The synthesis of highly functionalised pyridines using Ghosez-type reactions of dihydropyrazoles

Abstract

The aza-Diels–Alder reaction of αβ-unsaturated hydrazones is a general methodology that has been applied both to the synthesis of natural products and to the development of multicomponent reactions. Trends have emerged as to the effect of substituents on the efficiency of this reaction with substituents at the C2 and C4-positions of the aza-diene in general suppressing the reaction. Here we report that 4,5-dihydropyrazoles can function as substrates in this process despite the presence of substituents at both of these positions. A one pot, four chemical step sequence carried out under standard thermal or microwave conditions results in the formation of the corresponding pyridine-containing compounds. The scope of the reaction is explored and additional insights into the proposed mechanism of this reaction are provided.