Desenvolvimento de reações catalíticas envolvendo isoxazolonas

Abstract

Isoxazol-5-one is a heterocycle with a five-membered ring containing nitrogen and oxygen, in addition to the presence of a carbonyl in position 5. Many isoxazol-5- one derivatives have been exhibited important biological properties, for example, antiinflammatory, anti-obesity, anticancer, anti-inflammatory, antibacterial and antiandrogenic activities. Some derivatives have also been associated with applications as agrochemicals. In recent decades, a large increase in the use of isoxazol-5-one derivatives as substrates in organic synthesis has also been observed, with the aim of obtaining a multitude of new complex molecules. Due to the great demand for isoxazol-5-one derivatives, there is a need to develop new low-cost and high-efficiency methodologies capable of accessing new derivatives of this molecule. In this work we present two new methodologies to access new ixosazol-5-one derivatives. In the first part of this work, we developed a highly regioselective methodology through Steglich rearrangement, to access novel N-substituted and Csubstituted isoxazolones in moderate to good yields. In the second part, a robust catalytic protocol for the addition of the aza-Michael type between isoxazol-5-ones and conjugated enones was described, allowing the formation of the desired aza-Michael products in up to 91% isolated yield. The reaction was carried out in the presence of either hydrochloric acid or p-sulfonic acid calix[4]arene as catalysts.