Metal-free synthesis of 3,5-disubstituted 1H- and 1-aryl-1H-pyrazoles from 1,3-diyne-indole derivatives employing two successive hydroaminations

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

RSC Advances

ROYAL SOC CHEMISTRY

Lugar: Londres; Año: 2015 vol. 5 p. 21112 - 21124

A robust and efficient atom-economic one-pot synthesis of 3,5-disubstituted 1H- and 1-aryl-1Hpyrazoles under base, acid and metal-free reaction conditions, is reported. The transformation conveniently takes place between 1,4-disubstituted 1,3-diynes and hydrazines in PEG-400 as an ecofriendly solvent, and involves two successive hydroaminations. The reaction was optimized for both, symmetric and non- symmetric 1,3-diyne-indole derivatives, as well as for hydrazine and substituted phenylhydrazines. The scope and limitatons of the transformation were examined, observing that it is not sensitive to moisture or atmospheric oxygen, and that it tolerates a variety of functional groups. Even sterically hindered substrates afforded the expected pyrazoles in good to excellent yields, under mild conditions. A detailed reaction mechanism, which explains its regioselectivity, was also proposed.