Easy construction of furo[2,3-f]isoindole core by the IMDAV reaction between 3-(furyl)allylamines and α,β-unsaturated acid anhydrides

Abstract

The vinylogues of furfurylamines, easily available in two steps from furylacroleins (3-(furyl)allylamines), were studied in a tandem N-acylation/intramolecular [4+2] cycloaddition with maleic, pyrocinchonic, and citraconic anhydrides, as well as furylacryloyl and cinnamoyl chlorides. By using a domino reaction of 3-(furyl)allylamines and α,β-unsaturated acid anhydrides under mild conditions, various hexahydro-4H-furo[2,3-f]isoindoles and their carboxyl derivatives were synthesized efficiently. The domino sequence includes three steps: acylation of the nitrogen atom in 3-(furyl)allylamines, intramolecular Diels–Alder cycloaddition in the resulting N-acyl vinylfurans (IMDAV reaction), and prototropic shift of the adducts followed by recovery of aromaticity of the furan nucleus. The key step, IMDAV reaction, leads to the target products, furo[2,3-f]isoindoles, diastereoselectively and with relatively high yields.