R = H, 4-(3,4,4A,5,6,10B-Hexahydro-2H-Pyrano- 3,2-C Quinolin-5-Yl)-1-Butanol (3A)

Supplementary material

R = H, 4-(3,4,4a,5,6,10b-Hexahydro-2H-pyrano-[3,2-c] quinolin-5-yl)-1-butanol (3a).

A mixture of aniline (0.093 g, 1 mmol), DHP (0.188 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 4 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.232 g, 89%) as oil. Rf (23% ethyl acetate: n-hexane).

Compound 3a (exo/endo isomers): IR (KBr, cm-1): 3360, 2930, 2862, 1615, 1505, 1455, 1300, 1065, 810, 755. 13C NMR (300 MHz, CDCl3): δ 145.01, 127.77, 126.90, 120.0, 117.65, 114.0, 72.50, 62.50, 60.73, 54.10, 35.50, 32.60, 31.90, 25.36, 22.10, 17.87. MS (m/z): 261.17

Compound 3a: endo-isomer, 1H NMR (300 MHz, CDCl3): δ 7.280 (d, J = 7.5 Hz, 1H, H4), 6.97 (t, J = 7.5 Hz, 1H, H3), 6.65 (t, J = 7.5 Hz, 1H, H2), 6.36 (d, J = 7.5 Hz, 1H, H1), 4.98 (d, J = 5.7 Hz, 1H, H5), 3.69 (t, J = 6.3 Hz, 2H, H11 and H11′), 3.64 (ddt, J = 1.56, 4.34, 11.36 Hz, 1H, H14), 3.35 (dt, J = 2.33,11.45 Hz, 1H, H14′), 3.29 (dt, J = 2.2, 7.0 Hz, 1H, H7), 2.0 (dddd, J = 3.0, 5.4, 7.1, 12.1 Hz, 1H, H6), 1.65-1.30 (m, 10H, H8, H9, H10, H12, H13).

Compound 3a: exo-isomer, 1H NMR (300 MHz, CDCl3): δ 7.20 (d, J = 7.5 Hz, 1H, H4), 6.96 (t, J = 7.5 Hz, 1H, H3), 6.58 (t, J = 7.5 Hz, 1H, H2), 6.42 (d, J = 7.5 Hz, 1H, H1), 4.44 (d, J = 3.2 Hz, 1H, H5), 3.90 (m, 1H, H14), 3.66 (m, 3H, H14′, H11), 3.58 (m,1H, H7), 1.92 (m, 1H, H6), 1.65-1.30 (m, 10H, H8, H9, H10, H12, H13).

R = p-OCH3, 4-(9-Methoxy-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-5-yl)-1-butanol (3b).

A mixture of 4-methoxyaniline (0.123 g, 1 mmol), DHP (0.188 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 3.5 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.268 g, 92%) as oil. Rf (23% ethyl acetate: n-hexane).

Compound 3b (exo/endo isomers): IR (KBr, cm-1): 3455, 2935, 2845, 1485, 1440, 1260, 1010, 800, 755. 13C NMR (300 MHz, CDCl3): δ 148.9, 137.8, 120.7, 114.3, 112.3, 79.1, 66.7, 62.7, 55.8, 55.2, 47.7, 33.2, 23.3. MS (m/z): 291.39

Compound 3b: endo-isomer, 1H NMR (300 MHz, CDCl3): δ 6.90 (d, J = 2.6 Hz, 1H, H1), 6.66 (dd, J = 2.6, 8.0 Hz, 1H, H3), 6.46 (d, J = 8.0 Hz, 1H, H2), 5.00 (d, J = 5.4 Hz, 1H, H5), 3.75 (s, 3H, OCH3), 3.65 (t, J = 6.3 Hz, 2H, H11 and H11′), 3.60 (m, 2H, H14 and H14′), 3.31 (dt, J = 2.6, 7.3 Hz, 1H, H7), 2.00 (dddd, J = 3.0, 5.4, 7.1, 12.1 Hz, 1H, H6), 1.68-1.30 (m, 10H, H8, H9, H10, H12, H13).

Compound 3b: exo-isomer, 1H NMR (300 MHz, CDCl3): δ 6.80 (d, 1H, J = 2.6 Hz, H1), 6.68 (dd, J = 2.6, 8.0 Hz, 1H, H3), 6.50 (d, J = 8.0 Hz, 1H, H2), 4.44 (d, J = 5.4 Hz, 1H, H4), 3.92 (m, 1H), 3.72 (s, 3H, OCH3), 3.68 (m, 3H, H14, H11), 3.48 (m, 1H, H14′), 1.97 (m, 1H, H6), 1.68-1.30 (m, 10H, H8, H9, H10, H12, H13).

R = p-CH3, 4-(9-Methyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-5-yl)-1-butanol (3c).

A mixture of 4-methylaniline (0.109 g, 1 mmol), DHP (0.188 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 3.5 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.247 g, 90%) as oil. Rf (23% ethyl acetate: n-hexane).

Compound 3c (exo/endo isomers): IR (KBr, cm-1): 3362, 2930, 2864, 1620, 1504, 1461, 1302, 1070, 812, 755. 13C NMR (300 MHz, CDCl3): δ 142.68, 129.67, 128.53, 127.03, 120.02, 114.0, 72.49, 62.48, 60.70, 54.26, 35.64, 32.775, 32.01, 25.38, 22.13, 20.56, 17.81. MS (m/z): 275.19

Compound 3c: endo-isomer, 1H NMR (300 MHz, CDCl3): δ 7.16 (d, J = 1.5 Hz, 1H, H1), 6.79 (dd, J = 1.5, 7.5 Hz, 1H, H2), 6.41 (d, J = 7.5 Hz, 1H, H3), 5.00 (d, J = 5.7 Hz, 1H, H5), 3.63 (t, J = 6.3 Hz, 2H, H11 and H11′), 3.58 (ddt, J = 1.6, 4.4, 11.4 Hz, 1H, H14), 3.40 (dt, J = 2.3, 11.4 Hz, 1H, H14′), 3.30 (dt, J = 2.2, 7.0 Hz, 1H, H7), 2.23 (s, 3H, CH3), 2.00 (dddd, J = 3.0, 5.4, 7.1, 12.1 Hz, 1H, H6), 1.68-1.30 (m, 10H, H8, H9, H10, H12, H13).

Compound 3c: exo-isomer, 1H NMR (300 MHz, CDCl3): δ 7.00 (d, J = 1.5 Hz, 1H, H1), 6.96 (dd, J = 1.5, 7.5 Hz, 1H, H2), 6.50 (d, J = 7.5 Hz, 1H, H3), 4.41 (d, J = 3.2 Hz, 1H, H4), 3.96 (m, 1H), 3.62 (m, 3H), 3.58 (m, 1H), 2.20 (s, 3H, CH3), 1.96 (m, 1H, H5), 1.70-1.30 (m, 10H, H8, H9, H10, H12, H13).

R = p-OH, 4-(9-Hydroxy-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-5-yl)-1-butanol (3d).

A mixture of 4-hydroxyaniline (0.11 g, 1 mmol), DHP (0.188 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 3.5 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.241 g, 87%) as oil. Rf ( 23% ethyl acetate: n-hexane).

Compound 3d (exo/endo isomers): IR(KBr, cm-1): 3410, 2930, 2833, 1618, 1506, 1445, 1369, 1204, 1075, 860, 743. 13C NMR (300MHz, DMSO): δ 146.7, 138.2, 121.2, 114.7, 79.1, 66.8, 62.9, 55.2, 47.7, 33.2, 24.3, 23.3. MS (m/z): 277.17

Compound 3d: endo-isomer 1H NMR (300MHz, DMSO): δ 6.75 (d, J = 1.8 Hz, 1H, Ar-H), 6.52 (dd, J = 7.5, 1.8 Hz, 1H, Ar-H), 6.41 (d, J = 7.4 Hz, 1H, Ar-H), 4.92 (d, J = 5.45 Hz, 1H, H5), 3.52 (t, J = 6.1 Hz, 2H), 3.40-3.31 (m, 2H), 3.25 (m, 1H), 1.94 (m, 1H, H6), 1.7-1.28 (m, 10H, H8, H9, H10, H12, H13).

Compound 3d: exo-isomer 1H NMR (300MHz, DMSO): δ 7.61 (d, J = 1.8 Hz, 1H, Ar-H), 6.56 (dd, J = 7.5, 1.8 Hz, 1H, Ar-H), 6.32 ( d, J = 7.6 Hz, 1H, Ar-H), 4.35 (d, J = 2.41 Hz, 1H, H5), 3.71 (m, 1H), 3.33 (m, 1H), 3.42 (m, 3H), 1.8 (m, 1H, H6), 1.70-125 (m, 10H, H8, H9, H10, H12, H13).

R = p-Cl, 4-(9-Chloro-3,4,4a,5,6,10b-hexahydro-2H-pyrano [3,2-c]quinolin-5-yl)-1-butanol (3e).

A mixture of 4-chloroaniline (0.128 g, 1 mmol), DHP (0.188 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 11 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.236 g, 80%) as oil. Rf ( 23% ethyl acetate: n-hexane).

Compound 3e (exo/endo isomers): IR (KBr, cm-1): 3356, 2937, 2878, 1472, 1292, 1052, 805, 757. 13C NMR (300 MHz, CDCl3): δ 143.58, 129.53, 128.82, 123.50, 122.52, 115.33, 72.98, 66.67, 50.19, 36.09, 32.97, 24.10, 23.03, 22.68, 21.28, 17.87. MS(m/z): 295.13.

Compound 3e: endo-isomer, 1H NMR (300 MHz, CDCl3): δ 7.30 (d, J = 2.6 Hz, 1H, H3), 6.96 (dd, J = 2.6, 8.0 Hz, 1H, H2), 6.42 (d, J = 8.0 Hz, 1H, H1), 5.00 (d, J = 5.5 Hz, 1H, H4), 3.70 (t, J = 6.3 Hz, 2H, H11 and H11′), 3.65 (ddt, J = 1.6, 4.4, 11.4 Hz, 1H, H14), 3.50 (dt, J = 2.3, 11.4, 1H, H14′), 3.34 (dt, J = 2.2, 7.0 Hz, 1H, H6), 2.02 (dddd, J = 3.0, 5.4, 7.1, 12.1 Hz, 1H, H5), 1.70-1.32 (m, 10H, H8, H9, H10, H12, H13).

Compound 3e: exo-isomer, 1H NMR (300 MHz, CDCl3): δ 7.18 (d, J = 2.6 Hz, 1H, H3), 6.98 (dd, J = 2.6, 8.0 Hz, 1H, H2), 6.44 (d, J = 8.0 Hz, 1H, H1), 4.42 (d, J = 3.0 Hz, 1H, H4), 3.86 (m, 1H), 3.65 (m, 3H), 3.50 (m, 1H), 1.88 (m, 1H, H5), 1.70-1.32 (m, 10H, H8, H9, H10, H12, H13).

R = p-Br, 4-(9-Bromo-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-5-yl)-1-butanol (3f).

A mixture of 4-bromoaniline (0.175 g, 1 mmol), DHP (0.188 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 12 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.265 g, 78%) as oil. Rf ( 23% ethyl acetate: n-hexane).

Compound 3f (exo/endo isomers): IR (KBr, cm-1): 3350, 2935, 2875, 1598, 1470, 1290, 1055, 803, 755. 13C NMR (300MHz, DMSO): δ 144.6, 133.7, 129.7, 122.0, 115.5, 111.3, 78.1, 66.8, 62.9, 55.2, 47.7, 33.2, 24.3, 21.2. MS(m/z): 339.08

Compound 3f: endo-isomer, 1H NMR (300 MHz, CDCl3): δ 7.42 (d, J = 2.6 Hz, 1H, H3), 7.04 (dd, J = 2.6, 8.0 Hz, 1H, H2), 6.38 (d, J = 8.0 Hz, 1H, H1), 4.98 (d, J = 5.5 Hz, 1H, H4), 3.62 (m, 2H, H11 and H11′), 3.60 (m, 1H, H14), 3.42 (m, 1H, H14′), 3.36 (m, 1H, H6), 2.0 (m, 1H, H5), 1.70-1.32 (m, 10H, H8, H9, H10, H12, H13).

Compound 3f: exo-isomer, 1H NMR (300 MHz, CDCl3): δ 7.30 (d, J = 2.6 Hz, 1H, H3), 7.10 (dd, J = 2.6, 8.0 Hz, 1H, H2), 6.40 (d, J = 8.0 Hz, 1H, H1), 4.40 (d, J = 3.0 Hz, 1H, H4), 3.86 (m, 1H), 3.65 (m, 3H), 3.46 (m, 1H), 1.84 (m, 1H, H5), 1.70-1.32 (m, 10H, H8, H9, H10, H12, H13).

R = p-NO2, 4-(9-Nitro-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-5-yl)-1-butanol (3g).

A mixture of 4-nitroaniline (0.14 g, 1 mmol), DHP (0.188 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 14 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.159 g, 52%) as oil. Rf ( 23% ethyl acetate: n-hexane).

Compound 3g (exo/endo isomers): IR (KBr, cm-1): 3409, 2949, 2860, 1600, 1515, 1430, 1320, 1280, 807, 757. 13C NMR (300MHz, CDCl3): δ 151.7, 136.6, 124.2, 120.7, 119.1, 114.2, 77.8, 66.8, 62.9, 55.2, 47.7, 33.2, 23.3, 21.2. MS(m/z): 306.16

Compound 3g: endo-isomer 1H NMR (300MHz, CDCl3): δ 7.35 (d, J = 1.7 Hz, 1H, Ar-H), 7 (dd, J = 7.8, 1.7 Hz, 1H, Ar-H), 6.47 (d, J = 7.8 Hz, 1H, Ar-H), 5.1 (d, J = 5.2 Hz, 1H, H5), 3.69 (t, J = 6.1 Hz, 2H), 3.52-3.64 (m, 2H), 3.33 (m, 1H), 2.01 ( m, 1H, H6), 1.32-1.70 (m, 10H, H8, H9, H10, H12, H13).

Compound 3g: exo-isomer 1H NMR (300MHz, CDCl3): δ 7.20 (d, J = 1.7 Hz, 1H, Ar-H), 7 (dd, J = 8, 1.7 Hz, 1H, Ar-H), 6.52 (d, J = 8 Hz, 1H, Ar-H), 4.5 (d, J = 3.7 Hz, 1H, H5), 3.59 (m, 3H), 3.83 (m, 1H), 3.52 (m, 1H), 1.89 (m, 1H, H6), 1.32-1.70 (m, 10H, H8, H9, H10, H12, H13).

R = o-Cl, 4-(7-Chloro-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-5-yl)-1-butanol (3h).

A mixture of 2-chloroaniline (0.128 g, 1 mmol), DHP (0.188 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 11.5 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.236 g, 80%) as oil. Rf ( 23% ethyl acetate: n-hexane).

Compound 3h (exo/endo isomers): IR (KBr, cm-1): 3356, 2937.11, 2878, 1611, 1511, 1465, 1366, 1204, 1073, 854, 744. 13C NMR (300MHz, CDCl3): δ 143.7, 127.1, 122.2, 121.2, 118.4, 78.3, 66.8, 62.9, 54.7, 47.7, 33.3, 23.2, 21.2. MS(m/z): 295.13

Compound 3h: endo-isomer 1H NMR: (300MHz, CDCl3): δ 6.7 (d, J = 7.5 Hz, 1H, Ar-H), 6.58 (d, J = 7.5 Hz, 1H, Ar-H), 6.33 (t, J = 7.6 Hz, 1H, Ar-H), 4.9 (d, J = 5.3 Hz, 1H, H5), 3.56 (t, J = 6.5 Hz, 2H), 3.38-3.42 (m, 2H), 3.30 (m, 1H), 2 (m, 1H, H6), 1.27-1.7 (m, 10H, H8, H9, H10, H12, H13).

Compound 3h: exo-isomer 1H NMR (300MHz, CDCl3): δ 7.65 (d, J = 7.5 Hz, 1H, Ar-H), 6.54 (d, J = 7.5 Hz, 1H, Ar-H), 6.3 (t, J = 7.6 Hz, 1H, Ar-H), 4.33 (d, J = 2.45 Hz, 1H, H5), 3.72 (m, 1H), 3.4 (m, 3H), 3.32 (m, 1H), 1.8 (m, 1H ,H6), 1.27-1.7 (m, 10H, H8, H9, H10, H12, H13).

R = o,p-DiMe, 4-(7,9-dimethyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-5-yl)-1-butanol (3i)

A mixture of 2,4-dimethylaniline (0.122 g, 1 mmol), DHP (0.188 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 4 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.245 g, 85%) as oil. Rf ( 23% ethyl acetate: n-hexane).

Compound 3i (exo/endo isomers): IR (KBr, cm-1): 3390.3, 2932.78, 2854.42, 1587.90, 1507.22, 1468.06, 1360.22, 12130, 1077.60, 860.9, 769. 13C NMR (300MHz, CDCl3): δ 141.3, 128.9, 127.8, 125.9, 119.6, 79.4, 66.8, 62.9, 55.5, 47.7, 33.2, 24.9, 23.3, 21.2, 16.1. MS(m/z): 289.2

Compound 3i: endo-isomer 1H NMR (300MHz, CDCl3): δ 6.84 (d, J = 2.2 Hz, 1H, Ar-H), 6.45 (d, J = 2.2 Hz, 1H, Ar-H), 4.98 (d, J = 5/7 Hz, 1H, H5), 3.61-3.65 (m, 4H), 3.35 (m, 1H ), 2.3 (s, 6H), 2.09 (m, 1H, H6), 1.4-1.79 (m, 10H, H8, H9, H10, H12, H13).

Compound 3i: exo-isomer 1H NMR (300MHz, CDCl3): δ 6.87 (d, J = 2.2 Hz, 1H, Ar-H), 6.46 (d, J = 2.16 Hz, 1H, Ar-H), 4.4 (d, J = 2.33 Hz, 1H, H5), 3.98 (m, 1H), 3.75 (m, 3H), 3.54 (m, 1H), 2.2 (s, 6H), 1.95 (m, 1H ,H6), 1.4-1.79 (m, 10H, H8, H9, H10, H12, H13).

R = 7,8-Dibenz, 4-(2,3,4a,11,12,12a-hexahydro-1H-benzo [h] pyrano[3,2-c]quinolin-12-yl)-1-butanol (3j).

A mixture of 1-naphthylamine (0.145 g, 1 mmol), DHP (0.188 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 6 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.250 g, 80%) as oil. Rf ( 23% ethyl acetate: n-hexane).

Compound 3j (exo/endo isomers): IR (KBr, cm-1): 3396, 2934, 2861, 1575, 1521, 1469, 1212, 1079, 1032, 807, 759. 13C NMR (300MHz, CDCl3): δ 1407, 132.3, 128.1, 124.8, 120.4, 118.2, 79.2, 66.8, 62.9, 55.6, 47.7, 33.2, 24.3, 21.2. MS(m/z): 311.19

Compound 3j: endo-isomer, 1H NMR (300 MHz, CDCl3): δ 7.70 (m, 2H, H3 and H2), 7.48 (d, J = 8.0 Hz, 1H, H5), 7.38 (m, 2H, H1 and H4), 7.22 (d, J = 8.0 Hz, 1H, H6), 5.20 (d, J = 5.6 Hz, 1H, H7), 3.70 (m, 2H, H11 and H11′), 3.60 (m, 1H, H14), 3.42 (m, 1H, H14′), 3.32 (m, 1H, H6), 2.08 (m, 1H, H8), 1.70-1.32 (m, 10H).

Compound 3j: exo-isomer 1H NMR (300MHz, CDCl3): δ 7.65 (m, 2H, Ar-H), 7.4 (d, J = 8 Hz, 1H, Ar-H), 7.29 (m, 2H, Ar-H), 6.98 (d, J = 8 Hz, 1H, Ar-H), 4.29 (d, J = 2.5 Hz, 1H, H5), 3.65 (m, 1H), 3.5 (m, 3H), 3.35 (m, 1H), 1.9 (m, 1H, H6), 1.3-1.72 (m, 10H).

R = H, 3-(2,3,3a,4,5,9b-hexahydrofuro[3,2-c]quinolin-4-yl)-1-propanol (4a).

A mixture of aniline (0.093 g, 1 mmol), THF (0.155 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 3.5 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.205 g, 88%) as oil. Rf ( 32% ethyl acetate: n-hexane).

Compound 4a (exo/endo isomers): IR (KBr, cm-1): 3336, 2932, 2865, 1610, 1500, 1314, 1063, 822,749. 13C NMR (300MHz, CDCl3): 24.22, 29.21, 30.93, 42.69, 52.68, 62.52, 66.81, 76.02, 114.86, 118.94, 122.84, 128.55, 130.25, 145.24. MS(m/z): 233.14

Compound 4a: endo-isomer 1H NMR: (300MHz, CDCl3): δ 7.18 (d, J = 7.8 Hz, 1H, Ar-H), 7.05 (m, 1H, Ar-H), 6.76 (m, 1H, Ar-H), 6.30 (d, J = 8 Hz, 1H, Ar-H), 5.08 (d, J = 8 Hz, 1H), 3.74 (m, 2H), 3.66 (m, 2H), 3.45 (m,1H), 2.61 (m,1H), 2.03-2.0 (m,1H), 1.56-1.88 (m, 5H).

Compound 4a: exo-isomer 1H NMR (300MHz, CDCl3): δ 7.30 (d, J = 7.7, 1H, Ar-H), 7.10 (m, 1H, Ar-H), 6.75 (m, 1H, Ar-H), 6.62(d, J = 8 Hz, 1H, Ar-H), 4.52 (d, J = 5.6 Hz, 1H), 3.85 (m,1H), 3.80 (m, 2H), 3.70 (m, 2H), 2.80 (m, 1H), 2.17-2.19 (m, 1H), 1.54-1.90 (m, 5H).

R = ρ-OCH3, 3-(8-methoxy-2,3,3a,4,5,9b-hexahydrofuro[3,2-c]quinolin-4-yl)-1-propanol (4b).

A mixture of 4-methoxyaniline (0.123 g, 1 mmol), THF (0.155 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 2.75 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.236 g, 90%) as oil. Rf (32% ethyl acetate: n-hexane).

Compound 4b (exo/endo isomers): IR (KBr, cm-1): 3335.61, 2934.01, 2860.12, 1618.30, 1504.91, 1304, 1059.1, 830, 755. 13C NMR (300MHz, CDCl3): δ 24.10, 29.25, 30.97, 42.67, 53.09, 55.90, 62.43, 66.90, 76.24, 114.05, 115.76, 116.18, 123.72, 139.31, 152.90. MS(m/z): 263.15

Compound 4b: endo-isomer 1H NMR (300MHz, CDCl3): δ 6.80 (d, J = 2.5 Hz, 1H, Ar-H), 6.63 (dd, J = 8.4, 2.5 Hz, 1H, Ar-H), 6.55 (d, J = 8.4 Hz, 1H, Ar-H), 5.05 (d, J = 7.9 Hz, 1H), 3.81 (m, 2H), 3.76 (s, 3H), 3.70 (m, 2H), 3.38 (m, 1H), 2.63 (m, 1H), 2.03 -2.04 (m, 1H), 1.50-1.92 (m, 5H).

Compound 4b: exo-isomer 1H NMR: (300MHz, CDCl3): δ 6.9 (d, J = 2.7 Hz, 1H, Ar-H), 6.78 (dd, J= 8.3, 2.5 Hz, 1H, Ar-H), 6.54 (d, J = 8.3 Hz, 1H, Ar-H), 4.5 (d, J = 5.3 Hz, 1H), 3.92 (m, 1H), 3.79 (s, 3H), 3.73 (m, 2H), 3.60 (m, 2H), 2.76 (m, 1H), 2.20-2.22 (m, 1H), 1.50-1.92 (m, 5H).

R = ρ-CH3, 3-(8-methyl-2,3,3a,4,5,9b-hexahydrofuro[3,2-c]quinolin-4-yl)-1-propanol (4c).

A mixture of 4-methylaniline (0.109 g, 1 mmol), THF (0.155 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 2.75 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.215 g, 87%) as oil. Rf ( 32% ethyl acetate: n-hexane).

Compound 4c (exo/endo isomers): IR (KBr, cm-1): 3342, 2935, 2853, 1620, 1499, 1307, 1060, 814, 714. 13C NMR (300MHz, CDCl3): δ 20.73, 28.86, 29.45, 30.17, 41.65, 52.55, 62.65, 65.87, 76.14, 115.24, 120.74, 127.74, 129.81, 131.33, 142.77. MS(m/z): 247.16.

Compound 4c: endo-isomer 1H NMR (300MHz, CDCl3): δ 7.1 (d, J = 2.2 Hz, 1H, Ar-H), 6.88 (dd, J = 8.0, 2.01 Hz, 1H, Ar-H), 6.49 (d, J = 8.0 Hz, 1H, Ar-H), 5.08 (d, J = 7.6 Hz, 1H), 3.80 (m, 2H), 3.75 (m, 2H), 3.46 (m, 1H), 2.59 (m, 1H), 2.22 (s, 3H), 2.02-2.04 (m, 1H), 1.55-1.92 (m, 5H).

Compound 4c: exo-isomer 1H NMR (300MHz, CDCl3): δ 7.18 (d, J = 2.18 Hz, 1H, Ar-H), 6.90 (dd, J = 8.4, 2.3 Hz, 1H, Ar-H), 6.59 (d, J = 8.4 Hz, 1H, Ar-H), 4.52 (d, J = 5.6 Hz, 1H), 3.95 (m, 1H), 3.76 (m, 2H), 3.70 (m, 2H), 2.78 (m, 1H), 2.20 (s, 3H), 2.16-2.19 (m, 1H), 1.55-1.9 (m, 5H).

R = ρ-OH, 3-(8-Hydroxy-2,3,3a,4,5,9b-hexahydrofuro[3,2-c]quinolin-4-yl)-1-propanol (4d).

A mixture of 4-hydroxyaniline (0.11 g, 1 mmol), THF (0.155 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 2.75 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.209 g, 84%) as oil. Rf ( 32% ethyl acetate: n-hexane).

Compound 4d (exo/endo isomers): IR (KBr, cm-1): 3342, 2937, 2850, 1619, 1500, 1310, 1055, 820, 750. 13C NMR (300MHz, DMSO): δ 29.08, 29.41, 30.31, 41.74, 52.81, 61.70, 65.46, 76.81, 116.53, 116.88, 121.61, 148.94. MS(m/z): 249.14

Compound 4d: endo-isomer 1H NMR (300MHz, DMSO): δ 6.50 (d, J = 2.4 Hz, 1H, Ar-H), 6.43 (dd, J = 8.01, 2.4 Hz, 1H, Ar-H), 6.39 (d, J = 8.01 Hz, 1H, Ar-H), 4.9 (d, J = 7.88 Hz, 1H), 3.80 (m, 2H), 3.65 (m, 2H), 3.45 (m, 1H), 2.8 (m,1H), 2.10-2.12 (m, 1H), 1.60-1.95 (m, 5H).

Compound 4d: exo-isomer 1H NMR: (300MHz, DMSO): δ 6.60 (d, J = 2.34 Hz, 1H, Ar-H), 6.48 (dd, J = 8.1, 2.4 Hz, 1H, Ar-H), 6.39 (d, J = 8.1 Hz, 1H, Ar-H), 4.39 (d, J = 5.9 Hz, 1H), 3.91 (m, 1H), 3.78 (m, 2H), 3.72 (m, 2H), 2.80 (m, 1H), 2.22-2.25 (m, 1H), 1.45-1.85 (m, 5H).

R = ρ-Cl, 3-(8-Chloro-2,3,3a,4,5,9b-hexahydrofuro[3,2-c]quinolin-4-yl)-1-propanol (4e).

A mixture of 4-chloroaniline (0.128 g, 1 mmol), THF (0.155 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 9 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.206 g, 77%) as oil. Rf ( 32% ethyl acetate: n-hexane).

Compound 4e (exo/endo isomers): IR (KBr, cm-1): 3356, 2935, 2851, 1620, 1492, 1304, 1069, 812, 755. 13C NMR (300MHz, CDCl3): 24.01, 29.10, 30.88, 42.29, 52.37, 62.39, 66.91, 75.56, 116.02, 122.86, 124.09, 128.39, 129.66, 143.78. MS(m/z): 267.1

Compound 4e: endo-isomer 1H NMR: (300MHz, CDCl3): δ 7.25 (d, J = 2.4 Hz, 1H, Ar-H), 6.98 (dd, J = 8.4, 2.4 Hz, 1H, Ar-H), 6.44 (d, J = 8.4 Hz, 1H, Ar-H), 3.79 (m, 2H), 5.03 (d, J = 8 Hz, 1H), 3.70 (m, 2H), 3.43 (m, 1H), 2.59 (m, 1H), 1.97-2.00 (m, 1H), 1.55-1.90 (m, 5H).

Compound 4e: exo-isomer 1H NMR (300MHz, CDCl3): δ 7.30 (d, J = 2.4 Hz, 1H, Ar-H), 7.03 (dd, J = 8.4, 2.4 Hz, 1H, Ar-H), 6.55 (d, J = 8.4 Hz, 1H, Ar-H), 4.50 (d, J = 5.6 Hz, 1H), 3.93 (m, 1H), 3.79 (m, 2H), 3.70 (m, 2H), 2.79 (m, 1H), 2.18-2.20 (m, 1H), 1.55-1.90 (m, 5H).

R = ρ-Br, 3-(8-Bromo-2,3,3a,4,5,9b-hexahydrofuro[3,2-c]quinolin-4-yl)-1-propanol (4f).

A mixture of 4-bromoaniline (0.175 g, 1 mmol), THF (0.155 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 9 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.234 g, 75%) as oil. Rf ( 32% ethyl acetate: n-hexane).

Compound 4f (exo/endo isomers): IR (KBr, cm-1): 3343, 2936, 2851, 1609, 1489, 1311, 1062, 823, 720. 13C NMR (300MHz, CDCl3): δ 24.03, 29.17, 30.97, 42.38, 52.33, 62.58, 66.90, 75.50, 110.20, 116.36, 124.75, 131.21, 132.66, 144.10. MS(m/z): 311.05

Compound 4f: endo-isomer 1H NMR (300MHz, CDCl3): δ 7.40 (d, J = 2.4 Hz, 1H, Ar-H), 7.12 (dd, J = 8.8, 2.4 Hz, 1H, Ar-H), 6.43 (d, J = 8.75 Hz, 1H, Ar-H), 5.04 (d, J = 7.6 Hz, 1H), 3.80 (m, 2H), 3.73 (m, 2H), 3.44 (m, 1H), 2.61 (m, 1H), 1.99-2.06 (m, 1H), 1.55-1.90 (m, 5H).

Compound 4f: exo-isomer 1H NMR (300MHz, CDCl3): δ 7.47 (d, J = 2.4 Hz, 1H, Ar-H), 7.18 (dd, J = 8.8, 2.4 Hz, 1H, Ar-H), 6.58 (d, J = 8.8 Hz, 1H, Ar-H), 4.53 (d, J = 5.6 Hz, 1H), 3.95 (m, 1H), 3.80 (m, 2H), 3.72 (m, 2H), 2.81 (m, 1H), 2.20-2.22 (m, 1H), 1.55-1.90 (m, 5H).

R = ρ-NO2, 3-(8-Nitro-2,3,3a,4,5,9b-hexahydrofuro[3,2-c] quinolin-4-yl)-1-propanol (4g).

A mixture of 4-nitroaniline (0.14 g, 1 mmol), THF (0.155 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 12 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.153 g, 55%) as oil. Rf ( 32% ethyl acetate: n-hexane).

Compound 4g (exo/endo isomers): IR (KBr, cm-1): 3342, 2935, 2853, 1620, 1499, 1307, 1060, 814, 714. 13C NMR (300MHz, CDCl3): δ 27.8, 29.0, 47.4, 54.9, 62.9, 68.6, 80.2, 114.2, 119.1, 120.7, 124.3, 136.6, 151.7. MS(m/z): 278.13

Compound 4g: endo-isomer 1H NMR: (300MHz, CDCl3): δ 7.12 (d, J = 2.2 Hz, 1H, Ar-H), 6.99 (dd, J = 7.8, 2.2 Hz, 1H, Ar-H), 6.50 (d, J = 8 Hz, 1H, Ar-H), 5.05 (d, J = 7.4 Hz, 1H), 3.79 (m, 2H), 3.75 (m, 2H), 3.47 (m, 1H), 2.55 (m, 1H), 2.02-2.05 (m,1H), 1.50-1.90 (m, 5H).

Compound 4g: exo-isomer 1HNMR (300MHz,CDCl3): δ 7.30 (d, J = 2.3 Hz, 1H, Ar-H), 7.20 (dd, J = 8.4, 2.2 Hz, 1H, Ar-H), 6.59 (d, J = 8.4 Hz, 1H, Ar-H), 4.55 (d, J = 5.6 Hz, 1H), 3.92 (m, 1H), 3.78 (m, 2H), 3.70 (m, 2H), 2.78 (m, 1H), 2.17-2.19 (m, 1H), 1.50-1.90 (m, 5H).

R = ο-Cl, 3-(6-Chloro-2,3,3a,4,5,9b-hexahydrofuro[3,2-c] quinolin-4-yl)-1-propanol (4h).

A mixture of 2-chloroaniline (0.128 g, 1 mmol), THF (0.155 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 8 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.219 g, 82%) as oil. Rf ( 32% ethyl acetate: n-hexane).

Compound 4h (exo/endo isomers): IR (KBr, cm-1): 3427, 2941, 2848, 1594, 1510, 1315, 1075, 867.48, 743.17. 13C NMR (300MHz, CDCl3): δ 27.8, 29.0, 47.4, 54.4, 62.9, 68.6, 80.7, 118.4, 121.2, 122.2, 127.0, 143.7. MS(m/z): 267.1

Compound 4h: endo-isomer 1H NMR (300MHz, CDCl3): δ 7.17 (d, J = 7.8 Hz, 1H), 7.12 (d, J = 7.8 Hz, 1H), 6.65 (t, J = 7.3 Hz, 1H), 5.08 (d, J = 7.0 Hz, 1H), 3.65 (m, 2H), 3.53 (m, 2H), 3.43 (m, 1H), 2.60 (m, 1H), 1.96-2.01 (m, 1H), 1.72-1.86 (m, 5H).

Compound 4h: exo-isomer 1H NMR: (300MHz, CDCl3): δ 7.20 (d, J = 7.9 Hz, 1H), 7.12 (d, J = 7.8 Hz, 1H), 6.59 (t, J = 7.3 Hz, 1H), 4.55 (d, J = 5.25 Hz, 1H), 3.96 (m, 1H), 3.77 (m, 2H), 3.65 (m, 2H), 2.62 (m, 1H), 1.97-2.1 (m, 1H), 1.72-1.86 (m, 5H).

R = o,p-DiMe, 3-(6,8-Dimethyl-2,3,3a,4,5,9b-hexa hydro furo[3,2-c]quinolin-4-yl)-1-propanol (4i).

A mixture of 2,4-dimethylaniline (0.122 g, 1 mmol), THF (0.155 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 3 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.209 g, 80%) as oil. Rf ( 32% ethyl acetate: n-hexane).

Compound 4i (exo/endo isomers): IR (KBr, cm-1): 3418, 2933, 2857, 1588, 1505, 1309, 1058, 865, 794. 13C NMR (300MHz, CDCl3): δ 16.1, 24.9, 27.8, 29.0, 47.4, 55.2, 62.9, 68.6, 81.8, 119.6, 126.5, 127.8, 128.8, 141.3. MS(m/z): 261.17.

Compound 4i: endo-isomer 1H NMR: (300MHz, CDCl3): δ 7.82 (d, J = 2.1 Hz, 1H, Ar-H), 6.54 (d, J = 2.1 Hz, 1H, Ar-H), 5.26 (d, J = 8.1 Hz, 1H), 3.90 (m, 2H), 3.80 (m, 2H), 3.32 (m, 1H), 2.60 (m, 1H), 2.25 (s, 6H), 1.98-2.02 (m, 1H), 1.60-1.92 (m, 5H).

Compound 4i: exo-isomer 1H NMR (300MHz,CDCl3): δ 7.81 (d, J = 2.1 Hz, 1H, Ar-H), 6.54 (d, J = 2.1 Hz, 1H, Ar-H), 4.57 (d, J = 5.02 Hz, 1H), 3.98 (m, 1H), 3.74 (m, 2H), 3.69 (m, 2H), 2.60 (m, 1H), 2.25 (s, 6H), 1.98-2.02 (m, 1H), 1.60-1.92 (m, 5H).

R= 7,8-Dibenz, 3-(2,3,3a,10,11-hexahydro-1H- benzo[h] furano[3,2-c]quinolin-11-yl)-1-propanol (4j).

A mixture of 1-naphthylamine (0.145 g, 1 mmol), THF (0.155 g, 2.2 mmol) and Fe(ClO4)3/SiO2 (0.2 g) without solvent was stirred at ambient temperature or at 50 °C for 6 h. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane; 2:3). Upon completion of the reaction, dichloromethane (15 × 2 ml) was added and Fe(ClO4)3/SiO2 was filtered off. After drying of organic phase (Na2SO4), and evaporation of the solvent, the crude product was afforded which was directly subjected to thin layer chromatography. The product was as a mixture of endo/exo isomers (0.229 g, 81%) as oil. Rf ( 32% ethyl acetate: n-hexane).

Compound 4j (exo/endo isomers): IR (KBr, cm-1): 3347, 2936.21, 2860.12, 1618.30, 1509.87, 1312, 1070.1, 845, 735. 13C NMR (300MHz, CDCl3): δ 29.23, 29.39, 30.18, 40.98, 52.54, 62.70, 65.71, 114.21, 76.73, 117.77, 120.66, 123.26, 125.14, 126.25, 127.74, 128.75, 134.29, 140.40. MS(m/z): 297.17.

Compound 4j: endo-isomer 1H NMR (300MHz, CDCl3): δ 7.76 (m, 4H, Ar-H), 7.44 (m, 2H, Ar-H), 5.15 (d, J = 7.6 Hz, 1H), 3.80 (m, 2H), 3.77 (m, 2H), 3.55 (m, 1H), 2.70 (m, 1H), 2.10-2.12 (m, 1H), 1.70-1.95 (m, 5H).

Compound 4j: exo-isomer 1H NMR (300MHz, CDCl3): δ 7.81 (m, 2H, Ar-H), 7.43 (m, 4H, Ar-H), 4.68 (d, J = 5.2, 1H), 4.01 (m, 1H), 3.77 (m, 2H), 3.70 (m, 2H), 2.9 (m, 1H), 2.20-2.23 (m, 1H), 1.70-1.95 (m, 5H).