Synthesis of Ring-Fluorinated Thiophene Derivatives Based on Single C–F Bond Activation of CF3-Cyclopropanes: Sulfanylation and 5-endo-trig Cyclization
- Kohei FuchibeKohei FuchibeDivision of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571, JapanMore by Kohei Fuchibe,
- Tatsuki FushiharaTatsuki FushiharaDivision of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571, JapanMore by Tatsuki Fushihara, and
- Junji Ichikawa*Junji Ichikawa*Email: [email protected]Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571, JapanMore by Junji Ichikawa
Abstract
The treatment of CF3-bearing cyclopropanes with Et2AlCl generated stabilized difluorocarbocations, which underwent a nucleophilic addition of thiocarboxylic acids or thiols. The sulfur functionality was introduced at the position δ to the fluorine substituents in a regioselective manner (single activation of CF3-cyclopropanes). The formed 1,1-difluoro-1-alkenes underwent successive deesterification/5-endo-trig cyclization. Intramolecular vinylic substitution proceeded in an aprotic solvent, whereas intramolecular addition proceeded in a protic solvent to afford pharmaceutically and agrochemically promising 2-fluoro-4,5-dihydrothiophene and 2,2-difluorotetrahydrothiophene scaffolds, respectively.
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This article is cited by 2 publications.
- Dayanne R. Carvalho, Alec H. Christian. Modern approaches towards the synthesis of geminal difluoroalkyl groups. Organic & Biomolecular Chemistry 2021, 19 (5) , 947-964. https://doi.org/10.1039/D0OB02374D
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