C-F bond activation enables synthesis of aryl difluoromethyl bicyclopentanes as benzophenone-type bioisosteres.

ABSTRACT: Bioisosteric design has become an essential approach in the development of drug molecules. Recent advancements in synthetic methodologies have enabled the rapid adoption of this strategy into drug discovery programs. Consequently, conceptionally innovative practices would be appreciated by the medicinal chemistry community. Here we report an expeditous synthetic method for synthesizing aryl difluoromethyl bicyclopentane (ADB) as a bioisostere of the benzophenone core. This approach involves the merger of light-driven C-F bond activation and strain-release chemistry under the catalysis of a newly designed N-anionic-based organic photocatalyst. This defluorinative coupling methodology enables the direct conversion of a wide variety of commercially available trifluoromethylaromatic C-F bonds

SUBMITTER: Chen M 

PROVIDER: S-EPMC10781780 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature