Synthesis of novel isoxazole-containing pyrazolines and pyrazoles via cycloaddition and elimination/aromatization process

We presented a general approach for synthesizing isoxazole-containing pyrazolines and pyrazoles. The protocol involved [3 + 2] cycloaddition of the in situ generated nitrile imines with 3-methyl-4-nitro-5-alkenyl isoxazoles furnishing a sequence of trans-configured isoxazole-substituted pyrazolines in a fully regioselective manner. Elimination/aromatization of the prepared cycloadducts with the catalysis of MnO2 or SnCl2 provided a facile access to the poly-substituted pyrazoles. By controlling the catalysts, the aromatization process either led to isoxazole-substituted pyrazoles (MnO2) or 1,3,4-triarylpyrazoles (SnCl2) with excellent selectivity. Additionally, the approach permitted the synthesis of isoxazole-substituted pyrazoles via a one-pot operation.(c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

We presented a general approach for synthesizing isoxazole-containing pyrazolines and pyrazoles through a [3 + 2] cycloaddition reaction. The process involved the in situ generation of nitrile imines and their reaction with 3-methyl-4-nitro-5-alkenyl isoxazoles, resulting in a regioselective synthesis of trans-configured isoxazole-substituted pyrazolines. Aromatization of the cycloadducts with the catalysis of MnO2 or SnCl2 provided access to poly-substituted pyrazoles with excellent selectivity depending on the catalyst used. The method also allowed for the one-pot synthesis of isoxazole-substituted pyrazoles. (c) 2022 Elsevier Ltd. All rights reserved.