Modular Access to <i>N</i>-SF₅ Azetidines.

ABSTRACT: A general and modular strategy has been developed for the synthesis of N-SF₅ azetidines, a new class of scaffolds with potential utility in medicinal chemistry. This transformation leverages bench-stable and scalable SF₅-transfer reagents to generate the SF₅ radical, which engages azabicyclo[1.1.0]butanes bearing ketone, ester, alkyl, or aryl substituents in strain-release difunctionalization reactions. The method proceeds under mild reaction conditions, features broad functional group tolerance, and offers operational simplicity. The resulting N-SF₅ azetidines demonstrate high aqueous stability and increased lipophilicity, positioning them as a novel class of potential bioisosteres in medicinal chemistry.

SUBMITTER: Li R 

PROVIDER: S-EPMC12443333 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature