Synthesis of Indoles from 2-Vinylanilines with PIFA or TFA and Quinones

Abstract

The cyclizations involved in the synthesis of different indoles from 2-vinylanilines with PIFA {[bis(trifluoroacetoxy)iodo]benzene} and quinones have been developed under mild conditions. Various substituents on 2-vinylanilines induced good compatibility and gave the desired products in moderate to good yields.

Keywords

2-vinylanilines - PIFA - quinones - oxidant - indoles

• References and Notes

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• 9 General Procedure for the Synthesis of Substituted Indoles from 2-Vinylanilines with Oxidant PIFA: The 2-(1-phenylvinyl)aniline (1a; 0.2 mmol) and PIFA (2.4 mmol) were added weighed into a 10-mL vial equipped with a magnetic stir bar. 1,4-dioxane (1 mL) was added, and this mixture was stirred under air. After being stirred at r.t. for 1.5 h, the solvent was evaporated in vacuum and the crude product was purified by column chromatography, eluting with petroleum ether–EtOAc (10:1) to afford the desired product 2a as a colorless solid (32 mg, 78% yield); mp 75–77 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.01 (br s, 1 H), 7.93–7.95 (d, J = 8.0 Hz, 1 H), 7.64–7.67 (m, 2 H), 7.41–7.45 (m, 2 H), 7.33–7.35 (d, J = 8.0 Hz, 1 H), 7.16–7.29 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 136.72, 135.64, 128.87, 127.56, 126.07, 125.79, 122.48, 121.90, 120.41, 119.88, 118.32, 111.52. HRMS: m/z [M + H]⁺ calcd for C₁₄H₁₂N: 194.0964; found: 194.0960.
• 10 General Procedure for the Synthesis of Indole Derivatives from 2-Vinylanilines with Oxidant Quinones: The 2-(1-phenylvinyl)aniline (1a; 0.2 mmol), benzoquinone (1.2 equiv) and TFA (0.2 equiv) were added weighed into a 10-mL vial equipped with a magnetic stir bar, and DMA (1 mL) was added, this mixture was stirred under Ar. After being stirred at 70 °C for 5 h, the reaction mixture was cooled to r.t. and then extracted with EtOAc (3 × 15 mL). The combined organic phase was dried over anhyd Na₂SO₄. The solvent was evaporated in vacuum and the crude product was purified by column chromatography, eluting with petroleum ether–EtOAc (10:1) to afford the desired product 3a as a light pink solid; yield: 34 mg (80%); mp 82–84 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.98–8.00 (m, 1 H), 7.69–7.72 (m, 2 H), 7.42–7.48 (m, 4 H), 7.35–7.39 (m, 2 H), 7.21–7.32 (m, 3 H), 6.93–6.95 (d, J = 8 Hz, 2 H), 5.24 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 154.74, 135.59, 134.62, 132.26, 129.09, 127.82, 127.59, 127.18, 127.07, 126.51, 126.32, 122.95, 119.58, 118.22, 116.46, 111.96. HRMS: m/z [M + H]⁺ calcd for C₂₀H₁₆NO: 286.1227; found: 286.1225. 4-(5-Methoxy-3-phenyl-1H-indol-1-yl)phenol (3e): light pink solid; yield: 25 mg (64%); mp 89–91 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.94 (br s, 1 H), 6.96 (s, 1 H), 6.90–6.92 (d, J = 8.0 Hz, 2 H), 6.54–6.65 (m, 6 H), 6.42–6.46 (m, 1 H), 6.14–6.16 (d, J = 8.0 Hz, 2 H), 6.04–6.06 (m, 1 H), 2.98 (s, 3 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 156.74, 155.05, 135.60, 132.11, 130.90, 129.43, 127.66, 127.28, 126.91, 126.23, 126.05, 117.07, 116.65, 112.84, 112.11, 101.71, 55.92. HRMS: m/z [M + H]⁺ calcd for C₂₁H₁₈NO₂: 316.1332; found: 316.1334.