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Synlett 2016; 27(20): 2788-2794
DOI: 10.1055/s-0036-1588887
DOI: 10.1055/s-0036-1588887
letter
Hydrogen-Bond-Catalyzed Arylation of 3-(Aminoalkyl)indoles via C–N Bond Cleavage with Thiourea under Microwave Irradiation: An Approach to 3-(α,α-Diarylmethyl)indoles
Weitere Informationen
Publikationsverlauf
Received: 16. Mai 2016
Accepted after revision: 30. August 2016
Publikationsdatum:
14. September 2016 (online)
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Abstract
We have developed a simple and efficient method for the arylation of 3-(aminoalkyl)indoles with aryl alcohols and other aromatic nucleophiles through C–N bond cleavage under microwave irradiation to synthesize 3-(α,α-diarylmethyl)indoles. The method uses thiourea as catalyst, which is environmentally benign, water-tolerant and easy to handle. Notably, acid-sensitive substrates are tolerated under the reaction conditions. Thiourea activates the tertiary amine through double hydrogen bonding and converts it into a better leaving group. The reaction proceeds through the formation of vinylogous iminium ion as an intermediate.
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0036-1588887.
- Supporting Information
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- 17 Synthesis of 3a: Typical Procedure: A solution of 1a (1 mmol, 250 mg), 2-naphthol (1 mmol, 144 mg) and thiourea (30 mol%, 23 mg) in MeCN (0.5 mL) was irradiated in a closed vessel in a microwave reactor at 100 °C for the specified time. The progress of the reaction was monitored by TLC. Upon completion of the reaction, solvent was removed under vacuum and the crude mixture was purified by column chromatography (hexane/EtOAc) to obtain the desired product 3a. Yield: 335 mg (96%); gray solid; mp 168–170 °C. IR (KBr): 3420, 3369, 3065, 2925, 1619, 1455, 1207, 747 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.08 (d, J = 8.5 Hz, 1 H), 8.04 (br s, 1 H), 7.80 (d, J = 8.1 Hz, 1 H), 7.73 (d, J = 8.8 Hz, 1 H), 7.45–7.14 (m, 10 H), 7.02 (d, J = 8.8 Hz, 1 H), 6.95 (t, J = 7.5 Hz, 1 H), 6.63 (s, 1 H), 6.50 (s, 1 H), 6.15 (br s, 1 H). 13C NMR (100 MHz, CDCl3): δ = 153.7, 141.5, 137.0, 133.0, 129.5, 129.4, 128.9, 128.8, 128.6, 127.0, 126.8, 124.0, 123.1, 123.1, 122.5, 120.1, 119.6, 118.5, 117.5, 111.4, 40.9. Anal. Calcd for C25H19NO: C, 85.93; H, 5.48; N, 4.01. Found: C, 85.82; H, 5.34; N, 4.09.
- 18 CCDC 1478603 (3h) contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
For reviews on microwave-assisted organic synthesis, see: