Cascade of the Hinsberg / IMDAF reactions in the synthesis 2-arylsulfonyl-3a,6-epoxyisoindoles and 4a,7-epoxyisoquinolines in water

Abstract

N -Furfuryl allylamines, readily accessible from corresponding furfurals or furfuryl amines, react with a broad range of arylsulfonyl chlorides with the formation of a 3a,6-epoxyisoindole core in one synthetic stage. Usually, in boiling water, the interaction sequence involves two consecutive steps: the Hinsberg reaction and the intramolecular Diels–Alder furanе (IMDAF) reaction. The scope and limitations of the proposed method were thoroughly investigated, and it was revealed that the key [4 + 2] cycloaddition step proceeds through an exo -transition state, giving rise to the exclusive formation of a single diastereomer of the target heterocycle. The method allows the ability to obtain N -sulfaryl-substituted 3a,6-epoxyisoindoles and 4a,7-epoxyisoquinolines, which are potentially useful substrates for further transformations and subsequent bioscreening, in particular antimicrobial activity. • A short IMDAF strategy to give 2-(arylsulfonyl)-3a,6-epoxyisoindoles from readily available initial materials was proposed. • Cascade of the Hinsberg / IMDAF Reactions is very simple and strongly depends on the characteristics of substituents. • Aforesaid epoxyisoindoles possess antibacterial activity against gram-negative or gram-positive sensitive bacteria strains.