Domino reaction between 2-acylfurans and diethyl azodicarboxylate: a combined experimental, theoretical, X-ray and dynamic NMR study

Abstract

Treatment of 2-acetylfuran 6a with diethyl azodicarboxylate gave the cycloadduct 7, 6,7-diethoxycarbonyl-6,7-diaza-8-oxabicyclo[3.2.1]oct-3-en-2-one, whereas 5-methyl-2-formylfuran 6b reacted giving a simple hydrazide product derived from radical reaction on the formyl group. The structure of the bicyclic compound 7, established by NMR measurements, was confirmed by an X-ray crystallographic analysis. Variable temperature ¹H NMR and ¹³C NMR studies of 7 indicate that this compound undergoes two distinct dynamic conformational changes with ΔG ^‡ 10.2 and 13.1 kcal mol^–1 respectively. The reaction mechanism associated with the domino reaction between furfural 1 and dimethyl azodicarboxylate 9 to give the cycloadduct 10 has been theoretically characterized using ab initio methods at the RHF/6-31G* level. The reaction pathway can be described as a three-step process. The first step corresponds with a [4 + 2] cycloaddition between 1 and 9, while the two subsequent steps are associated with a structural isomerization of the initial formyl cycloadduct to a more stable final adduct.