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.

1-Azaspiro[3.3]heptanes were synthesized, characterized, and validated biologically in vivo as a new generation of saturated piperidine bioisosteres.