Experimental data

Ⅱ. Chapter 2. Synthesis of dihydropyran[4,3-b]indole and 2,3-Dihydrofurans based on Oxidative

2.8 Experimental data

Dimethyl 4-acetyl-3,5-dimethylpyrano[4,3-b]indole-1,1(5H)-dicarboxylate (3a)

m.p. 105-110 °C; ¹H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 7.9 Hz, 1H), 7.29 (d, J = 8.1 Hz, 1H), 7.25 – 7.20 (m, 1H), 7.18 – 7.13 (m, 1H), 3.84 (s, 6H), 3.57 (s, 3H), 2.42 (s, 3H), 2.28 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 198.55, 167.34, 157.20, 139.00, 131.15, 123.79, 122.06, 121.05, 119.04, 111.29, 109.77, 99.92, 84.82, 53.40, 32.09, 31.73, 18.17; IR (film): 2955, 1748, 1683, 1589, 1273, 1225, 1201, 744, 743 cm^-1; HRMS calcd for C19H19NNaO6+ 380.1105, observed 380.1105 [M+Na]⁺

Dimethyl 4-acetyl-8-methoxy-3,5-dimethylpyrano[4,3-b]indole-1,1(5H)-dicarboxylate (3b)

m.p. 100-105 °C; ¹H NMR (400 MHz, CDCl3) δ 8.42 (dd, J = 2.3, 0.5 Hz, 1H), 8.11 (ddd, J = 9.1, 2.2, 0.7 Hz, 1H), 7.32 (dd, J = 9.1, 0.5 Hz, 1H), 3.88 (s, 6H), 3.62 (s, 3H), 2.47 (s, 3H), 2.31 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 197.92, 166.54, 159.00, 142.72, 141.66, 134.52, 123.24, 117.48, 116.31, 110.79, 109.69, 101.45, 84.21, 53.72, 32.73, 32.10, 18.61; IR (film): 2955, 1747, 1680, 1607, 1256, 1233, 1190, 828, 791, 754 cm^-1; HRMS calcd for C20H21NNaO7+ 410.1210, observed 410.1210 [M+Na]⁺

Dimethyl 4-acetyl-8-((tert-butoxycarbonyl)amino)-3,5-dimethylpyrano[4,3-b]indole-1,1(5H)- dicarboxylate (3c)

m.p. 190-195 °C; ¹H NMR (400 MHz, CDCl3) δ 7.34 – 7.28 (m, 2H), 7.17 (d, J = 8.8 Hz, 1H), 6.53 (s, 1H), 3.85 (s, 6H), 3.52 (s, 3H), 2.41 (s, 3H), 2.26 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 198.55, 167.32, 157.19, 153.16, 135.91, 132.32, 131.78, 123.87, 115.36, 111.34, 109.88, 109.06, 99.59, 84.68, 53.49, 32.16, 31.76, 28.40, 18.18; IR (film): 3376, 2960, 1740, 1672, 1582, 1455, 1265, 1232, 1161, 805, 770 cm^-1; HRMS calcd for C24H28N2NaO8+ 495.1738, observed 495.1739 [M+Na]⁺

Dimethyl 4-acetyl-3,5-dimethyl-8-nitropyrano[4,3-b]indole-1,1(5H)-dicarboxylate (3d)

m.p. 190-195 °C; ¹H NMR (400 MHz, CDCl3) δ 7.17 (dd, J = 8.9, 0.6 Hz, 1H), 6.91 (d, J = 2.3 Hz, 1H), 6.87 (dd, J = 8.8, 2.5 Hz, 1H), 3.85 (s, 6H), 3.84 (s, 3H), 3.54 (s, 3H), 2.42 (s, 3H), 2.26 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 198.62, 167.36, 156.93, 155.01, 134.36, 131.56, 124.25, 111.83, 111.35, 110.45, 101.28, 99.51, 84.75, 55.87, 53.39, 32.17, 31.73, 18.15; IR (film): 2961, 1747, 1679, 1600,

1514, 1337, 1254, 1200 812, 750, 735 cm^-1; HRMS calcd for C19H18N2NaO8+ 425.0955, observed 425.0955 [M+Na]⁺

Trimethyl 4-acetyl-3,5-dimethylpyrano[4,3-b]indole-1,1,8(5H)-tricarboxylate (3e)

m.p. 190-195 °C; ¹H NMR (400 MHz, DMSO-d6) δ 8.01 (d, J = 1.6 Hz, 1H), 7.80 (dd, J = 8.7, 1.7 Hz, 1H), 7.59 (d, J = 8.7 Hz, 1H), 3.86 (s, 3H), 3.81 (s, 6H), 3.58 (s, 3H), 2.49 (s, 3H), 2.21 (s, 3H); ¹³C NMR (100 MHz, DMSO-d6) δ 199.10, 167.29, 167.22, 156.88, 141.19, 132.93, 123.10, 122.91, 122.57, 120.98, 111.60, 111.08, 100.36, 84.37, 54.12, 52.43, 32.77, 32.57, 18.59; IR (film): 2954, 1742, 1667, 1593, 1264, 1151, 810, 764, 743 cm^-1; HRMS calcd for C21H21NNaO8 438.1159⁺, observed 438.1159 [M+Na]⁺

Dimethyl 4-acetyl-8-bromo-3,5-dimethylpyrano[4,3-b]indole-1,1(5H)-dicarboxylate (3f)

m.p. 110-115 °C; ¹H NMR (400 MHz, CDCl3) δ 7.57 (dd, J = 1.9, 0.5 Hz, 1H), 7.28 (dd, J = 8.7, 1.9 Hz, 1H), 7.14 (dd, J = 8.7, 0.5 Hz, 1H), 3.85 (s, 6H), 3.53 (s, 3H), 2.42 (s, 3H), 2.27 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 198.33, 166.98, 157.86, 137.71, 132.26, 125.33, 124.90, 121.66, 114.47, 111.13, 111.02, 99.23, 84.48, 53.54, 32.26, 31.86, 18.32; IR (film): 2954, 1738, 1693, 1607, 1304, 1196, 1143, 773, 748, 639 cm^-1; HRMS calcd for C19H18BrNNaO6+ 458.0210, observed 458.0210 [M+Na]⁺

Dimethyl 4-acetyl-3-methylpyrano[4,3-b]indole-1,1(5H)-dicarboxylate (3g)

m.p. 175-180 °C; ¹H NMR (400 MHz, CDCl3) δ 10.17 (s, 1H), 7.49 (dq, J = 7.7, 0.9 Hz, 1H), 7.36 (dt, J = 8.2, 0.9 Hz, 1H), 7.25 – 7.07 (m, 2H), 3.83 (s, 6H), 2.57 (s, 3H), 2.52 (s, 3H); ¹³C NMR (100 MHz,

CDCl3) δ 197.17, 166.97, 164.69, 136.23, 129.41, 123.63, 121.91, 120.57, 119.33, 111.44, 110.01, 96.59, 85.24, 53.35, 32.18, 21.88; IR (film): 3403, 2962, 1751, 1641, 1273, 1201, 1167, 749, 731 cm^-1; HRMS calcd for C18H17NNaO6+ 366.0948, observed 366.0948 [M+Na]⁺

Dimethyl 4-acetyl-5-benzyl-3-methylpyrano[4,3-b]indole-1,1(5H)-dicarboxylate (3h)

m.p. 160-165 °C; ¹H NMR (400 MHz, CDCl3) δ 7.51 – 7.48 (m, 1H), 7.25 (d, J = 1.7 Hz, 1H), 7.24 – 7.18 (m, 3H), 7.16 – 7.13 (m, 2H), 6.96 – 6.92 (m, 2H), 5.21 (s, 2H), 3.86 (s, 6H), 2.21 (s, 3H), 2.08 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 199.2, 167.4, 155.9, 138.8, 136.6, 130.6, 128.8, 127.5, 126.2, 124.1, 122.2, 121.2, 119.2, 111.7, 110.5, 100.6, 84.7, 53.4, 48.4, 31.9, 18.5; IR (film): 2952, 1736, 1680, 1597, 1247, 1190, 1167, 795, 740 cm^-1; HRMS calcd for C25H24NO6+ 434.1598, observed 434.1598 [M+H]⁺

Dimethyl 4-acetyl-3-methyl-5-(p-tolyl)pyrano[4,3-b]indole-1,1(5H)-dicarboxylate (3i)

m.p. 160-165 °C; ¹H NMR (400 MHz, CDCl3) δ 7.55 – 7.51 (m, 1H), 7.34 – 7.27 (m, 3H), 7.23 – 7.14 (m, 4H), 3.88 (s, 6H), 2.42 (s, 3H), 2.26 (s, 3H), 1.65 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 197.93, 167.36, 157.60, 138.67, 138.23, 134.54, 130.52, 130.27, 127.12, 123.95, 122.46, 121.68, 119.11, 111.29, 110.72, 101.46, 84.59, 53.46, 30.76, 21.20, 18.05; IR (film): 2955, 1752, 1686, 1604, 1289, 1211, 1164, 830, 782, 744 cm^-1; HRMS calcd for C25H23NNaO6+ 456.1418, observed 456.1418 [M+Na]⁺

Dimethyl 4,5-diacetyl-3-methylpyrano[4,3-b]indole-1,1(5H)-dicarboxylate (3j)

m.p. 140-145 °C; ¹H NMR (400 MHz, CDCl3) δ 7.74 – 7.71 (m, 1H), 7.47 – 7.43 (m, 1H), 7.35 – 7.27 (m, 2H), 3.85 (s, 6H), 2.73 (s, 3H), 2.38 (s, 3H), 2.27 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 195.5, 170.1, 166.7, 158.0, 136.5, 131.4, 126.3, 124.6, 124.0, 119.9, 114.4, 113.3, 109.3, 83.7, 53.6, 30.8, 27.0, 18.7; IR (film): 2924, 1746, 1687, 1625, 1290, 1218, 1160, 793, 740 cm^-1; HRMS calcd for C20H19NNaO7+ 408.1054, observed 408.1054 [M+Na]⁺

Dimethyl 4-benzoyl-5-methyl-3-phenylpyrano[4,3-b]indole-1,1(5H)-dicarboxylate (3k)

m.p. 185-190 °C; ¹H NMR (400 MHz, CDCl3) δ 7.86 (dd, J = 8.2, 1.0 Hz, 2H), 7.78 – 7.74 (m, 2H), 7.57 – 7.53 (m, 1H), 7.45 – 7.40 (m, 1H), 7.31 – 7.26 (m, 3H), 7.25 (d, J = 3.6 Hz, 2H), 7.21 (dd, J = 4.9, 1.2 Hz, 2H), 7.17 (d, J = 8.0 Hz, 1H), 3.91 (s, 6H), 3.47 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 194.13, 167.75, 152.90, 138.93, 137.60, 133.68, 133.08, 131.15, 129.96, 129.79, 129.64, 128.64, 127.91, 123.47, 122.17, 120.89, 119.50, 109.47, 108.20, 99.16, 85.02, 53.39, 31.66; IR (film): 2955, 1764, 1668, 1613, 1591, 1274, 1241, 1218, 1142, 775, 743 cm^-1; HRMS calcd for C29H23NNaO6+ 504.1418, observed 504.1418 [M+Na]⁺

Dimethyl 4-cyano-5-methyl-3-phenylpyrano[4,3-b]indole-1,1(5H)-dicarboxylate (3l)

m.p. 170-175 °C; ¹H NMR (400 MHz, CDCl3) δ 8.14 – 8.10 (m, 2H), 7.57 – 7.50 (m, 4H), 7.36 (d, J = 8.2 Hz, 1H), 7.28 (ddd, J = 8.3, 6.9, 1.2 Hz, 1H), 7.20 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H), 4.05 (s, 3H), 3.87 (d, J = 0.9 Hz, 6H); ¹³C NMR (100 MHz, CDCl3) δ 166.69, 164.68, 138.99, 132.07, 131.11, 129.52, 128.56, 126.77, 123.07, 122.89, 121.42, 119.43, 116.75, 109.71, 99.24, 85.61, 81.15, 53.66, 30.61; IR

(film): 2215, 1749, 1588, 1567, 1275, 1244, 1223, 1154, 740, 701 cm^-1; HRMS calcd for C23H19N2O5+

403.1288, observed 403.1288 [M+H]⁺

Dimethyl 4-(dimethoxyphosphoryl)-3,5-dimethylpyrano[4,3-b]indole-1,1(5H)-dicarboxylate (3m)

m.p. 145-150 °C; ¹H NMR (400 MHz, CDCl3) δ 7.36 (dt, J = 8.0, 1.0 Hz, 1H), 7.31 (dt, J = 8.3, 0.9 Hz, 1H), 7.20 (ddd, J = 8.2, 7.0, 1.2 Hz, 1H), 7.12 (ddd, J = 8.0, 7.0, 1.1 Hz, 1H), 3.86 (s, 3H), 3.83 (s, 6H), 3.77 (s, 3H), 3.74 (s, 3H), 2.45 (d, J = 2.3 Hz, 3H); ¹³C NMR (100 MHz, CDCl3) δ 167.71, 167.50, 167.14, 139.46, 131.60, 131.57, 123.04, 121.90, 120.76, 118.25, 110.13, 100.50, 100.43, 96.09, 94.05, 84.75, 53.46, 52.56, 52.51, 32.98, 21.10, 21.08; IR (film): 2953, 1748, 1608, 1572, 1464, 1284, 1243, 1049, 1025, 756 cm^-1; HRMS calcd for C19H23NO8P⁺ 424.1156, observed 424.1156 [M+H]⁺

dimethyl 8-acetyl-7,9-dimethylpyrano[3',4':4,5]pyrrolo[2,3-b]pyridine-5,5(9H)-dicarboxylate (3n)

m.p. 115 - 120 °C; ¹H NMR (400 MHz, CDCl3) δ 8.29 (dd, J = 4.7, 1.5 Hz, 1H), 7.79 (dd, J = 8.0, 1.5 Hz, 1H), 7.10 (dd, J = 8.0, 4.7 Hz, 1H), 3.85 (s, 6H), 3.70 (s, 3H), 2.47 (s, 3H), 2.27 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 198.5, 167.0, 157.2, 149.5, 142.7, 131.3, 127.2, 117.1, 116.8, 110.9, 97.3, 84.00, 53.5, 32.1, 30.4, 18.3; HRMS calcd for C18H19N2O6+ 359.1238 observed 359.1238 [M+H]⁺

Diethyl 2-((2R,3S)-4-acetyl-2-(methoxycarbonyl)-5-methyl-3-(methyl(phenyl)amino)-2,3- dihydrofuran-2-yl)malonate (5a)

Yellow oil; ¹H NMR (400 MHz, CDCl3) δ 7.29 – 7.23 (m, 2H), 6.88 (d, J = 8.3 Hz, 2H), 6.81 (t, J = 7.3

Hz, 1H), 5.75 (s, 1H), 4.35 – 4.30 (m, 1H), 4.25 (s, 1H), 4.23 – 4.10 (m, 3H), 3.55 (s, 3H), 2.64 (s, 3H), 2.39 (s, 3H), 1.85 (s, 3H), 1.28 (d, J = 7.1 Hz, 3H), 1.23 (d, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl3) δ 194.7, 170.5, 167.6, 166.0, 165.9, 149.3, 129.4, 118.6, 113.5, 111.5, 91.2, 69.2, 62.5, 62.4, 57.0, 52.7, 32.7, 29.4, 15.1, 14.1, 14.0; IR (film):2980, 1728, 1678, 1598, 1434, 1311, 1204, 750, 693 cm^-1; HRMS calcd for C23H30NO8+ 447.1966, observed 448.1978 [M+H]⁺

Diethyl 2-((2R,3S)-4-acetyl-2-(methoxycarbonyl)-5-methyl-3-(methyl(m-tolyl)amino)-2,3- dihydrofuran-2-yl)malonate (5b)

Colorless oil; ¹H NMR (400 MHz, CDCl3) δ 7.18 – 7.10 (m, 1H), 6.73 – 6.61 (m, 3H), 5.73 (s, 1H), 4.35 – 4.11 (m, 5H), 3.56 (s, 3H), 2.62 (s, 3H), 2.38 (s, 3H), 2.33 (s, 3H), 1.84 (s, 3H), 1.29 (t, J = 7.1 Hz, 3H), 1.24 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl3) δ 194.6, 170.2, 167.5, 165.8, 165.8, 149.3, 138.8, 129.0, 119.4, 114.0, 111.4, 110.7, 91.1, 69.0, 62.3, 62.3, 56.8, 52.6, 32.6, 29.4, 21.9, 15.0, 13.9, 13.9; IR (film): 2981, 1728, 1678, 1600, 1495, 1304, 1218, 937, 628 cm^-1; HRMS calcd for C24H32NO8+ 461.2122, observed 462.2131 [M+H]⁺

Diethyl 2-((2R,3S)-4-acetyl-2-(methoxycarbonyl)-5-methyl-3-(methyl(p-tolyl)amino)-2,3- dihydrofuran-2-yl)malonate (5c)

Colorless oil; ¹H NMR (400 MHz, CDCl3) δ 7.07 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.5 Hz, 2H), 5.68 (s, 1H), 4.32 (dq, J = 10.6, 7.3 Hz, 2H), 4.25 (s, 1H), 4.18 – 4.10 (m, 2H), 3.58 (s, 3H), 2.61 (s, 3H), 2.38 (s, 3H), 2.26 (s, 3H), 1.84 (s, 3H), 1.28 (d, J = 7.1 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl3) δ 194.6, 170.2, 167.6, 165.8, 165.8, 147.2, 129.7, 127.6, 113.4, 111.4, 91.2, 69.5, 62.3, 62.3, 56.8, 52.6, 32.6, 29.4, 20.3, 14.9, 13.9, 13.9; IR (film):2980, 1728, 1678, 1607, 1434, 1305, 1230, 1202, 806, 631 cm^-1; HRMS calcd for C24H32NO8+ 461.2122, observed 462.2092 [M+H]⁺

Diethyl 2-((2R,3S)-4-acetyl-2-(methoxycarbonyl)-3-((4-methoxyphenyl)(methyl)amino)-5- methyl-2,3-dihydrofuran-2-yl)malonate (5d)

Yellow oil; ¹H NMR (400 MHz, CDCl3) δ 6.84 (d, J = 2.1 Hz, 4H), 5.62 (s, 1H), 4.35 – 4.12 (m, 5H), 3.77 (s, 3H), 3.60 (s, 3H), 2.60 (s, 3H), 2.38 (s, 3H), 1.84 (s, 3H), 1.29 (t, J = 7.1 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl3) δ 194.7, 170.0, 167.7, 165.8, 165.8, 152.5, 143.9, 114.8, 114.6, 111.6, 91.4, 70.3, 62.3, 56.8, 55.6, 52.6, 32.9, 29.5, 14.9, 13.9, 13.9; IR (film):2982, 1728, 1677, 1605, 1435, 1280, 1244, 1202, 818, 633 cm^-1; HRMS calcd for C24H32NO9+ 477.2072, observed 478.2090 [M+H]⁺

Diethyl 2-((2R,3S)-4-acetyl-3-((4-bromophenyl)(methyl)amino)-2-(methoxycarbonyl)-5-methyl- 2,3-dihydrofuran-2-yl)malonate (5e)

Yellow oil; ¹H NMR (400 MHz, CDCl3) δ 7.33 (d, J = 9.2 Hz, 2H), 6.75 (d, J = 9.1 Hz, 2H), 5.70 (s, 1H), 4.32 – 4.12 (m, 5H), 3.57 (s, 3H), 2.59 (s, 3H), 2.38 (s, 3H), 1.86 (s, 3H), 1.29 (t, J = 7.1 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl3) δ 194.1, 170.3, 167.4, 165.7, 165.7, 148.2, 132.0, 115.0, 111.3, 110.5, 91.0, 68.8, 62.4, 62.4, 56.7, 52.7, 32.7, 29.3, 15.0, 13.9, 13.9; IR (film):2979, 1728, 1679, 1608, 1492, 1435, 1308, 1203, 812, 629, 517 cm^-1; HRMS calcd for C23H29BrNO8+ 525.1071, observed 526.1065 [M+H]⁺

Diethyl 2-((2R,3S)-4-acetyl-2-(methoxycarbonyl)-3-((4-

(methoxycarbonyl)phenyl)(methyl)amino)-5-methyl-2,3-dihydrofuran-2-yl)malonate (5f)

Yellow oil; ¹H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.9 Hz, 2H), 6.89 (d, J = 8.9 Hz, 2H), 5.91 (s, 1H), 4.37 – 4.21 (m, 3H), 4.19 (d, J = 2.3 Hz, 1H), 4.19 – 4.09 (m, 2H), 3.87 (s, 3H), 3.51 (s, 3H), 2.69 (s, 3H), 2.40 (s, 3H), 2.05 (s, 1H), 1.88 (s, 3H), 1.30 (t, J = 7.2 Hz, 3H), 1.25 (d, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl3) δ 193.9, 170.7, 167.1, 167.0, 165.6, 165.6, 152.3, 131.3, 119.6, 112.1, 111.1, 90.8, 67.7, 62.5, 62.4, 56.7, 52.6, 51.6, 32.7, 29.1, 15.0, 13.9, 13.9; IR (film):2977, 1770, 1710, 1680, 1602, 1434, 1279, 1188, 1114, 832, 630 cm^-1; HRMS calcd for C25H32NO10+ 505.2021, observed 506.2190 [M+H]⁺

Diethyl 2-((2R,3S)-4-acetyl-2-(methoxycarbonyl)-5-methyl-3-(methyl(4- (trifluoromethyl)phenyl)amino)-2,3-dihydrofuran-2-yl)malonate (5g)

Colorless oil; ¹H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 8.5 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 5.86 (s, 1H), 4.35 – 4.19 (m, 3H), 4.18 (s, 1H), 4.17 – 4.11 (m, 1H), 3.56 (s, 3H), 2.67 (s, 3H), 2.40 (d, J = 1.0 Hz, 3H), 1.89 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.26 (d, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl3) δ 193.8, 170.5, 167.3, 165.7, 165.6, 151.3, 126.6, 126.6, 126.5, 126.5, 126.1, 123.4, 120.5, 120.1, 119.8, 119.5, 117.1, 112.5, 111.3, 90.9, 68.1, 62.5, 62.4, 56.7, 52.7, 32.7, 29.1, 15.0, 13.9, 13.9; IR (film):

2983, 1729, 1680, 1612, 1436, 1318, 1253, 1200, 1153, 821, 628 cm^-1; HRMS calcd for C24H29F3NO8+

515.1840, observed 516.1842 [M+H]⁺

Dimethyl (2R,3S)-2-(1,3-diethoxy-1,3-dioxopropan-2-yl)-5-methyl-3-(methyl(phenyl)amino)-2,3- dihydrofuran-2,4-dicarboxylate (5h)

Colorless oil; ¹H NMR (400 MHz, CDCl3) δ 7.23 (t, J = 7.6 Hz, 2H), 6.82 (dd, J = 14.5, 7.8 Hz, 3H), 5.56 (s, 1H), 4.33 – 4.11 (m, 5H), 3.59 (s, 3H), 3.50 (s, 3H), 2.59 (s, 3H), 2.36 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H), 1.21 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl3) δ 170.5, 167.7, 165.9, 165.8, 165.0, 150.5, 128.7, 118.4, 114.4, 102.9, 91.2, 70.0, 62.2, 62.2, 56.8, 52.6, 51.1, 32.7, 14.3, 13.9, 13.8; IR (film): 2952, 1731, 1705, 1654, 1597, 1434, 1311, 1191, 1146, 750, 693 cm^-1; HRMS calcd for C23H30NO9+ 463.1915, observed 464.1915 [M+H]⁺

Diethyl 2-((2R,3R)-2-(methoxycarbonyl)-5-methyl-3-(methyl(phenyl)amino)-4-(phenylsulfonyl)- 2,3-dihydrofuran-2-yl)malonate (5i)

Yellow oil; ¹H NMR (400 MHz, CDCl3) δ 7.55 (dd, J = 22.7, 7.4 Hz, 3H), 7.36 (t, J = 7.1 Hz, 2H), 7.22 (t, J = 7.1 Hz, 2H), 6.80 (t, J = 7.0 Hz, 1H), 6.70 (d, J = 7.7 Hz, 2H), 5.80 (s, 1H), 4.32 – 4.14 (m, 4H), 4.05 (s, 1H), 3.50 (s, 3H), 2.45 (s, 3H), 2.15 (s, 3H), 1.30 (t, J = 6.9 Hz, 3H), 1.23 (d, J = 7.1 Hz, 3H);

13C NMR (100 MHz, CDCl3) δ 168.1, 165.4, 165.4, 148.4, 141.0, 133.1, 129.0, 128.9, 127.6, 118.4, 113.7, 111.7, 90.7, 68.2, 62.5, 62.4, 56.7, 52.6, 31.9, 14.0, 13.9, 13.8; IR (film):2981, 1729, 1637, 1597, 1446, 1318, 1255, 1204, 1157, 750, 688 cm^-1; HRMS calcd for C27H32NO9S⁺ 545.1792, observed 546.1800 [M+H]⁺

Diethyl 2-((2R,3R)-4-(dimethoxyphosphoryl)-2-(methoxycarbonyl)-5-methyl-3- (methyl(phenyl)amino)-2,3-dihydrofuran-2-yl)malonate (5j)

Yellow oil; ¹H NMR (400 MHz, CDCl3) δ 7.22 (t, J = 7.9 Hz, 2H), 6.86 (d, J = 8.2 Hz, 2H), 6.76 (t, J = 7.3 Hz, 1H), 5.77 (d, J = 2.9 Hz, 1H), 4.38 – 4.19 (m, 4H), 4.06 (s, 1H), 3.60 (d, J = 11.2 Hz, 3H), 3.58 (s, 3H), 3.52 (d, J = 11.2 Hz, 3H), 2.67 (s, 3H), 2.29 – 2.26 (m, 3H), 1.29 (td, J = 7.1, 1.4 Hz, 6H); ¹³C NMR (100 MHz, CDCl3) δ 170.5, 170.2, 167.5, 165.8, 165.8, 149.6, 128.8, 118.1, 114.0, 97.6, 95.4, 91.4, 91.2, 70.3, 70.2, 62.3, 62.2, 56.6, 52.5, 52.4, 52.3, 52.3, 52.2, 32.7, 14.2, 13.9, 13.9; IR (film):

2953, 1729, 1644, 1597, 1434, 1311, 1245, 1203, 1022, 750, 693 cm^-1; HRMS calcd for C23H33NO10P⁺ 513.1837, observed 514.1841 [M+H]⁺

Dimethyl 4-acetyl-3,5-dimethyl-2-(p-tolyl)-2,5-dihydro-1H-pyrido[4,3-b]indole-1,1-dicarboxylate (9a)

Prepared according to the general procedure (A) using p-toluidine (0.12 mmol, 1.2 equiv.) at 80 °C. 90%

yield; m.p. 195-200 °C; ¹H NMR (400 MHz, CDCl3) δ 7.30 – 7.26 (m, 3H), 7.23 (d, J=7.9, 1H), 7.21 – 7.16 (m, 1H), 7.15 – 7.08 (m, 3H), 3.62 (s, 3H), 3.54 (s, 6H), 2.37 (s, 3H), 2.34 (s, 3H), 2.08 (s, 3H);

13C NMR (100 MHz, CDCl3) δ 197.9, 168.9, 149.7, 139.4, 139.1, 137.9, 134.2, 129.5, 129.3, 124.1, 121.2, 120.5, 117.5, 109.7, 107.7, 102.2, 76.3, 52.9, 32.5, 31.7, 21.1, 20.3; IR (film):2949, 1738, 1661, 1467, 1326, 1302, 1238, 829, 751 cm^-1; HRMS calcd for C26H26N2NaO5+ 469.1734, observed 469.1734 [M+Na]⁺

Dimethyl 4-acetyl-2-(4-methoxyphenyl)-3,5-dimethyl-2,5-dihydro-1H-pyrido[4,3-b]indole-1,1- dicarboxylate (9b)

Prepared according to the general procedure (A) using p-anisidine (0.12 mmol, 1.2 equiv.) at 80 °C. 90%

yield; m.p. 65-70 °C; ¹H NMR (400 MHz, CDCl3) δ 7.34 (d, J=9.0, 2H), 7.29 (d, J=8.1, 1H), 7.24 – 7.21 (m, 1H), 7.21 – 7.16 (m, 1H), 7.11 (ddd, J=8.0, 7.2, 1.0, 1H), 6.84 (d, J=9.1, 2H), 3.81 (s, 3H), 3.62 (s, 3H), 3.56 (s, 6H), 2.38 (s, 3H), 2.08 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 197.9, 168.9, 159.0, 150.0, 139.4, 134.4, 134.2, 131.0, 124.0, 121.2, 120.5, 117.6, 113.9, 109.8, 107.3, 102.0, 76.4, 55.4, 55.4, 53.0, 53.0, 32.5, 32.5, 31.7, 20.2; IR (film):2950, 1738, 1660, 1564, 1464, 1303, 1231, 1194, 728 cm^-1; HRMS calcd for C26H26N2NaO6+ 485.1683, observed 485.1683 [M+Na]⁺

Dimethyl 4-acetyl-2-(4-bromophenyl)-3,5-dimethyl-2,5-dihydro-1H-pyrido[4,3-b]indole-1,1- dicarboxylate (9c)

Prepared according to the general procedure (A) using 4-bromoaniline (0.12 mmol, 1.2 equiv.) at 100 °C.

80% yield; m.p. 185-190 °C; ¹H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 8.7 Hz, 2H), 7.31 – 7.27 (m, 3H), 7.24 – 7.18 (m, 2H), 7.14 – 7.09 (m, 1H), 3.62 (s, 3H), 3.57 (s, 6H), 2.38 (s, 3H), 2.05 (s, 3H); ¹³C NMR (100 MHz, CDCl3) δ 198.2, 169.0, 148.0, 140.9, 139.3, 133.6, 132.1, 131.0, 123.9, 121.7, 121.5, 120.7, 117.5, 109.9, 108.9, 102.5, 76.2, 53.2, 32.4, 31.7, 20.4; IR (film):2947, 1745, 1666, 1607, 1578, 1464, 1323, 1302, 1225, 771, 760, 544 cm^-1; HRMS calcd for C25H24BrN2O5+ 510.0863, observed 511.0874 [M+H]⁺

Chapter 3. Electrochemical C(sp ³ )-H

Functionalization of ɣ-Lactams based

on Hydrogen Atom Transfer

45 3.1 Reaction design for γ-lactam functionalization

The general method for γ-lactam functionalization is nucleophilic addition reaction via N-acylimium (NAI) intermediate. Electrochemical hydrogen atom transfer (HAT) generates γ-lactam radical intermediate, which reacts with electrophilic coupling partner to form a new C-C bond (Figure 3-1).

The γ-lactam radical intermediate can be easily oxidized, however, it can undergo radical addition reaction with alkene under mild electrochemical reaction by using azide as HAT mediator. In addition, sulfonamide can be introduced by using N-sulfonyl imine as a coupling partner.

Figure 3-1. Electrochemical γ-lactam functionalization.

3.2 Optimization for 3-substituted lactams

We started reaction optimization with N-methyl isoindolinone 1a and methyl cinnamate 2a. Using a catalytic amount of ⁿBu4NN3 (30 mol%) as HAT mediator, desired product 3aa is obtained in 82% yield at constant current mode (3 mA, glassy carbon (GC) as anode and carbon felt (CF) as cathode) in MeCN (0.1 M ⁿBu4NBF4). The reaction at twice higher current (6 mA) or constant voltage mode (2.5 V) showed decreased yield (Table 3-1, entry 2 and 3). In case of electrolyte, ⁿBu4NPF6 also performed the reaction as well as ⁿBu4NBF4, however, when LiClO4 was used, the conversion rate of the starting material 1a was decreased (Table 3-1, entry 4 and 5).

There was a large difference in reactivity, depending on the solvent (Table 3-1, entry 6-8). The reaction proceeded in DMF, a polar aprotic solvent, however, no product was obtained in polar protic MeOH or non-polar solvent DCM. When we changed the cathode or anode to graphite, conversion of 1a was low (Table 3-1, entry 9-11). The bond dissociation energies (BDEs) of other HAT mediators indicate that HAT from 1a are thermodynamically available, however, they showed poor efficiency (Table 3-1, entry 12-15). When we reduced the loading amount of ⁿBu4NN3, the reaction yield was decreased (Table 3-1, entry 16). The desired product 3aa was not obtained without ⁿBu4NN3 or electricity, indicating that the reaction is an azide-mediated electrocatalytic reaction (Table 3-1, entry 17 and 18). Air had a detrimental effect in our reaction (Table 3-1, entry 19).

46 Table 3-1. Reaction optimization^a.

Entry Variation from the standard conditions Yield (%)

1 none 78 (82, 1.1:1)^b

2 6 mA 75

3 2.5 V 55

4 LiClO4 instead of ⁿBu4NBF4 NR

5 ⁿBu4NPF6 instead of ⁿBu4NBF4 76

6 DMF instead of MeCN 53

7 DCM instead of MeCN NR

8 MeOH instead of MeCN NR

9 C (+) | C (-) instead of GC (+) | CF (-) 59

10 GC (+) | C (-) instead of GC (+) | CF (-) 70

11 C (+) | CF (-) instead of GC (+) | CF (-) 69

12 NaN3 instead of ⁿBu4NN3 trace

13 DABCO instead of ⁿBu4NN3 28

14 quinuclidine instead of ⁿBu4NN3 4

15 methyl thioglycolate instead of ⁿBu4NN3 NR

16 ⁿBu4NN3 (5 mol%) 45

17 no ⁿBu4NN3 NR

18 no electricity NR

19 under air 14

[a] Reaction conditions: Undivided cell, GC anode, CF cathode, 1a (0.1 mmol), 2a (0.15 mmol), ⁿBu4NN3 (0.03 mmol),

nBu4BF4 (0.1 M), MeCN (0.03 M). Yield determined by HPLC analysis of the crude reaction mixture using triphenylphosphine, GC = glassy carbon, CF = carbon felt, NR = no reaction, DABCO = 1,4-diazabicyclo[2.2.2]octane. [b] Isolated yield.

47 3.3 Substrate scope of 3-substituted lactams

The 3-substituted lactams could be synthesized using 1a and various types of alkenes 2 under our optimized reaction conditions (Table 3-2). For the electron-rich alkenes (2b-2f), the product was obtained in high yield, however, for the electron-deficient alkene 2k, few amount of product was obtained. Reactive functional group substituted alkenes, including amine (2af), halide (2ag-2ai), and keto group (2aj) gave the desired products (3af and 3ag-3aj). Heteroaryl substituted lactams could be obtained in good to moderate yield (3an-3ar). The alkyl group substituted alkenes were well tolerated to give product (3as-3au). In case of 1,3-diene 2v, only beta substituted product was selectively formed.

In addition to methyl ester, other electron withdrawing groups such as ketone, amide, nitrile, phosphonate, phenyl sulfone, and sulfonamide substituted alkenes proceed the reaction well (3aw-3aac).

Moreover, late-stage functionalization was also possible in our reaction, estrone derivatives could be synthesized in good yield (3aad).

The spirocyclic compound with a quaternary carbon center is complex structure and not easy to synthesize. When 1,2-divinyl substituted arenes were used as coupling partner in our reaction conditions, the spirocyclic compound could be synthesized in good yields and diastereoselectivies (3aae-3aah).

After the formation of C-C bond by radical addition, the methine proton undergoes second HAT and intramolecular radical addition to form spirocyclic compound.

Next, the reaction according to the type of lactam was examined (Table 3-3). Regardless of electron donating or withdrawing group substituted isoindolinone, all reactions proceeded well (3ba-3fa). The reactions proceeded smoothly with N-aryl isoindolinones in high yield (3ga-3ma), and the redox labile iodo group turned out to be stable in our reaction (3ka). The N-benzyl substituted isoindolinones gave the high yield of products (3na-3oa), and interestingly, N-α methylene proton was selectively activated over the benzyl proton. To confirm the steric effect, C3 substituted isoindolinones were applied to the reaction. The methyl substituted isoindolinone 1p reacted well with 2a and methyl acrylate 2ai, however, phenyl substituted isoindolinone 1q reacted only with mono substituted alkene 2ai and 2aj. The N-H isoindolinone 1r was able to obtain the coupling products (3ra and 3raj). In addition, 1,2- dihydroisoquinolinone also participated in coupling reaction to produce the desired product (3sa) in high yield. The α, β-unsaturated lactam performed the reaction in good to moderate yield. Both α- or β- mono- and di-substituted lactams are well tolerated in our reaction (5aa-5hai). In addition, bicyclic lactam can be used to synthesize new C-C bond at the ring junction (5iai-5iak).

48 Table 3-2. Substrate scope of alkene^a,b,c.

[a] Reaction conditions: Reactions were performed with 1a (0.1 mmol), 2 (0.15 mmol), ⁿBu4NN3 (0.03 mmol) and ⁿBu4NBF4

(0.1 M) in dry MeCN (0.03 M) under Ar. Isolated yield. [b] The ratio in parenthesis is the diastereomeric ratio. [c] Relative stereochemistry could not be assigned for the compounds without denotation. [d] 3.0 equiv of alkene was used. [e] The product was obtained as a racemic mixture. [f] The potential range of reaction: 3-5 V.

49 Table 3-3. Substrate scope of lactam^a,b,c.

[a] Reaction conditions: Reactions were performed with 1/4 (0.1 mmol), 2 (0.15 mmol), ⁿBu4NN3 (0.03 mmol) and ⁿBu4NBF4

(0.1 M) in dry MeCN (0.03 M) under Ar. Isolated yield. [b] The ratio in parenthesis is the diastereomeric ratio. [c] Relative stereochemistry could not be assigned for the compounds without denotation. [d] 3.0 equiv of alkene was used. [e] Reactions were run under constant voltage mode (2.5 V). [f] The product was obtained as a racemic mixture. [g] The potential range of reaction: 3-5 V.

3.4 Substrate scope of polycyclic compounds

We established the broad scope of functionalized lactam by intermolecular coupling, and we were interested in whether our reaction could be extended to intramolecular coupling (Table 3-4). The spirocyclic compounds were synthesized when tethers were placed in N-α methylene carbons (7a and 7b). With the N-alkyl tether substrate, we could synthesize the 5- and 6-membered fused cycles (7c-7f).

All intramolecular annulation substrates provide the desired product in very short reaction time, 20 minutes.

50 Table 3-4. Substrate scope of intramolecular annulation^a,b.

[a] Reaction conditions: Undivided cell, GC anode, CF cathode, 6 (0.1 mmol), ⁿBu4NN3 (0.03 mmol) and ⁿBu4NBF4 (0.1 M) in dry MeCN (0.03 M) under Ar. Isolated yield. [b] The ratio in parenthesis is the diastereomeric ratio. [c] Owing to an inseparable side-product, Mg cathode was employed. [d] The product was obtained as a racemic mixture. [e] The potential range of reaction: 4-5 V.

3.5 Substrate scope of sulfonamide

The N-sulfonyl imines were examined as a coupling partner (Table 3-5). Although an initial attempt employing 1a and 8a as substrates afforded sulfonamide 9aa in 33% yield under the standard conditions for the reaction with alkenes, much improved 75% yield was obtained when performed in higher concentration of 0.1 M. Under the optimized conditions, the scope of the reaction was investigated.

Whereas various substituted imines afforded the corresponding sulfonamides in good to moderate yields, electron-deficient imine 8g turned out poorly tolerated. We also examined the reactivity of heteroaryl imines including thiophene and furan, in which thiophene 8i displayed superior reactivity to furan 8j.

In addition, the use of alkyl imine 8k gave the corresponding product, albeit in low yield.

51 Table 3-5. Substrate scope of imine^a,b.

[a] Reaction conditions: Reactions were performed with 1a (0.4 mmol) and 8 (1.2 mmol) in dry MeCN (0.1 M) under Ar.

Isolated yield. [b] The ratio in parenthesis is the diastereomeric ratio. [c] Reactions were run under constant voltage mode (6 V).

3.6 Synthetic application

Our reaction showed good efficiency on the gram scale (Scheme 3-1a). 77% of the 3aa can be obtained using 1a (1.03 g). Aristolactam is a natural product alkaloid found in several types of plants. Depending on the reaction temperature, dihydroaristolactam and aristolactam derivatives could be synthesized by Pd-mediated cross-coupling using functionalized lactam 3ai (Scheme 3-1b). Pyrrolizidine is known to have biological activity, and can be synthesized in two steps with 3ja (Scheme 3-1c).

Scheme 3-1. Synthetic application.

3.7 Mechanistic studies

3.7.1 Mechanistic studies of coupling reaction with alkene

We performed control experiments and density functional theory (DFT) calculations to investigate the reaction mechanism. To determine the role of ⁿBu4NN3, we ran the reaction without azide, and found no conversion of 1a (Scheme 3-2a). Therefore, it was found that azide is required for 1a activation.

These experimental results support the reaction involving the HAT by the azido radical generated by oxidation of azide. In addition, calculated BDEs (78.7 kcal/mol for 1a vs. 88.4 kcal/mol for HN3, DFT calculations at B3LYP-D3/6-31G(d) in SMD (MeCN) appears that energetically HAT from 1a by azido radical is favorable. The reaction was completely inhibited by radical scavenger, 2,6-Di-tert-butyl-4- methylphenol (BHT), and the 1a-BHT adduct was detected by HRMS (Scheme 3-2b). We can confirm that 1a radical intermediates are generated in our reaction conditions.

Scheme 3-2. Mechanistic study of reaction with 2a.

-2.E-04 0.E+00 2.E-04 4.E-04 6.E-04 8.E-04 1.E-03

0 0.5 1 1.5 2 2.5 3 3.5

Current (A)

Voltage (V) blank

nBu4NN3 1a 2a

Figure 3-2. Cyclic voltammetry graph.

We performed a current on/off experiment (Scheme 3-3 and Figure 3-3), and found that the reaction mainly proceeds through a non-chain mechanism. When the current is off, the reaction proceeds slightly, suggesting that a chain mechanism may also be involved to a small extent.

Scheme 3-3. Current on and off experiment.

Figure 3-3. Current on/off experiment graph.

3.7.2 Mechanistic studies of coupling reaction with N-sulfonyl imine

We proceeded to probe the reaction mechanism involving N-sulfonyl imine. Under standard reaction with 8a, we observed the formation of imine dimer 8′aa in 22% yield, which suggests the formation of a radical species derived from 8a. This was further corroborated by performing a reaction in the absence of 1a, which led to the formation of 8′aa in 29% yield (Scheme 3-4b). Similar to the reaction with alkene, that the reaction without azide provided only a trace amount of 9aa and 18% yield of 8′aa (Scheme 3-4a). In addition, the formation of a radical species derived from 1a was confirmed by the observation of the corresponding BHT adduct (Scheme 3-4c). These results strongly indicate that the reaction involving 8a radical anion and 1a radical intermediate.

Scheme 3-4. Mechanistic study of reaction with 8a.

Figure 3-4. Cyclic voltammetry graph of 8a.

3.8 DFT calculations and proposed reaction mechanism

The reaction mechanism and DFT calculation are described in Figure 3-4. For the coupling reaction between 1a and 2a, generated azido radicals performed HAT from 1a (Figure 3-5a and b). It gives radical intermediate A that undergoes radical addition to 2a with ∆G^ǂ = 20.0 kcal/mol. Subsequent HAT provides the product 3aa from B.

Figure 3-5. Proposed reaction mechanism with 2a.

On the other hand, to elucidate the reaction mechanism between 1a and 8a, we performed the DFT calculation to compare the energy barrier between radical-radical coupling pathway a and radical addition pathway b (Figure 3-6b). Compared to barrierless pathway a, the energy barrier of pathway b is relatively high, ∆G^ǂ = 24.2 kcal/mol. Moreover, pathway a is highly exergonic process ∆G = -24.8 kcal/mol. Therefore, we could find that the reaction proceeds with pathway a rather than pathway b.

The N-sulfonyl imine 8a undergoes cathodic reduction to give radical anion intermediate C, which subsequently undergoes the radical-radical cross-coupling reaction with A to give anion intermediate E. After the protonation of E, 9aa is synthesized (Figure 3-6a).

Figure 3-6. Proposed reaction mechanism with 2a.

3.9 Conclusions

In conclusion, we developed the electrochemical HAT reaction to functionalize the lactam by activation of C(sp³)-H. The wide range of functionalized lactams were synthesized using catalytic amount of

nBu4NN3 as HAT mediator. Depending on the coupling partner, different types of reactions were performed. In addition, various types of polycyclic compounds can be synthesized through double HAT processes and intramolecular reactions. The control experiments and DFT calculation provides detailed mechanism studies.

3.10 Procedure for the electrolysis Electrode materials/dimensions:

For 0.1 mmol scales, the glassy carbon (GC) anode and carbon felt (CF) cathode with dimensions of 0.8 cm x 0.2 cm x 5.2 cm and 0.8 cm x 0.2 cm x 3.5 cm, respectively, were employed. For experiments for larger scales, the dimensions are specified in the relevant experimental section and it carried out in an undivided cell.

Graphical guide for electrochemical amination of ElectraSyn 2.0

a. b.

Figure 3-7. a: ElectraSyn 2.0. b: ElectraSyn vial (5 mL).

a. b.

Figure 3-8. a: Upper: ElectraSyn 2.0 vial cap; middle: electrodes (carbon felt and glassy carbon);

lower: electrode holders. b: The electrode holders were plugged into the vial cap.

General Procedure (A) for ElectraSyn and characterization of 3-substituted lactam

The reaction was carried out in an undivided cell. A 5 mL vial was charged with the lactam derivative 1/4 (0.1 mmol, 1.0 equiv.), alkene 2 (x equiv.), ⁿBu4NN3 (0.3 M solution in MeCN) (0.1 ml, 30 mol%), MeCN (3.7 mL, 0.1 M ⁿBu4NBF4) and a stir bar, and was closed with a cap attached with a glassy carbon anode and a carbon felt cathode. The solution was stirred at 900 rpm for 10 minutes at room

temperature before current was turned on. The electrolysis was performed at a constant current of 3 mA.

Upon full consumption of the lactam starting material as determined by thin-layer chromatography analysis, electrolysis was terminated, the solvent was removed under reduced pressure. The product was purified by flash chromatography. Structural assignments were made with additional information from gHSQC and gHMBC experiments

General Procedure (B) for ElectraSyn and characterization of polycyclic compound (inter- intramolecular cyclization)

The reaction was carried out in an undivided cell. A 5 mL vial was charged with the 2-methylisoindolin- 1-one 1a (0.1 mmol, 1.0 equiv.), alkene 2 (1.5 equiv.), ⁿBu4NN3 (0.3 M solution in MeCN) (0.1 ml, 30 mol%), MeCN (3.7 mL, 0.1 M ⁿBu4NBF4) and a stir bar, and was closed with a cap attached with a glassy carbon anode and a carbon felt cathode. The solution was stirred at 900 rpm for 10 minutes at room temperature before current was turned on. The electrolysis was performed at a constant current of 3 mA. Upon full consumption of the isoindolinone starting material as determined by thin-layer chromatography analysis, electrolysis was terminated, the solvent was removed under reduced pressure.

The product was purified by flash chromatography. Structural assignments were made with additional information from gHSQC, gHMBC and NOESY experiments

General Procedure (C) for ElectraSyn and characterization of polycyclic compound (intramolecular cyclization)

The reaction was carried out in an undivided cell. A 5 mL vial was charged with the isoindolinone derivative 6 (0.1 mmol, 1.0 equiv.), ⁿBu4NN3 (0.3 M solution in MeCN) (0.1 ml, 30 mol%), MeCN (3.7 mL, 0.1 M ⁿBu4NBF4) and a stir bar, and was closed with a cap attached with a glassy carbon anode and a carbon felt cathode. The solution was stirred at 900 rpm for 10 minutes at room temperature before current was turned on. The electrolysis was performed at a constant current of 3 mA. Upon full consumption of the isoindolinone starting material as determined by thin-layer chromatography analysis, electrolysis was terminated, the solvent was removed under reduced pressure. The product was purified by flash chromatography.

General Procedure (D) for ElectraSyn and characterization of sulfonamide

The reaction was carried out in an undivided cell. A 5 mL vial was charged with the 2-methylisoindolin-

Dalam dokumen 비영리 (Halaman 49-62)

Ⅱ. Chapter 2. Synthesis of dihydropyran[4,3-b]indole and 2,3-Dihydrofurans based on Oxidative

2.8 Experimental data

Chapter 3.

Electrochemical C(sp 3 )-H

Functionalization of ɣ-Lactams based

on Hydrogen Atom Transfer

Electrochemical C(sp ³ )-H