Palladium-Catalyzed [4+1] Cycloaddition of 3,3-Difluoropent-4-en-2-ones with Amines: A Modular Approach to 3-Fluoropyrroles
3-Fluoropyrroles are privileged scaffolds in pharmaceutical and agrochemical applications, yet their synthesis remains challenging. Herein, we report a palladium(0)-catalyzed [4+1] cycloaddition/dehydration strategy for the efficient construction of 3-fluoropyrroles from readily available 3,3-difluoropent-4-en-2-ones and primary amines. This transformation proceeds via C-F bond activation to generate a key π-allyl-Pd(II) intermediate, followed by intramolecular addition/dehydration to furnish the heterocyclic core. The method features broad substrate compatibility, mild conditions, and scalability, enabling access to diverse 3-fluoropyrroles that are otherwise difficult to synthesize. This work provides a practical and versatile platform for the discovery of fluorinated pyrrole-based bioactive molecules.
Authors
- Zhenli Luo
- Zhuang Xiong (ORCID: https://orcid.org/0000-0002-2571-2456)
- Jia‐Qiang Wu (ORCID: https://orcid.org/0000-0001-5067-7616)
- Jinhui Hu (ORCID: https://orcid.org/0000-0001-7924-1656)
- Chunming Chen (ORCID: https://orcid.org/0000-0002-9173-5488)
- Mei Xie
Institutions
- Wuyi University (CN)
- Wuyi University (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-09-04
- DOI
- https://doi.org/10.1021/acs.orglett.5c02884
- Citations
- 4
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 3.16
Funders
- Wuyi University
- Basic and Applied Basic Research Foundation of Guangdong Province