The Journal of Organic Chemistry
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127.8, 127.7, 127.1, 121.2, 51.7, 21.3; HRMS (ESI) m/z calcd for
C22H22NO4 (M + H)+ 364.1543, found 364.1550; IR (neat) 3445,
3294, 2952, 1710, 1464, 1438, 1305, 1252, 1037, 782, 494, 458, 421
cm−1.
= 8.0 Hz, 6H), 7.01 (d, J = 7.6 Hz, 2H), 3.58 (s, 6H), 2.29 (s, 6H); 13
C
NMR (100 MHz, CDCl3) δ ppm 160.4, 144.7, 135.0, 134.3, 129.8,
126.4, 125.8, 124.4, 123.4, 123.1, 122.1, 120.4, 114.7, 113.3, 51.8, 21.5;
HRMS (ESI) m/z calcd for C38H31N3O8S2K (M + K)+ 760.1184,
found 760.1193; IR (neat) 3408, 2924, 2854, 2361, 2324, 1715, 1407,
1374, 1261, 1166, 1076, 1025, 803, 751, 703, 664, 403 cm−1.
Tetramethyl 1H-pyrrole-2,3,4,5-tetracarboxylate (5v): 28 mg;
Dimethyl 3,4-bis(3-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate
1
(5n): 39 mg; isolated yield 71%; yellow solid; mp 156−158 °C; H
NMR (400 MHz, CDCl3) δ 9.84 (brs, 1H), 7.13 (t, J = 3.6 Hz, 2H),
6.77−6.74 (m, 4H), 6.64 (s, 2H), 3.78 (s, 6H), 3.63 (s, 6H); 13C NMR
(100 MHz, CDCl3) δ ppm 160.7, 158.7, 134.1, 131.3, 128.3, 123.4,
121.2, 116.1, 113.1, 55.1, 51.8; HRMS (ESI) m/z calcd for C22H22NO6
(M + H)+ 396.1442, found 396.1441; IR (neat) 3294, 2922, 2852,
2363, 1711, 1607, 1584, 1466, 1435, 1304, 1254, 1218, 1049, 1023,
783, 716, 627 cm−1.
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isolated yield 67%; yellow solid; mp 123−125 °C; H NMR (400
MHz, CDCl3) δ ppm 10.23 (brs, 1H), 3.92 (s, 6H), 3.89 (s, 6H); 13
C
NMR (100 MHz, CDCl3) δ ppm 163.2, 159.1, 123.3, 121.7, 52.7, 52.5;
HRMS (ESI) m/z calcd for C12H14NO8 (M + H)+300.0714, found
300.0721; IR (neat) 3242, 2956, 1725, 1571, 1450, 1262, 1058, 991,
792, 631, 545, 514, 470, 412 cm−1.
Dimethyl 3,4-diisopropyl-1H-pyrrole-2,5-dicarboxylate (5w): 16
mg; isolated yield 44%; yellow solid; mp 104−106 °C; 1H NMR (400
MHz, CDCl3) δ ppm 9.45 (brs, 1H), 3.87 (s, 6H), 3.63−3.59 (m, 2H),
1.33 (d, J = 7.2 Hz, 12H); 13C NMR (100 MHz, CDCl3) δ ppm 160.6,
137.5, 120.3, 51.5, 25.2, 21.5; HRMS (ESI) m/z calcd for C14H22NO4
(M + H)+ 268.1543, found 268.1555; IR (neat) 3389, 3353, 2958,
2941, 2868, 1715, 1467, 1442, 1372, 1248, 1029, 754, 663, 630, 514,
470, 410 cm−1.
Dimethyl 3,4-di-o-tolyl-1H-pyrrole-2,5-dicarboxylate (5o): 22 mg;
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isolated yield 44%; yellow solid; mp 182−184 °C; H NMR (400
MHz, CDCl3) δ ppm 9.88 (brs, 1H), 7.11−7.05 (m, 4H), 7.02 (d, J =
3.6 Hz, 2H), 7.97−6.94 (m, 1H), 6.84 (d, J = 7.6 Hz, 1H), 3.724 (s,
3H), 3.720 (s, 3H), 2.14 (s, 3H), 2.03 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ ppm 160.71, 160.70, 137.1, 136.7, 133.1, 132.6, 131.2, 131.2,
131.1, 129.8, 129.4, 129.2, 127.34, 127.31, 124.9, 124.6, 122.0, 121.9,
51.8, 20.2, 19.8; HRMS (ESI) m/z calcd for C22H22NO4 (M + H)+
364.1543, found 364.1544; IR (neat) 3290, 2923, 1711, 1463, 1296,
1243, 1011, 764, 732, 555, 468, 408 cm−1.
Dimethyl 3,4-dipropyl-1H-pyrrole-2,5-dicarboxylate (5x): 14 mg;
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isolated yield 38%; yellow solid; mp 53−55 °C; H NMR (400 MHz,
Dimethyl 3,4-bis(2-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate
CDCl3) δ ppm 9.39 (brs, 1H), 3.87 (s, 6H), 2.68 (q, J = 6.0 Hz, 4H),
1.57−1.47 (m, 4H), 0.95 (t, J = 7.2 Hz, 6H); 13C NMR (100 MHz,
CDCl3) δ ppm 161.1, 132.1, 121.3, 51.5, 26.5, 24.5, 14.2; HRMS (ESI)
m/z calcd for C14H22NO4 (M + H)+ 268.1543, found 268.1541; IR
(neat) 3457, 3319, 2958, 2869, 1711, 1559, 1464, 1438, 1349, 1261,
1201, 1144, 1097, 1030, 981, 789, 630, 514, 485, 413 cm−1.
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(5p): 23 mg; isolated yield 42%; yellow solid; mp 169−171 °C; H
NMR (400 MHz, CDCl3) δ ppm 9.85 (brs, 1H), 7.20−7.15 (m, 2H),
7.00−6.98 (m, 2H), 6.81−6.76 (m, 4H), 3.73 (s, 6H), 3.54 (s, 6H);
13C NMR (100 MHz, CDCl3) δ ppm 160.8, 157.1, 131.7, 128.5, 127.9,
122.7, 122.1, 119.6, 110.2, 55.2, 51.6; HRMS (ESI) m/z calcd for
C22H22NO6 (M + H)+ 396.1442, found 396.1440; IR (neat) 3428,
3288, 2923, 1714, 1464, 1246, 1028, 756, 447 cm−1.
Dimethyl 3,4-bis(2,5-dimethoxyphenyl)-1H-pyrrole-2,5-dicarbox-
ylate (5q): 28 mg, Isolated yield 45%; yellow solid; mp 149−150 °C;
1H NMR (400 MHz, CDCl3) δ ppm 9.84 (brs, 1H), 6.72 (d, J = 2.4
Dimethyl 3,4-diethyl-1H-pyrrole-2,5-dicarboxylate (5y): 9 mg;
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isolated yield 27%; yellow solid; mp 80−81 °C; H NMR (400 MHz,
CDCl3) δ ppm 9.40 (brs, 1H), 3.91 (s, 6H), 2.76 (q, J = 7.6 Hz, 4H),
1.16 (t, J = 7.6 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ ppm 161.1,
133.4, 121.0, 51.5, 17.7, 15.8; HRMS (ESI) m/z calcd for C12H18NO4
(M + H)+ 240.1230, found 240.1228; IR (neat) 3288, 2969, 2923,
2852, 1716, 1463, 1422, 1264, 1201, 1139, 1088, 983, 787, 414 cm−1.
Dimethyl 3-(4-chlorophenyl)-4-phenyl-1H-pyrrole-2,5-dicarboxy-
late (5ae): 19 mg; isolated yield 37%; yellow solid; mp 167−169 °C;
1H NMR (400 MHz, CDCl3) δ 9.87 (brs, 1H), 7.26−7.16 (m, 5H),
Hz, 4H), 6.58 (s, 2H), 3.74 (s, 6H), 3.60 (s, 6H), 3.52 (s, 6H); 13C
NMR (100 MHz, CDCl3) δ ppm 160. 8, 152.7, 127.5, 123.4, 120.2,
117.2, 113.8, 111.3, 55.8, 55.7, 51.7; HRMS (ESI) m/z calcd for
C24H26NO8 (M + H)+ 456.1653, found 456.1658; IR (neat) 3368,
2950, 2846, 1711, 1599, 1460, 1205, 1155, 1065, 1029, 984, 847, 776,
643, 550, 407 cm−1.
7.10−7.09 (m, 2H), 7.04 (d, J = 8.4 Hz, 2H), 3.78 (s, 3H), 3.76 (s,
3H); 13C NMR (100 MHz, CDCl3) δ ppm 160.6, 160.5, 133.1, 132.5,
132.1, 131.4, 131.3, 130.7, 130.2, 127.7, 127.5, 127.3, 127.2, 121.4,
121.2, 51.9, 51.8; HRMS (ESI) m/z calcd for C20H17ClNO4 (M + H)+
370.0841, found 370.0848; IR (neat) 3432, 3283, 2954, 1712, 1469,
1438, 1300, 1247, 1092, 1008, 911, 779, 733, 702, 647, 612, 539, 503,
451 cm−1.
Dimethyl 3-(3,5-dimethoxyphenyl)-4-(3-hydroxy-5-methoxy-
phenyl)-1H-pyrrole-25-dicarboxylate (5r): 33 mg; isolated yield
1
52%; yellow solid; mp 150−152 °C; H NMR (400 MHz, CDCl3)
δ 9.84 (brs, 1H), 6.34−6.31 (m, 6H), 3.79 (s, 6H), 3.64 (s, 12H); 13C
NMR (100 MHz, CDCl3) δ ppm 160.7, 159.8, 134.7, 131.2, 121.2,
108.9, 99.8, 55.3, 51.9; HRMS (ESI) m/z calcd for C24H26NO8 (M +
H)+ 456.1653, found 456.1658; IR (neat) 3284, 2997, 2948, 2837,
1714, 1495, 1461, 1439, 1262, 1223, 1151, 1044, 878, 806, 742, 653,
631, 489, 471, 450, 434, 410 cm−1.
General Procedure for the Synthesis of the Intermediate 6
and 7. To a solution of the phenylalanine methyl ester 4a (370 mg,
2.067 mmol) in anhydrous toluene (15 mL) was added Cu(OAc)2
(380 mg, 2.093 mmol) in dry air. After being stirred in refluxing
toluene for 20 min, the mixture was cooled to room temperature and
evaporated under reduced pressure, and the resulting residue was
purified by flash column chromatography (FCC) (SiO2, EtOAc/PE =
1:16, EA) to give colorless oil 6 100 mg (67%), colorless oil 7 21 mg
(7%), and 4a 219 mg with 59% in recovery.
Dimethyl 3,4-bis(3,4,5-trimethoxyphenyl)-1H-pyrrole-2,5-dicar-
boxylate (5s): 34 mg; isolated yield 48%; yellow solid; mp 124−126
°C; 1H NMR (400 MHz, CDCl3) δ ppm 9.84 (brs, 1H), 6.38 (s, 4H),
3.83 (s, 12H), 3.65 (s, 12H); 13C NMR (100 MHz, CDCl3) δ ppm
160.6, 152.4, 137.4, 131.2, 128.1, 121.0, 108.5, 60.9, 56.1, 51.9; HRMS
(ESI) m/z calcd for C26H30NO10 (M + H)+ 516.1864, found
516.1866; IR (neat) 3457, 3292, 3008, 2924, 2854, 1714, 1586,
1460, 1341, 1238, 1123, 1008, 83, 832, 768, 689, 659, 553, 407 cm−1.
Dimethyl 3,4-di(naphthalen-2-yl)-1H-pyrrole-2,5-dicarboxylate
1
(Z)-Methyl 2-amino-3-phenylacrylate (6): H NMR (400 MHz,
CDCl3) δ ppm 7.44 (d, J = 7.6 Hz, 2H), 7.37 (t, J = 7.8 Hz, 2H),
7.25−7.20 (m, 1H), 6.48 (s, 1H), 4.22 (brs, 2H), 3.86 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ ppm 166.3, 136.2, 132.2, 128.8 (2C),
128.3 (2C), 126.8, 109.2, 52.6; HRMS (ESI) m/z calcd for
C10H12NO2 (M + H)+ 178.0863, found 178.0865; IR (neat) 3447,
3368, 3024, 2952, 2711, 1633, 1593, 1441, 1398, 1276, 1228, 1076,
988, 856, 769, 694, 592, 531, 498, 454, 415 cm−1
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(5t): 52 mg; isolated yield 86%; yellow solid; mp 212−214 °C; H
NMR (400 MHz, CDCl3) δ ppm 9.99 (brs, 1H), 7.72 (d, J = 7.6 Hz,
2H), 7.66−7.60 (m, 6H), 7.40−7.33 (m, 4H), 7.23 (d, J = 7.6 Hz,
2H), 3.73 (s, 6H); 13C NMR (100 MHz, CDCl3) δ ppm 160.8, 132.8,
132.4, 131.5, 130.3, 129.9, 128.8, 128.0, 127.5, 126.8, 125.8, 125.6,
121.6, 51.8; HRMS (ESI) m/z calcd for C28H21NO4K (M + K)+
474.1102, found 474.1104; IR (neat) 3423, 2360, 2342, 1736, 1701,
1295, 1252, 1224, 751, 479, 459, 420 cm−1.
(Z)-Methyl 2-((1-methoxy-1-oxo-3-phenylpropan-2-yl)amino)-3-
1
phenylacrylate (7): H NMR (400 MHz, CDCl3) δ ppm 7.29−7.18
(m, 8H), 7.07 (m, 2H), 6.66 (s, 1H), 4.70 (d, J = 11.2 Hz, 1H), 4.20−
4.18 (m, 1H), 3.82 (s, 3H), 3.57 (s, 3H), 3.98−2.87 (m, 2H);13C
NMR (100 MHz, CDCl3) δ ppm 173.3, 166.6, 136.4, 135.3, 133.3,
129.3 (3C), 129.0 (2C), 128.3 (3C), 127.3, 126.9, 114.8, 58.5, 52.6,
51.8, 39.2; HRMS (ESI) m/z calcd for C20H22NO4 (M + H)+
Dimethyl 3,4-bis(1-tosyl-1H-indol-3-yl)-1H-pyrrole-2,5-dicarboxy-
late (5u): 54 mg; isolated yield 54%; yellow solid; mp 198−199 °C;
1H NMR (400 MHz, CDCl3) δ ppm 10.16 (brs, 1H), 7.85 (d, J = 8.0
Hz, 2H), 7.37 (d, J = 8.0 Hz, 6H), 7.17 (d, J = 7.6 Hz, 2H), 7.07 (d, J
F
dx.doi.org/10.1021/jo500740w | J. Org. Chem. XXXX, XXX, XXX−XXX