Bridged Azabicycles from Pyridines and Pyrrole
FULL PAPER
125.46 (CH), 117.86 (2×CH2), 55.14 (CH), 53.55 (CH), 41.88 17.1 Hz, 1 H), 1.67 (s, 3 H), 1.40 (s, 9 H) ppm. 13C NMR
(CH2), 41.85 (CH2), 37.80 (CH2), 24.16 (CH3) ppm. MS (70 eV, (100 MHz, [D6]DMSO): δ = 154.79 (C=O), 137.28 (CH), 136.81
EI): m/z 177 [M]+ (3), 162 (5), 136 (100), 95 (20), 80 (25), 69 (23), (CH), 130.32 (C), 120.45 (CH), 118.05 (CH2), 117.89 (CH2), 79.82
57 (66), 44 (27), 41 (51), 40 (65). C12H19N (177.3): calcd. C 81.30,
H 10.80, N 7.90; found C 81.16, 10.83, N 8.00.
(C–O), 52.12 (br.), 48.12 (br.), 42.17 (br.), 39.92, 33.25 (br.), 29.18
(3×CH3), 24.54 ppm. MS (70 eV, EI): m/z 277 [M]+ (0.2), 236 (10),
196 (21), 180 (54), 152 (20), 136 (35), 94 (52), 69 (87), 57 (100), 55
(22), 41 (70), 39 (35). C17H27NO2 (277.4): calcd. C 73.61, H 9.81,
N 5.05; found: C 73.47, H 9.76, N 5.11.
trans-2,6-Diallyl-4-bromo-1,2,3,6-tetrahydropyridine (1c): The pro-
cedure was the same as that used for 1b. Yield: 75% as a colorless
liquid, which became red upon standing, b.p. 93–94 °C (1 Torr). 1H
NMR (400 MHz, CDCl3): δ = 6.00 (s, 1 H), 5.76–5.65 (m, 2 H),
5.10–5.03 (m, 4 H), 3.41 (s, 1 H), 3.04 (m, 1 H), 2.40 (dd, J = 4.4,
17.1 Hz, 1 H), 2.28–2.17 (m, 4 H), 2.12 (m, 1 H), 1.91 (br. s, 1 H,
NH) ppm. 13C NMR (75 MHz, C6D6): δ = 135.24, 134.90, 130.84,
120.21, 117.55, 117.38, 53.89, 48.69, 41.13, 39.51, 38.95 ppm.
C11H16BrN (242.2): calcd. C 54.56, H 6.66, N 5.78, Br 33.00; found
C 54.48, H 6.67, N 5.71, Br 32.91.
tert-Butyl cis-2,6-Diallyl-1,2,3,6-tetrahydropyridine-1-carboxylate
(3a): Yield: 97%, as a colorless oil, b.p. 96–97 °C (0.1 Torr) 1H
NMR (400 MHz, [D6]DMSO): δ = 5.79–5.71 (m, 1 H), 5.70–5.67
(m, 3 H), 5.09–4.99 (m, 4 H), 4.36 (br. 1 H), 4.13 (br. 1 H), 2.41
(br. 1 H), 2.20–2.10 (br. 4 H), 2.00 (dd, J = 4.9, 17.1 Hz, 1 H), 1.40
(s, 9 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 153.29,
135.97, 135.37, 125.68, 121.67, 116.96, 116.65, 78.66, 50.93 (br.),
45.98 (br.), 40.40 (br.), 38.52, 27.93, 27.93, 27.14 (br.) ppm. MS
(70 eV, EI): m/z 263 [M]+ (1), 222 (16), 167 (28), 166 (80), 122 (73),
85 (46), 80 (73), 71 (60), 69 (41), 57 (100), 55 (36), 41 (61).
C16H25NO2 (263.4): calcd. C 72.96, H 9.57, N 5.32; found C 72.94,
H 9.62, N 5.08.
cis-2,6-Diallyl-4-bromo-1,2,3,6-tetrahydropyridine (2c): The pro-
cedure was the same as that used for 2b. Yield: 92% as a colorless
liquid, which became red upon standing. 1H NMR (400 MHz,
CDCl3): δ = 5.95 (s, 1 H), 5.79–5.68 (m, 2 H), 5.18–5.07 (m, 4 H),
3.42 (s, 1 H), 2.92 (m, 1 H), 2.37–2.12 (m, 6 H), 1.93 (br. s, 1 H,
NH) ppm. 13C NMR (75 MHz, C6D6): δ = 134.47, 134.41, 131.16,
120.82, 117.84, 117.62, 56.05, 53.68, 41.75, 40.25, 40.01 ppm. MS
(70 eV, EI): m/z 243 [M]+ (0.6), 202 (46), 200 (55), 160 (96), 158
(100), 120 (87), 93 (33), 91 (44), 80 (76), 79 (57), 77 (50), 65 (27),
57 (23), 51 (36), 41 (69), 39 (69). C11H16BrN (242.2): calcd. C 54.56,
H 6.66, N 5.78, Br 33.00; found: C 54.51, H 6.69, N 5.73, Br 32.89.
tert-Butyl cis-2,6-Diallyl-4-bromo-1,2,3,6-tetrahydropyridine-1-car-
boxylate (3c): Yield: 95%, as a colorless oil, b.p. 122–123 °C
(0.1 Torr). 1H NMR (300 MHz, C6D6): δ = 6.09 (s, 1 H), 5.82–5.68
(m, 2 H), 5.12–5.03 (m, 4 H), 4.63–4.22 (br. m, 2 H), 2.61–2.48 (br.
m, 2 H), 2.34–2.26 (m, 2 H), 2.19–2.08 (m, 2 H), 1.53 (s, 9 H) ppm.
13C NMR (75 MHz, C6D6): δ = 153.73, 135.43, 134.74, 126.91,
117.47, 117.19, 79.31, 53.80, 49.28 (br.), 40.59 (br.), 39.02, 37.46,
28.12 (3×CH3) ppm. MS (70 eV, EI): m/z 342 [M]+ (0.6), 246 (20),
244 (21), 202 (39), 200 (42), 160 (38), 158 (38), 120 (42), 91 (45),
82 (58), 80 (55), 79 (43), 77 (42), 57 (100), 56 (28), 51 (40), 41 (90),
39 (77). C16H24BrNO2 (342.3): calcd. C 56.15, H 7.07, N 4.09, Br
23.35; found: C 56.11, H 7.12, N 4.05, Br 23.30.
cis-1,3-Diallyl-1,2,3,4-tetrahydroisoquinoline (2e): trans-1,3-Diallyl-
1,2,3,4-tetrahydroisoquinoline 1e[6] (9.5 g, 46.8 mmol) and neat tri-
allylborane (8.4 mL, 6.7 g, 50 mmol) were mixed with stirring at
room temperature and the mixture was heated at 130–135 °C for
2 h. After being cooled the reaction mixture was quenched with
MeOH (20 mL) and heated under reflux for 1 h. In order to com-
plete deboronation, NaOH (5 n, 30 mL, 150 mmol) was added with
stirring, and the organic layer was diluted with hexane (30 mL)
and separated, dried with K2CO3, filtered, and concentrated under
reduced pressure. According to 1H NMR the residue was a mixture
of 1e and 2e in 1:1 ratio, yield of the mixture 9.1 g (96%) as a
reddish oil. The mixture was subjected to flash chromatography on
silica gel in hexane/AcOEt/Et3N, 30:8:1; Rf(1e) = 0.38 and Rf(2e)
= 0.5. Isomer 2e was isolated as a white crystalline solid, yield 4.5 g
(98%) calculated from the relative content in the mixture of iso-
mers. It was also possible to separate 2e by consecutive crystalli-
zations of the mixture from chilled hexane, which gave 2e in 85%
tert-Butyl cis-2,6-Diallyl-5-bromo-1,2,3,6-tetrahydropyridine-1-car-
boxylate (3d): Yield: 94%, as colorless oil, b.p. 138–139 °C
(0.2 Torr). 1H NMR (400 MHz, CDCl3): δ = 6.06 (m, 1 H), 5.91
(dq, J = 7.8, 16.8 Hz, 1 H), 5.79–5.69 (m, 1 H), 5.09–5.01 (m, 4
H), 4.63–4.51 (br. m, 2 H), 2.86 (m, 1 H), 2.41–2.25 (m, 4 H), 2.11
(dd, J = 5.9, 17.4 Hz, 1 H), 1.45 (s, 9 H) ppm. 13C NMR (75 MHz,
C6D6): δ = 154.10, 135.73, 133.57, 127.17, 122.09, 117.86, 116.87,
79.43, 59.26, 50.57, 38.36, 36.27, 28.88, 28.14 (3 CH3) ppm.
C16H24BrNO2 (342.3): calcd. C 56.15, H 7.07, N 4.09, Br 23.35;
found: C 56.14, H 7.09, N 4.00, Br 23.28.
tert-Butyl cis-1,3-Diallyl-1,2,3,4-tetrahydroisoquinoline-1-carboxyl-
ate (3e): Yield: 98%, as a yellow oil. Rf = 0.77 (hexane/AcOEt,
4:1). 1H NMR (400 MHz, CDCl3): δ = 7.16 (s, 3 H), 7.11 (m, 1 H),
5.94–5.79 (br. m, 2 H), 5.26–5.05 (br. m, 4 H), 5.27 and 4.90 (br.
signal, total 1 H), 4.37 and 4.05 (br. signal, total 1 H), 2.96 (dd, J
= 6.8, 15.6 Hz, 1 H), 2.80 (dd, J = 7.8, 15.8 Hz, 1 H), 2.64 (br. s,
1 H), 2.59–2.48 (br. m, 2 H), 2.32–2.25 (m, 1 H), 1.48 (s, 9 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 154.98, 135.54 (br.), 134.90,
132.93 (br.), 128.26/127.92 (br. d), 126.70, 126.26 (br.), 125.89,
117.09, 116.65, 79.67, 54.94, 51.00/49.43 (br. d), 42.49/41.79 (br. d),
41.37 (br.), 39.68 (br.), 32.14 (br.), 28.19 (3×CH3) ppm. MS (70 eV,
EI): m/z 313 [M]+ (0.5), 272 (12), 216 (80), 172 (80), 130 (92), 115
(25), 83 (46), 77 (28), 69 (55), 57 (100), 56 (41), 41 (81), 39 (47).
C20H27NO2 (313.4): calcd. C 76.64, H 8.68, N 4.47; found C 76.69,
H 8.59, N 4.51.
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total yield, m.p. 60–61 °C. H NMR (400 MHz, CDCl3): δ = 7.22
(d, J = 6.8 Hz, 1 H), 7.17–7.11 (m, 2 H), 7.08 (d, J = 6.2 Hz, 1 H),
5.87–5.74 (m, 2 H), 5.24–5.12 (m, 4 H), 4.05 (d, J = 7.5 Hz, 1 H),
2.95–2.84 (m, 2 H), 2.73 (dd, J = 3.1, 15.9 Hz, 1 H), 2.62 (dd, J =
11.2, 15.8 Hz, 1 H), 2.49 (br. s, 1 H, NH), 2.45–2.23 (m, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 133.96, 131.46, 131.00, 130.83,
125.15, 122.10, 121.87, 120.93, 114.41, 113.79, 51.71, 48.44, 36.89,
36.02, 32.28 ppm. MS (70 eV, EI): m/z 213 [M]+ (1), 212 (4), 172
(92), 131 (37), 130 (100), 129 (27), 116 (10), 115 (16), 91 (16), 77
(22), 58 (26), 41 (32), 39 (38). C15H19N (213.3): calcd. C 84.46, H
8.98, N 6.57; found C 84.67, H 9.12, N 6.55.
tert-Butyl cis-2,6-Diallyl-4-methyl-1,2,3,6-tetrahydropyridine-1-car-
boxylate (3b): Amine 2b (4 g, 22.6 mmol) and Boc2O (5.2 g,
24 mmol) in THF (5 mL) solution were heated under reflux for
1 hour. The solvent was removed by evaporation and the residue
was distilled in vacuo to give 3b (5.7 g, 91%) as a colorless oil, b.p.
tert-Butyl 2,5-Diallylpyrrolidine-1-carboxylate (mixture of cis and
trans isomers, 2.3:1) (3f): The isomerization of trans-2,5-diallylpyr-
102–104 °C (0.1 Torr). 1H NMR (400 MHz, [D6]DMSO): δ = 5.85– rolidine was carried out at 185–190 °C over 5 hours.[7b] The reac-
5.67 (m, 2 H), 5.39 (s, 1 H), 5.08–4.98 (m, 4 H), 4.36 (br. s, 1 H), tion with Boc2O was conducted as described for 3b. Yield: 98%,
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4.10 (br. s, 1 H), 2.39 (br. s, 1 H), 2.16 (m, 4 H), 1.83 (d, J =
as a colorless oil, b.p. 105–108 °C (0.5 Torr). H NMR (400 MHz,
Eur. J. Org. Chem. 2006, 113–120
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