Rh₂(OAc)₄-Catalyzed Regioselective Intermolecular C-H Insertion Reactions: Novel Synthesis of 2-Pyrrol-3′-yloxindoles

Abstract

Regioselective synthesis of 2-pyrrol-3′-yloxindoles has been achieved by the reactions of cyclic diazo carbonyl compounds 1a-e with pyrrole and substituted pyrroles (2a-d) in the presence of rhodium(II) acetate catalyst via intermolecular C-H insertion reaction.

C-H insertion reaction - oxindole - pyrrole - rhodium(II) acetate

References

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12

General Procedure for the Synthesis of 2-Pyrrol-3′-yloxindoles: In an oven-dried flask, a solution containing 1.2 equiv of pyrrole and 1 mol% of rhodium(II) acetate dimer in 10 mL of dry dichloromethane (dried over phosphorous pentoxide) was degasified under an argon atmosphere. To this reaction mixture, a solution of 1 equiv of appropriate cyclic diazoamide in dry dichloromethane was added dropwise slowly for 1 h period under an argon atmosphere at r.t. The reaction mixture was allowed to stir and followed by TLC till the disappearance of the starting material. The solvent was removed under reduced pressure and the residue purified by flash silica gel column chromatography to afford the respective C-H insertion products.

13

All new compounds exhibited spectral data consistent with their structures. Selected spectral data: 3-(1-Benzyl-1 H -pyrrol-2-yl)-1-methyl-1,3-dihydro-indol-2-one (3a): Colorless solid. Mp 115-117 °C (hexane/EtOAc). IR (KBr): 2932, 1716, 1609, 1490, 1464, 1368, 1345, 1302, 1253, 1180, 1085, 714 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 3.09 (s, 3 H, N-CH₃), 4.55 (s, 1 H), 5.14 (d, 1 H, J = 16.3 Hz), 5.51 (d, 1 H, J = 16.3 Hz), 5.78-5.80 (m, 1 H), 6.09 (t, 1 H, J = 2.5 Hz), 6.69 (t, 1 H, J = 2.5 Hz), 6.79 (d, 1 H, J = 7.7 Hz), 6.97-7.04 (m, 3 H), 7.12-7.33 (m, 5 H). ¹³C NMR (50.3 MHz, CDCl₃): δ = 26.9 (N-CH₃) 45.1 (CH), 51.7 (N-CH₂), 108.0 (CH), 108.7 (CH), 109.3 (CH), 123.2 (CH), 124.0 (CH), 125.7 (CH), 126.1 (quat-C), 127.2 (CH), 127.7 (CH), 128.0 (quat-C), 128.1 (CH), 128.9 (CH), 129.3 (CH), 138.9 (quat-C), 144.9 (quat-C), 175.4 (quat-C). MS: m/z = 302 (38.5) [M⁺], 212 (23.7), 211(100), 168 (14.3), 157 (17.6), 156 (94.5), 154(13), 91(84). Anal. Calcd for C₂₀H₁₈N₂O: C, 79.44; H, 6.00; N, 9.26. Found: C, 79.26; H, 5.98; N, 9.23. 3-(1-Benzyl-1 H -pyrrol-3-yl)-1-methyl-1,3-dihydro-indol-2- one (4a): Colorless solid. Mp 96-98 °C (hexane/EtOAc). IR (KBr): 2928, 1718, 1627, 1469, 1463, 1368, 1355, 1309, 1263, 1187, 1066, 720 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 3.18 (s, 3 H, N-CH₃), 4.56 (s, 1 H), 4.99 (s, 2 H, N-CH₂), 6.11 (t, 1 H, J = 2.2 Hz), 6.61-6.73 (m, 2 H), 6.93 (d, 1 H, J = 7.1 Hz), 7.05-7.36 (m, 8 H). MS:
m/z = 212 [M⁺]. Anal. Calcd for C₂₀H₁₈N₂O: C, 79.44; H, 6.00; N, 9.26. Found: C, 79.19; H, 6.02; N, 9.29. 1-Methyl-3-[1-(4-methyl-benzyl)-1 H -pyrrol-2-yl]-1,3-dihydro-indol-2-one (3f): Colorless oil. IR (neat): 2983, 1713, 1613, 1493, 1470, 1421, 1372, 1349, 1305, 1265, 1125, 1086, 740 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 2.29 (s, 3 H, ArCH₃), 3.09 (s, 3 H, N-CH₃), 4.55 (s, 1 H), 5.10 (d, 1 H, J = 16.1 Hz), 5.46 (d, 1 H, J = 16.1 Hz), 5.77 (t, 1 H, J = 1.7 Hz), 6.07 (t, 1 H, J = 2.9 Hz), 6.67 (t, 1 H, J = 1.7 Hz), 6.77 (d, 1 H, J = 7.8 Hz), 6.99-7.29 (m, 7 H). ¹³C NMR (50.3 MHz, CDCl₃): δ = 21.8 (CH₃), 27.0 (CH₃,) 45.2 (CH), 51.6 (N-CH₂), 107.9 (CH), 108.7 (CH), 109.3 (CH), 123.2 (CH), 124.0 (CH), 125.7 (CH), 127.3 (CH), 128.3 (quat-C), 129.0 (CH), 130.0 (CH), 135.8 (quat-C), 137.7 (quat-C), 145.0 (quat-C), 175.4 (quat-C). MS: m/z = 316 [M⁺]. Anal. Calcd for C₂₁H₂₀N₂O: C, 79.72; H, 6.37; N, 8.85. Found: C, 79.92; H, 6.35; N, 8.82. 1-Methyl-3-[1-(4-methyl-benzyl)-1 H -pyrrol-3-yl]-1,3-dihydro-indol-2-one (4f): Colorless oil. IR (neat): 2965, 1715, 1612, 1486, 1467, 1451, 1363, 1347, 1320, 1280, 1116, 1085, 735 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 2.26 (s, 3 H, ArCH₃), 3.19 (s, 3 H, N-CH₃), 4.55 (s, 1 H), 4.94 (s, 2 H, N-CH₂), 6.10 (t, 1 H, J = 2.4 Hz), 6.59-6.64 (m, 2 H), 6.83 (d, 1 H, J = 7.4Hz), 7.01-7.17 (m, 5 H), 7.26-7.32 (m, 2 H). MS: m/z = 316 [M⁺]. Anal. Calcd for C₂₁H₂₀N₂O: C, 79.72; H, 6.37; N, 8.85. Found: C, 79.89; H, 6.39; N, 8.87. 3-[1-(3,5-Dimethyl-benzyl)-1 H -pyrrol-2-yl]-1-methyl-1,3-dihydro-indol-2-one (3k): Gray color solid. Mp 156-158 °C (hexane/EtOAc). IR (KBr): 2920, 1717, 1609, 1492, 1467, 1372, 1343, 1304, 1127, 1086, 843, 750 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 2.25 (s, 6 H, ArCH₃), 3.13 (s, 3 H, N-CH₃), 4.59 (s, 1 H), 5.07 (d, 1 H, J = 16.2 Hz), 5.45 (d, 1 H, J = 16.2 Hz), 5.79 (t, 1 H, J = 1.8 Hz), 6.09 (t, 1 H, J = 2.9 Hz), 6.64 (s, 2 H), 6.69 (t, 1 H, J = 1.8 Hz), 6.75-6.86 (m, 2 H), 7.01 (t, 1 H, J = 7.45 Hz), 7.14 (d, 1 H, J = 7.18 Hz), 7.28 (t, 1 H, J = 7.59 Hz). ¹³C NMR (50.3 MHz, CDCl₃): δ = 21.9 (CH₃), 26.9 (CH₃,) 45.2 (CH), 51.7 (N-CH₂), 107.8 (CH), 108.6 (CH), 109.2 (CH), 123.1 (CH), 124.0 (CH), 125.1 (CH), 125.6 (CH), 127.2 (quat-C), 127.3 (quat-C), 128.3 (quat-C), 129.0 (CH), 129.7 (CH), 138.7 (quat-C), 138.9 (quat-C), 144.9 (quat-C), 175.5 (quat-C). MS: m/z = 330 [M⁺]. Anal. Calcd for C₂₂H₂₂N₂O: C, 79.97; H, 6.71; N, 8.48. Found: C, 79.74; H, 6.69; N, 8.51.

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