E. Dubost, D. Le Nouën, J. Streith, C. Tarnus, T. Tschamber
[Pd(PPh3)4] (48 mg, 0.30 mmol) and CuI (12 mg, 0.06 mmol) by from a solution of 29 (474 mg, 0.68 mmol) in DMF (15 mL) and
FULL PAPER
heating for 12 h analogously to 45. It was isolated after chromatog-
phenylacetylene (375 µL, 3.42 mmol), NEt3 (480 µL, 3.42 mmol),
[Pd(PPh3)4] (53 mg, 0.34 mmol) and CuI (13 mg, 0.068 mmol) by
heating for 12 h analogously to 45. It was isolated after chromatog-
raphy (EtOAc/cyclohexane, 1:9) as a brownish oil (299 mg, quant.)
and used directly for the next step. [α]2D0 = –24 (c = 1, CHCl3). H
1
NMR (400 MHz, CDCl3): δ = 1.50–1.65 (m, 4 H, CH2 of cyclohex- raphy (EtOAc/cyclohexane, 1:9) as a brownish oil (311 mg, 71%).
ene), 2.1 (m, 2 H, CH2 of cyclohexene), 2.2 (m, 2 H, CH2 of cyclo-
hexene), 4.00 (dd, 1 H, H-5a), 4.05 (dd, 1 H, H-5b), 4.11 (dd, 1 H,
H-7), 4.32 (ddd, 1 H, H-6), 4.50 and 4.56 (AB, Jgem = 11.9 Hz, 2
H, CH2Ph), 4.61 and 4.64 (AB, Jgem = 12.5 Hz, 2 H, CH2Ph), 4.67
[α]2D0 = +40 (c = 1, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 4.07
(dd, 1 H, H-5a), 4.15 (dd, 1 H, H-7), 4.20 (dd, 1 H, H-5b), 4.38
(ddd, 1 H, H-6), 4.57 and 4.63 (AB, Jgem = 11.9 Hz, 2 H, CH2Ph),
4.68 (s, 2 H, CH2Ph), 4.70 and 4.90 (AB, Jgem = 11.9 Hz, 2 H,
(d, 1 H, H-8), 4.65 and 4.85 (AB, Jgem = 11.9 Hz, 2 H, CH2Ph), CH2Ph), 4.73 (br. d, 1 H, H-8), 7.21–7.40, 7.50–7.54 (m, 25 H, CH
6.17 (m, 1 H, H-2Ј), 6.94 (s, 1 H, H-3), 7.21–7.34 (m, 15 H, CH arom.) ppm; J5a,6 = 9.8, J5b,6 = 5.8, J5a,5b = 12.1, J6,7 = 1.8, J7,8
arom.) ppm; J5a,6 = 6.4, J5b,6 = 8.5, J5a,5b = 11.7, J6,7 = 1.5, J7,8
3.8 Hz. 13C NMR (100.6 MHz, CDCl3): δ = 43.8 (C-5), 70.7 (C-8),
3.6 Hz. 13C NMR (100.6 MHz, CDCl3): δ = 21.4, 22.2, 25.6, 28.9
71.8 (CH2Ph), 71.8 (CH2Ph), 71.9 (C-6), 72.6 (CH2Ph), 74.4 (C-7),
=
=
(CH2 of cyclohexene), 44.5 (C-5), 70.5 (C-8), 71.4, 71.5, 71.7, 72.3 76.5 (C-3-CCPh), 82.5 (C-2-CCPh), 92.7 (C-3-CCPh), 99.9 (C-2-
(3×CH2Ph, C-6), 74.7 (C-7), 80.2, 90.9 (CC-cyclohex.), 120.5 (C- CCPh), 119.3 (C-3), 122.3, 123.1 (2 × Cquat. of phenyls), 127.6–
1Ј), 122.2 (C-3), 124.7 (C-2), 127.4–128.3 (CH of phenyls), 134.6
(C-2Ј), 137.5, 137.6, 137.9 (Cquat. of phenyls), 142.4 (C-8a) ppm.
128.9 (CH of phenyls of benzyls, C-2), 131.5, 131.6 (CH of phen-
yls), 137.6, 137.7, 137.8 (3×Cquat. of phenyls of benzyls), 143.5 (C-
8a) ppm. HR-MS: calcd. for [M]+ (C44H36N2O3) 640.2726; found
640.2723.
(6S,7S,8S)-6,7,8-Tris(benzyloxy)-3-(pyridin-2-ylethynyl)-5,6,7,8-te-
trahydroimidazo[1,2-a]pyridine (50): This compound was prepared
from a solution of 28 (222 mg, 0.39 mmol) in DMF (8 mL) and
2-ethynylpyridine (198 µL, 1.96 mmol), NEt3 (275 µL, 1.96 mmol),
[Pd(PPh3)4] (31 mg, 0.19 mmol) and CuI (22 mg, 0.12 mmol) by
heating for 3 h analogously to 45. It was isolated after chromatog-
raphy (EtOAc/cyclohexane, 4:6) as a brownish oil (220 mg, quant.).
{(6S,7S,8S)-6,7,8-Tris(benzyloxy)-2-(phenylethynyl)-5,6,7,8-tetrahy-
droimidazo[1,2-a]pyridin-3-yl}methanol (53): This compound was
prepared from a solution of 37 (100 mg, 0.167 mmol) in DMF
(3 mL) and phenylacetylene (93 µL, 0.84 mmol), NEt3 (117 µL,
0.84 mmol), [Pd(PPh3)4] (13 mg, 0.08 mmol) and CuI (3 mg,
0.02 mmol) by heating for 12 h analogously to 45. It was isolated
after chromatography (EtOAc/cyclohexane, 3:7) as a brownish oil
(72 mg, 75%). [α]2D0 = +11 (c = 0.7, CH2Cl2). 1H NMR (400 MHz,
CDCl3): δ = 4.08 (dd, 1 H, H-5a), 4.11 (dd, 1 H, H-7), 4.24 (dd, 1
H, H-5b), 4.33 (ddd, 1 H, H-6), 4.54 and 4.57 (AB, Jgem = 11.9 Hz,
2 H, CH2Ph), 4.62 and 4.65 (AB, Jgem = 12.2 Hz, 2 H, CH2Ph),
20
20
1
[α] = +86 (c = 0.9, CHCl3), [α] = +92 (c = 0.9, CHCl3). H
578
546
NMR (400 MHz, CDCl3): δ = 4.13 (dd, 1 H, H-7), 4.14 (dd, 1 H,
H-5a), 4.28 (dd, 1 H, H-5b), 4.35 (ddd, 1 H, H-6), 4.58 and 4.61
(AB, Jgem = 12.0 Hz, 2 H, CH2Ph), 4.68 (s, 2 H, CH2Ph), 4.71 and
4.88 (AB, Jgem = 11.9 Hz, 2 H, CH2Ph), 4.78 (d, 1 H, H-8), 7.17–
7.23 (m, 1 H, H-5Ј), 7.25–7.36 (m, 15 H, CH arom.), 7.43–7.49 (m,
2 H, H-2, H-3Ј), 7.57–7.65 (m, 1 H, H-4Ј), 8.56–8.59 (m, 1 H, H-
4.68 (d, 1 H, H-8), 4.70 and 4.76 (AB, 2 H, CH2OH, Jgem
13.5 Hz), 4.66 and 4.86 (AB, Jgem = 11.9 Hz, 2 H, CH2Ph), 7.24–
7.36, 7.48–7.52 (m, 20 H, CH of phenyls) ppm; J5a,6 = 9.6, J5b,6
=
6Ј) ppm; J5a,6 = 9.3, J5b,6 = 5.5, J5a,5b = 12.1, J6,7 = 1.5, J7,8
=
4.0 Hz. 13C NMR (100.6 MHz, CDCl3): δ = 43.5 (C-5), 70.9 (C-
8), 71.6 (2×CH2Ph), 72.0 (C-6), 72.6 (CH2Ph), 74.6 (C-7), 80.9
(CH2CH2-pyr.), 96.0 (CH2CH2-pyr.), 114.5 (C-3), 122.8 (C-5Ј),
126.8 (C-3Ј), 127.7–128.4 (CH phenyls), 135.6 (C-2), 136.1 (C-4Ј),
137.5, 137.6, 137.7 (Cquat. of phenyls), 142.8 (C-2Ј), 144.0 (C-8a),
150.0 (C-6Ј) ppm. HR-MS: calcd. for [M + H]+ (C35H32N3O3)
542.2444; found 542.2447.
=
5.7, J5a,5b = 12.0, J6,7 = 1.8, J7,8 = 4.0 Hz. 13C NMR (100.6 MHz,
CDCl3): δ = 43.2 (C-5), 53.8 (CH2OH), 70.9 (C-8), 71.6 (CH2Ph),
71.7, 71.8 (C-6, CH2Ph), 72.5 (CH2Ph), 74.5 (C-7), 82.1, 91.5 (C-
9, C-10), 123.1, 123.2 (C-2, C-3), 127.6–128.5 (CH of phenyls),
131.5 (CH of phenyls), 133.9 (Cquat. of phenyl),137.6, 137.7, 137.9
(3×Cquat. of phenyls of benzyls), 143.4 (C-8a) ppm. HR-MS: calcd.
for [M]+ (C37H34N2O4) 570.2519; found 570.2517.
(6S,7S,8S)-6,7,8-Tris(benzyloxy)-2-(pyridin-2-ylethynyl)-5,6,7,8-te-
trahydroimidazo[1,2-a]pyridine (51): This compound was prepared
from a solution of 31 (209 mg, 0.37 mmol) in DMF (8 mL) and
2-ethynylpyridine (187 µL, 1.84 mmol), NEt3 (260 µL, 1.84 mmol),
[Pd(PPh3)4] (29 mg, 0.18 mmol) and CuI (21 mg, 0.11 mmol) by
heating for 5 h analogously to 45. It was isolated after chromatog-
raphy (EtOAc/cyclohexane, 4:6) as a brownish foam (165 mg,
(6S,7S,8S)-3-(2-Phenylethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyr-
idine-6,7,8-triol (54): This compound was prepared from 45
(184 mg, 0.34 mmol) and EtOH/AcOH (1:1, 6 mL) and Pd(OH)2/
C (200 mg) under H2 analogously to 38. It was isolated after
chromatography (CH2Cl2/MeOH, 8:2) as a colourless oil (63 mg,
20
20
68%). [α] = +27 (c = 1.0, MeOH), [α] = +30 (c = 1.0, MeOH).
1
82%). [α]2D0 = –9 (c = 1, CHCl3). H NMR (400 MHz, CDCl3): δ
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546
1H NMR (400 MHz, CD3OD): δ = 2.82–2.96 (m, 4 H, CH2CH2),
3.73 (dd, 1 H, H-5a), 3.84 (dd, 1 H, H-5b), 3.95 (dd, 1 H, H-7),
4.33 (ddd, 1 H, H-6), 4.69 (d, 1 H, H-8), 6.72 (s, 1 H, H-2), 7.15–
7.19 (m, 3 H, CH arom.), 7.24–7.27 (m, 2 H, CH arom.) ppm; J5a,6
= 7.6, J5b,6 = 5.1 Hz, J5a,5b = 12.1, J6,7 = 2.0, J7,8 = 5.1 Hz. 13C
NMR (100.6 MHz, CD3OD): δ = 27.02 (CH2CH2Ph), 36.2
(CH2CH2Ph), 46.2 (C-5), 66.9 (C-6), 68.2 (C-8), 74.2 (C-7), 126.5
(C-2), 127.7 and 129.9 (CH of phenyls), 132.9 (C-3), 142.6 (Cquat.
of phenyl), 146.3 (C-8a) ppm. HR-MS: calcd. for [M + H]+
(C15H19N2O3) 275.1390; found 275.1389.
= 4.08 (dd, 1 H, H-5a), 4.12 (dd, 1 H, H-5b), 4.14 (dd, 1 H, H-7),
4.35 (ddd, 1 H, H-6), 4.54 and 4.60 (AB, Jgem = 12.0 Hz, 2 H,
CH2Ph), 4.66 (s, 2 H, CH2Ph), 4.68 and 4.87 (AB, Jgem = 11.9 Hz,
2 H, H-9), 4.70 (d, 1 H, H-8), 7.16 (s, 1 H, H-3), 7.17 (ddd, 1 H,
H-5Ј), 7.2–7.4 (m, 15 H, CH arom.), 7.52 (dt, 1 H, H-3Ј), 7.62 (td,
1 H, H-4Ј), 8.57 (ddd, 1 H, H-6Ј) ppm; J5a,6 = 6.7, J5b,6 = 8.7, J5a,5b
= 11.8, J6,7 = 1.6, J7,8 = 3.9, J3Ј,4Ј = 7.7, J3Ј,5Ј = 1.3, J4Ј,5Ј = 7.6,
J4Ј,6Ј = 1.8, J5Ј,6Ј = 5.0, J6Ј,3Ј = 1.2 Hz. 13C NMR (100.6 MHz,
CDCl3): δ = 44.7 (C-5), 70.5 (C-8), 71.5, 71.6, 71.7 (C-6 and
2×CH2Ph), 72.5 (CH2Ph), 74.7 (C-7), 83.3 (CC-pyr.), 88.7 (CC-
pyr.), 122.4 (C-5Ј), 123.6 (C-2), 124.3 (C-3), 126.9 (C-3Ј), 127.5–
128.5 (CH of phenyls), 136.0 (C-4Ј), 137.5, 137.6, 137.8 (Cquat. of
phenyls), 143.1, 143.4 (C-8a, C-2Ј), 149.8 (C-6Ј) ppm. HR-MS:
calcd. for [M + H]+ (C35H32N3O3) 542.2444; found 542.2448.
(6S,7S,8S)-2-(2-Phenylethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyr-
idine-6,7,8-triol (55): This compound was prepared from 46
(213 mg, 0.39 mmol) and EtOH/AcOH (1:1, 6 mL) and Pd(OH)2/
C (200 mg) under H2 analogously to 38. It was isolated after
(6S,7S,8S)-6,7,8-Tris(benzyloxy)-2,3-bis(phenylethynyl)-5,6,7,8-tetra- chromatography (CH2Cl2/MeOH, 95:5) as a colourless oil (60 mg,
= +3.6 (c = 1.1, MeOH). 1H NMR (400 MHz,
20
hydroimidazo[1,2-a]pyridine (52): This compound was prepared
56%). [α]
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622
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Eur. J. Org. Chem. 2006, 610–626