An eco-friendly synthesis of novel 3,5-disubstituted-1,2-isoxazoles in PEG-400, employing the Et3N-promoted hydroamination of symmetric and unsymmetric 1,3-diyne-indole derivativesElectronic supplementary information (ESI) available: Selected spectra of intermediates and final products. CCDC 1027013. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ra11571f

• Main Authors: Bassaco, Mariana M, Fortes, Margiani P, Back, Davi F, Kaufman, Teodoro S, Silveira, Claudio C
• Format: Article
• Language: English
• ISSN: 2046-2069
• DOI: 10.1039/c4ra11571f

A facile, efficient and atom-economic synthesis of 3,5-disubstituted 1,2-isoxazoles bearing indole moieties, is reported. The synthesis of these isoxazoles was carried out by the triethylamine-promoted reaction of symmetric and unsymmetric 1,3-diyne indole derivatives with hydroxylamine in PEG-400, as an eco-friendly solvent, under relatively mild conditions. The synthesis of the starting 1,3-diyne indole derivatives was performed by the aerobic self-coupling of diversely functionalized N -propargyl indoles and N -propargyl carbazole under copper catalysis, or by the reaction of the propargyl derivatives with phenyl- or p -tolyl-acetylene under combined nickel and copper catalysis. The isoxazolation reaction was optimized, its scope and limitations were studied and a detailed reaction mechanism was proposed. PEG-400 proved to be a useful solvent for the mild and efficient synthesis of 3,5-disubstituted 1,2-isoxazoles derived from 1,3-diyne indoles. The scope and limitations of the reaction were also studied.