0009-3122/12/4803-0505©2012 Springer Science+Business Media, Inc. 505 ×Chemistry of Heterocyclic Compounds, Vol. 48, No. 3, June, 2012 (Russian Original Vol. 48, No. 3, March, 2012) CYCLOADDITION OF FURFURYLAMINES TO MALEIC ANHYDRIDE AND ITS SUBSTITUTED DERIVATIVES V. P. Zaytsev 1 *, N. M. Mikhailova 1 , I. K. Airiyan 1 , E. V. Galkina 1 , V. D. Golubev 1 , E. V. Nikitina 1 , F. I. Zubkov 1 , and A. V. Varlamov 1 The regio- and stereoselectivity of the [4+2] cycloaddition of maleic, citraconic, dichloromaleic, and dibromomaleic anhydrides to difurfuryl amines and secondary furfurylamines were studied. N-Furfuryl-, N-phenyl-, and N-benzylhexahydrooxoepoxyisoindole-7-carboxylic acids were synthesized. An approach was developed for obtaining hexahydroepoxyoxoisoindole-7-carboxylic acid unsubstituted at the nitrogen atom. Aromatization of the oxabicycloheptene fragment of the dihaloepoxyiso- indolonecarboxylic acids gave a series of 7-carboxy-2-R-isoindol-1-ones. Keywords: furfurylamines, isoindolones, maleic anhydride, [4+2] cycloaddition. Functionally substituted epoxyisoindolones hold interest for use in organic synthesis. Pseudo-sugars annelated with azaheterocycles [1-3], and various condensed heterocyclic compounds containing an isoindole fragment may be obtained on the basis of these compounds [4-10]. A recently developed method for the synthesis of isoindol-1-ones holds considerable promise in this regard. This method is based on the acylation of N-aryl- or N-alkylfurfurylamines by unsaturated acid derivatives with subsequent intramolecular [4+2] cycloaddition of the resultant unsaturated amides [11-19]. The development of this approach is an elaboration of the two-step preparative method for the synthesis of 7-carboxy-2-R-isoindol-1-ones [20] based on [4+2] cycloaddition of maleic anhydride to N-substituted furfurylamines. We studied the scope of this reaction and showed the effect of the substituent at the furfuryl- amine nitrogen atom on the cycloaddition. Conditions were found for the aromatization of the oxabicyclo- heptene fragment to give 7-carboxyphthalimidines [21]. In the present work, we have studied the regio- and stereoselectivity of the cycloaddition of maleic, citraconic, dibromomaleic, and dichloromaleic anhydrides to difurfurylamines as well as to phenyl- and benzyl- furfurylamines. An attempt was made to evaluate the effect of substituents in the oxabicycloheptene fragment on the capacity of the Diels-Alder adducts to undergo aromatization. Starting furfurylamines 1a-h were obtained as light, mobile oils by the reduction of the corresponding Schiff bases using sodium borohydride in ethanol. _______ *To whom correspondence should be addressed, e-mail: vzaitsev@sci.pfu.edu.ru. 1 Peoples' Friendship University of Russia, 6 Miklukho-Maklaya St., Moscow 117198, Russia. _________________________________________________________________________________________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, pp. 538-548, March, 2012. Original article submitted April 26, 2011.