Metal-Free N-Arylation of Indolines with Diaryliodonium Salts

Abstract

The N-arylation of indolines using diaryliodonium salts as electrophilic arylating reagents is described. Without the use of any additional additives, the desired N-aryl indolines could be obtained in up to 85% yield.

Key words

amination - hypervalent iodine - metal-free - arylation - indoline

• References and Notes

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• 27 General Procedure for the N-Arylation of Indoline (1a) with Diphenyliodonium Triflate (2a) to 1-Phenylindoline (3a) Diphenyliodonium triflate (2a, 0.1 g, 0.23 mmol, 1.1 equiv) was charged in a vial and sealed with a septum. After adding TFE (3 mL), indoline (1a, 0.024 mL, 0.21 mmol) was added dropwise slowly to the solution, which was then heated to 70 °C for 14 h. After the solution was cooled to r.t., the mixture was diluted with H₂O and sat. NaHCO₃. The aqueous phase was extracted several times with CH₂Cl₂. The organic phase is washed with H₂O, dried over MgSO₄, filtered, and concentrated in vacuo. The crude residue was purified by column chromatography on silica gel, eluting with cyclohexane–CH₂Cl₂ (2:1, v/v) giving 34 mg (83%) of 3a as a colorless solid. 2,3-Dihydro-1-(4-methylphenyl)-1H-indole (3b) Pale yellow oil, partially crystalline (18 mg, 41%); eluent: cyclohexane–CH₂Cl₂ (20:1 → 15:1 → 10:1, v/v); mp 66–70 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.17–7.13 (m, 5 H), 7.07–7.04 (m, 2 H), 6.75–6.69 (m, 1 H), 3.93 (t, 2 H, J = 8.5 Hz), 3.12 (t, 2 H, J = 8.5 Hz), 2.33 (s, 3 H). ¹³C{¹H} NMR (100.6 MHz, CDCl₃): δ = 147.7, 141.9, 131.2, 130.8, 129.8, 127.2, 125.1, 118.6, 118.3, 108.0, 52.5, 28.3, 20.9. IR (neat): 2360, 2341, 1770, 1742, 1597, 1515, 1482, 1456, 1384, 1312, 1296, 1246, 1166, 1127, 1063, 1049, 924, 869, 815, 742, 703 cm^–1. HRMS (APCI): m/z calcd for C₁₅H₁₅N: 209.12045; found [M + H]⁺: 210.12714. 1-(4-Chlorophenyl)-2-methylindoline (6f) Pale yellow oil (15 mg, 29%); eluent: cyclohexane–CH₂Cl₂ (5:1, v/v). ¹H NMR (500 MHz, CDCl₃): δ = 7.31 (d, 2 H, J = 8.8 Hz), 7.18 (d, 2 H, J = 8.8 Hz), 7.14 (d, 1 H, J = 7.2 Hz), 7.03 (t, 1 H, J = 7.5 Hz), 6.78 (d, 1 H, J = 7.9 Hz), 6.74 (t, 1 H, J = 7.4 Hz), 4.36–4.30 (m, 1 H), 3.33 (dd, 1 H, J ₁ = 8.8 Hz, J ₂ = 15.5 Hz), 2.76 (dd, 1 H, J ₁ = 7.4 Hz, J ₂ = 15.4 Hz), 1.31 (d, 3 H, J = 6.1 Hz). ¹³C{¹H} NMR (125.8 MHz, CDCl₃): δ = 148.4, 142.3, 129.7, 129.4, 127.7, 127.3, 125.1, 122.9, 119.3, 108.5, 60.1, 37.3, 20.1. HRMS (APCI): m/z calcd for C₁₅H₁₄ClN: 243.08148 (100%), found [M + H]⁺: 244.08851.