Diels–Alder Reactions of 2-Vinylindoles with Cyclic Dienophiles: Synthesis of [c]-Annulated Tetrahydrocarbazoles

Abstract

Diels–Alder reactions of 2-vinylindoles with cyclic carbo- and heterodienophiles, in the presence of suitable Lewis acids, led to uncommon [c]-carbo- and furoannulated tetrahydrocarbazoles. The obtained compounds encompass a carbonyl group in an angular position, suitable for further transformations, and represent useful intermediates for the synthesis of more complex structures.

Key words

Diels–Alder reaction - heterocycles - polycycles - Lewis acids - indoles

• References

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• 12 General Procedure, Method A: To a nitrogen-flushed solution of Sc(OTf)₃ (13 mol%) in CH₂Cl₂ (1 mL) a solution of 1a (1.00 mmol) and 2a,b,d,f,g (1.00 mmol) in CH₂Cl₂ (3 mL) was added and the mixture was refluxed for 24 h. The solvent was then removed in vacuo and the residue was purified by flash silica gel chromatography. 4a: yield: 60.7%; yellow oil. IR (KBr): 3047, 2934, 2871, 2693, 1728, 1612, 1513, 1458 cm^–1. ¹H NMR (300 MHz, C₆D₆): δ = 9.46 (s, 1 H), 8.59 (d, J = 8.2 Hz, 1 H), 7.52 (d, J = 7.5 Hz, 1 H), 7.42 (m, 1 H), 7.34 (m, 1 H), 7.12 (d, J = 8.0 Hz, 2 H), 7.05 (d, J = 8.0 Hz, 2 H), 4.10 (q, J = 7.1 Hz, 2 H), 3.56 (m, 1 H), 3.39 (m, 2 H), 3.22 (m, 1 H), 2.21 (s, 3 H), 2.17 (m, 1 H), 1.92 (m, 2 H), 1.84 (m, 1 H), 1.60 (m, 1 H), 1.47 (m, 1 H), 1.01 (t, J = 7.1 Hz, 3 H). ¹³C NMR (75.45 MHz, C₆D₆): δ = 203.8 (CH), 152.0 (C_q), 138.6 (C_q), 137.2 (C_q), 136.9 (C_q), 134.3 (C_q), 129.7 (CH), 129.5 (C_q), 128.8 (CH), 124.4 (CH), 123.3 (CH), 119.2 (CH), 118.7 (C_q), 116.4 (CH), 62.9 (CH₂), 62.4 (C_q), 44.4 (CH), 39.1 (CH), 30.1 (CH₂), 29.4 (CH₂), 24.5 (CH₂), 24.3 (CH₂), 21.1 (Me), 14.3 (Me). MS (ESI, +): m/z (%) = 402 (100) [M + 1]⁺. Anal. Calcd for C₂₆H₂₇NO₃ (401.50): C, 77.78; H, 6.78; N, 3.49. Found: C, 77.75; H, 6.69; N, 3.43. 3a: yield: 30.3%; yellow solid; mp 130–131 °C. IR (KBr): 3052, 2942, 2871, 2699, 1735, 1615, 1514, 1475 cm^–1. ¹H NMR (300 MHz, C₆D₆): δ = 9.68 (s, 1 H), 8.60 (d, J = 8.1 Hz, 1 H), 7.51 (d, J = 7.5 Hz, 1 H), 7.43 (m, 1 H), 7.36 (m, 1 H), 7.19 (d, J = 7.8 Hz, 2 H), 7.01 (d, J = 7.8 Hz, 2 H), 4.05 (q, J = 7.1 Hz, 2 H), 3.81 (dd, J = 18.4, 9.6 Hz, 1 H), 3.53 (dd, J = 18.4, 5.5 Hz, 1 H), 3.43 (m, 1 H), 3.08 (dd, J = 9.6, 5.5 Hz, 1 H), 2.35 (m, 1 H), 2.18 (s, 3 H), 1.96 (m, 1 H), 1.75 (m, 3 H), 1.58 (m, 1 H), 0.97 (t, J = 7.1 Hz, 3 H). ¹³C NMR (75.45 MHz, C₆D₆): δ = 203.0 (CH), 152.0 (C_q), 139.1 (C_q), 137.2 (C_q), 136.8 (C_q), 134.5 (C_q), 129.9 (C_q), 129.6 (CH), 129.5 (CH), 124.5 (CH), 123.3 (CH), 119.0 (CH), 118.9 (C_q), 116.5 (CH), 62.8 (CH₂), 60.0 (C_q), 44.8 (CH), 39.3 (CH), 32.3 (CH₂), 31.0 (CH₂), 30.3 (CH₂), 24.0 (CH₂), 21.1 (Me), 14.2 (Me). MS (ESI, +): m/z (%) = 402 (100) [M + 1]⁺. Anal. Calcd for C₂₆H₂₇NO₃ (401.50): C, 77.78; H, 6.78; N, 3.49. Found: C, 77.62; H, 6.83; N, 3.47. General Procedure, Method B: To a nitrogen-flushed solution of 1a–e (1.00 mmol) and 2a,c,d,e (1.5 mmol) in toluene (6 mL) was added BF₃·OEt₂ (15 mol%) at –20 °C and, unless otherwise detailed, the mixture was stirred at the same temperature for the stated time. The solvent was then removed in vacuo and the residue was purified by flash silica gel chromatography. 4d: yield: 7.6%; yellow solid; mp 167–168 °C. IR (KBr): 3027, 2925, 2854, 2747, 1733, 1722, 1612, 1512, 1492 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 9.62 (s, 1 H), 8.16 (d, J = 8.3 Hz, 1 H), 7.35 (m, 5 H), 7.28 (m, 1 H), 7.19 (d, J = 8.2 Hz, 2 H), 7.14 (d, J = 8.2 Hz, 2 H), 7.07 (m, 1 H), 6.76 (d, J = 7.7 Hz, 1 H), 4.62 (d, J = 5.8 Hz, 1 H), 4.50 (q, J = 7.1 Hz, 2 H), 4.48 (d, J = 9.5 Hz, 1 H), 4.31 (d, J = 9.5 Hz, 1 H), 4.06 (d, J = 5.8 Hz, 1 H), 3.61 (m, 1 H), 3.48 (m, 2 H), 2.38 (s, 3 H), 1.49 (t, J = 7.1 Hz, 3 H). ¹³C NMR (75.45 MHz, CDCl₃): δ = 204.6 (CH), 152.3 (C_q), 140.6 (C_q), 137.8 (C_q), 136.7 (C_q), 136.5 (C_q), 134.4 (C_q), 130.0 (CH), 129.0 (CH), 128.9 (CH), 128.8 (C_q), 128.6 (CH), 128.1 (CH), 124.6 (CH), 123.2 (CH), 119.5 (CH), 117.5 (C_q), 115.9 (CH), 90.3 (CH), 69.1 (CH₂), 63.6 (CH₂), 62.8 (C_q), 47.3 (CH), 44.6 (CH), 29.1 (CH₂), 21.4 (Me), 14.8 (Me). MS (ESI, +): m/z (%) = 502 (100) [M + Na]⁺. Anal. Calcd for C₃₁H₂₉NO₄ (479.31): C, 77.64; H, 6.10; N, 2.92. Found: C, 77.56; H, 5.97; N, 3.07. 3d: yield: 68.4%; yellow solid; mp 186–187 °C. IR (KBr): 3031, 2918, 2852, 2737, 1733, 1513, 1492 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 9.85 (s, 1 H), 8.10 (d, J = 8.4 Hz, 1 H), 7.42 (m, 5 H), 7.23 (m, 5 H), 6.85 (m, 1 H), 5.98 (d, J = 7.8 Hz, 1 H), 4.95 (d, J = 8.7 Hz, 1 H), 4.52 (d, J = 9.7 Hz, 1 H), 4.50 (q, J = 7.1 Hz, 2 H), 4.15 (d, J = 9.7 Hz, 1 H), 3.75 (d, J = 8.7 Hz, 1 H), 3.72 (m, 3 H), 2.36 (s, 3 H), 1.47 (t, J = 7.1 Hz, 3 H). ¹³C NMR (75.45 MHz, CDCl₃): δ = 201.1 (CH), 152.2 (C_q), 140.9 (C_q), 137.7 (C_q), 137.2 (C_q), 136.4 (C_q), 135.6 (C_q), 129.9 (CH), 129.7 (CH), 129.1 (CH), 129.1 (CH), 128.9 (C_q), 127.9 (CH), 124.4 (CH), 122.9 (CH), 119.7 (CH), 113.7 (CH), 115.7 (C_q), 87.9 (CH), 72.0 (CH₂), 63.5 (CH₂), 60.9 (C_q), 49.6 (CH), 43.8 (CH), 31.1 (CH₂), 21.4 (Me), 14.8 (Me). MS (ESI, +): m/z (%) = 502 (100) [M + Na]⁺. Anal. Calcd for C₃₁H₂₉NO₄ (479.31): C, 77.64; H, 6.10; N, 2.92. Found: C, 77.49; H, 6.03; N, 3.12.
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