ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 8, pp. 1192–1206 © Pleiades Publishing, Ltd., 2010. Original Russian Text © F.I. Zubkov, V.P. Zaitsev, A.M. Piskareva, M.N. Eliseeva, E.V. Nikitina, N.M. Mikhailova, A.V. Varlamov, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 8, pp. 1191–1204. 1192 Perhydrofuro[3,2-c]-, Perhydropyrano[3,2-c]-, and 4-Ethoxy-2-(5-R-furan-2-yl)tetrahydroquinolines. Synthesis and Transformations F. I. Zubkov, V. P. Zaitsev, A. M. Piskareva, M. N. Eliseeva, E. V. Nikitina, N. M. Mikhailova, and A. V. Varlamov Russian University of Peoples’ Friendship, ul. Miklukho-Maklaya 6, Moscow, 117198 Russia e-mail: fzubkov@sci.pfu.edu.ru Received July 20, 2009 Abstract—Partly hydrogenated 2-[5-methyl(bromo, nitro)furan-2-yl]-substituted furo[3,2-c]quinolines, pyrano- [3,2-c]quinolines, and 4-ethoxyquinolines were synthesized by the imino Diels–Alder (Povarov) reaction. Cycloadditions of these compounds with maleic, citraconic, and dibromomaleic anhydrides, as well as with acryloyl, methacryloyl, and cinnamoyl chlorides led to the formation of substituted epoxyisoindolo[2,1-a]- quinolines and -quinolinecarboxylic acids. Oxidation of the double C=C bond in the adducts, esterification of the carboxy group, and aromatization of the 7-oxabicycloheptene fragment were accomplished. We previously synthesized 4-substituted 6-R-2-fur- yltetrahydroquinolines and those fused at the C 3 –C 4 bond and studied their [4 + 2]-cycloaddition reactions with maleic anhydride and acryloyl chloride [1–3] and the effect of electronic properties of the R substituents in the aryl fragment on the cyclization of N-furfuryli- deneanilines with vinyl ethers and vinyl amides to the corresponding tetrahydroquinolines (Povarov reac- tion) [4, 5]. The goal of the present work was to study the be- havior of N-furfurylideneanilines with different sub- stituents in position 5 of the furan ring in the Povarov reaction and reveal general relations holding in the cycloaddition of 2-furyltetrahydroquinolines thus ob- tained with maleic, citraconic, and dibromomaleic an- hydrides, as well as with substituted acryloyl chlorides. N-Furfurylideneanilines I were synthesized by conden- sation of the corresponding 5-substituted furan-2-carb- aldehydes with ortho- and para-substituted anilines. Compounds I were brought into cycloadditions with dihydrofuran, dihydropyran, and ethyl vinyl ether (Scheme 1). The reactions were carried out in diethyl ether or benzene at 0–20°C in the presence of boron trifluoride–diethyl ether complex (5 mol %). We previously showed that electron-withdrawing substituents in the aniline fragment reduce the yield of furyl-substituted tetrahydroquinolines [1]. In the present work we found that increase in the electron- acceptor power of the substituent R 3 in the furan ring favors formation of cycloaddition products II. Schiff base Ic having a hydroxy group in the ortho-position of the benzene ring was considerably less active in the Povarov reaction. According to the 1 H NMR data, 5-nitrofuryl-substituted tetrahydroquinoline IIf was formed as an equimolar mixture of two stereoisomers differing by mutual arrangement of the 5-nitrofuryl substituent and fused tetrahydrofuran ring. The cou- pling constants for the cis isomer of IIf are J 4, 3a = 2.7, J 3a, 9b = 7.4 Hz, and for the trans isomer, J 4, 3a = 5.4, J 3a, 9b = 10.1 Hz. Tetrahydroquinolines III and IV were reported by us previously [1, 2]. 2-Furyl-substituted tetrahydroquinolines IIa, IIc– IIe, III, and IV readily reacted with maleic anhydride at 0–5°C, following the Diels–Alder pattern (Scheme 2), to produce mixtures of stereoisomeric exo-tetrahydro- furano- ( Va , Vc –Ve ), tetrahydropyrano- ( VI ), and 4-ethoxyisoindolo[2,1- a]quinolinecarboxylic acids (VII). In the reactions with furano- and pyranoquino- lines IIa, IId, IIe, and III, the major products were isomers V and VI with trans orientation of the epoxy bridge and the fused heteroring, whereas 8-hydroxy- substituted derivative IIc gave rise to only trans iso- mer Vc. The adduct obtained from 4-ethoxyquinoline DOI: 10.1134/S1070428010080142