Modular Access to <i>N</i>-SF<sub>5</sub> Azetidines
A general and modular strategy has been developed for the synthesis of <i>N</i>-SF<sub>5</sub> azetidines, a new class of scaffolds with potential utility in medicinal chemistry. This transformation leverages bench-stable and scalable SF<sub>5</sub>-transfer reagents to generate the SF<sub>5</sub> 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 <i>N</i>-SF<sub>5</sub> azetidines demonstrate high aqueous stability and increased lipophilicity, positioning them as a novel class of potential bioisosteres in medicinal chemistry.
Authors
- Yuzuru Kanda (ORCID: https://orcid.org/0000-0003-2200-2667)
- Tian Qin (ORCID: https://orcid.org/0000-0001-7225-3224)
- Chao Hu (ORCID: https://orcid.org/0000-0003-3237-5934)
- Renzhe Li (ORCID: https://orcid.org/0009-0006-9775-3587)
- Eric Crossley
- Rohan R. Merchant (ORCID: https://orcid.org/0000-0002-5472-8780)
- Noelle Sevilir Williams (ORCID: https://orcid.org/0000-0003-1894-5742)
- Bryan S. Matsuura (ORCID: https://orcid.org/0000-0001-6003-2686)
- Chang Liu (ORCID: https://orcid.org/0000-0001-7100-9983)
- Wenyuan Li (ORCID: https://orcid.org/0009-0001-9595-7301)
- Chen‐Yan Cai
- Thomas Lyness
Institutions
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Novartis (China) (CN)
- Novartis (United States) (US)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-09-12
- DOI
- https://doi.org/10.1021/jacs.5c10954
- Citations
- 13
- Primary Topic
- Synthesis and Catalytic Reactions
- Type
- article
- Field-Weighted Citation Impact
- 12.17