Microwave Domino Diastereoselective Synthesis of NovelTrans-4,5-Dihydro-1H-Furo[2,3-c]Pyrazoles Using Pyridinium Salts in an Aqueous Medium

Abstract

Novel fused 4,5-dihydro-1 H-furo[2,3- c]pyrazole derivatives containing both biologically active pyrazole and furan templates are synthesised by a one-pot two-step four-component domino reaction involving hydrazine hydrate, a β-keto ester, an aromatic aldehyde and a pyridinium salt catalysed by DABCO with high diastereoselectivity in H2O under microwave irradiation. To minimise the formation of byproducts, the hydrazine hydrate and ethyl acetoacetate were first irradiated until a pyrazolone was formed. Next, the aryl aldehyde, the pyridinium salt and DABCO were added and the reaction could be completed in good to excellent yields. The salient features of this eco-friendly methodology are highlighted by its short reaction time (10–12 min), high yields, high atom-economy, efficiency of producing five new bonds (2C–C, C=N, C–N and one C–O), two new rings and two stereocentres in a single operation, absence of any tedious work-up or purification and avoidance of separation of intermediates.