New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

A new tandem sequence involving the Ugi reaction and Diels-Alder [4 + 2] cycloaddition based on vinylfuran and 1,3-butadienylfuran derivatives was designed and studied. It was found that in the case of 3-(furan-2-yl)acrylaldehyde, a one-pot Ugi reaction and intramolecular Diels-Alder vinylarene (IMDAV) reaction leads to the formation of the insufficiently studied furo[2,3-<i>f</i>]isoindole derivatives. Ugi adducts formed from (<i>E</i>)-3-(furan-2-yl)acrylaldehyde, maleic acid monoanilide, isonitrile, and an amine spontaneously underwent the IMDAV reaction with a high level of stereoselectivity, leading to single pairs of enantiomers of 4,4a,5,6,7,7a-hexahydro-3a<i>H</i>-furo[2,3-<i>f</i>]isoindole core in excellent yields. Under the same conditions, the (2<i>E</i>,4<i>E</i>)-5-(furan-2-yl)penta-2,4-dienal gives an Ugi adduct that undergoes the IMDA reaction without involving the furan core. The cycloaddition leads to the formation of 2,3,3a,4,5,7a-hexahydro-1<i>H</i>-isoindoles in high yields. The studied tandem Ugi and intramolecular Diels-Alder reactions allow high substituent variation in the named isoindoles.