A Ketone Synthesis via Cu(I)-Catalyzed Regioselective Coupling of 2-Pyridylthioesters with Grignard Reagents: In Quest of Straightforward Access to Pharmaceuticals
For commercial production of SGLT2 inhibitors, cryogenic conditions (-78 °C) were required at the key <i>C</i>-glycosidation step, which has restricted their supply to the world market. To address the challenge, reported herein is a new synthetic method based on a new ketone synthesis by means of copper(I)-catalyzed coupling of 2-pyridylthioesters with Grignard reagents. The facile transformation from the ketones to the final APIs was realized under mild conditions due to the use of readily cleavable acetyl protecting groups.
Authors
- Kazushi Mashima (ORCID: https://orcid.org/0000-0002-1316-2995)
- Masahiko Seki (ORCID: https://orcid.org/0000-0002-9942-377X)
- Shaheen Kasim Mulani
- Sandeep Ramesharao Tapkir
- Shantanu Nandi (ORCID: https://orcid.org/0000-0003-2861-4859)
- Subarna Jyoti Kalita (ORCID: https://orcid.org/0000-0001-5061-2919)
- Gaurav K. Shukla (ORCID: https://orcid.org/0000-0002-8994-1944)
- Runlin Yang (ORCID: https://orcid.org/0000-0001-5205-0024)
Institutions
- Tokuyama (Japan) (JP)
- Kumamoto University (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- The Journal of Organic Chemistry
- Published
- 2025-02-05
- DOI
- https://doi.org/10.1021/acs.joc.4c02752
- Primary Topic
- Catalytic C–H Functionalization Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Japan Society for the Promotion of Science