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还原胺化2


PAPER

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Fast and Efficient Synthesis of Pyrano[3,2-c]quinolines Catalyzed by Niobium(V) Chloride
SLuiz Carlos da Silva-Filho,a,b Valdemar Lacerda Júnior,a,c Maur

icio Gomes Constantino,*a Gil Valdo José da Silvaa ynthesi ofPyrano[3,2-c]quinolines
Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeir?o Preto, Universidade de S?o Paulo, Av. Bandeirantes 3900, 14040-901 Ribeir?o Preto, SP, Brazil Fax +55(16)36338151; E-mail: mgconsta@usp.br b Centro de Estudos de Insetos Sociais, Instituto de Biociências, Universidade Estadual Paulista, Av. 24A, n? 1515, 13506-900 Rio Claro, SP, Brazil c Departamento de Química, Centro de Ciências Exatas, Universidade Federal do Espirito Santo, Av. Fernando Ferrari 514, 29060-900 Vitória, ES, Brazil Received 10 March 2008; revised 14 April 2008
a

Key words: Diels–Alder reactions, Lewis acids, catalysis, quinolines, Schiff bases

Table 1
1R

Preparation of Aldimines 3a–p
1

Starting R1 aldehyde 1a 1b 1c 1d 1e 1f 1g 1h 1i 1j 1k 1l 1m 1n 1o 1p H H H Me Me H NO2 H H H H Cl H H

R2 H H Me H H NO2 H

R3 H Me H H Me H H

R4 H H H H H H H H H H H H

R5 H H H H Me H H NO2 H H H H Me H H

Time Aldimine Yield (h) (%) 72 72 72 72 72 96 96 120 120 72 72 72 96 96 96 120 3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 3k 3l 3m 3n 3o 3p 98 95 98 96 94 92 90 93 94 96 97 96 93 95 91 90

Generally, Lewis acids11–14 are employed to catalyze such reactions (there are also one-pot versions).15–18 However, several Lewis acids are deactivated or decomposed by nitrogen-containing substrates.19 Some of the Lewis acids are not easily available or are expensive, require longer reaction times, and form the products with poor yields. Therefore, developing simple and efficient synthetic methods for the preparation of this type of compound becomes more and more important. Niobium(V) chloride, a low-cost and commercially available reagent, has been used by our group and other researchers as an effective catalyst for synthetic methodologies in a variety of reactions.20–32 In the present report a highly efficient two-step method for the synthesis of pyranoquinolines using niobium(V) chloride as catalyst is described.

OCH2O OCH2O H Cl H H Cl H H

OMe H H H

OMe H H

OMe H H

OMe OMe OMe H

SYNTHESIS 2008, No. 16, pp 2527–2536xx. 208 Advanced online publication: 24.07.2008 DOI: 10.1055/s-2008-1067186; Art ID: M01408SS ? Georg Thieme Verlag Stuttgart · New York

2R

3R

4R

p–a3

5R

N

d 5–3 ,.t.r

HOtE

2HN

2

+

H

5

R

p–a1

4R

2R

3

R

Pyranoquinoline derivatives are an important class of natural products that are present in many alkaloids.1,2 They exhibit a wide spectrum of biological activity in various fields,3–6 such as psychotropic, antiallergenic, anti-inflammatory, and estrogenic activity. In addition, these derivatives are also found to posses a vast range of pharmacological activities.7 It is therefore not surprising that many synthetic methods have been developed for these compounds.8–11 Among the various methods, the imino-Diels–Alder reaction between N-arylimines and nucleophilic alkenes is probably one of the most powerful synthetic tools for the construction of nitrogen-containing six-membered heterocyclic compounds.

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Abstract: A highly efficient two-step method for the synthesis of pyranoquinoline derivatives from imino-Diels–Alder reactions between aldimines and 3,4-dihydro-2H-pyran using niobium(V) chloride as catalyst under mild conditions is described.

For the proposed studies, aldimines 3a–p were prepared in good yields by treatment of the respective aromatic aldehydes 1a–p with aniline (2) at room temperature (Table 1).

R

O

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L. C. da Silva-Filho et al.

PAPER

R1 N R
5

H R2 + R
3

O H N H R5 R
4

H R1 R
2

O H R1 R2 R3 R – exo p a6
4

O

NbCl5 (0.5, 0.25, or 0.125 equiv) MeCN, r.t.

+

N H R5

R4 –

R3

– endo

Scheme 1 Synthesis of pyranoquinoline derivatives from the imino-Diels–Alder reaction between aldimines 3a–p and 3,4-dihydro-2H-pyran (4) catalyzed by niobium(V) chloride Table 2 Niobium(V) Chloride Catalyzed Synthesis of Pyranoquinoline Derivatives 5a–p (endo) and 6a–p (exo) Aldimine NbCl5 (equiv) 3a 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 Time (min) 1 5 15 1 5 15 1 5 15 1 10 15 30 80 150 1 5 10 5 20 50 30 100 190 15 60 150 1 5 15 1 5 15 1 5 15 5 25 75 Yield (%) 92 89 90 90 90 84 85 85 81 85 87 84 80 81 75 85 82 82 79 77 74 88 85 84 75 72 73 89 90 86 87 87 85 83 84 80 87 81 78 Ratio 5a–p/6a–p (endo/exo) 44:56 44:56 33:67 44:56 39:41 22:78 31:69 31:69 22:78 31:69 28:72 13:87 0:100 0:100 0:100 49:51 48:52 43:57 50:50 48:52 30:70 41:59 41:59 40:60 46:54 34:66 18:82 40:60 42:58 34:66 42:58 42:58 35:65 40:60 44:56 35:65 40:60 19:81 0:100 Table 2 Niobium(V) Chloride Catalyzed Synthesis of Pyranoquinoline Derivatives 5a–p (endo) and 6a–p (exo) (continued) Aldimine NbCl5 (equiv) 3n 0.500 0.250 0.125 0.500 0.250 0.125 0.500 0.250 0.125 Time (min) 5 35 100 10 50 180 15 50 190 Yield (%) 88 86 83 70 67 68 79 80 76 Ratio 5a–p/6a–p (endo/exo) 41:59 37:63 26:74 36:64 26:74 23:77 35:65 20:80 07:93

3b

3o

3c

3p

3d

3e

3f

Imino-Diels–Alder reactions between aldimines 3a–p and 3,4-dihydro-2H-pyran (4) in the presence of niobium(V) chloride in acetonitrile at room temperature afforded the corresponding pyranoquinoline derivatives 5a–p and 6a– p in high yields. In most of the cases, a mixture of endoisomers 5 and exo-isomers 6 were obtained (Scheme 1, Table 2). All products were isolated and characterized by spectroscopic and spectrometric methods (1H NMR, 13C NMR, IR, and mass spectra). The product ratios were determined by 1H NMR analysis of the crude product. The relative stereochemistry of the Diels–Alder adducts was determined using the 1H–1H scalar coupling constant values between H1 and H2 (J1,2) and comparison with literature data. Adducts 5a–p (endo), show smaller coupling constants J1,2 (5.5–5.7 Hz), typical for a gauche conformation. This is consistent with an orientation where the pyran ring and the phenyl group are on the same side (Figure 1). In adducts 6a–p (exo), the coupling constants are significantly higher, J1,2 between 8.1 and 11.1 Hz, indicative of the anti orientation of H1/H2, which is only possible when the pyran ring and the phenyl group are on opposite sides of the quinoline ring. As can be observed from Table 2, in all cases the reactions proceed smoothly to give the pyranoquinoline derivatives, which could be separated by column chromatography. Substitution on the aromatic ring has a remarkable influence on reactivity: methylated 3e or oxygenated 3p aldimines, for example, are less reactive. The use of a lower molar ratio of niobium(V) chloride leads to an enhancement of diastereoselectivity, although the required reaction times are longer.

3g

3h

3i

3j

3k

3l

3m

Synthesis 2008, No. 16, 2527–2536

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p a5

4

p a3

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Synthesis of Pyrano[3,2-c]quinolines

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specified, all reagents were purchased from commercial sources and were used without further purification. N-[(E)-Arylmethylene]anilines 3a–p; General Procedure35 Aniline (2, 2 mmol) and the appropriate aromatic aldehyde (2 mmol) were dissolved together in EtOH (10 mL) and left to stand overnight at r.t. The solvent was removed under vacuum, and the products were dissolved in EtOH (10 mL) and left to stand at r.t. for the time shown in Table 1. The yields were 90–98%. N-[(E)-Phenylmethylene]aniline (3a)36 IR (film): 3028, 2863, 1700, 1627, 1484, 1191, 873, 767 cm–1.
1 H NMR (400 MHz, CDCl3): d = 8.44 (s, 1 H), 7.87–7.93 (m, 2 H), 7.44–7.49 (m, 3 H), 7.36–7.42 (m, 2 H), 7.19–7.20 (m, 3 H).

Figure 1 Coupling constant values used for determining stereochemistry

N-[(E)-(4-Methylphenyl)methylene]aniline (3b)36 IR (film): 3039, 2869, 1623, 1484, 1173, 815, 753 cm–1.
1 H NMR (400 MHz, CDCl3): d = 8.40 (s, 1 H), 7.79 (d, J = 8.1 Hz, 2 H), 7.34–7.40 (m, 2 H), 7.26 (d, J = 8.1 Hz, 2 H), 7.18–7.23 (m, 3 H), 2.40 (s, 3 H). 13 C NMR (100 MHz, CDCl3): d = 160.3 (CH), 152.2 (C), 141.8 (C), 133.7 (C), 129.5 (CH), 129.1 (CH), 128.8 (CH), 125.7 (CH), 120.9 (CH), 21.6 (CH3).

Table 3 Comparison of Imino Diels–Alder Reactions of Aldimine 3a with 3,4-Dihydro-2H-pyran Catalyzed by Various Lewis Acids Lewis acid NbCl5 InCl313 LiBF433 K10/Fe3+ 34 Time (min) 1 30 120 1020 Yield (%) 92 80 88 86 Ratio endo/exo 44:56 41:59 15:85 42:58

MS: m/z = 195 (M)+, 180, 152, 116, 104, 91, 77, 65, 51. N-[(E)-(3-Methylphenyl)methylene]aniline (3c)37 IR (film): 3036, 2863, 1627, 1603, 1487, 1205, 1148, 786 cm–1. H NMR (400 MHz, CDCl3): d = 8.36 (s, 1 H), 7.62 (s, 1 H), 7.63 (d, J = 7.5 Hz, 1 H), 7.33–7.39 (m, 2 H), 7.31 (t, J = 7.5 Hz, 1 H), 7.24 (d, J = 7.5 Hz, 1 H), 7.15–7.22 (m, 3 H), 2.37 (s, 3 H). C NMR (100 MHz, CDCl3): d = 160.6 (CH), 152.1 (C), 138.4 (C), 136.1 (C), 132.2 (CH), 129.1 (CH), 129.0 (CH), 128.6 (CH), 126.4 (CH), 125.8 (CH), 120.8 (CH), 21.2 (CH3). MS: m/z = 195 (M)+, 180, 152, 116, 104, 91, 77, 65, 51 N-[(E)-(2-Methylphenyl)methylene]aniline (3d)38 IR (film): 3027, 2908, 1734, 1623, 1491, 1201, 763 cm–1. H NMR (400 MHz, CDCl3): d = 8.74 (s, 1 H), 8.08 (dd, J1 = 7.5 Hz, J2 = 1.1 Hz, 1 H), 7.18–7.42 (m, 8 H), 2.58 (s, 3 H).
13 C NMR (100 MHz, CDCl3): d = 159.0 (CH), 152.6 (C), 138.5 (C), 134.1 (C), 131.0 (CH), 129.1 (CH), 127.8 (CH), 126.3 (CH), 120.9 (CH), 19.3 (CH3). 1 13 1

In summary, this paper describes an efficient two-step method for the synthesis of pyranoquinoline derivatives from imino Diels–Alder reactions between aldimines and 3,4-dihydro-2H-pyran (4) using niobium(V) chloride as a catalyst. As compared to other Lewis acids (e.g., InCl3),13 niobium(V) chloride is more effective, requiring shorter reaction times, giving in most cases better yields and good diastereoselectivity, especially with lower molar concentrations of niobium(V) chloride. These notable features make this procedure an useful and attractive process for the synthesis of fused pyrano[3,2-c]quinolines of biological importance.
NMR spectra were measured using a Bruker DRX 400 instrument [400 MHz for 1H NMR and 100 MHz for the 13C NMR (proton decoupled)] using CDCl3 as solvent and TMS as internal standard. IR spectra were measured with a Perkin Elmer Spectrum RX IFTIR System, and the most intense or representative bands are reported. EI-MS (70 eV) used a HP 5988-A spectrometer with fused silica capillary GC columns: HP-1 (25 m × 0.2 mm i.d. × 0.33 mm phase thickness), column temperature was 100 °C (3 min) ramped to 220 °C at 20 °C min–1. Mass spectral analyses of new compounds were performed on a high-resolution q-TOF. ESI-MS were acquired on a UltrOTOF apparatus (Bruker Daltonics, Billerica, MA, USA), with flux 150 mL/h in MeCN, in positive mode. Column chromatography was performed with silica gel (60–230 mesh, Acros). Except where

MS: m/z = 195 (M)+, 178, 152, 115, 104, 91, 77, 65, 51 N-[(E)-Mesitylmethylene]aniline (3e)39 IR (film): 2953, 2917, 1588, 1450, 1194, 969, 853, 758 cm–1. H NMR (400 MHz, CDCl3): d = 8.75 (s, 1 H), 7.35–7.41 (m, 2 H), 7.14–7.23 (m, 3 H), 6.90 (s, 2 H), 2.51 (s, 6 H), 2.29 (s, 3 H).
13 C NMR (100 MHz, CDCl3): d = 160.8 (CH), 153.1 (C), 139.8 (C), 138.6 (C), 130.5 (C), 129.7 (CH), 129.1 (CH), 125.5 (CH), 120.7 (CH), 21.2 (CH3), 21.0 (CH3). 1

MS: m/z = 223 (M)+, 206, 140, 131, 115, 103, 91, 77, 65, 51. N-[(E)-(3-Nitrophenyl)methylene]aniline (3f)39 IR (film): 3075, 2880, 2355, 1528, 1352, 1191, 814, 764 cm–1.

Synthesis 2008, No. 16, 2527–2536

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A remarkable aspect of this work is the higher efficiency of niobium(V) chloride, as compared to other Lewis acid catalysts. The strong activation of the aldimine system exerted by niobium(V) chloride is demonstrated by the shorter reaction times required. Table 3 shows some examples comparing our results for aldimine 3a with literature data using other Lewis acids.

zH 8.2–3.2 :eulav 6,2J zH 1.11–1.8 :eulav 2,1J H
2

p–a6

HH N

1

6

O

H

zH 7.5–5.5 :eulav 2,1J

zH 5.2–0.2 :eulav 6,2J H
2 1

p–a5

HH N

6

O

H

C NMR (100 MHz, CDCl3): d = 160.4 (CH), 151.9 (C), 136.1 (C), 131.4 (CH), 129.1 (CH), 128.8 (CH), 128.7 (CH), 125.9 (CH), 120.9 (CH). MS: m/z (%) = 181 (M)+, 152, 149, 104, 89, 77, 63, 51.

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N-[(E)-(2-Chlorophenyl)methylene]aniline (3l)43 IR (film): 3056, 2926, 1616, 1565, 1487, 1442, 1272, 1190, 1052, 763 cm–1.
1 H NMR (400 MHz, CDCl3): d = 8.90 (s, 1 H), 8.23 (dd, J1 = 7.6 Hz, J2 = 2.5 Hz, 1 H), 7.30–7.42 (m, 5 H), 7.21–7.27 (m, 3 H).

H NMR (400 MHz, CDCl3): d = 8.62 (s, 1 H), 8.41 (s, 1 H), 8.20 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 8.14 (d, J = 8.1 Hz, 1 H), 7.54 (t, J = 8.1 Hz, 1 H), 7.33–7.40 (m, 2 H), 7.17–7.26 (m, 3 H).

13 C NMR (100 MHz, CDCl3): d = 157.1 (CH), 150.7 (C), 148.5 (C), 137.7 (C), 134.1 (CH), 129.7 (CH), 129.2 (CH), 126.8 (CH), 125.4 (CH), 123.1 (CH), 120.9 (CH).

MS: m/z = 227 (M) , 179, 152, 104, 77, 63, 51. N-[(E)-(2-Nitrophenyl)methylene]aniline (3g)40 IR (film): 3048, 2910, 2365, 1522, 1346, 1190, 858, 767 cm–1.
1 H NMR (400 MHz, CDCl3): d = 8.93 (s, 1 H), 8.30 (dd, J1 = 7.6 Hz, J2 = 1.3 Hz, 1 H), 8.06 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 7.72 (t, J = 7.6 Hz, 1 H), 7.60 (ddd, J1 = 8.1, J2 = 7.6 Hz, J3 = 1.3 Hz, 1 H), 7.39–7.44 (m, 2 H), 7.25–7.31 (m, 3 H).

+

C NMR (100 MHz, CDCl3): d = 156.8 (CH), 151.8 (C), 136.0 (C), 133.2 (C), 132.1 (CH), 129.9 (CH), 129.2 (CH), 128.5 (CH), 127.1 (CH), 126.3 (CH), 121.0 (CH). MS: m/z = 217 (M + 2)+, 215 (M)+, 180, 152, 112, 104, 89, 77, 63, 51. N-[(E)-(4-Methoxyphenyl)methylene]aniline (3m)36 IR (film): 3056, 2968, 2849, 1569, 1506, 1248, 1165, 1022, 843, 764 cm–1. H NMR (400 MHz, CDCl3): d = 8.37 (s, 1 H), 7.84 (d, J = 8.8 Hz, 2 H), 7.34–7.40 (m, 2 H), 7.19 (d, J = 8.8 Hz, 2 H), 6.95–7.01 (m, 3 H), 3.85 (s, 3 H).
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13 C NMR (100 MHz, CDCl3): d = 162.3 (C), 159.8 (CH), 152.2 (C), 130.6 (CH), 129.1 (CH), 125.6 (CH), 120.9 (CH), 114.3 (C), 114.2 (CH), 55.4 (OCH3). 1

13

C NMR (100 MHz, CDCl3): d = 155.8 (CH), 151.1 (C), 149.3 (C), 133.6 (CH), 131.2 (CH), 131.1 (C), 129.7 (CH), 129.3 (CH), 126.9 (CH), 124.5 (CH), 121.2 (CH). MS: m/z = 227 (M)+, 209, 195, 179, 167, 152, 77, 51. N-[(E)-(6-Nitro-1,3-benzodioxol-5-yl)methylene]aniline (3h)40 IR (film): 3067, 2908, 2354, 1516, 1507, 1326, 1041, 924, 687 cm–1.
1

13

MS: m/z = 211 (M)+, 195, 167, 139, 104, 77, 63, 51. N-[(E)-(3-Methoxyphenyl)methylene]aniline (3n)37 IR (film): 2946, 2834, 1580, 1487, 1268, 1213, 1152, 1041, 844, 787 cm–1. H NMR (400 MHz, CDCl3): d = 8.38 (s, 1 H), 7.51 (dd, J1 = 2.5 Hz, J2 = 1.3 Hz, 1 H), 7.32–7.41 (m, 4 H), 7.17–7.24 (m, 3 H), 7.01 (ddd, J1 = 8.0, J2 = 2.8 Hz, J3 = 1.3 Hz, 1 H), 3.83 (s, 3 H).
13 C NMR (100 MHz, CDCl3): d = 160.2 (CH), 160.0 (C), 151.9 (C), 137.6 (C), 129.7 (CH), 129.1 (CH), 125.9 (CH), 122.3 (CH), 120.9 (CH), 118.3 (CH), 111.9 (CH), 55.3 (OCH3). 1

H NMR (400 MHz, CDCl3): d = 8.92 (s, 1 H), 7.73 (s, 1 H), 7.54 (s, 1 H), 7.39–7.44 (m, 2 H), 7.25–7.30 (m, 3 H), 6.18 (s, 2 H).

C NMR (100 MHz, CDCl3): d = 155.7 (CH), 152.1 (C), 150.9 (C), 149.7 (C), 144.6 (C), 129.3 (CH), 128.3 (CH), 126.8 (CH), 121.2 (CH), 107.8 (CH), 105.1 (CH), 103.4 (CH2). MS: m/z = 271 (M) , 253, 222, 167, 139, 93, 77, 51. N-[(E)-1,3-Benzodioxol-5-ylmethylene]aniline (3i)41 IR (film): 2879, 1584, 1436, 1264, 1042, 936, 767 cm–1. H NMR (400 MHz, CDCl3): d = 8.32 (s, 1 H), 7.53 (d, J = 1.5 Hz, 1 H), 7.35–7.41 (m, 2 H), 7.27 (dd, J1 = 7.8 Hz, J2 = 1.5 Hz, 1 H), 7.15–7.23 (m, 3 H), 6.87 (d, J = 7.8 Hz, 1 H), 6.02 (s, 2 H). C NMR (100 MHz, CDCl3): d = 159.4 (CH), 152.6 (C), 149.9 (C), 147.7 (C), 134.1 (C), 129.1 (CH), 125.9 (CH), 125.8 (CH), 120.9 (CH), 108.2 (CH), 106.9 (CH), 101.6 (CH2). MS: m/z = 225 (M)+, 194, 166, 139, 121, 104, 93, 77, 63, 51. N-[(E)-(4-Chlorophenyl)methylene]aniline (3j)36 IR (film): 3056, 2869, 1623, 1490, 1405, 1088, 1013, 763 cm–1. H NMR (400 MHz, CDCl3): d = 8.39 (s, 1 H), 7.82 (d, J = 8.3 Hz, 2 H), 7.43 (d, J = 8.3 Hz, 2 H), 7.35–7.41 (m, 2 H), 7.16–7.27 (m, 3 H). C NMR (100 MHz, CDCl3): d = 158.8 (CH), 151.6 (C), 137.3 (C), 134.7 (C), 129.9 (CH), 129.2 (CH), 129.1 (CH), 126.2 (CH), 120.8 (CH). MS: m/z = 217 (M + 2)+, 215 (M)+, 178, 152, 137, 104, 89, 77, 63, 51. N-[(E)-(3-Chlorophenyl)methylene]aniline (3k)42 IR (film): 3061, 2873, 1623, 1569, 1487, 1188, 1074, 763 cm–1. H NMR (400 MHz, CDCl3): d = 8.27 (s, 1 H), 7.86 (s, 1 H), 7.64 (d, J = 7.8 Hz, 1 H), 7.31–7.37 (m, 3 H), 7.28 (t, J = 7.8 Hz, 1 H), 7.14–7.22 (m, 3 H). C NMR (100 MHz, CDCl3): d = 158.5 (CH), 151.3 (C), 137.8 (C), 134.8 (C), 131.1 (CH), 129.9 (CH), 129.1 (CH), 128.2 (CH), 127.1 (CH), 126.3 (CH), 120.8 (CH). MS: m/z = 217 (M + 2)+, 215 (M)+, 196, 194, 180, 151, 112, 104, 89, 77, 63, 51.
13 1 13 1 13 1 +

13

MS: m/z = 211 (M)+, 198, 181, 167, 139, 116, 104, 92, 77, 63, 51. N-[(E)-(2-Methoxyphenyl)methylene]aniline (3o)38 IR (film): 2926, 2837, 1589, 14917, 1286, 1252, 1187, 1025, 758 cm–1.
1 H NMR (400 MHz, CDCl3): d = 8.91 (s, 1 H), 8.16 (dd, J1 = 7.6 Hz, J2 = 1.6 Hz, 1 H), 7.44 (ddd, J1 = 8.5 Hz, J2 = 7.6 Hz, J3 = 1.8 Hz, 1 H), 7.35–7.40 (m, 2 H), 7.17–7.25 (m, 3 H), 7.01 (t, J = 7.6 Hz, 1 H), 6.94 (d, J = 8.5 Hz, 1 H), 3.87 (s, 3 H). 13 C NMR (100 MHz, CDCl3): d = 159.5 (C), 156.6 (CH), 152.6 (C), 136.0 (CH), 132.8 (CH), 129.1 (CH), 127.6 (CH), 125.7 (CH), 124.6 (CH), 120.9 (CH), 111.1 (CH), 55.5 (OCH3).

MS: m/z = 211 (M)+, 198, 180, 167, 139, 119, 104, 93, 77, 63, 51. N-[(E)-(3,4,5-Trimethoxyphenyl)methylene]aniline (3p)44 IR (film): 3067, 2908, 2354, 1516, 1507, 1326, 1041, 924, 687 cm–1.
1 H NMR (400 MHz, CDCl3): d = 8.34 (s, 1 H), 7.36–7.42 (m, 2 H), 7.19–7.24 (m, 3 H), 7.16 (s, 2 H), 3.93 (s, 6 H), 3.91 (s, 3 H). 13 C NMR (100 MHz, CDCl3): d = 159.9 (CH), 153.5 (C), 151.6 (C), 141.1 (C), 131.5 (C), 129.2 (CH), 126.0 (CH), 120.9 (CH), 105.9 (CH), 61.0 (OCH3), 56.3 (OCH3).

MS: m/z = 271 (M)+, 256, 225, 196, 153, 104, 93, 77, 66, 51. 5-Aryl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolines 5 and 6; General Procedure To a soln of NbCl5 (0.500, 0.250 or 0.125 mmol) in anhyd MeCN (1.0 mL), maintained at r.t., under N2 atmosphere, was added a soln of the aldimine (1.0 mmol) and DHP (4, 2 mmol) in anhyd MeCN (2.0 mL). The mixture was quenched with 10% aq citric acid (2.0 mL). The mixture was diluted with H2O (5.0 mL) and EtOAc (10.0 mL), the organic layer was separated and washed with 5% aq

Synthesis 2008, No. 16, 2527–2536

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NaHCO3 (3 × 10.0 mL), sat. brine (2 × 10.0 mL), and dried (anhyd MgSO4). The solvent was removed under vacuum and the products were purified by column chromatography (silica gel, hexane– EtOAc, 9.5:0.5). rac-(4aS,5S,10bS)-5-Phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5a)11,45,46 IR (film): 3312, 2941, 2865, 1608, 1486, 1317, 1265, 1069, 737 cm–1. H NMR (400 MHz, CDCl3): d = 7.35–7.44 (m, 5 H), 7.30 (m, 1 H), 7.09 (td, J1 = 7.7 Hz, J2 = 0.8 Hz, 1 H), 6.79 (td, J1 = 7.7 Hz, J2 = 1.0 Hz, 1 H), 6.60 (dd, J1 = 7.7 Hz, J2 = 0.8 Hz, 1 H), 5.33 (d, J = 5.6 Hz, 1 H), 4.69 (d, J = 2.3 Hz, 1 H), 3.85 (NH, 1 H), 3.58 (m, 1 H), 3.43 (td, J1 = 11.6 Hz, J2 = 2.5 Hz, 1 H), 2.16 (m, 1 H), 1.47– 1.58 (m, 2 H), 1.43 (m, 1 H), 1.31 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 145.6 (C), 141.5 (C), 129.2 (CH), 128.8 (CH), 128.7 (CH), 128.5 (CH), 128.0 (CH), 127.9 (CH), 127.2 (CH), 120.3 (C), 118.7 (CH), 114.8 (CH), 73.2 (CH), 61.0 (CH2), 59.7 (CH), 39.3 (CH), 25.8 (CH2), 18.4 (CH2). 1

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4.68 (d, J = 10.9 Hz, 1 H), 4.39 (d, J = 2.3 Hz, 1 H), 4.10 (m, 1 H), 3.72 (td, J1 = 11.6 Hz, J2 = 1.8 Hz, 1 H), 2.36 (s, 3 H), 2.07 (m, 1 H), 1.83 (tdt, J1 = 13.6 Hz, J2 = 12.4 Hz, J3 = 4.5 Hz, 1 H), 1.64 (tt, J1 = 13.6 Hz, J2 = 4.5 Hz, 1 H), 1.48 (m, 1 H), 1.32 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 143.7 (C), 138.1 (C), 136.5 (C), 129.8 (CH), 128.3 (CH), 128.2 (CH), 126.6 (CH), 119.6 (C), 116.3 (CH), 113.1 (CH), 73.5 (CH), 67.6 (CH2), 53.4 (CH), 37.7 (CH), 23.0 (CH2), 20.9 (CH2), 20.1 (CH3).

MS: m/z = 279 (M)+, 249, 235, 221, 203, 188, 91, 77, 51. rac-(4aS,5S,10bS)-5-(3-Methylphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5c) IR (film): 3373, 2937, 2855, 1610, 1488, 1365, 1080, 914, 748 cm–1. H NMR (400 MHz, CDCl3): d = 7.19–7.29 (m, 3 H), 7.42 (dt, J1 = 7.7 Hz, J2 = 1.3 Hz, 1 H), 7.11 (d, J = 6.8 Hz, 1 H), 7.08 (m, 1 H), 6.79 (td, J1 = 7.6 Hz, J2 = 1.0 Hz, 1 H), 6.60 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.32 (d, J = 5.6 Hz, 1 H), 4.65 (d, J = 2.5 Hz, 1 H), 3.94 (NH, 1 H), 3.59 (ddt, J1 = 11.4, J2 = 4.0 Hz, J3 = 2.0 Hz, 1 H), 3.43 (td, J1 = 11.4 Hz, J2 = 2.5 Hz, 1 H), 2.36 (s, 3 H), 2.16 (m, 1 H), 1.47–1.59 (m, 2 H), 1.43 (m, 1 H), 1.32 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 146.4 (C), 142.2 (C), 139.2 (C), 129.4 (CH), 129.3 (CH), 129.2 (CH), 128.9 (CH), 128.7 (CH), 125.0 (CH), 121.1 (C), 119.4 (CH), 115.5 (CH), 73.9 (CH), 61.8 (CH2), 60.4 (CH), 40.0 (CH), 26.6 (CH2), 22.7 (CH3), 19.2 (CH2). 1

MS: m/z = 265 (M)+, 234, 220, 194, 129, 117, 91, 77. rac-(4aS,5R,10bS)-5-Phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6a)11,45,46 IR (film): 3360, 2940, 2865, 1610, 1488, 1315, 1265, 1070, 737 cm–1. H NMR (400 MHz, CDCl3): d = 7.30–7.44 (m, 5 H), 7.22 (dd, J1 = 7.7 Hz, J2 = 1.3 Hz, 1 H), 7.09 (td, J1 = 7.7 Hz, J2 = 1.3 Hz, 1 H), 6.71 (td, J1 = 7.3 Hz, J2 = 0.7 Hz, 1 H), 6.53 (dd, J1 = 7.7 Hz, J2 = 0.7 Hz, 1 H), 4.72 (d, J = 10.9 Hz, 1 H), 4.39 (d, J = 2.8 Hz, 1 H), 4.10 (dt, J1 = 11.4 Hz, J2 = 2.3 Hz, 1 H), 3.72 (td, J1 = 11.4 Hz, J2 = 2.5 Hz, 1 H), 2.11 (m, 1 H), 1.84 (tdt, J1 = 13.4 Hz, J2 = 12.4 Hz, J3 = 4.5 Hz, 1 H), 1.65 (tt, J1 = 13.4 Hz, J2 = 4.5 Hz, 1 H), 1.47 (m, 1 H), 1.33 (m, 1 H). C NMR (100 MHz, CDCl3): d = 145.1 (C), 142.7 (C), 131.3 (CH), 129.8 (CH), 129.0 (CH), 128.3 (CH), 128.2 (CH), 121.0 (C), 117.9 (CH), 114.5 (CH), 74.9 (CH), 69.0 (CH2), 55.2 (CH), 39.3 (CH), 24.5 (CH2), 22.4 (CH2). MS: m/z = 265 (M)+, 234, 220, 194, 129, 117, 91, 77. rac-(4aS,5S,10bS)-5-(4-Methylphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5b)47 IR (film): 3307, 2926, 2861, 1608, 1505, 1318, 12645, 1071 cm–1. H NMR (400 MHz, CDCl3): d = 7.41 (dt, J1 = 7.5 Hz, J2 = 1.0 Hz, 1 H), 7.29 (d, J = 7.8 Hz, 2 H), 7.18 (d, J = 7.8 Hz, 2 H), 7.08 (dddd, J1 = 8.0 Hz, J2 = 7.5, J3 = 1.5 Hz, J4 = 1.0 Hz, 1 H), 6.78 (td, J1 = 7.5 Hz, J2 = 1.0 Hz, 1 H), 6.58 (dd, J1 = 8.0 Hz, J2 = 1.0 Hz, 1 H), 5.31 (d, J = 5.7 Hz, 1 H), 4.65 (d, J = 2.4 Hz, 1 H), 3.93 (NH, 1 H), 3.58 (dtt, J1 = 11.4, J2 = 4.0 Hz, J3 = 1.8 Hz, 1 H), 3.42 (td, J1 = 11.4 Hz, J2 = 2.7 Hz, 1 H), 2.36 (s, 3 H), 2.13 (dddd, J1 = 11.9 Hz, J2 = 5.7 Hz, J3 = 4.3 Hz, J4 = 2.7 Hz, 1 H), 1.46–1.56 (m, 2 H), 1.42 (m, 1 H), 1.32 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 145.5 (C), 140.3 (C), 139.4 (C), 131.3 (CH), 130.3 (CH), 129.9 (CH), 129.0 (CH), 122.1 (C), 120.4 (CH), 116.6 (CH), 75.0 (CH), 62.9 (CH2), 61.3 (CH), 41.2 (CH), 27.7 (CH2), 23.4 (CH3), 20.3 (CH2). 1 13 1

MS: m/z = 279 (M)+, 249, 235, 221, 203, 188, 91, 77, 51. HRMS (ESI): m/z [M + H] calcd for C19H22NO: 280.1695; found: 280.1699. rac-(4aS,5R,10bS)-5-(3-Methylphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6c) IR (film): 3374, 2940, 2865, 1607, 1488, 1365, 1088, 737 cm–1. H NMR (400 MHz, CDCl3): d = 7.19–7.28 (m, 4 H), 7.13 (d, J = 7.3 Hz, 1 H), 7.08 (ddd, J1 = 8.1, J2 = 7.3 Hz, J3 = 1.5 Hz, 1 H), 6.71 (t, J = 7.3 Hz, 1 H), 6.51 (d, J = 8.1 Hz, 1 H), 4.68 (d, J = 10.9 Hz, 1 H), 4.39 (d, J = 2.5 Hz, 1 H), 4.10 (m, 1 H), 3.71 (td, J1 = 11.6 Hz, J2 = 2.5 Hz, 1 H), 2.36 (s, 3 H), 2.09 (m, 1 H), 1.84 (tdt, J1 = 13.4, J2 = 12.4 Hz, J3 = 4.3 Hz, 1 H), 1.65 (tt, J1 = 13.4 Hz, J2 = 4.5 Hz, 1 H), 1.49 (m, 1 H), 1.33 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 144.9 (C), 142.5 (C), 138.7 (C), 131.3 (CH), 129.8 (CH), 129.1 (CH), 128.9 (CH), 128.8 (CH), 125.4 (CH), 121.3 (C), 118.0 (CH), 114.7 (CH), 75.0 (CH), 69.1 (CH2), 55.2 (CH), 39.1 (CH), 24.6 (CH2), 22.4 (CH2), 21.9 (CH3). 1

MS: m/z = 279 (M)+, 249, 235, 221, 203, 188, 91, 77, 51. HRMS (ESI): m/z [M + H] calcd for C19H22NO: 280.1695; found: 280.1698. rac-(4aS,5S,10bS)-5-(2-Methylphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5d) IR (film): 3373, 2940, 2865, 1608, 1486, 1316, 1265, 1088, 736 cm–1. H NMR (400 MHz, CDCl3): d = 7.62 (d, J = 6.6 Hz, 1 H), 7.45 (d, J = 7.3 Hz, 1 H), 7.19–7.25 (m, 3 H), 7.10 (t, J = 7.3 Hz, 1 H), 6.81 (t, J = 7.3 Hz, 1 H), 6.62 (d, J = 7.3 Hz, 1 H), 5.32 (d, J = 5.6 Hz, 1 H), 4.89 (d, J = 2.2 Hz, 1 H), 3.60 (ddt, J1 = 11.5 Hz, J2 = 4.1 Hz, J3 = 2.0 Hz, 1 H), 3.43 (td, J1 = 11.5 Hz, J2 = 2.6 Hz, 1 H), 2.34 (s, 3 H), 2.18 (m, 1 H), 1.49–1.67 (m, 3 H), 1.34 (m, 1 H).
13 1

MS: m/z = 279 (M)+, 249, 235, 221, 203, 188, 91, 77, 51. rac-(4aS,5R,10bS)-5-(4-Methylphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6b)47 IR (film): 3328, 2942, 2850, 1611, 1486, 1366, 1080, 736 cm–1. H NMR (400 MHz, CDCl3): d = 7.30 (d, J = 7.7 Hz, 2 H), 7.21 (d, J = 7.4 Hz, 1 H), 7.18 (d, J = 7.7Hz, 2 H), 7.07 (dd, J1 = 7.6 Hz, J2 = 7.4 Hz, 1 H), 6.69 (t, J = 7.4 Hz, 1 H), 6.51 (d, J = 7.6 Hz, 1 H),
1

C NMR (100 MHz, CDCl3): d = 138.6 (C), 135.02 (C), 130.7 (CH), 128.1 (CH), 127.7 (CH), 127.3 (C), 127.2 (CH), 126.5 (CH), 125.7 (CH), 118.3 (CH), 114.5 (CH), 99.6 (C), 72.8 (CH), 60.8 (CH2), 55.4 (CH), 35.6 (CH), 25.5 (CH2), 18.9 (CH3), 18.3 (CH2).

MS: m/z = 279 (M)+, 249, 235, 221, 203, 188, 91, 77, 51.

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1 H), 7.55 (dd, J1 = 8.0 Hz, J2 = 7.8 Hz, 1 H), 7.23 (dd, J1 = 7.5 Hz, J2 = 1.4 Hz, 1 H), 7.12 (ddd, J1 = 8.1 Hz, J2 = 7.5 Hz, J3 = 1.4 Hz, 1 H), 6.75 (td, J1 = 7.5 Hz, J2 = 1.0 Hz, 1 H), 6.57 (d, J = 8.1 Hz, 1 H), 4.83 (d, J = 10.6 Hz, 1 H), 4.40 (d, J = 2.8 Hz, 1 H), 4.11 (m, 1 H), 3.74 (td, J1 = 11.5 Hz, J2 = 2.0 Hz, 1 H), 2.11 (m, 1 H), 1.84 (m, 1 H), 1.70 (tt, J1 = 13.8 Hz, J2 = 5.0 Hz, 1 H), 1.40 (m, 2 H).
13 C NMR (100 MHz, CDCl3): d = 148.6 (C), 144.8 (C), 144.7 (C), 134.0 (CH), 130.9 (CH), 129.6 (CH), 129.5 (CH), 123.0 (CH), 122.7 (CH), 120.7 (C), 118.2 (CH), 114.4 (CH), 74.1 (CH), 68.5 (CH2), 54.5 (CH), 39.0 (CH), 24.1 (CH2), 22.1 (CH2).

HRMS (ESI): m/z [M + H] calcd for C19H22NO: 280.1695; found: 280.1699. rac-(4aS,5R,10bS)-5-(2-Methylphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6d) IR (film): 3374, 2936, 2865, 1609, 1485, 1320, 1264, 1088, 736 cm–1. H NMR (400 MHz, CDCl3): d = 7.46 (d, J = 4.4 Hz, 1 H), 7.28 (d, J = 7.6 Hz, 1 H), 7.23 (s, 3 H), 7.12 (t, J = 7.6 Hz, 1 H), 6.75 (t, J = 7.6 Hz, 1 H), 6.54 (d, J = 8.1 Hz, 1 H), 5.00 (d, J = 10.3 Hz, 1 H), 4.49 (d, J = 2.6 Hz, 1 H), 4.10 (d, J = 10.9 Hz, 1 H), 3.74 (td, J1 = 10.9 Hz, J2 = 1.9 Hz, 1 H), 2.50 (s, 3 H), 2.29 (m, 1 H), 1.88– 1.66 (m, 2 H), 1.56 (m, 1 H), 1.43 (m, 1 H). C NMR (100 MHz, CDCl3): d = 144.9 (C), 140.5 (C), 136.9 (C), 131.2 (CH), 131.1 (CH), 129.7 (CH), 128.2 (CH), 127.9 (CH), 126.9 (CH), 120.9 (C), 117.9 (CH), 114.5 (CH), 74.7 (CH), 68.4 (CH2), 51.5 (CH), 38.1 (CH), 24.5 (CH2), 23.3 (CH2), 20.4 (CH3). MS: m/z = 279 (M) , 249, 235, 221, 203, 188, 91, 77, 51. HRMS (ESI): m/z [M + H] calcd for C19H22NO: 280.1695; found: 280.1689. rac-(4aS,5R,10bS)-5-Mesityl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5e) IR (film): 3384, 2944, 2853, 1610, 1496, 1365, 1265, 1080, 736 cm–1. H NMR (400 MHz, CDCl3): d = 7.22 (dd, J1 = 7.3 Hz, J2 = 1.5 Hz, 1 H), 7.07 (ddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, 1 H), 6.86 (s, 2 H), 6.68 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.48 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.21 (d, J = 11.6 Hz, 1 H), 4.39 (d, J = 2.8 Hz, 1 H), 4.11 (dd, J1 = 11.4 Hz, J2 = 4.0 Hz, 1 H), 3.88 (NH, 1 H), 3.69 (td, J1 = 11.4 Hz, J2 = 2.2 Hz, 1 H), 2.64 (m, 1 H), 2.45 (s, 6 H), 2.27 (s, 3 H), 1.66–1.77 (m, 2 H), 1.47–1.60 (m, 2 H). C NMR (100 MHz, CDCl3): d = 145.4 (C), 136.9 (C), 133.5 (C), 131.3 (CH), 129.3 (CH), 120.9 (C), 117.1 (CH), 114.3 (CH), 75.4 (CH), 68.9 (CH2), 50.0 (CH), 34.6 (CH), 23.9 (CH2), 22.4 (CH2), 21.3 (CH3), 20.7 (2 CH3). MS: m/z = 307 (M)+, 277, 263, 249, 231, 188, 119, 91, 77, 51. HRMS (ESI): m/z [M + H] calcd for C21H26NO: 308.2008; found: 308.2024. rac-(4aS,5S,10bS)-5-(3-Nitrophenyl)-3,4,4a,5,6,10b-hexahydro2H-pyrano[3,2-c]quinoline (5f)47 IR (film): 3369, 2950, 2857, 1606, 1528, 1349, 1087, 759 cm–1.
1 H NMR (400 MHz, CDCl3): d = 8.32 (t, J = 2.0 Hz, 1 H), 8.16 (ddd, J1 = 8.0 Hz, J2 = 2.0 Hz, J3 = 1.0 Hz, 1 H), 7.76 (d, J = 7.8 Hz, 1 H), 7.56 (dd, J1 = 8.0 Hz, J2 = 7.8 Hz, 1 H), 7.42 (d, J = 7.3 Hz, 1 H), 7.12 (dd, J1 = 7.8 Hz, J2 = 7.3 Hz, 1 H), 6.84 (td, J1 = 7.3 Hz, J2 = 0.8 Hz, 1 H), 6.67 (dd, J1 = 7.8 Hz, J2 = 1.0 Hz, 1 H), 5.34 (d, J = 5.6 Hz, 1 H), 4.79 (d, J = 2.3 Hz, 1 H), 3.94 (NH, 1 H), 3.59 (m, 1 H), 3.43 (td, J1 = 11.4 Hz, J2 = 2.5 Hz, 1 H), 2.20 (m, 1 H), 1.46– 1.63 (m, 2 H), 1.44 (m, 1 H), 1.19 (m, 1 H). 13 C NMR (100 MHz, CDCl3): d = 148.4 (C), 144.5 (C), 143.5 (C), 133.0 (CH), 129.4 (CH), 128.3 (CH), 127.6 (CH), 122.6 (CH), 121.7 (CH), 119.9 (C), 119.1 (CH), 114.9 (CH), 72.4 (CH), 60.6 (CH2), 58.8 (CH), 38.8 (CH), 25.26 (CH2), 17.9 (CH2). 13 1 + 13 1

MS: m/z = 310 (M)+, 266, 251, 205, 179, 130, 115, 91, 77, 65, 51. rac-(4aS,5S,10bS)-5-(2-Nitrophenyl)-3,4,4a,5,6,10b-hexahydro2H-pyrano[3,2-c]quinoline (5g) IR (film): 3373, 2939, 2850, 1608, 1526, 1505, 1352, 1265, 1073, 736 cm–1. H NMR (400 MHz, CDCl3): d = 7.97 (dd, J1 = 7.6 Hz, J2 = 1.0 Hz, 1 H), 7.95 (dd, J1 = 8.0 Hz, J2 = 1.3 Hz, 1 H), 7.64 (td, J1 = 7.6 Hz, J2 = 1.0 Hz, 1 H), 7.46 (ddd, J1 = 8.0 Hz, J2 = 7.6 Hz, J3 = 1.0 Hz, 1 H), 7.44 (d, J = 7.6 Hz, 1 H), 7.10 (dd, J1 = 8.1 Hz, J2 = 7.6 Hz, 1 H), 6.83 (t, J = 7.6 Hz, 1 H), 6.61 (d, J = 8.1 Hz, 1 H), 5.34 (d, J = 5.5 Hz, 1 H), 5.15 (d, J = 2.0 Hz, 1 H), 3.60 (m, 1 H), 3.43 (td, J1 = 11.6 Hz, J2 = 2.5 Hz, 1 H), 2.52 (m, 1 H), 1.51–1.70 (m, 2 H), 1.46 (m, 1 H), 1.32 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 148.5 (C), 144.5 (C), 135.5 (C), 132.3 (CH), 129.1 (CH), 128.0 (CH), 127.8 (CH), 127.5 (CH), 124.5 (CH), 120.2 (C), 118.8 (CH), 114.6 (CH), 72.0 (CH), 60.2 (CH2), 54.2 (CH), 36.0 (CH), 25.0 (CH2), 18.2 (CH2). 1

MS: m/z = 310 (M)+, 266, 251, 217, 204, 188, 130, 115, 89, 77, 63, 51. HRMS (ESI): m/z [M + H] calcd for C18H19N2O3: 311.1390; found: 311.1367. rac-(4aS,5R,10bS)-5-(2-Nitrophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6g) IR (film): 3373, 2939, 2850, 1608, 1526, 1505, 1352, 1265, 1073, 736 cm–1. H NMR (400 MHz, CDCl3): d = 7.81 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 7.67 (dd, J1 = 7.8 Hz, J2 = 1.0 Hz, 1 H), 7.57 (td, J1 = 7.8 Hz, J2 = 1.5 Hz, 1 H), 7.43 (ddd, J1 = 8.1 Hz, J2 = 7.8 Hz, J3 = 1.5 Hz, 1 H), 7.28 (dd, J1 = 7.6 Hz, J2 = 1.5 Hz, 1 H), 7.13 (ddd, J1 = 8.1 Hz, J2 = 7.6 Hz, J3 = 1.5 Hz, 1 H), 6.76 (td, J1 = 7.6 Hz, J2 = 1.0 Hz, 1 H), 6.59 (d, J = 8.1 Hz, 1 H), 5.14 (d, J = 8.1 Hz, 1 H), 4.46 (d, J = 3.6 Hz, 1 H), 4.25 (NH, 1 H), 3.88 (m, 1 H), 3.64 (ddd, J1 = 11.4 Hz, J2 = 8.4 Hz, J3 = 2.9 Hz, 1 H), 2.24 (m, 1 H), 1.77 (m, 1 H), 1.62 (m, 1 H), 1.41–1.50 (m, 2 H). C NMR (100 MHz, CDCl3): d = 149.9 (C), 143.9 (C), 137.2 (C), 132.9 (CH), 129.8 (CH), 129.4 (CH), 129.2 (CH), 128.4 (CH), 124.0 (CH), 119.8 (C), 119.0 (CH), 114.1 (CH), 72.2 (CH), 61.8 (CH2), 50.8 (CH), 36.7 (CH), 24.5 (CH2), 23.1 (CH2). MS: m/z = 310 (M)+, 266, 251, 217, 204, 188, 130, 115, 89, 77, 63, 51. HRMS (ESI): m/z [M + H] calcd for C18H19N2O3: 311.1390; found: 311.1390. rac-(4aS,5S,10bS)-5-(6-Nitro-1,3-benzodioxol-5-yl)3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5h) IR (film): 3374, 2925, 1732, 1480, 1333, 1269, 1036, 737 cm–1.
1 H NMR (400 MHz, CDCl3): d = 7.53 (s, 1 H), 7.44 (dd, J1 = 7.4 Hz, J2 = 1.5 Hz, 1 H), 7.42 (s, 1 H), 7.09 (dddd, J1 = 8.1 Hz, J2 = 7.4 Hz, J3 = 1.5 Hz, J4 = 0.7 Hz, 1 H), 6.83 (td, J1 = 7.4 Hz, J2 = 1.0 Hz, 1 H), 6.60 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 6.14 (d, J = 1.2 Hz, 1 H), 6.12 (d, J = 1.2 Hz, 1 H), 5.33 (d, J = 5.6 Hz, 1 H), 5.18 (d, 13 1

MS: m/z = 310 (M)+, 266, 251, 205, 179, 130, 115, 91, 77, 65, 51. rac-(4aS,5R,10bS)-5-(3-Nitrophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6f)47 IR (film): 3386, 2943, 2828, 1608, 1524, 1482, 1344, 1059, 759 cm–1.
1 H NMR (400 MHz, CDCl3): d = 8.31 (t, J = 1.8 Hz, 1 H), 8.18 (ddd, J1 = 8.1 Hz, J2 = 2.3 Hz, J3 = 1.0 Hz, 1 H), 7.76 (d, J = 7.8 Hz,

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J = 2.0 Hz, 1 H), 3.60 (m, 1 H), 3.42 (td, J1 = 11.4 Hz, J2 = 2.0 Hz, 1 H), 2.53 (m, 1 H), 1.55–1.64 (m, 2 H), 1.48 (m, 1 H), 1.37 (m, 1 H). C NMR (100 MHz, CDCl3): d = 151.6 (C), 147.0 (C), 144.8 (C), 142.6 (C), 133.6 (C), 128.0 (CH), 127.8 (CH), 120.6 (C), 119.1 (CH), 115.0 (CH), 108.2 (CH), 105.9 (CH), 103.0 (CH2), 72.3 (CH), 60.5 (CH2), 54.7 (CH), 36.2 (CH), 25.3 (CH2), 18.7 (CH2). MS: m/z = 354 (M)+, 324, 310, 296, 279, 194, 188, 164, 91, 77, 51. HRMS (ESI): m/z [M + H] calcd for C19H19N2O5: 355.1288; found: 355.1298. rac-(4aS,5R,10bS)-5-(6-Nitro-1,3-benzodioxol-5-yl)3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6h) IR (film): 3375, 2930, 1729, 1479, 1331, 1271, 1036, 737 cm–1. H NMR (400 MHz, CDCl3): d = 7.37 (s, 1 H), 7.27 (dd, J1 = 7.6 Hz, J2 = 1.5 Hz, 1 H), 7.12 (ddd, J1 = 8.1 Hz, J2 = 7.6 Hz, J3 = 1.5 Hz, 1 H), 7.04 (s, 1 H), 6.76 (td, J1 = 7.6 Hz, J2 = 1.0 Hz, 1 H), 6.58 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 6.09 (d, J = 1.0 Hz, 1 H), 6.08 (d, J = 1.0 Hz, 1 H), 5.19 (d, J = 7.6 Hz, 1 H), 4.48 (d, J = 3.8 Hz, 1 H), 3.85 (m, 1 H), 3.63 (ddd, J1 = 11.4 Hz, J2 = 8.1 Hz, J3 = 3.0 Hz, 1 H), 2.16 (m, 1 H), 1.78 (m, 1 H), 1.59 (m, 1 H), 1.43–1.52 (m, 2 H).
13 C NMR (100 MHz, CDCl3): d = 151.8 (C), 147.1 (C), 143.8 (C), 142.9 (C), 134.7 (C), 129.7 (CH), 129.1 (CH), 119.7 (C), 118.0 (CH), 114.0 (CH), 107.8 (CH), 105.2 (CH), 102.9 (CH2), 71.5 (CH), 60.4 (CH2), 51.1 (CH), 37.8 (CH), 24.5 (CH2), 23.3 (CH2). 1 13

Synthesis of Pyrano[3,2-c]quinolines

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MS: m/z = 309 (M)+, 279, 265, 225, 233, 218, 188, 121, 91, 77, 51. rac-(4aS,5S,10bS)-5-(4-Chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5j)49,50 IR (film): 3387, 2940, 1604, 1486, 1276, 1085, 1014, 750 cm–1. H NMR (400 MHz, CDCl3): d = 7.42 (dt, J1 = 7.3 Hz, J2 = 1.5 Hz, 1 H), 7.35 (s, 4 H), 7.09 (dddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, J4 = 0.8 Hz, 1 H), 6.80 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.60 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.30 (d, J = 5.6 Hz, 1 H), 4.65 (d, J = 2.5 Hz, 1 H), 3.80 (NH, 1 H), 3.59 (ddt, J1 = 11.4 Hz, J2 = 4.0 Hz, J3 = 2.0 Hz, 1 H), 3.42 (td, J1 = 11.4 Hz, J2 = 2.5 Hz, 1 H), 2.12 (m, 1 H), 1.41–1.55 (m, 3 H), 1.26 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 144.9 (C), 139.6 (C), 133.1 (C), 128.5 (CH), 128.1 (CH), 127.6 (CH), 119.9 (C), 118.6 (CH), 114.5 (CH), 72.6 (CH), 60.6 (CH2), 58.8 (CH), 38.9 (CH), 25.3 (CH2), 17.9 (CH2). 1

MS: m/z = 301 (M + 2)+, 299 (M)+, 268, 266, 240, 217, 154, 127, 115, 89, 77, 63, 51. rac-(4aS,5R,10bS)-5-(4-Chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6j)49,50 IR (film): 3364, 2935, 2851, 1609, 1486, 1262, 1050, 913, 750 cm–1.
1 H NMR (400 MHz, CDCl3): d = 7.35 (d, J = 1.4 Hz, 4 H), 7.22 (dd, J1 = 7.3 Hz, J2 = 1.5 Hz, 1 H), 7.09 (ddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, 1 H), 6.72 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.53 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 4.69 (d, J = 10.6 Hz, 1 H), 4.38 (d, J = 2.8 Hz, 1 H), 4.09 (m, 1 H), 3.72 (td, J1 = 11.4 Hz, J2 = 2.3 Hz, 1 H), 2.04 (m, 1 H), 1.81 (m, 1 H), 1.66 (tt, J1 = 13.7 Hz, J2 = 4.5 Hz, 1 H), 1.44 (m, 1 H), 1.34 (m, 1 H). 13 C NMR (100 MHz, CDCl3): d = 144.5 (C), 140.8 (C), 133.5 (C), 130.9 (CH), 129.4 (CH), 129.1 (CH), 128.8 (CH), 120.7 (C), 117.8 (CH), 114.2 (CH), 74.4 (CH), 60.6 (CH2), 54.3 (CH), 38.9 (CH), 24.1 (CH2), 21.9 (CH2).

MS: m/z = 354 (M)+, 324, 310, 296, 279, 194, 188, 164, 91, 77, 51. HRMS (ESI): m/z [M + H] calcd for C19H19N2O5: 355.1288; found: 355.1265. rac-(4aS,5S,10bS)-5-(1,3-Benzodioxol-5-yl)-3,4,4a,5,6,10bhexahydro-2H-pyrano[3,2-c]quinoline (5i)15,48 IR (film): 3380, 2925, 1732, 1480, 1333, 1269, 1036, 737 cm–1. H NMR (400 MHz, CDCl3): d = 7.41 (dt, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 7.09 (dddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, J4 = 0.8 Hz, 1 H), 6.92 (d, J = 1.8 Hz, 1 H), 6.88 (ddd, J1 = 8.1, J2 = 1.8 Hz, J3 = 0.7 Hz, 1 H), 6.81 (d, J = 8.1 Hz, 1 H), 6.79 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.58 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.70 (m, 2 H), 5.30 (d, J = 5.6 Hz, 1 H), 4.60 (d, J = 2.5 Hz, 1 H), 3.59 (m, 1 H), 3.42 (td, J1 = 11.4 Hz, J2 = 2.5 Hz, 1 H), 2.11 (m, 1 H), 1.43– 1.48 (m, 3 H), 1.36 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 147.7 (C), 146.8 (C), 145.1 (C), 135.1 (C), 128.1 (CH), 127.6 (CH), 119.9 (C), 119.8 (CH), 118.4 (CH), 114.4 (CH), 108.1 (CH), 107.4 (CH), 101.1 (CH2), 72.7 (CH), 60.7 (CH2), 59.1 (CH), 39.1 (CH), 25.4 (CH2), 18.1 (CH2). 1

MS: m/z = 301 (M + 2)+, 299 (M)+, 268, 266, 240, 216, 188, 130, 115, 89, 77, 65, 51. rac-(4aS,5S,10bS)-5-(3-Chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5k) IR (film): 3314, 2941, 2865, 1607, 1476, 1264, 1071, 737 cm–1. H NMR (400 MHz, CDCl3): d = 7.40–7.44 (m, 2 H), 7.29 (m, 3 H), 7.10 (dddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, J4 = 0.7 Hz, 1 H), 6.81 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.61 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.31 (d, J = 5.6 Hz, 1 H), 4.65 (d, J = 2.5 Hz, 1 H), 3.83 (NH, 1 H), 3.59 (m, 1 H), 3.42 (td, J1 = 11.4 Hz, J2 = 2.5 Hz, 1 H), 2.15 (m, 1 H), 1.42–1.56 (m, 3 H), 1.27 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 144.8 (C), 143.3 (C), 134.4 (C), 129.7 (CH), 128.1 (CH), 127.7 (CH), 127.6 (CH), 126.9 (CH), 125.0 (CH), 119.9 (C), 118.6 (CH), 114.6 (CH), 72.6 (CH), 60.6 (CH2), 58.9 (CH), 38.8 (CH), 25.3 (CH2), 17.9 (CH2). 1

MS: m/z = 309 (M)+, 279, 265, 225, 233, 218, 188, 121, 91, 77, 51. rac-(4aS,5R,10bS)-5-(1,3-Benzodioxol-5-yl)-3,4,4a,5,6,10bhexahydro-2H-pyrano[3,2-c]quinoline (6i)15,48 IR (film): 3375, 2930, 1729, 1479, 1331, 1271, 1036, 737 cm–1. H NMR (400 MHz, CDCl3): d = 7.21 (dd, J1 = 7.3 Hz, J2 = 1.5 Hz, 1 H), 7.09 (ddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, 1 H), 6.93 (d, J = 1.6 Hz, 1 H), 6.87 (dd, J1 = 7.8 Hz, J2 = 1.6 Hz, 1 H), 6.79 (d, J = 7.8 Hz, 1 H), 6.70 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.52 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.97 (s, 2 H), 4.64 (d, J = 11.2 Hz, 1 H), 4.38 (d, J = 2.8 Hz, 1 H), 4.10 (ddt, J1 = 11.4 Hz, J2 = 4.3 Hz, J3 = J4 = 2.3 Hz, 1 H), 3.72 (td, J1 = 11.4 Hz, J2 = 2.5 Hz, 1 H), 2.01 (m, 1 H), 1.81 (tdt, J1 = 13.4 Hz, J2 = 11.9 Hz, J3 = 4.3 Hz, 1 H), 1.66 (tt, J1 = 13.6 Hz, J2 = 4.6 Hz, 1 H), 1.52 (m, 1 H), 1.34 (m, 1 H). C NMR (100 MHz, CDCl3): d = 148.0 (C), 147.2 (C), 144.7 (C), 136.1 (C), 130.9 (CH), 129.4 (CH), 121.3 (CH), 120.7 (C), 117.6 (CH), 114.2 (CH), 108.1 (CH), 107.7 (CH), 74.6 (CH), 68.7 (CH2), 54.5 (CH), 38.9 (CH), 24.1 (CH2), 21.9 (CH2).
13 1

MS: m/z = 301 (M + 2)+, 299 (M)+, 268, 266, 254, 240, 217, 144, 130, 115, 102, 89, 77, 63, 51. HRMS (ESI): m/z [M + H] calcd for C18H19ClNO: 300.1149; found: 300.1125. rac-(4aS,5R,10bS)-5-(3-Chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6k) IR (film): 3356, 2925, 2839, 1609, 1490, 1368, 1260, 1053, 749 cm–1. H NMR (400 MHz, CDCl3): d = 7.42 (s, 1 H), 7.29 (m, 3 H), 7.21 (dd, J1 = 7.3 Hz, J2 = 1.5 Hz, 1 H), 7.09 (ddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, 1 H), 6.71 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.52 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 4.67 (d, J = 10.6 Hz, 1 H), 4.37 (d, J = 2.8 Hz, 1 H), 4.08 (m, 1 H), 3.71 (td, J1 = 11.4 Hz, J2 = 2.5
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PAPER
(CH), 113.7 (CH), 72.8 (CH), 60.7 (CH2), 58.8 (CH3), 55.3 (CH), 39.0 (CH), 25.4 (CH2), 18.0 (CH2). MS: m/z = 295 (M)+, 276, 262, 248, 218, 204, 191, 130, 109, 89, 77, 63. rac-(4aS,5R,10bS)-5-(4-Methoxyphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6m)15,47 IR (film): 3384, 2939, 2853, 1610, 1513, 1249, 1174, 1080, 750 cm–1. H NMR (400 MHz, CDCl3): d = 7.36 (d, J = 8.8 Hz, 2 H), 7.24 (dd, J1 = 7.3 Hz, J2 = 1.5 Hz, 1 H), 7.11 (ddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, 1 H), 6.93 (d, J = 8.8 Hz, 2 H), 6.72 (td, J1 = 7.3 Hz, J2 = 1.3 Hz, 1 H), 6.55 (dd, J1 = 8.1 Hz, J2 = 1.3 Hz, 1 H), 4.70 (d, J = 11.1 Hz, 1 H), 4.41 (d, J = 2.8 Hz, 1 H), 4.12 (m, 1 H), 3.84 (s, 3 H), 3.74 (td, J1 = 11.6 Hz, J2 = 2.5 Hz, 1 H), 2.08 (m, 1 H), 1.85 (m, 1 H), 1.67 (tt, J1 = 13.4 Hz, J2 = 4.6 Hz, 1 H), 1.52 (m, 1 H), 1.35 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 159.6 (C), 145.0 (C), 134.5 (C), 131.2 (CH), 129.6 (CH), 129.1 (CH), 121.1 (C), 117.8 (CH), 114.5 (CH), 114.3 (CH), 75.0 (CH), 69.0 (CH2), 55.6 (CH3), 54.4 (CH), 39.2 (CH), 24.4 (CH2), 22.2 (CH2). 1

Hz, 1 H), 2.04 (m, 1 H), 1.81 (tdt, J1 = 13.1 Hz, J2 = 11.6 Hz, J3 = 4.3 Hz, 1 H), 1.66 (tt, J1 = 13.1 Hz, J2 = 4.5 Hz, 1 H), 1.46 (m, 1 H), 1.36 (m, 1 H). C NMR (100 MHz, CDCl3): d = 144.5 (C), 144.4 (C), 134.5 (C), 130.9 (CH), 129.9 (CH), 129.4 (CH), 128.1 (CH), 127.8 (CH), 126.1 (CH), 120.6 (C), 117.7 (CH), 114.2 (CH), 74.3 (CH), 68.5 (CH2), 54.5 (CH), 38.9 (CH), 24.1 (CH2), 22.0 (CH2). MS: m/z = 301 (M + 2)+, 299 (M)+, 254, 240, 228, 144, 130, 115, 102, 89, 77, 65, 51. HRMS (ESI): m/z [M + H] calcd for C18H19ClNO: 300.1149; found: 300.1154. rac-(4aS,5S,10bS)-5-(2-Chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5l)47 IR (film): 3363, 2938, 2864, 1605, 1479, 1317, 1089, 928, 754 cm–1.
1 H NMR (400 MHz, CDCl3): d = 7.69 (dd, J1 = 7.6 Hz, J2 = 1.8 Hz, 2 H), 7.44 (dt, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 7.40 (dd, J1 = 7.6 Hz, J2 = 1.5 Hz, 1 H), 7.30 (td, J1 = 7.6 Hz, J2 = 1.5 Hz, 1 H), 7.24 (td, J1 = 7.6 Hz, J2 = 1.8 Hz, 1 H), 7.10 (dddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, J4 = 0.8 Hz, 1 H), 6.82 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.62 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.34 (d, J = 5.6 Hz, 1 H), 5.07 (d, J = 2.3 Hz, 1 H), 3.60 (m, 1 H), 3.43 (td, J1 = 11.5 Hz, J2 = 2.5 Hz, 1 H), 2.41 (m, 1 H), 1.52–1.60 (m, 2 H), 1.44 (m, 1 H), 1.22 (m, 1 H). 13 C NMR (100 MHz, CDCl3): d = 145.2 (C), 138.0 (C), 132.7 (C), 129.9 (CH), 128.5 (CH), 128.3 (CH), 128.0 (CH), 127.7 (CH), 126.5 (CH), 120.2 (C), 118.6 (CH), 114.7 (CH), 72.4 (CH), 60.6 (CH2), 55.7 (CH), 34.8 (CH), 25.4 (CH2), 18.5 (CH2). 13

MS: m/z = 295 (M)+, 264, 250, 236, 224, 193, 167, 132, 1121, 91, 77, 65. rac-(4aS,5S,10bS)-5-(3-Methoxyphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5n) IR (film): 3370, 2940, 2853, 1608, 1488, 1265, 1154, 1071, 736 cm–1. H NMR (400 MHz, CDCl3): d = 7.42 (dt, J1 = 7.3 Hz, J2 = 1.3 Hz, 1 H), 7.29 (dd, J1 = 8.1 Hz, J2 = 7.6 Hz, 1 H), 7.09 (dddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, J4 = 0.7 Hz, 1 H), 6.99 (d, J = 7.6 Hz, 1 H), 6.98 (s, 1 H), 6.84 (ddd, J1 = 8.2 Hz, J2 = 2.5 Hz, J3 = 1.0 Hz, 1 H), 6.79 (td, J1 = 7.3 Hz, J2 = 1.3 Hz, 1 H), 6.60 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.32 (d, J = 5.6 Hz, 1 H), 4.66 (d, J = 2.3 Hz, 1 H), 3.82 (s, 3 H), 3.58 (ddt, J1 = 11.6 Hz, J2 = 4.0 Hz, J3 = 1.7 Hz, 1 H), 3.43 (td, J1 = 11.6 Hz, J2 = 2.5 Hz, 1 H), 2.17 (m, 1 H), 1.47– 1.57 (m, 2 H), 1.43 (m, 1 H), 1.33 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 159.6 (C), 145.1 (C), 142.9 (C), 124.4 (CH), 128.8 (CH), 127.6 (CH), 119.9 (C), 119.12 (CH), 118.3 (CH), 114.4 (CH), 112.6 (CH), 112.5 (CH), 72.7 (CH), 60.6 (CH2), 59.3 (CH3), 55.3 (CH), 38.9 (CH), 25.4 (CH2), 18.1 (CH2). 1

MS: m/z = 301 (M + 2)+, 299 (M)+, 254, 240, 220, 204, 144, 130, 115, 102, 91, 77, 51. rac-(4aS,5R,10bS)-5-(2-Chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6l)47 IR (film): 3362, 2939, 2858, 1609, 1464, 1264, 1083, 928, 736 cm–1. H NMR (400 MHz, CDCl3): d = 7.48 (dd, J1 = 7.6 Hz, J2 = 1.8 Hz, 1 H), 7.37 (dd, J1 = 7.6 Hz, J2 = 1.5 Hz, 1 H), 7.22–7.28 (m, 2 H), 7.20 (dd, J1 = 7.3 Hz, J2 = 1.5 Hz, 1 H), 7.10 (ddd, J1 = 7.8 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, 1 H), 6.71 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.52 (d, J = 7.8 Hz, 1 H), 5.17 (d, J = 9.3 Hz, 1 H), 4.43 (d, J = 3.3 Hz, 1 H), 4.05 (NH, 1 H), 3.98 (m, 1 H), 3.67 (td, J1 = 11.1 Hz, J2 = 2.7 Hz, 1 H), 2.20 (m, 1 H), 1.92 (m, 1 H), 1.70 (m, 1 H), 1.38–1.51 (m, 2 H).
13 C NMR (100 MHz, CDCl3): d = 144.4 (C), 140.1 (C), 133.8 (C), 130.3 (CH), 129.5 (CH), 129.2 (CH), 129.0 (CH), 128.7 (CH), 127.3 (CH), 120.1 (C), 117.5 (CH), 113.9 (CH), 73.3 (CH), 67.2 (CH2), 51.4 (CH), 38.0 (CH), 24.3 (CH2), 23.1 (CH2). 1

MS: m/z = 295 (M)+, 264,, 250, 236, 224, 193, 167, 132, 121, 91, 77, 65. HRMS (ESI): m/z [M + H] calcd for C19H22NO2: 296.1645; found: 296.1651. rac-(4aS,5R,10bS)-5-(3-Methoxyphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6n) IR (film): 3373, 2939, 2837, 1609, 1487, 1253, 1155, 1039, 750 cm–1. H NMR (400 MHz, CDCl3): d = 7.28 (t, J = 7.6 Hz, 1 H), 7.21 (dd, J1 = 7.1 Hz, J2 = 1.3 Hz, 1 H), 7.09 (ddd, J1 = 7.8 Hz, J2 = 7.1 Hz, J3 = 1.5 Hz, 1 H), 7.00 (d, J = 7.1 Hz, 1 H), 6.98 (s, 1 H), 6.86 (ddd, J1 = 7.6 Hz, J2 = 2.5 Hz, J3 = 0.6 Hz, 1 H), 6.71 (t, J1 = 7.1 Hz, 1 H), 6.53 (d, J = 7.6 Hz, 1 H), 4.68 (d, J = 10.9 Hz, 1 H), 4.38 (d, J = 2.8 Hz, 1 H), 4.10 (ddt, J1 = 11.1 Hz, J2 = 4.5 Hz, J3 = 2.3 Hz, 1 H), 3.80 (s, 3 H), 3.72 (td, J1 = 11.1 Hz, J2 = 2.3 Hz, 1 H), 2.08 (m, 1 H), 1.84 (tdt, J1 = 13.6 Hz, J2 = 11.1 Hz, J3 = 4.5 Hz, 1 H), 1.65 (tt, J1 = 13.6 Hz, J2 = 4.5 Hz, 1 H), 1.50 (m, 1 H), 1.34 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 159.9 (C), 144.5 (C), 143.8 (C), 130.9 (CH), 129.6 (CH), 129.4 (CH), 120.7 (C), 120.3 (CH), 117.6 (CH), 114.3 (CH), 113.2 (CH), 74.5 (CH), 68.6 (CH2), 55.2 (CH3), 54.8 (CH), 38.8 (CH), 24.1 (CH2), 22.0 (CH2). 1

MS: m/z = 301 (M + 2)+, 299 (M)+, 254, 240, 220, 204, 144, 130, 115, 102, 89, 77, 65, 41. rac-(4aS,5S,10bS)-5-(4-Methoxyphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5m)15,47 IR (film): 3375, 2939, 1700, 1607, 1512, 1245, 1176, 1033, 751 cm–1. H NMR (400 MHz, CDCl3): d = 7.42 (dt, J1 = 7.3 Hz, J2 = 1.4 Hz, 1 H), 7.33 (d, J = 8.6 Hz, 2 H), 7.09 (dddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.4 Hz, J4 = 0.8 Hz, 1 H), 6.92 (d, J = 8.6 Hz, 2 H), 6.79 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.59 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.32 (d, J = 5.6 Hz, 1 H), 4.65 (d, J = 2.5 Hz, 1 H), 3.82 (s, 3 H), 3.59 (m, 1 H), 3.43 (td, J1 = 11.4 Hz, J2 = 2.6 Hz, 1 H), 2.12 (m, 1 H), 1.42–1.60 (m, 3 H), 1.34 (m, 1 H). C NMR (100 MHz, CDCl3): d = 159.0 (C), 143.3 (C), 133.1 (C), 128.0 (CH), 127.9 (CH), 127.6 (CH), 119.9 (C), 118.2 (CH), 114.3
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MS: m/z = 295 (M)+, 264, 250, 236, 224, 210, 193, 167, 144, 130, 115, 92, 77, 65. HRMS (ESI): m/z [M + H] calcd for C19H22NO2: 296.1645; found: 296.1647. rac-(4aS,5S,10bS)-5-(2-Methoxyphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (5o)51 IR (film): 3373, 2937, 2865, 1602, 1488, 1241, 1090, 753 cm–1.
1 H NMR (400 MHz, CDCl3): d = 7.55 (dd, J1 = 7.6 Hz, J2 = 1.5 Hz, 1 H), 7.42 (dt, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 7.28 (td. J1 = 8.1 Hz, J2 = 7.6 Hz, J3 = 1.5 Hz, 1 H), 7.08 (dddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, J4 = 0.8 Hz, 1 H), 6.98 (td, J1 = 7.6 Hz, J2 = 1.0 Hz, 1 H), 6.90 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 6.78 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.60 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.32 (d, J = 5.6 Hz, 1 H), 5.03 (d, J = 2.3 Hz, 1 H), 3.82 (s, 3 H), 3.58 (m, 1 H), 3.43 (td, J1 = 11.6 Hz, J2 = 2.4 Hz, 1 H), 2.33 (m, 1 H), 1.48– 1.58 (m, 3 H), 1.42 (m, 1 H).

Synthesis of Pyrano[3,2-c]quinolines

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rac-(4aS,5R,10bS)-5-(3,4,5-Trimethoxyphenyl)-3,4,4a,5,6,10bhexahydro-2H-pyrano[3,2-c]quinoline (6p) IR (film): 3353, 2938, 2838, 1593, 1495, 1238, 1126, 1083, 749 cm–1. H NMR (400 MHz, CDCl3): 7.22 (dd, J1 = 7.3 Hz, J2 = 1.5 Hz, 1 H), 7.10 (ddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, 1 H), 6.71 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.65 (s, 2 H), 6.54 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 4.64 (d, J = 10.9 Hz, 1 H), 4.38 (d, J = 2.8 Hz, 1 H), 4.11 (m, 1 H), 3.86 (s, 9 H), 3.73 (td, J1 = 11.6 Hz, J2 = 2.5 Hz, 1 H), 2.04 (m, 1 H), 1.85 (tdt, J1 = 13.4 Hz, J2 = 12.1 Hz, J3 = 4.5 Hz, 1 H), 1.67 (tt, J1 = 13.4 Hz, J2 = 4.8 Hz, 1 H), 1.53 (m, 1 H), 1.36 (m, 1 H).
13 C NMR (100 MHz, CDCl3): d = 153.7 (C), 145.0 (C), 138.4 (C), 137.8 (C), 131.4 (CH), 129.8 (CH), 121.1 (C), 118.0 (CH), 114.6 (CH), 104.9 (CH), 75.0 (CH), 69.0 (CH2), 61.3 (CH3), 56.6 (CH3), 55.5 (CH), 39.4 (CH), 24.5 (CH2), 22.4 (CH2). 1

MS: m/z = 355 (M)+, 325, 311, 297, 279, 264, 188, 167, 91, 77, 51.
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C NMR (100 MHz, CDCl3): d = 156.4 (C), 145.7 (C), 129.1 (C), 128.1 (CH), 127.9 (CH), 127.7 (CH), 127.1 (C), 120.2 (CH), 120.1 (CH), 118.0 (CH), 114.5 (CH), 110.3 (CH), 72.8 (CH), 60.7 (CH2), 55.3 (CH3), 52.6 (CH), 35.2 (CH), 25.6 (CH2), 18.5 (CH2). MS: m/z = 295 (M)+, 264, 250, 236, 224, 209, 188, 130, 115, 91, 77, 65. rac-(4aS,5R,10bS)-5-(2-Methoxyphenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (6o)51 IR (film): 3362, 2938, 2837, 1609, 1491, 1244, 1079, 755 cm–1.
1 H NMR (400 MHz, CDCl3): d = 7.44 (dd, H, J1 = 7.6 Hz, J2 = 1.5 Hz, 1 H), 7.25 (ddd, J1 = 8.1 Hz, J2 = 7.6 Hz, J3 = 1.5 Hz, 1 H), 7.23 (dd, J1 = 7.3 Hz, J2 = 1.5 Hz, 1 H), 7.07 (ddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, 1 H), 6.96 (td, J1 = 7.6 Hz, J2 = 0.8 Hz, 1 H), 7.84 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 6.68 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.51 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.19 (d, J = 10.1 Hz, 1 H), 4.41 (d, J = 3.0 Hz, 1 H), 4.01 (m, 1 H), 3.84 (s, 3 H), 3.68 (td, J1 = 11.1 Hz, J2 = 2.8 Hz, 1 H), 2.13 (m, 1 H), 1.92 (m, 1 H), 1.65 (tt, J1 = 13.6 Hz, J2 = 4.1 Hz, 1 H), 1.49 (dqd, J1 = 13.6 Hz, J2 = 4.1 Hz, J3 = 1.3 Hz, 1 H), 1.35 (m, 1 H). 13 C NMR (100 MHz, CDCl3): d = 157.5 (C), 145.1 (C), 130.9 (C), 130.5 (CH), 129.1 (CH), 128.4 (CH), 128.1 (CH), 120.9 (CH), 120.4 (C), 117.1 (CH), 114.0 (CH), 110.4 (CH), 74.1 (CH), 67.7 (CH2), 53.3 (CH3), 47.6 (CH), 38.2 (CH), 24.5 (CH2), 22.7 (CH2).

13

HRMS (ESI): m/z [M + H] calcd for C21H26NO4: 356.1856; found: 296.1852.

Acknowledgment
The authors thank the Funda??o de Amparo à Pesquisa do Estado de S?o Paulo (FAPESP), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Coordenadoria de Aperfei?oamento de Pessoal do Nível Superior (CAPES) and the Financiadora de Estudos e Projetos (FINEP) for financial support. We also thank CBMM - Companhia Brasileira de Mineralogia e Minera??o for NbCl5 samples.

References
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MS: m/z = 295 (M)+, 264, 250, 236, 224, 209, 167, 130, 115, 91, 77, 65. rac-(4aS,5S,10bS)-5-(3,4,5-Trimethoxyphenyl)-3,4,4a,5,6,10bhexahydro-2H-pyrano[3,2-c]quinoline (5p) IR (film): 3353, 2937, 2838, 1591, 1465, 1328, 1235, 1126, 1089, 735 cm–1. H NMR (400 MHz, CDCl3): d = 7.43 (dt, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 7.10 (dddd, J1 = 8.1 Hz, J2 = 7.3 Hz, J3 = 1.5 Hz, J4 = 0.8 Hz, 1 H), 6.81 (td, J1 = 7.3 Hz, J2 = 1.0 Hz, 1 H), 6.64 (s, 2 H), 6.63 (dd, J1 = 8.1 Hz, J2 = 1.0 Hz, 1 H), 5.32 (d, J = 5.6 Hz, 1 H), 4.61 (d, J = 2.5 Hz, 1 H), 3.89 (s, 6 H), 3.86 (s, 3 H), 3.60 (ddt, J1 = 11.4 Hz, J2 = 4.0 Hz, J3 = 2.0 Hz, 1 H), 3.43 (td, J1 = 11.4 Hz, J2 = 2.2 Hz, 1 H), 2.15 (m, 1 H), 1.45–1.59 (m, 3 H), 1.38 (m, 1 H). C NMR (100 MHz, CDCl3): d = 153.2 (C), 145.0 (C), 137.2 (C), 136.9 (C), 128.1 (CH), 127.7 (CH), 120.1 (C), 118.5 (CH), 114.5 (CH), 106.7 (CH), 103.7 (CH), 72.7 (CH), 60.9 (CH3), 60.6 (CH2), 59.6 (CH), 56.3 (CH3), 56.2 (CH3), 39.1 (CH), 25.4 (CH2), 18.3 (CH2). MS: m/z = 355 (M)+, 325, 311, 297, 279, 264, 188, 167, 91, 77, 51. HRMS (ESI): m/z [M + H] calcd for C21H26NO4: 356.1856; found: 296.1874.
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