Intramolecular cycloaddition reaction of bromo and nitro substituted furanyl amides

Abstract

The intramolecular Diels-Alder reaction (IMDAF) of an N-alkenyl substituted furanyl amide was investigated. Upon thermolysis at 80-110 o C, a smooth IMDAF reaction occurred to provide a stable aza-7-oxabicyclo[2.2.1]heptane cycloadduct in high yield. The intramolecular cyclization of the related 5-bromo substituted furanyl amide was found to proceed at a much faster rate and in higher yield than the unsubstituted variant. The rate enhancement observed by incorporating a bromine in the 5-position of the furan ring appears to be general. The origin of the increased rate of cycloaddition for the 5-bromo substituted furan when compared to the unsubstituted example can be attributed to an increase in reaction exothermicity; this both decreases the activation enthalpy, and increases the barrier to retrocycloaddition. Bromine substitution on furan also increases reactant energy and stabilizes the product due to the preference of the electronegative bromine atom to be attached to a more highly alkylated, and therefore more electropositive framework. An unusual isomerization-cyclization reaction of a 5-nitro substituted furanyl amide was also found to occur under microwave conditions and provided a 1,4-dihydro-2Hbenzo[4.5]furo[2,3-c]pyridin-3-one derivative.