A. Arcadi, G. Bianchi, A. Inesi, F. Marinelli, L. Rossi
SHORT COMMUNICATION
Ethyl 2-[(4-Phenylcyclohex-1-en-1-yl)ethynyl]phenylcarbamate (1n):
M.p. 78–79 °C. 1H NMR (200 MHz, CDCl3): δ = 8.19 (d, J =
8.3 Hz, 1 H), 7.41–7.18 (m, 8 H), 6.95 (t, J = 7.6 Hz, 1 H), 6.31
(br. s, 1 H), 4.23 (q, J = 7.0 Hz, 2 H), 2.90–2.65 (m, 1 H), 2.60–
2.26 (m, 4 H), 2.20–1.65 (m, 2 H), 1.31 (t, J = 7.1 Hz, 3 H) ppm.
13C NMR (50.3 MHz, CDCl3): δ = 153.0, 145.9, 138.8, 138.7,
135.2, 131.4, 129.1, 128.3, 126.6, 126.1, 124.8, 122.2, 120.0, 117.4,
111.8, 97.9, 82.2, 61.1, 38.9, 33.7, 29.8, 29.3, 14.4 ppm. MS (EI):
m/z (%) = 345 (100) [M]+. C23H23NO2 (345.43): calcd. C 79.97, H
6.71; found C 80.02, H 6.72.
nitrogen atom by its protection as carbamate functionality
(CO2Et); the formation of indole 2j (95% yield) was ac-
complished by annulation of ethyl 2-ethynylphenylcarb-
amate (1j; Table 2, Entry 10). Furthermore, deprotection of
the indolic nitrogen atom by removal of the ethoxycarbonyl
group was observed. Interestingly, when added before the
start of the electrolysis, 1i underwent reduction of the CϵC
bond to give vinyl derivative 3 in 73% yield (Table 2, En-
try 9). Although the electrochemical reduction of acetylene
is a known procedure,[16] the reduction of terminal alkynes
under these mild conditions may offer a new synthetic op-
portunity. Moreover, comparison of the results obtained in
the cyclization of 1n with the lack of formation of 2m from
1m suggests that the pKa values of the N–H bond and/or
the polarization of the triple bond were closely related to
the efficiency of the cyclization reaction.
2-(7-Chloro-5-nitro-1H-indol-2-yl)butan-2-ol (2h): Yield: 234 mg,
87%. M.p. 145–146 °C. 1H NMR (200 MHz, [D6]acetone): δ =
10.62 (br. s, 1 H), 8.32 (d, J = 1.9 Hz, 1 H), 7.86 (d, J = 2.0 Hz, 1
H), 6.56 (d, J = 2.0 Hz, 1 H), 4.36 (br. s, 1 H), 1.95–1.70 (m, 2 H),
1.50 (s, 3 H), 0.72 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR (50.3 MHz,
[D6]acetone): δ = 152.5, 142.5, 136.9 129.8, 116.9, 116.5, 116.4,
102.0, 72.3, 36.3, 28.4, 8.7 ppm. MS (EI): m/z (%) = 268 (100)
[M]+. C12H13ClN2O3 (268.7): calcd. C 53.64, H 4.88; found C
53.72, H 4.85.
In no case was neutralization of the reaction mixture re-
quired during workup. Simple evaporation of the solvent
and filtration through silica gel, if needed, afforded the re-
action products in very good yields.
Acknowledgments
Work supported by the Ministero dell’Università e della Ricerca,
Rome and by the University of L’Aquila (Italy).
Conclusions
We developed a new application of the electrogenerated
cyanomethyl anion that involves its use, as an electrogener-
ated base, in the synthesis of functionalized indoles from
alkynylanilines. The approach proposed is very clean and
safe and avoids the use of metal catalysts or classical or-
ganic acids and bases. The workup is very easy and simply
requires filtration or flash chromatography of the evapo-
rated reaction mixture without any extractive workup. [3] a) X. Wang, D. V. Gribkov, D. Sames, J. Org. Chem. 2007, 72,
Thus, this electrochemical approach represents a valuable
and competitive alternative to the reported procedures.
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General Procedure for Electrochemical-Mediated Cyclization of Alk-
ynylanilines: A solution (12.0 mL) of CH3CN/0.1 TEATFB was
electrolyzed under galvanostatic control (Pt cathode 1.5 cm2; J =
25 mAcm–2, Q = 2.5 Fmol–1 of 1) at 0 °C. No pre-electrolysis was
required. At the end of electrolysis, 2-alkynylaniline 1 (0.4 mmol)
was added to the cathode compartment, and the reaction was pro-
longed at the temperature and for the time reported in Table 2. The
solvent was evaporated under reduced pressure. The crude mixture
yielded pure indole 2 after simple filtration through silica gel. 2-
Alkynylanilines 1a–c, 1e–g, 1i–m and indoles 2a–c, 2e–g, 2j,m are
known compounds.[5o,12e,15b,15d,17a] Compound 1d was obtained ac-
cording to ref.[17d]; carbamate 1n was obtained from corresponding
amide 1m by classical reaction with ethyl chloroformate in pyridine.
2-{[3-(Trifluoromethyl)phenyl]ethynyl}aniline (1d): M.p. 166–167 °C.
1H NMR (200 MHz, CDCl3): δ = 7.63 (br. s, 1 H), 7.50 (d, J =
7.7 Hz, 1 H), 7.39 (d, J = 7.9 Hz, 1 H), 7.30–7.21 (m, 2 H), 7.04–
6.96 (m, 1 H), 6.57 (t, J = 7.7 Hz, 2 H), 4.12 (br. s, 2 H) ppm. 13C
NMR (50.3 MHz, CDCl3): δ = 148.0, 134.4, 132.3, 131.2, 130.3 (q,
J = 28 Hz), 130.2, 128.9, 128.0 (q, J = 3.7 Hz), 124.6 (q, J =
3.6 Hz), 123.8 (q, J = 272 Hz), 117.9, 114.4, 107.1, 93.0, 87.7 ppm.
MS (EI): m/z (%) = 261 (100) [M]+. C15H10F3N (261.24): calcd. C
68.96, H 3.86; found C 69.04, H 3.84.
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