Modular Access to N-SF5 Azetidines
Renzhe Li1, Chao Hu1, Chang Liu1
1Department of Biochemistry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390, United States.
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.
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