Visible-Light-Enabled Aerobic Denitrative C3-Alkenylation of Indoles with β-Nitrostyrenes

Abstract

Herein, we unveil the first visible-light-mediated alkenylation reaction of indoles. The reaction follows a denitrative radical pathway where β-nitrostyrenes have been utilized as the alkene precursors for the C3-styrenylation of indoles under visible-light irradiation to afford biologically and synthetically important 3-alkenylindoles. High regioselectivity, absence of any photocatalyst, metal, external oxidant, acid or base, and the use of visible light and air as inexpensive clean reagents are the key highlights of the developed method.

Key words

indoles - β-nitrostyrenes - 3-alkenylindoles - visible light - radical reaction - photocatalyst-free

• References and Notes

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• 17 General Procedure for the Synthesis of 3-Alkenylindoles 3 A mixture of indole 1 (1.5 mmol) and β-nitrostyrene (2, 1.0 mmol) in CH₃CN (3 mL) was irradiated with visible light (white-light-emitting diode, 7.0 W) at a distance of 0.75 cm in a 10 mL round-bottom flask with stirring at r.t. for 18 h. Upon completion of the reaction (monitored by TLC), water (5 mL) was added, and the mixture was extracted with EtOAc (3 × 15 mL). The combined organic phases were dried with anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (EtOAc/n-hexane, 1:19) to afford an analytically pure sample of 3-alkenylindole 3. Characterization Data of Representative 3-Alkenylindoles 3 (E)-3-(4-Methoxystyryl)-1H-indole (3c) ^{18,9b 1}H NMR (400 MHz, DMSO): δ = 11.25 (s, 1 H), 7.98 (d, J = 8.0 Hz, 1 H), 7.58 (d, J = 2.4 Hz, 1 H), 7.50 (d, J = 8.8 Hz, 2 H), 7.42 (d, J = 8.0 Hz, 1 H), 7.26 (d, J = 16.6 Hz, 1 H), 7.15 (t, J = 7.6 Hz, 1 H), 7.10 (t, J = 6.9 Hz, 1 H), 7.04 (d, J = 16.4 Hz, 1 H), 6.92 (d, J = 8.2 Hz, 2 H), 3.76 (s, 3 H). ¹³C NMR (100 MHz, DMSO): δ = 158.0, 137.0, 131.2, 126.6, 125.3, 125.2, 123.2, 121.7, 120.3, 119.8, 119.5, 114.1, 113.9, 111.9, 55.1. HRMS (ESI): m/z calcd for C₁₇H₁₆NO [M + H]⁺: 250.1226; found: 250.1196. 3-[(E)-2-(Thiophen-2-yl)vinyl]-1H-indole (3i) ^{18,19 1}H NMR (400 MHz, DMSO): δ = 11.34 (s, 1 H), 7.94 (d, J = 7.6 Hz, 1 H), 7.64 (s, 1 H), 7.41 (d, J = 7.6 Hz, 1 H), 7.32–7.31 (m, 2 H), 7.17–7.10 (m, 4 H), 7.01 (s, 1 H). ¹³C NMR (100 MHz, DMSO): δ = 144.1, 137.0, 127.8, 126.4, 124.9, 124.3, 123.0, 122.3, 121.8, 119.8, 119.7, 117.1, 113.2, 111.9. HRMS (ESI): m/z calcd for C₁₄H₁₂NS [M + H]⁺: 226.0685; found: 226.0681. (E)-5-Fluoro-3-styryl-1H-indole (3l) ^{19 1}H NMR (400 MHz, DMSO): δ = 11.47 (s, 1 H), 7.82 (d, J = 10.0 Hz, 1 H), 7.75 (s, 1 H), 7.60 (d, J = 7.2 Hz, 2 H), 7.45–7.41 (m, 2 H), 7.35 (t, J = 6.8 Hz, 2 H), 7.19 (t, J = 6.6 Hz, 1 H), 7.10 (d, J = 17.1 Hz, 1 H), 7.03 (t, J = 8.4 Hz, 1 H). ¹³C NMR (100 MHz, DMSO): δ = 159.0, 138.9, 134.0, 129.0, 128.1, 126.7, 126.0, 125.8, 123.9, 122.4, 114.4, 113.3, 110.4, 105.3. HRMS (ESI): m/z calcd for C₁₆H₁₃FN [M + H]⁺: 238.1027; found: 238.1007.
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