A Practical and Scalable Approach to Fluoro-Substituted Bicyclo[1.1.1]pentanes.

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.

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.

Synthesis of Functionalized Difluorocyclopropanes: Unique Building Blocks for Drug Discovery.

Difluorocyclopropane-containing building blocks for drug discovery were synthesized from the functionalized alkenes and TMSCF3 /NaI. Novel fluorinated acids, amines, amino acids, alcohols, ketones and sulfonyl chlorides were obtained.