An Indium(III) Triflate Catalyzed Simple and Efficient One-Pot Synthesis of Substituted 3,3-Diaryloxindoles and Bis(indol-3-yl) methanes from Indoles and Isatins or Aryl Aldehydes

Abstract

Indium(III) triflate was found to be an efficient metal catalyst for the electrophilic substitution reaction of substituted indoles with various isatins or aryl aldehydes in acetonitrile solvent to afford the corresponding 3,3-diaryloxindoles or bis(indol-3-yl)methanes, respectively, in high yields at room temperature. This new procedure has remarkable features such as experimental simplicity, high conversions, good to excellent yields, short reaction times, and simple workup procedures

Key words

indium catalysis - indoles - isatins - aryl aldehydes - diaryloxindoles - bisindolylmethanes

Publication History

Received: 15 May 2024

Accepted after revision: 24 June 2024

Accepted Manuscript online:
24 June 2024

Article published online:
15 July 2024

• References and Notes

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• 26 1H,1′′H-3,3′:3′,3′′-Terindol-2′(1′H)-one (3a);²⁸ Typical Procedure A mixture of isatin (1a; 1.0 mmol), indole (2a; 2.1 mmol), MeCN (5 ml), and In(OTf)₃ (5 mol%) was stirred at rt in the presence of ambient air until the reaction was complete (TLC). The reaction was then quenched with H₂O (15 mL), and the mixture was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were dried (Na₂SO₄) and concentrated under reduced pressure. The resulting crude product was purified by column chromatography [silica gel, EtOAc–hexanes (3:7)] to give a white solid; yield: 96%; mp 278–281 °C. ¹H NMR (400M Hz, DMSO-d ₆): δ = 10.91 (s, 2 H), 10.57 (s, 1 H), 7.36–7.33 (m, 2 H), 7.27–7.18 (m, 4 H), 7.02–6.98 (t, J = 8.0 Hz, 3 H), 6.93–6.89 (t, J = 8.0 Hz, 3 H), 6.87–6.81 (d, J = 2.0 Hz, 2 H), 6.79–6.77 (m, 2 H). ¹³C NMR (100MHz, DMSO-d ₆): δ = 179.2, 141.8, 137.4, 135.1, 128.3, 126.2, 125.4, 124.7, 121.9, 121.4, 121.2, 118.7, 114.8, 112.1, 110.0, 53.0. 5,5′′,6′-Tribromo-1H,1′′H-3,3′:3′,3′′-terindol-2′(1′H)-one (3o) Yellow solid; yield: 79%; mp 288–290 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 11.28 (s, 2 H), 10.91 (s, 1 H), 7.35 (s, 4 H), 7.17–7.16 (d, J = 6.9 Hz, 3 H), 7.05 (s, 2 H), 6.93 (s, 2 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 178.3, 142.6, 135.8, 132.5, 132.4, 127.1, 126.3, 126.1, 123.7, 122.4, 121.6, 113.9, 113.2, 111.1, 110.0, 51.8. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₄H₁₄Br₃N₃NaO; 619.8584; found: 619.8581. 6′-Bromo-5,5′′-dichloro-1H,1′′H-3,3′:3′,3′′-terindol-2′(1′H)-one Pink solid; yield: 81%; mp >300 ℃. ¹H NMR (400 MHz, DMSO-d ₆): δ = 11.29 (s, 2 H), 10.90 (s, 1 H), 7.48–7.46 (d, J = 8.0 Hz, 1 H), 7.40–7.17 (m, 7 H), 7.02–6.95 (m, 3 H). ¹³C NMR (100MHz, DMSO-d ₆): δ = 178.5, 141.1, 136.4, 136.2, 131.6, 128.0, 127.5, 126.7, 124.3, 122.9, 114.5, 114.0, 113.5, 112.4, 111.7, 52.9. HRMS (ESI) m/z [M + Na]⁺ calcd for C₂₄H₁₄BrCl₂N₃NaO: 531.9595; found: 531.9593.
• 27 3,3′-(Phenylmethylene)bis-1H-indole (5a);²⁹ Typical Procedure A mixture of PhCHO (1.0 mmol), indole (2a; 2.1 mmol), MeCN (5 mL), and In(OTf)₃ (5 mol%) was stirred at rt in the presence of ambient air until the reaction was complete (TLC). The reaction was then quenched with H₂O (15 mL), and the mixture was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were dried (Na₂SO₄) and concentrated under reduced pressure. The resulting crude product was purified by column chromatography [silica gel, EtOAc–hexanes (3:7)] to give a pink solid; yield: 93%; mp 123–126 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.46 (br s, 2 H), 7.26–7.24 (d, J = 8.0 Hz, 2 H), 7.20–7.18 (d, J = 8.0 Hz, 2 H), 7.14–7.07 (m, 5 H), 7.07–7.00 (t, J = 8.0 Hz, 2 H) 6.89–6.87 (t, J = 8.0 Hz, 2 H), 6.35 (s, 2 H), 5.73 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 143.0, 135.5, 127.6, 127.2, 126.0, 125.1, 122.6, 120.8, 118.8, 118.4, 118.1, 110.0, 39.1. 3,3′-[(4-Fluorophenyl)methylene]bis(4-chloro-1H-indole) (5g) Light-pink solid; yield: 81%; mp 164–166 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.97 (br s, 2 H), 7.43 (s, 2 H), 7.24–7.16 (m, 8 H), 6.56 (s, 2 H), 5.69 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 141.6, 135.3, 132.2, 129.9, 128.6, 128.5, 125.1, 124.8, 122.1, 118.5, 112.8, 39.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₆Cl₂FN₂: 408.0596; found: 409.0595. 3,3′-[(2,4-Dibromophenyl)methylene]bis-1H-indole (5j) Brown solid; yield: 89%; mp 100–102 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.89 (br s, 2 H), 7.42–7.32 (m, 4 H), 7.18–7.10 (m, 4 H), 7.06–6.99 (m, 4 H), 6.57 (s, 2 H), 6.25 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 140.0, 136.7, 134.6, 132.4, 131.2, 129.3, 127.0, 126.8, 123.8, 122.2, 119.7, 119.4, 117.7, 111.2, 36.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₇Br₂N₂: 477.9680; found: 478.9682. 3,3′-[(2,5-Dibromophenyl)methylene]bis-1H-indole (5k) Red solid; yield: 86%; mp 158–160 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.77 (br s, 2 H), 7.41–7.39 (d, J = 8.0 Hz, 2 H), 7.28–7.26 (d, J = 8.0 Hz, 2 H), 7.14–7.10 (t, J = 8.0 Hz, 2 H), 6.99–6.96 (m, 2 H), 6.86–6.84 (d, J = 8.0 Hz, 1 H), 6.74–6.68 (m, 2 H), 6.54 (s, 2 H), 6.30 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 153.4, 151.4, 136.7, 134.0, 127.2, 123.5, 121.7, 119.9, 119.3, 119.0, 116.8, 111.8, 110.9, 110.6, 32.1. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₇Br₂N₂: 477.9680; found: 478.9683.
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