Synthesis of 3-aminoindole derivatives: Combination of Thorpe-Ziegler cyclization and unexpected allylindium-mediated decyanation

Article abstract of DOI:10.1016/j.tetlet.2011.01.085

α-Anilinonitriles were unexpectedly converted to 3- iminodihydroindoles via the Thorpe-Ziegler cyclization during the benzoylation. 3-Iminodihydroindoles were transformed to 3-aminoindoles in good yields via an allylindium-mediated decyanative aromatizati

Full text of DOI:10.1016/j.tetlet.2011.01.085

Tetrahedron Letters 52 (2011) 1378–1382
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of 3-aminoindole derivatives: combination of Thorpe–Ziegler
cyclization and unexpected allylindium-mediated decyanation
Yu Mi Kim a, Ko Hoon Kim a, Sunhong Park b, Jae Nyoung Kim a,
⇑
a Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
b Department of Chemistry and Research Institute of Natural Science, Gyeongsang National University, Jinju 660-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
a
-Anilinonitriles were unexpectedly converted to 3-iminodihydroindoles via the Thorpe–Ziegler cycliza-
Received 4 January 2011
Revised 13 January 2011
Accepted 17 January 2011
Available online 23 January 2011
tion during the benzoylation. 3-Iminodihydroindoles were transformed to 3-aminoindoles in good yields
via an allylindium-mediated decyanative aromatization.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
3-Aminoindoles
Thorpe–Ziegler cyclization
Allylindium reagents
Decyanation
Allylindium reagents have been used extensively for the
introduction of allyl groups in a Barbier type manner to various
electrophiles.1,2 Various electrophiles including aldehydes, ke-
tones, imines, N-tosylimines, and nitriles have been used in the
CN
Ph
CN
BzCl
pyridine, rt
CN
allyl bromide
O
2-cyanoaniline
EtOH, reflux
OH
CN
N
In, THF, reflux
N
H
N
Ph
CN
N
Ph
Ph
1a
Ph
Ph
CN
3a
2a
Scheme 1.
EtN(i-Pr)2
excess BzCl
O
O
COPh
2a
Ph
N
N
N
N
Ph
BzCl
Ph CN
Ph
CN
I
4a
Scheme 2.
⇑
Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530 3389.
E-mail address: kimjn@chonnam.ac.kr (J.N. Kim).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.01.085

Y. M. Kim et al. / Tetrahedron Letters 52 (2011) 1378–1382
1379
Recently we reported the synthesis of alkenylimidazoles via an
In-mediated allylation of various
-aminonitrile derivatives.3 As a
a
continuation, we tried to prepare compound 3a having an ortho-
cyanoaniline moiety in order to synthesize allylimidazole deriva-
tives by the reaction of an allylindium reagent (Scheme 1). How-
ever, the benzoylation of 2a with benzoyl chloride in pyridine
failed at room temperature.3,4 The benzoylation reaction was also
ineffective even at elevated temperature (70 °C, 3 h) in pyridine
or in the presence of Et3N in CH2Cl2. The failure might be ascribed
to the steric hindrance around the nucleophilic nitrogen atom of 2a
and the presence of an electron-withdrawing ortho-CN group in
part.
After many trials, the 3-iminodihydroindole derivative 4a was
obtained unexpectedly from 2a in 87% in the presence of benzoyl
chloride and N,N-diisopropylethylamine in toluene at elevated
temperature (70 °C, Scheme 2).5 Compound 4a might be formed
via N-benzoylation, subsequent Thorpe–Ziegler cyclization6 of
a-
carbanion I and benzoylation of the imine intermediate. It is un-
clear at this stage as which step occurs first, the benzoylation or
the tandem Thorpe–Ziegler cyclization accompanying benzoyla-
tion of imine intermediate.4e,f The structure of 4a was confirmed
unequivocally by X-ray diffraction (Fig. 1), and the spectroscopic
data.7,8
We found an interesting reactivity of 4a toward allylin-
dium reagents (Scheme 3). To our surprise, the 3-aminoindole
derivative 5a was obtained in 73% under the influence of allyl
bromide and indium metal (THF, reflux, 40 min).7–10 We ex-
pected originally the formation of compound 6a by allylation
at the imine double bond (allylation to position-a) via the
six-membered chelated transition state III; however, we did
not observe any trace of 6a. Instead, the allyl group was
transferred from allylindium to the nitrile moiety (allylation
to position-b) to form an intermediate II in which indium is
chelated by two atoms of nitrogen in a six-membered transi-
tion state. This intermediate II was converted to the aromatic
indole derivative 5a by liberation of allyl cyanide.11 The struc-
ture of 5a was also confirmed by X-ray diffraction (Fig. 1),
and the spectroscopic data.7,8
The reaction of 4a and methallyl bromide instead of allyl bro-
mide under the same conditions produced 5a in a similar yield
(68%).11 We thought that an appropriate nucleophile could at-
tack the nitrile moiety and cause the decyanative aromatization;
however, various trials for the conversion of 4a to 5a failed
including the use of NaHCO3/aq THF, THF/c-HCl, NaBH4/EtOH,
InCl3/THF, FeCl3/THF, ZnBr2/THF, NaI/DMSO, and (MeO)3P/
toluene.
Encouraged by the results, we prepared a
-aminonitriles 2a–d3,4
and generated the dihydroindoles 4a–f. Subsequent treatment
with indium and allyl bromide afforded the 3-aminoindoles 5a–f.
The results are summarized in Table 1. The reactions of 2a with
p-toluoyl chloride and 2,6-difluorobenzoyl chloride afforded the
corresponding dihydroindoles 4b and 4c, respectively (entries 2
and 3). The reactions of 2b–d and benzoyl chloride produced 4d–
f in good yields similarly (entries 4–6). All of the dihydroindoles
4a–f were transformed to 3-aminoindoles 5a–f in moderate to
good yields (56–76%) under the influence of allylindium reagents.
In summary, we disclose a novel synthesis of 3-aminoindole
Figure 1. ORTEP drawing of compounds 4a and 5a.
indium-mediated allylation1,2 with the allyl transfer to the elec-
trophilic carbon atom occurring via a six-membered transition
state.1,2
derivatives from
a-aminonitriles via Thorpe–Ziegler cyclization
followed by an allylindium-mediated decyanative aromatization
process.

1380
Y. M. Kim et al. / Tetrahedron Letters 52 (2011) 1378–1382
NHCOPh
allyl bromide
(3.0 equiv)
O
COPh
Ph
NHCOPh
Ph CN
a
O
N
a
N
N
N
In (1.5 equiv)
THF, reflux, 40 min
Ph
Ph CN
b
O
Ph
Ph
4a
5a
6a (not formed)
Ph
L
O
L
In
N
COPh
O
InL2
a
N
NC
Ph
N
N
In
Ph
- allyl cyanide (?)
N
Ph
O
III
Ph
II
Scheme 3.
Table 1
Synthesis of 3-aminoindole derivatives
Entry
Substrate 2a (%)
Product 4b (%)
Indole 5c (%)
NC
O
O
Ph
N
Ph
N
H
H
N
1
N
N
N
C
Ph
Ph
Ph
CN
N
N
2a (65)
COPh
COPh
5a (73)
4a (87)
O
O
Ar
Ar
H
N
N
2d
3e
4
2a
C
Ph
Ph
COAr
N
N
COAr
5b (68)
4b (77)
O
O
Ar
Ar
H
N
N
2a
C
Ph
Ph
N
N
COAr
COAr
5c (69)
4c (93)
NC
Cl
O
O
Ph
Ph
H
H
N
N
N
Cl
Cl
N
C
Ph
Ph
Ph
CN
N
COPh
N
2b (54)
COPh
5d (56)
4d (86)
NC
OMe
OMe
O
O
Ph
Ph
H
N
H
N
N
MeO
MeO
MeO
MeO
5
N
C
Ph
Ph
Ph
CN
N
COPh
N
COPh
2c (80)
5e (58)
4e (88)

Y. M. Kim et al. / Tetrahedron Letters 52 (2011) 1378–1382
1381
Table 1 (continued)
Entry
Substrate 2a (%)
Product 4b (%)
Indole 5c (%)
NC
O
O
Ph
N
Ph
N
H
H
N
6f
N
C
Ar
N
Ar
Ar
CN
N
2d (51)
COPh
COPh
5f (76)
4f (79)
a
Prepared from mandelonitrile and 2-cyanoaniline derivatives in EtOH (reflux, 30 h).
b
c
d
e
f
Prepared from 2 and aroyl chloride (4.0 equiv), EtN(i-Pr)2 (4.0 equiv), toluene, 70 °C, 2 h.
Allyl bromide (3.0 equiv), In (1.5 equiv), THF, reflux, 40 min.
Ar is p-tolyl.
Ar is 2,6-difluorophenyl.
Ar is p-tolyl.
(258 mg, 2.0 mmol) and benzoyl chloride (280 mg, 2.0 mmol) at room
temperature. The reaction mixture was heated to 70 °C for 2 h. After the
usual aqueous extractive workup and column chromatographic purification
process (hexanes/CH2Cl2/EtOAc, 10:1:1), compound 4a was obtained as a white
solid, 192 mg (87%). Other compounds were synthesized similarly, and the
spectroscopic data of 4a–f are as follows.
Acknowledgments
This work was supported by the National Research Foundation
of Korea Grant funded by the Korean Government (2010-0015675).
Spectroscopic data were obtained from the Korea Basic Science
Institute, Gwangju branch.
Compound 4a: 87%; white solid, mp 182–184 °C; IR (KBr) 1688, 1667, 1466,
1338 cmÀ1
;
1H NMR (CDCl3, 300 MHz)
d
6.89 (d, J = 7.5 Hz, 1H), 7.07 (t,
J = 7.5 Hz, 1H), 7.34–7.57 (m, 15H), 7.80 (d, J = 7.5 Hz, 2H); 13C NMR (CDCl3,
75 MHz) 68.39, 115.46, 116.73, 119.59, 125.15, 125.73, 127.04, 127.71,
d
References and notes
128.65, 128.88, 129.24, 129.32, 129.69, 131.89, 131.96, 133.77, 134.06, 134.42,
135.79, 149.21, 161.99, 167.49, 177.42; ESIMS m/z 442 (M++H). Anal. Calcd for
1. For the general review on indium-mediated reactions, see: (a) Auge, J.; Lubin-
Germain, N.; Uziel, J. Synthesis 2007, 1739–1764; (b) Kargbo, R. B.; Cook, G. R.
Curr. Org. Chem. 2007, 11, 1287–1309; (c) Lee, P. H. Bull. Korean Chem. Soc. 2007,
28, 17–28; (d) Li, C.-J.; Chan, T.-H. Tetrahedron 1999, 55, 11149–11176; (e) Pae,
A. N.; Cho, Y. S. Curr. Org. Chem. 2002, 6, 715–737; (f) Kim, S. H.; Lee, H. S.; Kim,
K. H.; Kim, S. H.; Kim, J. N. Tetrahedron 2010, 66, 7065–7076.
2. For the In-mediated Barbier-type allylation of nitrile-containing substrates,
see: (a) Kim, S. H.; Lee, H. S.; Kim, K. H.; Kim, J. N. Tetrahedron Lett. 2009, 50,
1696–1698; (b) Kim, S. H.; Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron Lett.
2009, 50, 5744–5747; (c) Kim, S. H.; Lee, H. S.; Kim, K. H.; Kim, J. N. Tetrahedron
Lett. 2009, 50, 6476–6479; (d) Kim, S. H.; Kim, S. H.; Kim, K. H.; Kim, J. N.
Tetrahedron Lett. 2010, 51, 860–862; (e) Kim, S. H.; Kim, S. H.; Kim, T. H.; Kim, J.
N. Tetrahedron Lett. 2010, 51, 2774–2777.
C
29H19N3O2: C, 78.90; H, 4.34; N, 9.52. Found: C, 79.07; H, 4.56; N, 9.33.
Compound 4b: 77%; yellow solid, mp 96–98 °C; IR (KBr) 1688, 1666, 1466,
1335 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.34 (s, 3H), 2.39 (s, 3H), 6.79 (d,
;
J = 8.4 Hz, 1H), 7.00 (t, J = 8.1 Hz, 1H), 7.13–7.41 (m, 10H), 7.47–7.58 (m, 3H),
7.66–7.69 (d, J = 8.1 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 21.45, 21.52, 68.24,
115.40, 116.37, 119.26, 124.78, 125.50, 126.89, 127.75, 129.01, 129.09 (2C),
129.23, 129.39, 131.28, 134.11, 135.49, 142.70, 144.61, 149.02, 161.69, 167.19,
171.32 (one carbon is missing); ESIMS m/z 470 (M++H). Anal. Calcd for
C
31H23N3O2: C, 79.30; H, 4.94; N, 8.95. Found: C, 79.51; H, 4.98; N, 8.69.
Compound 4c: 93%; yellow solid, mp 172–174 °C; IR (KBr) 1678, 1622, 1468,
1354 cmÀ1 1H NMR (CDCl3, 300 MHz) d 6.32–6.46 (br m, 1H), 6.90 (t, J = 8.4 Hz,
;
2H), 6.96–7.72 (m, 11 H), 7.76 (d, J = 8.1 Hz, 1H); ESIMS m/z 514 (M++H). Anal.
Calcd for C29H15F4N3O2: C, 67.84; H, 2.94; N, 8.18. Found: C, 67.89; H, 3.25; N,
7.99.
3. Kim, Y. M.; Lee, S.; Kim, S. H.; Kim, K. H.; Kim, J. N. Tetrahedron Lett. 2010, 51,
5922–5926. and further references for the preparation of
cited therein.
a-aminonitriles were
Compound 4d: 86%; white solid, mp 100–102 °C; IR (KBr) 1688, 1668, 1463,
1329 cmÀ1 1H NMR (CDCl3, 300 MHz) d 6.94 (d, J = 7.5 Hz, 1H), 7.30–7.47 (m,
;
12H), 7.50–7.55 (m, 3H), 7.76 (d, J = 7.5 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d
68.60, 115.07, 117.94, 121.12, 125.77, 126.12, 127.60, 128.62, 128.87, 129.23,
129.32, 129.82, 130.67, 131.68, 132.03, 133.46, 133.91, 134.07, 135.72, 147.77,
160.81, 167.41, 176.88; ESIMS m/z 476 (M++H), 478 (M++H+2). Anal. Calcd for
4. For the synthesis of
a-aminonitriles and their acylation reactions, see: (a)
McEwen, W. E.; Grossi, A. V.; MacDonald, R. J.; Stamegna, A. P. J. Org. Chem.
1980, 45, 1301–1308; (b) Langridge, D. C.; Hixson, S. S.; McEwen, W. E. J. Org.
Chem. 1985, 50, 5503–5507; (c) Leblanc, J.-P.; Gibson, H. W. J. Org. Chem. 1994,
59, 1072–1077; (d) Spaltenstein, A.; Holler, T. P.; Hopkins, P. B. J. Org. Chem.
1987, 52, 2977–2979; (e) Cooney, J. V.; Beaver, B. D.; McEwen, W. E. J.
Heterocycl. Chem. 1985, 22, 635–642; (f) Michaelidou, S. S.; Koutentis, P. A.
Tetrahedron 2010, 66, 685–688. and further references cited therein.
5. The reaction of 2a and benzoyl chloride (4.0 equiv) in the presence of Et3N
(4.0 equiv) in toluene (90–100 °C, 3 h) also afforded 4a, albeit in low yield
(48%). In contrast, the reactions under the influence of Cs2CO3/DMF (rt–70 °C,
2 h), K2CO3/CH3CN (rt, 10 h), or t-BuOK/THF (rt, 2 h) were all ineffective for the
synthesis of 4a.
C
29H18ClN3O2: C, 73.19; H, 3.81; N, 8.83. Found: C, 73.44; H, 3.84; N, 8.95.
Compound 4e: 88%; yellow solid, mp 218–220 °C; IR (KBr) 1681, 1660, 1502,
1339 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.62 (s, 3H), 3.70 (s, 3H), 6.57 (br s,
;
1H), 6.91 (s, 1H), 7.24–7.58 (m, 13H), 7.80 (d, J = 7.5 Hz, 2H); 13C NMR (CDCl3,
75 MHz) d 56.00, 56.03, 68.73, 99.85, 106.31, 111.58, 115.60, 125.62, 127.54,
128.55, 128.67, 129.13, 129.22, 129.55, 131.39, 132.68, 133.51, 134.22, 134.76,
145.88, 147.27, 155.83, 161.69, 177.82 (one carbon is missing); ESIMS m/z 502
(M++H). Anal. Calcd for C31H23N3O4: C, 74.24; H, 4.62; N, 8.38. Found: C, 74.51;
H, 4.93; N, 8.32.
6. For Thorpe–Ziegler dinitrile cyclization, see: (a) Fleming, F. F.; Shook, B. C.
Tetrahedron 2002, 58, 1–23. and further references cited therein; (b) Schaefer, J.
P.; Bloomfield, J. J. Org. React. 1967, 15, 1–203; (c) Takaya, H.; Naota, T.;
Murahashi, S.-I. J. Am. Chem. Soc. 1998, 120, 4244–4245; (d) Toro, A.; Nowak, P.;
Deslongchamps, P. J. Am. Chem. Soc. 2000, 122, 4526–4527; (e) Winkler, M.;
Martinkova, L.; Knall, A. C.; Krahulec, S.; Klempier, N. Tetrahedron 2005, 61,
4249–4260.
Compound 4f: 79%; white solid, mp 204–206 °C; IR (KBr) 1677, 1663, 1465,
1342 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.28 (s, 3H), 6.81 (d, J = 6.6 Hz, 1H),
;
7.03–7.14 (m, 3H), 7.28–7.55 (m, 12H), 7.80 (d, J = 7.5 Hz, 2H); 13C NMR (CDCl3,
75 MHz) d 21.01, 68.06, 115.46, 116.52, 119.67, 125.00, 125.72, 126.81, 127.66,
128.49, 128.79, 129.14, 129.85, 130.81, 131.79, 131.94, 133.58, 134.35, 135.67,
139.73, 149.02, 162.01, 167.31, 177.46; ESIMS m/z 456 (M++H). Anal. Calcd for
C
30H21N3O2: C, 79.10; H, 4.65; N, 9.22. Found: C, 78.95; H, 4.81; N, 9.02.
7. Crystal data of 3-iminodihydroindole 4a: solvent of crystal growth (hexane);
Typical procedure for the synthesis of compound 5a: stirred mixture of
A
empirical
formula
C
29H19N3O2,
Fw = 441.47,
crystal
dimensions
compound 4a (132 mg, 0.3 mmol), allyl bromide (109 mg, 0.9 mmol), and
indium (52 mg, 0.45 mmol) in THF (0.5 mL) was heated to reflux for 40 min
under N2 atmosphere. After the usual aqueous extractive workup and column
chromatographic purification process (hexanes/CH2Cl2/EtOAc, 10:1:2),
compound 5a was obtained as a white solid, 91 mg (73%). Other compounds
were synthesized similarly, and the spectroscopic data of 5a–f are as follows.
Compound 5a: 73%; white solid, mp 228–230 °C; IR (KBr) 3210, 1680, 1649,
0.28 Â 0.15 Â 0.14 mm3, monoclinic, space group P2(1)/c, a = 8.959(2) Å,
b = 21.637(5) Å,
V = 2242.5(9) Å3,
c = 11.593(3) Å,
Z = 4,
a
= 90°,
b = 93.785(14)°,
F000 = 920,
c = 90°,
Dcalcd = 1.308 mg/m3,
Mo
Ka
(k = 0.71073 Å), R1 = 0.0559, wR2 = 0.1272 (I > 2r(I)). The X-ray data has been
deposited in CCDC with number 802632.
Crystal data of 3-aminoindole 5a: solvent of crystal growth (EtOH); empirical
formula C28H20N2O2, Fw = 416.46, crystal dimensions 0.29 Â 0.22 Â 0.09 mm3,
monoclinic, space group P2(1)/c, a = 14.2679(4) Å, b = 9.1186(3) Å,
1451 cmÀ1 1H NMR (CDCl3 + DMSO-d6, 300 MHz) d 7.07–7.19 (m, 3H), 7.24–
;
7.63 (m, 14H), 8.00 (d, J = 6.9 Hz, 2H), 9.75 (s, 1H); 13C NMR (CDCl3 + DMSO-d6,
75 MHz) d 112.67, 117.28, 118.21, 121.85, 123.57, 125.82, 126.47, 126.69,
126.85, 127.13 (2C), 128.07, 128.79, 129.73, 130.41, 131.73, 133.03, 133.61,
133.80, 134.76, 166.59, 168.24; ESIMS m/z 417 (M++H). Anal. Calcd for
c = 16.2940(4) Å,
a
= 90°, b = 103.187(2)°,
c
K
= 90°, V = 2064.00(10) Å3, Z = 4,
a (k = 0.71073 Å), R1 = 0.0389,
Dcalcd = 1.340 mg/m3, F000 = 872, Mo
wR2 = 0.0888 (I > 2r(I)). The X-ray data has been deposited in CCDC with
number 802633.
C
28H20N2O2: C, 80.75; H, 4.84; N, 6.73. Found: C, 80.87; H, 4.57; N, 6.56.
8. Typical procedure for the synthesis of compound 4a: To a stirred solution of
compound 2a (117 mg, 0.5 mmol) in toluene (1.0 mL) was added EtN(i-Pr)2
Compound 5b: 68%; yellow solid, mp 174–176 °C; IR (KBr) 3304, 1681, 1649,

1382
1453 cmÀ1
Y. M. Kim et al. / Tetrahedron Letters 52 (2011) 1378–1382
;
1H NMR (CDCl3, 300 MHz) d 2.29 (s, 3H), 2.40 (s, 3H), 7.03 (d,
56.08, 56.23, 97.92, 101.50, 117.99, 118.67, 127.36, 127.62, 127.96, 128.31,
128.75, 129.43, 130.04, 130.77, 130.87, 131.26, 132.01, 132.33, 133.86, 135.01,
147.01, 148.68, 166.94, 169.79; ESIMS m/z 477 (M++H). Anal. Calcd for
J = 7.8 Hz, 2H), 7.12–7.29 (m, 9H), 7.51–7.54 (m, 3H), 7.63–7.66 (m, 2H), 7.75
(d, J = 7.8 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 21.47, 21.58, 114.06, 117.66,
120.12, 123.09, 124.87, 125.92, 127.37, 127.91, 128.36, 128.93, 129.36 (2C),
130.39, 130.63, 131.03, 132.06, 133.51, 136.22, 142.51, 143.72, 166.98, 169.38;
ESIMS m/z 431 (M++H). Anal. Calcd for C30H24N2O2: C, 81.06; H, 5.44; N, 6.30.
Found: C, 81.41; H, 5.65; N, 6.19.
C
30H24N2O4: C, 75.61; H, 5.08; N, 5.88. Found: C, 75.68; H, 5.32; N, 5.68.
Compound 5f: 76%; white solid, mp 160–162 °C; IR (KBr) 3305, 1680, 1660,
1451 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.12 (s, 3H), 6.97 (d, J = 7.8 Hz, 2H),
;
7.11–7.69 (m, 15H), 7.86 (d, J = 7.8 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 21.15,
114.12, 117.49, 120.05, 123.23, 124.88, 125.93, 127.34, 127.49, 128.17, 128.71,
129.11, 129.25, 130.16, 131.94, 132.65, 133.63, 133.88, 134.91, 136.13, 137.96,
166.97, 169.56; ESIMS m/z 431 (M++H). Anal. Calcd for C29H22N2O2: C, 80.91; H,
5.15; N, 6.51. Found: C, 80.79; H, 5.43; N, 6.66.
Compound 5c: 69%; white solid, mp 248–250 °C; IR (KBr) 3347, 1677, 1667,
1467 cmÀ1 1H NMR (DMSO-d6, 300 MHz) d 6.89 (t, J = 8.4 Hz, 2H), 7.05–7.25
;
(m, 5H), 7.26–7.40 (m, 3H), 7.41–7.62 (m, 4H), 8.32 (d, J = 7.2 Hz, 1H), 10.34 (s,
1H); 13C NMR (DMSO-d6, 75 MHz) d 111.84, 112.09, 112.11, 114.35, 114.60,
114.68, 114.99, 115.22, 119.03, 119.19, 124.79, 126.26, 126.81, 127.89, 128.85,
129.01, 129.25, 131.95, 132.08, 132.21, 134.10, 134.19, 134.34, 134.48, 135.03,
156.64, 156.72, 157.12, 157.20, 159.97, 160.05, 160.20, 160.41, 160.50; ESIMS
m/z 489 (M++H). Anal. Calcd for C28H16F4N2O2: C, 68.85; H, 3.30; N, 5.74. Found:
C, 68.77; H, 3.29; N, 5.46.
9. For some leading reviews on indole derivatives, see: (a) Kochanowska-
Karamyan, A. J.; Hamann, M. T. Chem. Rev. 2010, 110, 4489–4497; (b) Trost,
B. M.; Brennan, M. K. Synthesis 2009, 3003–3025.
10. For the synthesis of similar indole derivatives, see: (a) Qu, J.; Kumar, N.;
Alamgir, M.; Black, D. S. C. Tetrahedron Lett. 2009, 50, 5628–5630; (b)
Przheval’skii, N. M.; Skvortsova, N. S.; Magedov, I. V. Khim. Geterotsikl. Soedin.
2003, 12, 189–195 (Chem. Heterocycl. Compd. 2003, 39, 161–167); (c) Petasis, N.
A.; Myslinska, M. WO 2009/121033, 2009.; (d) Michaelidou, S. S.; Koutentis, P.
A. Tetrahedron 2010, 66, 3016–3023; (e) Seong, C. M.; Park, C. M.; Choi, J.; Park,
N. S. Tetrahedron Lett. 2009, 50, 1029–1031; (f) Ryabova, S. Y.; Alekseeva, L. M.;
Lisitsa, E. A.; Granik, V. G. Russ. Chem. Bull. Int. Ed. 2006, 55, 1248–1254.
11. The formation of allyl cyanide in the reaction was difficult to confirm. Thus, we
performed the reaction of 4a with benzyl bromide or cinnamyl bromide in
order to confirm the formation of benzyl cyanide or 2-phenylbut-3-enenitrile;
however, the reaction failed to form 5a.
Compound 5d: 56%; white solid, mp 266–268 °C; IR (KBr) 3212, 1677, 1656,
1449 cmÀ1 1H NMR (DMSO-d6, 300 MHz) d 7.12–7.24 (m, 3H), 7.34–7.39 (m,
;
5H), 7.49–7.61 (m, 8H), 7.97 (d, J = 6.9 Hz, 2H), 10.10 (s, 1H); 13C NMR (DMSO-
d6, 75 MHz) d 115.19, 117.45, 118.60, 124.69, 127.54, 127.75, 128.03, 128.13,
128.20, 128.47, 128.62, 129.05, 129.85, 130.10, 131.83, 133.43, 133.72, 133.87,
134.05, 136.49, 166.98, 169.00; ESIMS m/z 451 (M++H), 453 (M++H+2). Anal.
Calcd for C28H19ClN2O2: C, 74.58; H, 4.25; N, 6.21. Found: C, 74.76; H, 4.34; N,
6.35.
Compound 5e: 58%; white solid, mp 214–216 °C; IR (KBr) 3322, 1679, 1649,
1482 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.87 (s, 3H), 3.93 (s, 3H), 7.02–7.31 (m,
;
9H), 7.44–7.55 (m, 7H), 7.87 (d, J = 6.9 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d