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doi.org/10.1002/ejoc.202000508
EurJOC
European Journal of Organic Chemistry
1H-NMR were reported relative to the solvent signal (CDCl3: δ =
7.26 ppm; [D6]DMSO: δ = 2.50 ppm). Chemical shifts of 13C NMR
were reported relative to the solvent signal (CDCl3: δ = 77.00 ppm;
[D6]DMSO: δ = 39.50 ppm). HRMS spectra were recorded on an
electrospray ionization quadrupole time-of-flight (ESI-Q-TOF) mass
spectrometer. The reactions were monitored by TLC visualized by
UV (254 nm). Column chromatography was performed on silica gel
(300–400 mesh). The substrates 2, 1a, 1c, 1e, and 5a were pur-
chased from Energy Chemical, substrate 1d was purchased from
Aladdin. Substrates 1b,[37] 1f,[38] 5b,[39] flavin I (8·Cl),[32c,33a] and
flavin II (8·TfO)[33c] were prepared according to the literature re-
ports.
catalyzed system, which then enters the next catalytic
cycle. In flavin-catalyzed system, HI and indolines could be oxid-
ized to I2 and indoles respectively.[35] The catalyst itself under-
goes reduction to form flavin Ired, which reacts with oxygen to
form hydroperoxy flavin IOOH. Oxidatively active IOOH promotes
the conversion of HI to I2, while producing flavin I and
water.[32,36] Similarly, thiol can also be converted to disulfide by
this flavin-catalyzed aerobic oxidation.[8]
General Procedure for the Synthesis of 3 and 4: A mixture of
indoline 1 (0.6 mmol), thiol 2 (0.5 mmol), I2 (0.05 mmol), and flavin
I (0.025 mmol) in DMSO (1 mL) was stirred at 60 °CC for 24 h under
oxygen atmosphere (1 atm). After the completion of the reaction
as indicated by TLC, it was quenched by adding brine (15 mL) at
room temperature and then extracted with ethyl acetate (10 mL
× 3). The combined organic phase was washed with water and
brine, dried with Na2SO4, filtered, and concentrated in vacuo. The
crude product was purified by flash chromatography on silica gel
to give the final product.
1,2-Di-p-tolyldisulfane (7): The product 7 was obtained as a white
solid (59 mg, 96 %). 1H NMR (400 MHz, CDCl3) δ = 7.41 (d, J =
8.2 Hz, 4H), 7.12 (d, J = 8.0 Hz, 4H), 2.34 (s, 6H).
1H-Indole (8): The product 8 was obtained as a white solid (40 mg,
68 %). 1H NMR (400 MHz, CDCl3) δ = 7.96 (br, 1H), 7.64 (d, J = 7.9 Hz,
1H), 7.33 (d, J = 8.0 Hz, 1H), 7.23–7.15 (m, 1H), 7.07–7.15 (m, 2H),
6.52–6.55 (m, 1H).
3-(p-Tolylthio)-1H-indole (3a): The product 3a was obtained as a
white solid (109 mg, 91 % yield). M.p. 119–121 °C. 1H NMR
(400 MHz, CDCl3) δ = 8.36 (br, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.46 (d,
J = 2.5 Hz, 1H), 7.43 (d, J = 7.8 Hz, 1H), 7.32–7.24 (m, 1H), 7.17 (t,
J = 7.5 Hz, 1H), 7.05 (d, J = 8.3 Hz, 2H), 6.99 (d, J = 8.2 Hz, 2H), 2.26
(s, 3H); 13C NMR (101 MHz, CDCl3) δ = 136.42, 135.43, 134.61, 130.40,
129.45, 129.06, 126.20, 122.94, 120.79, 119.65, 111.50, 103.42, 20.84;
ESI-MS m/z: 238.12 [M – H]–, the spectra data matched those previ-
ously reported.[33c]
3-[(4-Fluorophenyl)thio]-1H-indole (3b): The product 3b was ob-
tained as a white solid (122 mg, 86 %). M.p. 137–141 °C. H NMR
1
Scheme 4. Proposed mechanism for the reaction.
(400 MHz, [D6]DMSO) δ = 11.70 (br, 1H), 7.77 (d, J = 2.6 Hz, 1H),
7.48 (d, J = 8.1 Hz, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.18 (t, J = 7.5 Hz,
1H), 7.03–7.09 (m, 5H); 13C NMR (101 MHz, [D6]DMSO) δ = 160.14
(d, J = 241.6 Hz), 136.71, 134.57 (d, J = 3.0 Hz), 132.43, 128.46,
127.47 (d, J = 7.9 Hz), 122.17, 119.18 (d, J = 199.2 Hz), 115.98, 115.76,
112.38, 99.65; 19F NMR (376 MHz, [D6]DMSO) δ = –118.29; ESI-MS
m/z: 242.22 [M – H]–, the spectra data matched those previously
reported.[40]
Conclusion
In summary, an oxidative C-H sulfenylation of aryl-fused cyclic
amines with various thiols catalyzed by flavin/I2 system with
high atom-efficiency and excellent functional compatibility is
reported for the first time. Different flavin derivatives could cat-
alyze the C-H sulfenylation of aryl-fused cyclic amines to form
corresponding 3-sulfenylindoles and 6-sulfenylquinolines, re-
spectively. This metal-free reaction uses molecular oxygen as
the only terminal oxidant and produces environmental-friendly
H2O as the only by-product.
3-[(4-Chlorophenyl)thio]-1H-indole (3c): The product 3c was ob-
tained as a white solid (113 mg, 87 %). M.p. 128–130 °C. 1H NMR
(400 MHz, CDCl3) δ = 8.43 (br, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.49 (d,
J = 2.6 Hz, 1H), 7.45 (d, J = 8.2 Hz, 1H), 7.30 (t, J = 8.6 Hz, 1H), 7.18
(t, J = 7.3 Hz, 1H), 7.12 (d, J = 8.6 Hz, 2H), 7.03 (d, J = 8.6 Hz, 2H);
13C NMR (101 MHz, CDCl3) δ = 137.80, 136.49, 130.67, 130.53,
128.79, 128.73, 127.09, 123.19, 121.04, 119.49, 111.64, 102.45; ESI-
MS m/z: 258.18 [M – H]–, the spectra data matched those previously
reported.[31c]
Experimental Section
Unless otherwise stated, all substrates, reagents, and solvents were
obtained from commercial sources and without further purification.
NMR spectra were recorded using Varian Mercury Plus 400 MHz or
Bruker Avance III 600 MHz spectrometers. Chemical shifts of
3-[(4-Bromophenyl)thio]-1H-indole (3d): The product 3d was ob-
tained as a white solid (120 mg, 79 %). M.p. 145–148 °C. 1H NMR
(400 MHz, CDCl3) δ = 8.43 (br, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.49 (d,
J = 2.5 Hz, 1H), 7.45 (d, J = 8.2 Hz, 1H), 7.32–7.22 (m, 3H), 7.18 (t,
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