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 Derivatives

BASSACO, M. M.; FORTES, M. P.; DAVID F. BACK; KAUFMAN, T. S.; SILVEIRA, C. C.

RSC Advances

RSC

Lugar: Londres; Año: 2014 vol. 4 p. 60785 - 60797

2046-2069

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.