Synthesis of 5-(Trifluoromethyl)-2,3-dihydrofurans through N-Alkylation of Azoles Using Brominated Enones
Year: 2025
Type: article
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.
Source: Synthesis
Institution: Thieme Medical Publishers (Germany)
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: bronze
Awards: G3026333738, G3543758689
OpenAlex ID: W4409232770