One-Pot 2-Aryl/Vinylindole Synthesis Consisting of a Ruthenium-Catalyzed Hydroamination and a Palladium-Catalyzed Heck Reaction Using 2-Chloroaniline

Abstract

A one-pot synthesis of 2-aryl- and 2-vinylindoles based on a ruthenium-catalyzed hydroamination and a palladium-catalyzed intramolecular Heck reaction is reported. The ruthenium-­catalyzed addition reaction was applied to terminal as well as in­ternal alkynes. Intramolecular Heck reactions of the resulting 2-chloroanilino enamines were achieved using an in situ generated palladium complex derived from an N-heterocyclic carbene.

Key words

aryl chlorides - Heck reaction - hydroamination - palladium - ruthenium

References and Notes

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36

Representative Procedure: Synthesis of 2,3-Diphenyl-indole (4b) 2-Chloroaniline (1a; 133 mg, 1.04 mmol), and tolan (2b; 267 mg, 1.50 mmol) were added to a solution of Ru₃(CO)₁₂ (6.4 mg, 0.01 mmol, 1 mol%) and NH₄PF₆ (4.9 mg, 0.03 mmol, 3 mol%) in toluene (1 mL) and the resulting mixture was stirred for 18 h at 105 °C. Thereafter, t-BuOK (224 mg, 2.00 mmol), Pd(OAc)₂ (11.2 mg, 0.05 mmol, 5 mol%), 5 (21.3 mg, 0.05 mmol, 5 mol%), and toluene (2 mL) were added and the mixture was stirred at 105 °C for 24 h. Et₂O (50 mL) and brine (50 mL) were added to the cold suspension. The separated aqueous phase was washed with Et₂O (2 × 50 mL). Drying with MgSO₄ and purification by column chromatog-raphy (silica gel; n-pentane-Et₂O, 10:1 to 6:1) yielded 2,3-diphenylindole (4b; 248 mg, 89%) as a yellow solid; mp 129.8-130.0 °C. ¹H NMR (400 MHz): δ = 8.23 (s, 1 H), 7.71 (d, J = 8.6 Hz, 1 H), 7.49-7.14 (m, 13 H).
¹³C NMR (100 MHz): δ = 135.8, 135.0, 134.0, 132.7, 130.1, 128.7, 128.6, 128.5, 128.1, 127.7, 126.2, 122.7, 120.4, 119.7, 115.0, 110.8. IR (ATR): 3396, 3052, 1600, 1533, 1455, 1439, 1371, 1328, 1249, 1152, 1070, 1011, 965, 919, 828, 763, 740, 693 cm^-1. HRMS (EI): m/z calcd for C₂₀H₁₅N: 269.1204; found: 269.1202.