Diastereoselective Synthesis of Coumarin‐Based Fused Heterocycles via Intramolecular Diels‐Alder and 1,3‐Dipolar Cycloaddition Reactions

Abstract

AbstractIn this work, a two‐steps strategy for the synthesis of novel coumarin‐based fused heterocycles is presented. The strategy involved i) initial nucleophilic substitution / intramolecular Diels‐Alder reaction of furfurylamine with 4‐chloro‐3‐vinylcoumarins followed by ii) base‐mediated 1,3‐dipolar cycloaddition reaction of resultant coumarin‐based bicyclic products with dibromoformaldoxime. The methodology provides a straightforward access to compounds containing the coumarin, isoquinoline, and isoxazole motifs in a single molecular entity in satisfactory yields. The reaction proceeded with remarkable diastereoselectivity that leads to the formation of five new bonds and six new stereogenic centres. Furthermore, the observed diastereoselectivity was analysed with the help of DFT calculations to substantiate the thermodynamic stability of the obtained products.