was an addition of difluorocarbene (:CF₂) to electron-rich bicyclo[1.1.0]butanes by the CF₃TMS/NaI system. The obtained difluoro-bicyclo[1.1.1]pentanes are suggested to be used as saturated bioisosteres of benzene rings for the purpose of drug discovery projects.