Synthesis of Janus All-<i>Cis</i> Tetrafluorocyclohexanes Carrying 1,4-Diether Motifs
Nucleophilic aromatic substitutions (S<sub>N</sub>Ar) of alkoxides on pentafluoroaryl ethers are explored as a first step in a synthesis sequence to generate all-<i>cis</i> 2,3,5,6-tetrafluorocyclohexyl-1,4-dialkyl ethers <b>1</b>. The S<sub>N</sub>Ar reaction was explored both experimentally and theoretically to rationalize <i>ortho</i>/<i>para</i>/<i>meta</i> selectivities. <i>tert</i>-Butyl deprotection of products followed by phenol alkylations introduces versatility to the synthesis. The final Rh(CAAC) <b>3</b> catalyzed aryl hydrogenation step of intermediate tetrafluoroaryl-1,4-diethers generated cyclohexane products <b>1</b>. This chemistry introduces a new class of Janus fluorocyclohexane derivatives with ether substituents placed 1,4- to each other.
Authors
- Thomas J. Poskin
- Rodrigo A. Cormanich (ORCID: https://orcid.org/0000-0001-7659-1749)
- Bruno A. Piscelli (ORCID: https://orcid.org/0000-0002-4655-3511)
- David O’Hagan (ORCID: https://orcid.org/0000-0002-0510-5552)
- David B. Cordes (ORCID: https://orcid.org/0000-0002-5366-9168)
- Aidan P. McKay (ORCID: https://orcid.org/0000-0002-8578-7054)
- Shigeyuki Yamada (ORCID: https://orcid.org/0000-0002-6379-0447)
- Yuto Eguchi
Institutions
- University of St Andrews (GB)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Kyoto Institute of Technology (JP)
Publication Details
- Journal
- The Journal of Organic Chemistry
- Published
- 2024-11-27
- DOI
- https://doi.org/10.1021/acs.joc.4c02345
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Centro Nacional de Processamento de Alto Desempenho em São Paulo
- Engineering and Physical Sciences Research Council
- Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas