Modular Access to N-SF5 Azetidines

A general and modular strategy has been developed for the synthesis of N –SF 5 azetidines, a new class of scaffolds with potential utility in medicinal chemistry. This transformation leverages bench-stable and scalable SF 5 -transfer reagents to generate the SF 5 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 –SF 5 azetidines demonstrate high aqueous stability and increased lipophilicity, positioning them as a novel class of potential bioisosteres in medicinal chemistry.