Synthesis of 3-Arylindole-2-carboxylates via Copper-Catalyzed Hydroarylation
iodophosphonoacetate. The hydroarylation of the al- Acknowledgements
kynoates was successfully carried out using an inex-
This research was partially supported by the MEXT, Grant-
pensive copper catalyst and readily available arylbor-
onic acids to obtain 3,3-diarylacrylates, which were
subsequently converted to the desired 3-arylindole-2-
carboxylates via reductive cyclization under the modi-
fied Cadogan conditions using the molybdenum cata-
lyst and PPh3. The p-iodophenyl-substituted indole
product was applied to palladium-catalyzed cross-cou-
plings such as Suzuki–Miyaura, Sonogashira, or Mizo-
in-Aid for Scientific Research (B) (20350045), and the
Global COE program (Nagoya University). We thank Dr. K.
Oyama (NU) for mass measurements, and Mr. N. Kirai
(TIT) for preliminary experiments.
References
ACHTUNGTRENNUNGroki–Heck reactions, demonstrating successfully the
synthetic utility of our method.
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Synthesis of 3,3-Diarylacrylates 4. Representative
Procedure – Synthesis of 4a
To
a solution of o-nitrophenylpropiolate 3a (110 mg,
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(m, 5H), 7.57 (ddd, J=8.0, 7.5, 1.5 Hz, 1H), 7.68 (dt, J=7.5,
1.5 Hz, 1H), 8.21 (dd, J=8.0, 1.5 Hz, 1H); 13C NMR
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128.6, 129.6, 130.8, 133.0, 134.8, 137.9, 147.5, 153.1, 165.0; IR
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Synthesis of 3-Arylindole-2-carboxylates 5.
Representative Procedure – Synthesis of 5a
A solution of acrylate 4a (89.4 mg, 0.30 mmol), MoCl2O2
ACHTUNGTRENNUNG(dmf)2 (5.27 mg, 0.015 mmol), and triphenylphosphine
(188.4 mg, 0.72 mmol) in toluene (3.0 mL) was degassed at
À788C and then was stirred at 808C under an argon atmos-
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vacuum. The residue was purified by silica gel flash column
chromatography (hexane-CHCl3 5:1) to give indole 5a as a
white solid; yield: 75.8 mg (95%); mp 137.5–138.08C;
1H NMR (300 MHz, CDCl3): d=1.24 (t, J=7.2 Hz, 3H),
4.29 (q, J=7.2 Hz, 2H), 7.15 (ddd, J=8.0, 6.8, 1.5 Hz, 1H),
7.33–7.48 (m, 5H), 7.53–7.58 (m, 2H), 7.64 (dd, J=8.7,
1.5 Hz, 1H), 8.93 (br s, 1H); 13C NMR (75 MHz, CDCl3):
d=14.0, 60.9, 111.7, 120.8, 121.7, 122.8, 124.2, 125.8, 127.2,
127.7, 128.0, 130.6, 133.5, 135.8, 162.1; IR (KBr): n=3326
(NH), 1670 (C=O), 1254 (C-O) cmÀ1; MS (FAB): m/z (%)=
265 (53) [M]+, 219 (100) [MÀHOEt]+; anal. calcd. (%) for
C17H15NO2 (265.31): C 76.96, H 5.70, N 5.28; found: C 76.99,
H 5.69, N 5.14.
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Adv. Synth. Catal. 2011, 353, 701 – 706
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