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DOI: 10.1055/s-0043-1773529
Synthesis of 5-(Trifluoromethyl)-2,3-dihydrofurans through N-Alkylation of Azoles Using Brominated Enones
The authors are grateful for financial support from the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS/CNPq) (403.134/2021-8), and for fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (G.S.P., P.A.M., H.G.B., M.A.P.M and N.Z) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (M.M.).
Abstract
We herein present a chemo- and regioselective methodology for the N-alkylation/arylation of azoles (imidazoles, pyrazoles, and triazoles) using 5-bromo-1,1,1-trifluoro-4-alkoxypent-3-en-2-ones (brominated enones) as precursors, in order to selectively obtain N-alkylated azoles containing disubstituted furans or dihydrofurans. The key reaction steps are 1,4-conjugated addition followed by nucleophilic substitution (each promoted by a different nitrogen atom of the azole), which furnish the corresponding 2,5-disubstituted dihydrofurans (24 examples, yields of 37–97%). The limitations of the reaction are explored and it is found that when 2-chlorobenzimidazole is used as a dinucleophile, 5-trifluoromethyl-3-substituted furans are obtained (three examples, yields of 57–67%). The selectivity of the reactions is determined through NMR analysis (including two-dimensional techniques for the 15N nucleus) and single-crystal X-ray analysis.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/10.1055/s-0043-1773529.
- Supporting Information
Publication History
Received: 18 January 2025
Accepted after revision: 18 February 2025
Article published online:
07 April 2025
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