Copper-Mediated −CF(OCF<sub>3</sub>)(CF<sub>2</sub>H) Transfer to Organic Electrophiles
The integration of fluorine into medicinal compounds has become a widely used strategy to improve the biochemical and therapeutic properties of drugs. Inclusion of -CF<sub>2</sub>H and -OCF<sub>3</sub> fluoroalkyl groups has garnered attention due to their bioisosteric properties, enhanced lipophilicity, and potential hydrogen-bonding capability in bioactive substances. In this study, we prepared a series of stable Cu[CF(OCF<sub>3</sub>)(CF<sub>2</sub>H)]L <i><sub>n</sub></i> complexes by insertion of commercially available perfluoro(methyl vinyl ether), CF<sub>2</sub>=CF(OCF<sub>3</sub>), into Cu-H bonds derived from Stryker's reagent, [CuH(PPh<sub>3</sub>)]<sub>6</sub>, using ancillary ligands L. Notably, certain of these complexes effectively transfer the fluoroalkyl group to aroyl chlorides. Through reaction optimization and computational analysis, we identified dimethylsulfoxide as a pivotal coligand, playing a distinctive role in enabling the fluoroalkylation of a range of aroyl chlorides and aryl iodides. The latter also benefits from addition of CuBr to abstract PPh<sub>3</sub>, generating solvent-stabilized Cu[CF(OCF<sub>3</sub>)(CF<sub>2</sub>H)]. These methodologies allow for the introduction of geminal -OCF<sub>3</sub> and -CF<sub>2</sub>H groups in a single transformation.
Authors
- R. Tom Baker (ORCID: https://orcid.org/0000-0002-1133-7149)
- Christian Ehm (ORCID: https://orcid.org/0000-0002-2538-5141)
- Behnaz Ghaffari (ORCID: https://orcid.org/0000-0002-2050-9424)
- Luana L. T. N. Porto
- Jeffrey S. Ovens (ORCID: https://orcid.org/0000-0003-2114-0443)
- Nicole Johnson
Institutions
- University of Ottawa (CA)
- University of Naples Federico II (IT)
Publication Details
- Journal
- ACS Organic & Inorganic Au
- Published
- 2024-09-20
- DOI
- https://doi.org/10.1021/acsorginorgau.4c00038
- Citations
- 3
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.62
Funders
- Università degli Studi di Napoli Federico II
- University of Ottawa
- Ontario Ministry of Economic Development and Innovation
- Canada Foundation for Innovation
- Canada Research Chairs
- Mitacs
- Ministero dello Sviluppo Economico
- Arkema
- Natural Sciences and Engineering Research Council of Canada