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Letter
Synlett
water to form intermediate B through an E2 or E1cb elimi-
nation pathway. Intermediate B then reacts with the thio-
phenol anion 2a′, generated from 2a by base-mediated
deprotonation, to afford the final product 3aa.
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In conclusion, we have developed a metal-free, green,
and environmentally friendly method for the synthesis of
3-(thiomethyl)indoles under aqueous conditions.16 Para-
formaldehyde, which is stable and has low toxicity, was
used as an atom-economic one-carbon source. Various thio-
phenols used as the sulfur sources coupled smoothly with
various indoles. Ethylenediamine was used as a highly
effective base for this transformation. Functional groups
such as halogens and heterocycles were well tolerated
under the optimized reaction conditions. This novel meth-
od provides an alternative environmentally friendly and
easily handled approach to 3-(thiomethyl)indoles.
Funding Information
We gratefully acknowledge the support for this work provided by the
National Natural Science Foundation of China (21572194, 21502160).
The project was supported by the Scientific Research Fund of Hunan
Provincial Education Department (YB2016B024), the China Post-
doctoral Science Foundation Funded Project (2015M572257), and
Hunan Provincial Natural Science Foundation of China (16JJ3112).
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Supporting Information
Supporting information for this article is available online at
(13) Cheng, X.; Wang, H.; Xiao, F.; Deng, G.-J. Green Chem. 2016, 18,
5773.
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(16) 1-Methyl-3-{[(4-tolyl)thio]methyl}-1H-indole (3aa); Typical
Procedure
References and Notes
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London, 1970. (b) Indoles, Part Four: The Monoterpenoid Indole
Alkaloids; Saxton, J. E., Ed.; Wiley-Interscience: Hoboken, 1983.
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A 10 mL oven-dried reaction vessel was charged with 1-methyl-
1H-indole (1a, 50 μL, 0.4 mmol), paraformaldehyde (24 mg, 0.8
mmol), 4-methylbenzenethiol (2a, 24.8 mg, 0.2 mmol). The
vessel was sealed, and ethane-1,2-diamine (6.5 μL, 0.1 mmol)
and H2O (0.5 mL) were added from a syringe. The resulting solu-
tion was stirred at 130 °C for 4 h. The volatiles were removed
under vacuum, and the residue was purified by column chro-
matography [silica gel, PE–EtOAc ( 100:1)] to give a brown
liquid; yield: 41.7 mg (78%).
1H NMR (400 MHz, CDCl3): δ = 7.67 (d, J = 7.9 Hz, 1 H), 7.28–
7.20 (m, 4 H), 7.14–7.10 (m, 1 H), 7.08–7.06 (m, 2 H), 6.91 (s, 1
H), 4.30 (s, 2 H), 3.69 (s, 3 H), 2.30 (s, 3 H). 13C NMR (100 MHz,
CDCl3): δ = 137.0, 136.0, 133.6, 130.0, 129.5, 127.7, 127.2, 121.8,
119.2, 119.1, 110.2, 109.3, 32.66, 30.34, 21.00. HRMS (ESI): m/z
[M + H]+ calcd for C17H18NS: 268.11545; found: 268.11554.
(3) For selected recent examples, see: (a) Kagawa, N.; Malerich, J. P.;
Rawai, V. H. Org. Lett. 2008, 10, 2381. (b) Shaikh, R. R.; Mazzanti,
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A.; Ali, S.; Khan, A. T. Tetrahedron Lett. 2014, 55, 486. (c) Parnes,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–D