Synthesis of 2-Substituted Indoles
COMMUNICATIONS
Table 3. Indole synthesis in an one-pot, sequential fashion.
Acknowledgements
We gratefully thankthe NIH (GM69704) for their generous
funding. Partial support from the PSC-CUNY Research Award
Programs, and GRTI (The Graduate Research and Technology
Initiative) grants are also gratefully acknowledged. ZYT thanks
the CUNY for Mario Capelloni Dissertation Fellowships. We
also thankFrontier Scientific for its generous gifts of palladiu-
m(II) acetate and Combiphos Catalysts, Inc for its generous gifts
of tri-tert-butylphosphine.
References and Notes
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(1.2 mmol) and toluene (2 mL). The resulting mixture was
heated to 110–1208C for 14 hours. After quenching with water,
the reaction mixture was extracted with ethyl acetate and the
organic layer was washed with brine. Rota-evaporation and
flash chromatography on silica gel (hexane: ethyl acetate¼
5:95 to 15:85) gave 2-substituted indoles as the product.
Method B: Under an N2 atmosphere, to a mixture of o-alky-
nylchlorobenzene (1 mmol), K3PO4 (3 mmol), Pd(OAc)2
(0.03 mmol) and (t-Bu)3P (0.06 mmol) were added an amine
(1.2 mmol) and dimethylacetamide (2 mL). The resulting mix-
ture was heated to 1308C for 14 hours. After quenching with
water, the reaction mixture was extracted with ethyl acetate
and the organic layer was washed with brine. Rota-evaporation
and flash chromatography on silica gel (hexane: ethyl acetate¼
5:95 to 15:85) gave 2-substituted indoles as the product.
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General Procedure for One-Pot, Sequential
Preparation of 2-Substituted Indoles
Under an N2 atmosphere, to a mixture of 1-iodo-2-chlorobenze
(1 mmol), Pd(OAc)2 (0.03 mmol), CuI (0.1 mmol), t-BuOK
(3 mmol), and (t-Bu)3P (0.06 mmol) were added an alkyne
(1.2 mmol) and toluene (2 mL). After the resulting mixture
was heated to 1108C for 1 hour, an amine (1.2 mmol) was add-
ed and the mixture was heated at 1108C for another 12 h. After
quenching with water, the reaction mixture was extracted with
ethyl acetate and the organic layer was washed with brine.
Rota-evaporation and flash chromatography on silica gel (hex-
ane: ethyl acetate¼5:95 to 15:85) gave 2-substituted indoles
as the product.
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Cross-Coupling Reactions, 2nd edn., (Eds.: A. de Mei-
jere, F. Diederich), Wiley-VCH, Weinheim, 2004, 317–
394; b) K. Sonogashira, in: Comprehensive Organic Syn-
For detailed procedures and characterization data, see Sup-
porting Information.
Adv. Synth. Catal. 2006, 348, 846 – 850
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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