Síntese de furanos trissubstituídos via reações de oxopaladação aeróbica

Abstract

Furans are important heterocyclics with broad application in synthesis as a building block, frequently presented in a wide range of compounds that exhibit biological activity, including natural products. Intramolecular oxopallation chemistry has been widely applied for the preparation of furans and benzofurans, with particular emphasis on processes of intramolecular cycloisomerization of substituted carbonyl precursors. However, the use of 2-alkenylcarbonyls, more accessible and easily manipulated than the previous starting materials, is still unexplored with palladium II chemistry. It is well known that the use of oxidants to regenerate the reactive species of palladium is necessary and that an aerobic version of these reactions represents a major advance due to the widespread availability of molecular oxygen as a "green" oxidant. The present work demonstrates the development of an aerobic methodology for the direct use of molecular oxygen in the synthesis of trisubstituted furans using β-ketoesters derivatives and palladium II source. In the initial attempt to synthesize the furans, reactive systems such as alkenyl-substituted β-ketoesters were explored. In sequence, experiments were carried out with the variation of the catalyst source, solvents, additives and temperature, in order to find the optimized condition for the oxopallation reaction. Stands out the use of bis (acetonitrile) dichloro-palladium as catalyst, dimethylformamide and sodium acetate as solvent and base, respectively, and molecular sieve of 4 Å at 40 °C under an atmosphere of 1 atm of molecular oxygen. With the optimized reaction conditions, it was tested for other substrates in order to evaluate the scope of this methodology. The studies to verify the scope of the methodology were carried out providing yields up to 85% for the 21 substrates evaluated.