A. Takahashi, S. Kawai, I. Hachiya, M. Shimizu
FULL PAPER
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(19.8 mg, 86% yield). H NMR (CDCl3): δ = 1.00 (t, J = 6.9 Hz, 3.82 (s, 3 H, OCH3), 3.91 (q, J = 7.1 Hz, 2 H, CH2), 4.05 (q, J =
3 H, CH3), 1.43 (s, 9 H, tBu), 2.07 (s, 3 H, CH3), 2.30 (dd, J = 7.6,
7.1 Hz, 2 H, CH2), 6.51 (s, 1 H, Ar), 6.82–6.85 (m, 2 H, Ar), 7.01–
17.4 Hz, 1 H, CHH), 2.75 (dd, J = 9.5, 15.0 Hz, 1 H, CHH), 2.96 7.05 (m, 2 H, Ar) ppm. 13C NMR (CDCl3): δ = 14.3, 14.4, 14.5,
(dd, J = 4.5, 15.0 Hz, 1 H, CHH), 2.98 (dd, J = 2.4, 3.4 Hz, 1 H, 15.4, 55.8, 58.6, 60.0, 62.1, 97.5, 113.3, 114.1, 123.4, 129.1, 130.1,
CHH), 3.77 (s, 3 H, OCH3), 3.79–3.84 (m, 1 H), 3.94–4.00 (m, 1
H, NCH), 4.09–4.15 (m, 2 H, CH2), 6.76–6.80 (m, 2 H, Ar), 6.81–
6.94 (m, 2 H, Ar) ppm. 13C NMR (CDCl3): δ = 13.8, 14.2, 29.7,
29.7, 41.8, 48.2, 50.1, 55.4, 60.1, 64.4, 114.2, 124.2, 130.0, 134.7,
131.9, 136.3, 159.7, 161.8, 167.2 ppm. IR (neat): ν = 2979, 2933,
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1756, 1701, 1513, 1442, 1374, 1341, 1297, 1248, 1190, 1094, 1065,
832, 755, 665 cm–1. HRMS (EI): calcd. for C23H31NO7 [M]+
433.2101; found 433.2094.
142.3, 156.5, 162.9, 198.1 ppm. IR (neat): ν = 2963, 1679, 1512,
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Ethyl
5-(Ethoxycarbonyldiethoxymethyl)-1-(diphenylmethyl)-3-
1247, 1164, 1091, 1034 cm–1. HRMS (EI): calcd. for C21H29NO4S
[M]+ 391.1817; found 391.1823.
phenyl-1H-pyrrole-2-carboxylate (11c): Yellow oil (9.8 mg, 100%
yield). 1H NMR (CDCl3): δ = 0.68 (t, J = 7.0 Hz, 3 H, CH3), 1.07–
1.13 (m, 9 H, CH3), 3.38–3.50 (m, 6 H, CH2), 3.66 (q, J = 7.0 Hz,
2 H, CH2), 6.77 (s, 1 H, Ph2CH), 7.15–7.32 (m, 14 H, Ar), 7.38–
7.41 (m, 2 H, Ar) ppm. 13C NMR (CDCl3): δ = 13.4, 14.0, 14.6,
58.5, 60.4, 61.9, 63.8, 97.8, 111.9, 123.3, 126.3, 127.0, 127.5, 127.8,
Ethyl 5-Cyano-1-(4-methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyr-
role-2-carboxylate (10a): Yellow oil (41.8 mg, 100% yield). 1H
NMR (CDCl3): δ = 0.94 (t, J = 7.1 Hz, 3 H, CH3), 3.32 (dd, J =
8.3, 16.2 Hz, 1 H, CHH), 3.52 (dd, J = 10.9, 16.2 Hz, 1 H, CHH),
3.80 (s, 3 H, OCH3), 3.98–4.07 (m, 2 H, CH2), 4.50 (dd, J = 8.3, 128.4, 128.6, 128.9, 133.0, 135.5, 138.9, 162.6, 167.7 ppm. IR
10.9 Hz, 1 H, NCH), 6.88–6.91 (m, 2 H, Ar), 7.16–7.20 (m, 2 H, (neat): ν = 3062, 2980, 2935, 2898, 1718, 1497, 1451, 1392, 1349,
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Ar), 7.26–7.40 (m, 5 H, Ar) ppm. 13C NMR (CDCl3): δ = 13.5,
39.1, 55.4, 55.9, 61.2, 114.8, 118.7, 122.7, 125.5, 127.4, 127.7, 128.2,
1301, 1255, 1194, 1127, 1089, 856, 828, 758, 699, 668 cm–1. HRMS
(EI): calcd. for C34H37NO6 [M]+ 555.2621; found 555.2628.
133.3, 138.1, 158.1, 162.0 ppm. IR (neat): ν = 2922, 2853, 2227,
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Ethyl
2-(Ethoxycarbonyldiethoxymethyl)-1-[4-(dimethylamino)-
1718, 1512, 1461, 1254, 1181, 804, 763 cm–1. HRMS (EI): calcd.
for C21H20N2O3 [M]+ 348.1474; found 348.1477.
phenyl]-3-phenyl-1H-pyrrole-2-carboxylate (11d): Yellow oil
(5.9 mg, 66% yield). H NMR (CDCl3): δ = 0.88 (t, J = 7.0 Hz, 3
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Ethyl 5-Cyano-1-(4-methoxyphenyl)-3-methyl-4,5-dihydro-1H-pyr-
role-2-carboxylate (10b): Yellow oil (30.0 mg, 86% yield). 1H NMR
(CDCl3): δ = 1.02 (t, J = 7.1 Hz, 3 H, CH3), 2.08 (s, 3 H, CH3),
2.87 (dd, J = 7.8, 17.0 Hz, 1 H, CHH), 3.15 (dd, J = 10.9, 17.2 Hz,
1 H, CHH), 3.78 (s, 3 H, OCH3), 3.99–4.14 (m, 2 H, CH2), 4.26
(dd, J = 7.7, 10.7 Hz, 1 H, NCH), 6.83–6.86 (m, 2 H, Ar), 7.05–
7.02 (m, 2 H, Ar) ppm. 13C NMR (CDCl3): δ = 13.7, 40.8, 55.4,
H, CH3), 1.17 (t, J = 7.0 Hz, 3 H, CH3), 1.22 (t, J = 7.0 Hz, 6 H,
CH3), 2.97 [s, 6 H, N(CH3)2], 3.37–3.43 (m, 2 H, CH2), 3.47–3.53
(m, 2 H, CH2), 3.91–3.96 (m, 4 H, CH2), 6.62–6.65 (m, 2 H, Ar),
6.73 (s, 1 H, Ar), 7.00–7.05 (m, 2 H, Ar), 7.26–7.30 (m, 1 H, Ar),
7.33–3.36 (m, 2 H, Ar), 7.49–7.51 (m, 2 H, Ar) ppm. 13C NMR
(CDCl3): δ = 13.5, 14.0, 14.9, 40.4, 58.1, 59.9, 61.6, 97.0, 110.9,
112.6, 126.6, 127.6, 129.1, 129.3, 131.2, 135.9, 136.1, 150.2, 161.3,
56.0, 60.6, 114.5, 119.3, 124.3, 127.3, 134.3, 140.6, 157.4, 166.6 ppm. IR (neat): ν = 2979, 2933, 2894, 1757, 1710, 1612, 1523,
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161.8 ppm. IR (neat): ν = 2981, 1716, 1509, 1374, 1247, 1178, 1141,
1477, 1447, 1373, 1341, 1259, 1191, 1097, 1062, 820, 764, 730 cm–1.
HRMS (EI): calcd. for C29H36N2O6 [M]+ 508.2573; found
508.2580.
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1033, 832 cm–1. HRMS (EI): calcd. for C16H18N2O3 [M]+ 286.1317;
found 286.1321.
Typical Procedure for the Oxidation of Dihydro-1H-pyrroles 8–10
to -1H-pyrroles 11–13. Synthesis of Ethyl 5-(tert-Butylthiocarbon-
ylmethyl)-1-(4-methoxyphenyl)-3-phenyl-1H-pyrrole-2-carboxylate
(12a): Under argon, a solution of 9a (20.4 mg, 0.045 mmol) in 1,4-
dioxane (1.0 mL) was added to a solution of 2,3-dichloro-5,6-dicy-
ano-1,4-benzoquinone (DDQ; 10.5 mg, 0.04 mmol) in 1,4-dioxane
Ethyl
5-(tert-Butylthiocarbonylmethyl)-1-(4-methoxyphenyl)-3-
phenyl-1H-pyrrole-2-carboxylate (12a): Yellow oil (12.5 mg, 62%
yield). H NMR (CDCl3): δ = 0.88 (t, J = 7.1 Hz, 3 H, CH3), 1.40
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(s, 9 H, tBu), 3.53 (s, 2 H, CH2), 3.87 (s, 3 H, OCH3), 3.94 (q, J =
7.1 Hz, 2 H, CH2), 6.30 (s, 1 H, Ar), 6.92–6.95 (m, 2 H, Ar), 7.18–
7.22 (m, 2 H, Ar), 7.31–7.38 (m, 3 H, Ar), 7.48–7.51 (m, 2 H,
(1.0 mL) at room temperature. The mixture was stirred for 12.5 h Ar) ppm. 13C NMR (CDCl3): δ = 13.5, 29.6, 42.2, 48.2, 55.4, 59.7,
at room temperature. Saturated aqueous 10% NaHSO3 (5.0 mL)
was added to quench the reaction. The mixture was extracted with
ethyl acetate (10 mLϫ3) and the combined extracts were dried
with Na2SO4 and concentrated in vacuo to give a crude product.
Purification by TLC on silica gel (n-hexane/ethyl acetate = 1:1) gave
12a (12.5 mg, 62%).
112.4, 113.9, 121.2, 126.7, 127.5, 129.1, 129.5, 131.6, 131.9, 133.1,
136.0, 159.3, 161.0, 196.1 ppm. IR (neat): ν = 2962, 1701, 1607,
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1511, 1467, 1250, 1178, 1036, 978, 833, 759, 699 cm–1. HRMS (EI):
calcd. for C26H29NO4S [M]+ 451.1817; found 451.1822.
Ethyl 5-(tert-Butylthiocarbonylmethyl)-1-[4-(dimethylamino)phenyl]-
3-phenyl-1H-pyrrole-2-carboxylate (12b): Yellow oil (8.2 mg, 93%
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Ethyl
5-(Ethoxycarbonyldiethoxymethyl)-1-(4-methoxyphenyl)-3-
yield). H NMR (CDCl3): δ = 1.26 (t, J = 7.1 Hz, 3 H), 1.41 (s, 9
phenyl-1H-pyrrole-2-carboxylate (11a): Yellow oil (138.7 mg, 100%
yield). 1H NMR (CDCl3): δ = 0.88 (t, J = 7.0 Hz, 3 H, CH3), 1.16–
1.26 (m, 9 H, CH3), 3.36–3.42 (m, 2 H, CH2), 3.46–3.52 (m, 2 H,
H, tBu), 3.00 [s, 6 H, N(CH3)2], 3.54 (s, 2 H, CH2), 3.95 (q, J =
7.1 Hz, 2 H, CH2), 6.28 (s, 1 H, Ar), 6.69–6.72 (m, 2 H, Ar), 7.10–
7.13 (m, 2 H, Ar), 7.30–7.50 (m, 5 H, Ar) ppm. 13C NMR (CDCl3):
CH2), 3.84 (s, 3 H, OCH3), 3.93 (q, J = 7.0 Hz, 4 H, OCH2), 6.74 δ = 13.6, 29.7, 40.5, 42.4, 48.2, 59.7, 111.8, 112.0, 121.2, 126.6,
(s, 1 H, CH), 6.87–6.89 (m, 2 H, Ar), 7.12–7.14 (m, 2 H, Ar), 7.27–
7.30 (m, 1 H, Ar), 7.37–7.34 (m, 2 H), 7.49–7.51 (m, 2 H) ppm.
13C NMR (CDCl3): δ = 13.5, 14.0, 14.9, 55.3, 58.2, 60.0, 61.8, 97.0,
113.0, 122.7, 126.7, 127.6, 129.3, 129.7, 130.9, 131.6, 135.7, 135.8,
127.5, 128.6, 129.6, 132.2, 132.8, 136.4, 150.1, 161.2, 196.4 ppm.
IR (neat): ν = 2919, 1701, 1610, 1522, 1344, 1158, 1034, 760 cm–1.
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HRMS (EI): calcd. for C27H32N2O3S [M]+ 464.2134; found
464.2122.
159.5, 161.2, 166.7 ppm. IR (neat): ν = 3018, 2981, 2929, 1754,
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Ethyl 5-(tert-Butylthiocarbonylmethyl)-1-(2,4-dimethoxyphenyl)-3-
phenyl-1H-pyrrole-2-carboxylate (12c): Yellow oil (12.2 mg, 97%
yield). H NMR (CDCl3): δ = 0.89 (t, J = 7.1 Hz, 3 H, CH3), 1.39
1698, 1611, 1513, 1297, 1250, 1216, 1191, 1096, 1065, 756 cm–1.
HRMS (EI): calcd. for C28H33NO7 [M]+ 495.2257; found 495.2271.
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Ethyl
5-(Ethoxycarbonyldiethoxymethyl)-1-(4-methoxyphenyl)-3-
(s, 9 H, tBu), 3.42 (d, J = 16.5 Hz, 1 H, CHH) 3.58 (d, J = 16.5 Hz,
1 H, CHH), 3.74 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 3.95 (q, J
= 7.1 Hz, 2 H, CH2), 6.31 (s, 1 H, Ar), 6.53–6.55 (m, 2 H, Ar),
methyl-1H-pyrrole-2-carboxylate (11b): Yellow oil (7.3 mg, 95%
yield). 1H NMR (CDCl3): δ = 1.08 (t, J = 7.1 Hz, 3 H, CH3), 1.13–
1.25 (m, 9 H, CH3), 2.38 (s, 3 H, CH3), 3.30–3.48 (m, 4 H, CH2), 7.12–7.15 (m, 2 H, Ar), 7.29–7.37 (m, 3 H, Ar), 7.49–7.53 (m, 2 H,
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Eur. J. Org. Chem. 2010, 191–200