Benzene ring is the most popular fragment in drugs and natural compounds. In the context of a concept named escape from flatland, replacing benzene rings with saturated bioisosteres is an important strategy to obtain novel patent-free molecules with improved biological activity and physico-chemical profile. Bicyclo[1.1.1]pentyl (BCP) skeleton currently plays an important role as a bioisoster of para-substituted phenyl ring. Herein, we developed a strategy to synthesize the first generation of BCPs substituted at the side chain - difluoro-substituted bicyclo[1.1.1]pentanes. The key synthesis step was an addition of difluorocarbene (:CF2) to bicyclo[1.1.0]butanes.

Difluoro-substituted bicyclo[1.1.1]pentanes for medicinal chemistry

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.