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.

Difluorocyclopropane-containing building blocks for drug discovery were synthesized from the functionalized alkenes and TMSCF /NaI. Novel fluorinated acids, amines, amino acids, alcohols, ketones and sulfonyl chlorides were obtained.

After more than 20 years of trials, a practical scalable approach to fluoro-substituted bicyclo-[1.1.1]pentanes (F-BCPs) has been developed. The physicochemical properties of the F-BCPs have been studied, and the core was incorporated into the structure of the anti-inflammatory drug Flurbiprofen in place of the fluorophenyl ring.

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.

After more than 20 years of trials, a practical scalable approach to fluoro-substituted bicyclo-[1.1.1]pentanes (F-BCPs) has been developed. The physicochemical properties of the F-BCPs have been studied, and the core was incorporated into the structure of the anti-inflammatory drug Flurbiprofen in place of the fluorophenyl ring.