Et2Zn-catalyzed intramolecular hydroamination of alkynyl sulfonamides and the related tandem cyclization/addition reaction

Article abstract of DOI:10.1021/jo070681h

(Chemical Equation Presented) Intramolecular hydroamination of alkynyl amides was effected by a catalytic amount of Et₂Zn (20 mol %) to form indole derivatives, and a tandem cyclization/nucleophilic addition procedure involving reaction of the indole zinc salt intermediate with acid chlorides or halides was developed to provide an efficient approach to C3-substituted indole derivatives when an excess of Et₂Zn (120 mol %) was used.

Full text of DOI:10.1021/jo070681h

Et2Zn-Catalyzed Intramolecular Hydroamination of Alkynyl
Sulfonamides and the Related Tandem Cyclization/Addition
Reaction
Yan Yin, Wenying Ma, Zhuo Chai, and Gang Zhao*
Laboratory of Modern Synthetic Organic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai, 200032, China
zhaog@mail.sioc.ac.cn
ReceiVed April 10, 2007
Intramolecular hydroamination of alkynyl amides was effected by a catalytic amount of Et2Zn (20 mol
%) to form indole derivatives, and a tandem cyclization/nucleophilic addition procedure involving reaction
of the indole zinc salt intermediate with acid chlorides or halides was developed to provide an efficient
approach to C3-substituted indole derivatives when an excess of Et2Zn (120 mol %) was used.
Introduction
a tandem cyclization/nucleophilic addition procedure of N-
benzyl-protected alkynylanilines with electrophiles to form
indole derivatives mediated by 1 equiv of n-BuLi/ZnCl2/[Pd2-
(dba)3] or n-BuLi/ZnCl2/CuCN‚2LiCl.6 Inspired by this work,
we hypothesized that N-sulfonyl-protected alkynylanilines,
owing to a higher NH acidity, when treated with a weaker base
than n-BuLi that might allow a broader functionality tolerance,
would generate anions with sufficient nucleophilicity to cyclize
to form indoline derivatives. Herein, we report the cyclization
of alkynyl sulfonamides with a catalytic amount of Et2Zn to
synthesize nitrogen-containing molecules and a tandem cycliza-
tion/nucleophilic addition procedure, which was shown to be a
simple and efficient method to form C3-substituted indole
derivatives through an indole zinc salt intermediate.
Nitrogen-containing heterocycles, especially indole deriva-
tives, have attracted much attention because of their physiologi-
cal properties as important structural units in a variety of
biologically active natural products.1 Interest in the synthesis
of these compounds has sparked the development of numerous
methods for the construction of indole moieties and their
derivatives.2 Until now, many kinds of catalysts have been
reported for the synthesis of indole derivatives from 2-ethynyl-
aniline derivatives.3 Moreover, many applications including
sequential C3-functionalization of indole have also been estab-
lished.4 Our research group has previously reported the in-
tramolecular hydroamination of unsaturated sulfonamides pro-
moted by superacid.5 Recently, Nakamura’s group has reported
Results and Discussion
* Address correspondence to this author. Phone/fax: 0086-21-64166128.
(1) (a) Hibino, S.; Choshi, T. Nat. Prod. Rep. 2002, 19, 148. (b) Gupta,
R. R. Heterocyclic Chemistry; Springer Publishing: New York, 1999; Vol.
2, p 193. (c) Rahman, A.; Basha, A. Indole Alkaloids; Harwood Academic
Publishers: Amsterdam, The Netherlands, 1998; p 141. (d) Dewick, P. M.
Medicinal Natural Products; J. Wiley & Sons: Chichester, UK, 1997;
Chapter 6.
With sulfonamide 1a as our initial probe substrate, a survey
of different reaction conditions revealed that the intramolecular
hydroamination of 1a was best performed in the presence of
(2) (a) Sundlberg, R. J. Indoles; Academic: London, UK, 1996. (b) Islam,
M. S.; Brennan, C.; Wang, Q. W.; Hossain, M. M. J. Org. Chem. 2006,
71, 4675. (c) Taber, D. F.; Tian, W. W. J. Am. Chem. Soc. 2006, 128,
1058. (d) Fang, Y. Q.; Lautens, M. Org. Lett. 2005, 7, 3549.
(3) (a) Sakai, N.; Annaka, K.; Konakahara, T. Tetrahedron Lett. 2006,
47, 631. (b) Hiroya, K.; Itoh, S.; Sakamoto, T. J. Org. Chem. 2004, 69,
1126. (c) Hiroya, K.; Matsumoto, S.; Sakamoto, T. Org. Lett. 2004, 6, 2953.
(d) Kamijo, S.; Sasaki, Y.; Yamamoto, Y. Tetrahedron Lett. 2004, 45, 35.
(e) Koradin, C.; Dhohle, W.; Rodriguez, A. L.; Schmid, B.; Knochel, P.
Tetrahedron 2003, 59, 1571.
(4) (a) Alfonsi, M.; Arcadi, A.; Aschi, M.; Bianchi, G.; Marinelli, F. J.
Org. Chem. 2005, 70, 2265. (b) Amjad, M.; Knight, D. W. Tetrahedron
Lett. 2004, 45, 539. (c) Shimada, T.; Nakamura, I.; Yamamoto, Y. J. Am.
Chem. Soc. 2004, 126, 10546. (d) Cacchi, S.; Fabrizi, G.; Parisi, L. M.
Synthesis 2004, 1889.
(5) (a) Yin, Y.; Zhao, G. Heterocycles 2006, 68, 23. (b) Yin, Y.; Zhao,
G. J. Fluorine Chem. 2007, 128, 40.
(6) (a) Nakamura, M.; Ilies, L.; Otsubo, S.; Nakamura, E. Angew. Chem.,
Int. Ed. 2006, 45, 944. (b) Nakamura, M.; Ilies, L.; Otsubo, S.; Nakamura,
E. Org. Lett. 2006, 8, 2803.
10.1021/jo070681h CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/20/2007
J. Org. Chem. 2007, 72, 5731-5736
5731

Yin et al.
TABLE 1. Optimization of Cyclization Reaction Conditionsa
the same reaction conditions, the acyl-protected compounds
1g-i failed to give any detectable amount of the desired product
1
as determined by H NMR spectrum analysis (entries 7-9).
Additionally, when 1g was exposed to an excess of Et2Zn, only
a small amount of deacylated product 2-phenyl-1H-indole (10%)
along with the unreacted starting material was obtained while
no desired product was observed when the primary amine 1j
was subjected to the same reaction conditions (entry 10).
Therefore, sulfonyl groups are crucial to this Et2Zn-catalyzed
cyclization system.
catalyst loading
(mol %)
time
(h)
yield
(%)b
entry
base
1
2
3
4
5
6
7
8
Et2Zn
Et2Zn
Et2Zn
Et2Zn
K2CO3
NaHCO3
pyridine
Et3N
20
10
20
3
3
2
98
23
76
50
A number of synthetic methods for the cleavage of the N-S
bond were available,8 especially for N-detosylation of indoles.9
Thus, we turned our attention to compare a variety of 2-phe-
nylethynyl-N-tosylaniline derivatives bearing different substi-
tuted groups at the para position on the phenyl ring, which were
readily prepared by the palladium-catalyzed cross-coupling
reaction of 2-iodoanilines with phenylacetylene followed by
tosylation.10 Under the optimized reaction conditions, all the
para substituted substrates 1k-o were converted to N-tosylin-
dole derivatives in excellent yields and halogen, the nitro group,
as well as the allyl ether structure were well tolerated. The results
are shown in Table 3. The electronic nature of the aromatic
amines influenced the hydroamination reaction rate: electron-
poor substrates reacted faster, which was probably because
electron-withdrawing substituents could make the CtC triple
bond more electron-deficient to receive nucleophilic attack and
could stabilize the resulting indole zinc salt intermediate more
efficiently (entries 1-6). Compound 1p with substituted groups
at both the meta and para positions on the phenyl ring also
underwent the cyclization smoothly to gave product 2p in high
yield (entry 7). Moreover, compounds with alkyl and function-
alized alkyl substituents on the acetylene terminal (R1) were
also tested under similar reaction conditions (entries 8-12).
When substituents (n-C4H9, H, and CH2OH) were present in
the substrates 1q-s, the cyclization products could be obtained
in high yields (entries 8-10). However, only 82% cyclization
yield was obtained when 1t was used (entry 11). When the
substituent was TMS, the cyclization was inhibited completely
and only the deprotection of the trimethylsilyl group in the basic
condition was observed after 24 h (1u:1r 6:1) (entry 12).3a,11
To evaluate the scope of this reaction further, a series of
N-tosyl-protected aliphatic aminoalkynes were also investigated
in a similar procedure. The experimental results are summarized
in Table 4. Of all the examples examined, only five-membered
nitrogen-containing heterocyles were formed and the results
were highly susceptible to the structural variations of the
substrates. While δ-alkynylamine 3a and 2-propynyl N-tosyl
carbamate 3e12 underwent the 5-exo-dig cyclization smoothly
to give the corresponding cyclized products with an exo double
bond in moderate and high yields, respectively (entries 1 and
5), only partial triple bond migrated product along with the
recovered starting material were obtained for substrate 3d (entry
20
1
200
200
200
200
24
24
24
96
45c
20c
32c
tracec
a Reaction conditions: 1a (0.3 mmol), toluene (6 mL). b Isolated yield
after flash chromatography. c Recovered unconsumed 1a.
TABLE 2. Effect of the Protective Group of the Nitrogen on the
Reactiona
entry
PG
substrate
yield (%)b
1
2
3
4
5
6
7
8
9
Mbsc
Ts
1b
1a
1c
1d
1e
1f
98
98
96
93
95
98
0d
C6H5SO2
p-FC6H4SO2
p-NO2C6H4SO2
Ms
CF3CO
C6H5CO
Ac
1g
1h
1i
0d
0d
10
H
1j
0d
a Reaction conditions: amines (0.3 mmol), Et2Zn (0.06 mmol), toluene
(6 mL). b Isolated yield after flash chromatography. c Mbs ) p-MeOC6H4SO2.
d Recovered starting materials.
Et2Zn (0.2 equiv) in refluxing toluene for 3 h (Table 1, entry
1), and the resulting product 2a was obtained in 98% yield.
Decreasing either the amount of Et2Zn or the reaction time led
to lower yields (entries 2-4). Further, markedly lower yields
were found when K2CO3, pyridine, NaHCO3, or Et3N were
utilized as bases (entries 5-8). When the Et2Zn (1.2 equiv)-
promoted reaction system was quenched with deuterioxide,
96.8% deuterium incorporation at the C3 position of indole was
observed, which was in support of the existence of the zinc
salt intermediate that might serve as a useful intermediate to
synthesize polyfunctional indoles.7
Next, several N-protected 2-phenylethynylanilines were pre-
pared to examine the effects of different protective groups on
the nitrogen atom. The results are summarized in Table 2. All
sulfonamides underwent the 5-endo-dig cyclization to give
N-protected 2-phenylindoles in high yields after 3 h in the
presence of 20 mol % of Et2Zn (entries 1-6). However, under
(8) (a) Forshee, P. B.; Sibert, J. W. Synthesis 2006, 756. (b) Greene, T.
W.; Wuts, P. G. M. ProtectiVe Groups in Organic Chemistry, 2nd ed.;
Wiley-Interscience: New York, 1991. (c) Yasuhara, A.; Sakamoto, T.
Tetrahedron Lett. 1998, 39, 595. (d) Alonso, D. A.; Andersson, P. G. J.
Org. Chem. 1998, 63, 9455.
(9) Haskins, C. M.; Knight, D. W. Tetrahedron Lett. 2004, 45, 599.
(10) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
17, 4467.
(11) Gregory, Y. Y.; Stephenson, G. A.; Mitchell, S. Tetrahedron Lett.
2006, 47, 3811.
(12) (a) Baldwin, J. E. Chem. Commun. 1976, 734. (b) Baldwin, J. E.;
Cutting, J.; Dupont, W.; Kruse, L.; Sillberman, L.; Thomas, R. C. Chem.
Commun. 1976, 736.
(7) (a) Yang, C. X.; Patel, H. H.; Ku, Y. Y. Synth. Commun. 1997, 27,
2125. (b) Browder, C. C.; Mitchell, M. O.; Smith, R. L.; el-Sulayman, G.
Tetrahedron Lett. 1993, 34, 6245. (c) Knochel, P.; Singer, R. D. Chem.
ReV. 1993, 93, 2117 and references cited therein. (d) Bergman, J.;
Venemalm, L. Tetrahedron 1990, 46, 6061. See the Supporting Information
for experimental details.
5732 J. Org. Chem., Vol. 72, No. 15, 2007

Intramolecular Hydroamination of Alkynyl Sulfonamides
TABLE 3. Cyclization of a Series of 2-Ethynyl-N-Sulfonylanilinesa
a Reaction conditions: amines (0.3 mmol), Et2Zn (0.06 mmol), toluene (6 mL). b Isolated yield after flash chromatography. c Recovered 1u. d Ratio of 1u
1
to 1r was determined by H NMR spectroscopic analysis.
J. Org. Chem, Vol. 72, No. 15, 2007 5733

Yin et al.
TABLE 4. Cyclization of Aliphatic Alkynylaminesa
TABLE 5. Tandem Cyclization/Nucleophilic Additiona
a Reaction conditions: amines (0.3 mmol), Et2Zn (0.06 mmol), toluene
(6 mL). b Isolated yield after flash chromatography. c 33% 3a was recovered.
d 3b was recovered. e 89% 3d was recovered.
4). Interestingly, although alkyne 3c could be transformed to
2,3-dihydropyrrole in high yields through a 5-endo-dig cycliza-
tion favored by Baldwin rules (entry 3),13 phenyl-substituted
γ-alkynylamine 3b failed to react even under prolonged reaction
time (entry 2).
Presently, the methods14 of producing substitution at the C3-
position of indoles mainly consist of the Friedel-Crafts reaction
catalyzed by protic or Lewis acids15 and the addition reaction
of indole organometallic derivatives to electrophilic components
with or without catalysts.16 We found here that the reactive
indole zinc salt intermediate formed by the treatment of 1a with
1.2 equiv of Et2Zn could undergo C3 acylation smoothly through
nucleophilic addition to a variety of acid chlorides to give the
corresponding acylated indoles in high yields at room temper-
ature (Table 5, entries 1-6). In addition, 3-bromo-2-phenylin-
dole derivative 5g could also be obtained with NBS as the
electrophile in moderate yield (entry 7). A control experiment
demonstrated that 2a, the isolated cyclized product of 1a, did
not react with benzoyl chloride to give the acylated product 5b
in the absence of Et2Zn at room temperature. Thus these
acylation transformations may only be explained by a tandem
cyclization/nucleophilic addition process. The method thus
a All reactions were performed in refluxing toluene for 3 h with amines
(0.3 mmol) and Et2Zn (0.36 mmol), then the reaction systems were cooled
to room temperature and acid chlorides (0.36 mmol) were added. b Reaction
time of sequent nucleophilic addition reaction. c Isolated yield after flash
chromatography.
provided an easy access to 3-acylindoles, which are useful for
pharmacological studies.17
(13) Lei, A. W.; Lu, X. Y. Org. Lett. 2000, 2, 2357.
(14) (a) Wang, Y. Q.; Song, J.; Hong, R.; Li, H. M.; Deng, L. J. Am.
Chem. Soc. 2006, 128, 8186. (b) Trost, B. M.; Quancard, J. J. Am. Chem.
Soc. 2006, 128, 6314. (c) Li, D. P.; Guo, Y. C.; Ding, Y.; Xiao, W. J.
Chem. Commun. 2006, 799. (d) Bandini, M.; Melloni, A.; Tommasi, S.;
Umani-Ronchi, A. Synlett 2005, 1199 and references cited therein. (e)
Herrera, R. P.; Sgarzani, V.; Bernardi, L.; Ricci, A. Angew. Chem., Int.
Ed. 2005, 44, 6576. (f) Yasuda, M.; Somyo, T.; Baba, A. Angew. Chem.,
Int. Ed. 2005, 44, 1.
(15) (a) Arcadi, A.; Bianchi, G.; Chiarini, M.; D’Anniballe, G.; Marinelli,
F. Synlett 2004, 944. (b) Reddy, A. V.; Ravinder, K.; Goud, T. V.;
Krishnaiah, P.; Raju, T. V.; Venkateswarlu, Y. Tetrahedron Lett. 2003, 44,
6257. (c) Yadav, J. S.; Abraham, S.; Reddy, B. V. S.; Sabitha, G. Synthesis
2001, 2165. (d) Szmuszkovicz, J. J. Am. Chem. Soc. 1957, 79, 2819. (e)
Noland, W. E.; Christensen, G. M.; Sauer, G. L.; Dutton, G. G. S. J. Am.
Chem. Soc. 1955, 77, 456.
The mechanism of this Et2Zn-catalyzed cyclization was
probably similar to that of the intramolecular anionic cyclization
of the C-Li bond to alkenes or alkynes.18 A plausible
mechanism of the reaction comprised the following steps
(Scheme 1): The deprotonation of aminoalkynes 1 or 3 by
diethylzinc gave zinc amide A, which underwent an anionic
cyclization to afford B. The intermediate B could undergo
nucleophilic addition with electrophiles to provide the C3-
substituted indole derivatives 5.
(17) (a) Yang, Z.; Liu, H. B.; Lee, C. M.; Chang, H. M.; Wang, H. N.
C. J. Org. Chem. 1992, 57, 7248. (b) Allin, S. M.; Thomas, C. I.; Allard,
J. E.; Doyle, K.; Elsegood, M. R. J. Tetrahedron Lett. 2004, 45, 7103.
(18) (a) Fujita, H.; Tokuda, M.; Nitta, M.; Suginome, H. Tetrahedron
Lett. 1992, 33, 6359. (b) Luo, F. T.; Wang, R. T. Tetrahedron Lett. 1992,
33, 6835.
(16) (a) Lane, B. S.; Brown, M. A.; Sames, D. J. Am. Chem. Soc. 2005,
127, 8050. (b) Nunomoto, S.; Kawakami, Y.; Yamashita, Y.; Takeuchi,
H.; Eguchi, S. J. Chem. Soc., Perkin. Trans. 1 1990, 111. (c) Heacock, R.
A.; Kasparek, S. AdV. Heterocycl. Chem. 1969, 10, 61. (d) Powers, J.; Meyer,
W. P.; Parsons, T. G. J. Am. Chem. Soc. 1967, 89, 5812.
5734 J. Org. Chem., Vol. 72, No. 15, 2007

Intramolecular Hydroamination of Alkynyl Sulfonamides
SCHEME 1. Proposed Reaction Mechanism
2-Butyl-1-(toluene-4-sulfonyl)indole (2q): white solid, mp 79-
1
80 °C (from hexane); H NMR (300 MHz, CDCl3) δ 8.11-8.08
(m, 1H), 7.55-7.43 (m, 2H), 7.34-7.31 (m, 1H), 7.20-7.09 (m,
4H), 6.30 (s, 1H), 2.91 (t, J ) 7.8 Hz, 2H), 2.26 (s, 3H), 1.71-
1.62 (m, 2H), 1.41-1.34 (m, 2H), 0.89 (t, J ) 7.5 Hz, 3H); IR
(KBr, cm-1) 2970, 2870, 1738, 1452, 1366, 1217, 1174, 1091, 578,
542; MS (EI) (m/z) 327, 172, 155, 130, 91, 77, 65, 44; 13C NMR
(75 MHz, CDCl3) δ 144.6, 142.6, 137.2, 136.3, 129.9, 129.8, 126.3,
123.8, 123.5, 120.1, 114.9, 108.6, 31.0, 28.8, 22.5, 21.6, 14.0;
HRMS calcd for C19H21NO2S 327.1293, found 327.1298.
Conclusion
2-Allyloxymethyl-1-(toluene-4-sulfonyl)-1H-indole (2t): white
solid, mp 56-57 °C (from hexane); H NMR (300 MHz, CDCl3)
In summary, we have developed a new and efficient method
for the cyclization of alkynyl amides to form the corresponding
nitrogen-containing heterocycles and a tandem cyclization/
nucleophilic addition reaction of 2-phenylethynylanilines with
electrophiles to give the corresponding C3-substituted indoles
in high yields mediated by Et2Zn. Further studies toward the
synthetic application with our method are currently underway.
1
δ 8.12-8.09 (m, 1H), 7.82-7.80 (m, 2H), 7.49-7.46 (m, 1H),
7.32-7.17 (m, 4H), 6.67 (s, 1H), 6.02-5.89 (m, 1H), 5.35-5.22
(m, 2H), 4.90 (s, 2H), 4.10 (d, J ) 5.4 Hz, 2H), 2.33 (s, 3H); IR
(KBr, cm-1) 2921, 2849, 1738, 1451, 1371, 1228, 1176, 1091, 676,
581; 13C NMR (75 MHz, CDCl3) δ 144.8, 137.5, 137.0, 135.9,
134.5, 129.7, 129.1, 126.9, 124.6, 123.5, 120.9, 117.4, 114.5, 111.1,
71.5, 65.4, 21.5; MS (EI) (m/z) 341, 300, 285, 155, 130, 91, 77,
65, 55, 41. Anal. Calcd for C19H19NO3S: C, 66.84; H, 5.61; N,
4.10. Found: C, 66.67; H, 5.68; N, 3.90.
Experimental Section
General Information. For details, see the Supporting Informa-
tion.
General Procedure 2: Et2Zn-Catalyzed Tandem Cyclization/
Nucleophilic Addition of 1a with Electrophiles To Give 5a-g
(Table 5). Et2Zn (0.36 mmol) was added to a solution of 1a (0.3
mmol) in dry toluene (6 mL). The mixture was stirred in reflux for
3 h. At the end of the reaction, the mixture was cooled to room
temperature and dry electrophiles (0.36 mmol) were added. At the
end of the nucleophilic addition reaction, the mixture was quenched
with saturated NH4Cl (2 mL) solution. Then the mixture was
extracted with Et2O (3 × 25 mL), dried over Na2SO4, and
concentrated in vacuo. Purification of the crude products by silica
gel column chromatography afforded 5a-g.
1-[2-Phenyl-1-(toluene-4-sulfonyl)indol-3-yl]propenone (5a):
white solid, mp 124-125 °C (from hexane); 1H NMR (300 MHz,
CDCl3) δ 8.03-8.00 (m, 2H), 7.62-7.47 (m, 4H), 7.30-7.18 (m,
3H), 7.09-7.03 (m, 4H), 6.46-6.39 (m, 1H), 5.94-5.84 (m, 1H),
5.60-5.56 (m, 1H), 2.13 (s, 3H); IR (KBr, cm-1) 2924, 2853, 2220,
1698, 1365, 1169, 1087, 910, 578; MS (EI) (m/z) 401, 347, 246,
155, 55, 43; 13C NMR (75 MHz, CDCl3) δ 189.0, 145.0, 137.6,
136.6, 134.7, 131.6, 130.1, 129.8, 129.6, 129.5, 129.3, 127.5, 126.9,
126.1, 124.7, 119.9, 119.1, 116.3, 103.8, 21.6; HRMS calcd for
C24H19NO3S 401.1086, found 401.1100.
General Procedure 1: Et2Zn-Catalyzed Cyclization of Ami-
noalkynes To Give 2a-f, 2k-2t, 4a, and 4c-e (Tables 3 and
4). Et2Zn (0.06 mmol) was added to a solution of aminoalkynes
(0.3 mmol) in dry toluene (6 mL). The mixtures were stirred in
reflux. At the end of the reaction, the mixtures were cooled to room
temperature and quenched with saturated NH4Cl (2 mL) solution.
The mixture was extracted with Et2O (3 × 25 mL), washed with
brine, dried over Na2SO4, and concentrated. Purification of the crude
products by silica gel column chromatography afforded 2a-f, 2k-
t, 4a, and 4c-e.
N-(4-Methoxybenzenesulfonyl)-2-phenylindole (2b): white
solid, mp 105-106 °C (from hexane); 1H NMR (300 MHz, CDCl3)
δ 8.33-8.31 (m, 1H), 7.52-7.27 (m, 10H), 6.72-6.69 (m, 2H),
6.55 (s, 1H), 3.76 (s, 3H); IR (KBr, cm-1) 2927, 1712, 1594, 1496,
1371, 1188, 1169, 579; MS (EI) (m/z) 363, 362, 192, 171, 165,
107, 91, 77, 63; 13C NMR (75 MHz, CDCl3) δ 163.5, 142.2, 138.3,
132.5, 130.6, 130.3, 129.3, 129.0, 128.6, 127.5, 124.8, 124.3, 120.7,
116.7, 113.7, 113.6, 55.5. Anal. Calcd for C21H17NO3S: C, 69.40;
H, 4.71; N, 3.85. Found: C, 69.58; H, 4.68; N, 3.63.
1-(4-Nitrobenzenesulfonyl)-2-phenyl-1H-indole (2e): yellow
solid, mp 163-164 °C (from hexane); 1H NMR (300 MHz, CDCl3)
δ 8.30-8.27 (m, 1H), 8.09-8.06 (m, 2H), 7.54-7.25 (m, 10H),
6.60 (s, 1H); IR (KBr, cm-1) 3030, 1607, 1528, 1382, 1347, 1185,
757, 740; MS (EI) (m/z) 378, 192, 186, 165, 91, 77; 13C NMR (75
MHz, CDCl3) δ 150.5, 142.4, 142.0, 138.2, 131.8, 130.8, 130.2,
129.1, 128.1, 127.8, 125.4, 125.2, 123.8, 121.2, 116.7, 114.7; HRMS
calcd for C20H14N2O4S 378.0674, found 378.0691.
Phenyl[2-phenyl-1-(toluene-4-sulfonyl)indol-3-yl]metha-
none (5b): white solid, mp 194-195 °C (from hexane); 1H NMR
(300 MHz, CDCl3) δ 7.98-7.95 (m, 2H), 7.78-7.75 (m, 1H),
7.42-7.40 (m, 3H), 7.32-7.26 (m, 6H), 7.13-7.07 (m, 6H), 2.09
(s, 3H); IR (KBr, cm-1) 3074, 2919, 1701, 1442, 1361, 1254, 1172,
1084, 751, 710, 581; MS (ESI) (m/z) 452.2 [M + H+]; 13C NMR
(75 MHz, CDCl3) δ 169.7, 144.8, 138.7, 136.2, 134.3, 132.8, 132.6,
131.5, 131.3, 130.1, 129.2, 129.1, 129.0, 128.8, 128.7, 128.1, 127.6,
123.7, 122.1, 95.1, 85.4, 21.4. Anal. Calcd for C28H21NO3S: C,
74.48; H, 4.69; N, 3.10. Found: C, 74.57; H, 4.88; N, 2.95.
Furan-2-yl[2-phenyl-1-(toluene-4-sulfonyl)indol-3-yl]metha-
5-Bromo-2-phenyl-1-(toluene-4-sulfonyl)indole (2n): white
solid, mp 155-156 °C (from hexane); 1H NMR (300 MHz, CDCl3)
δ 8.20-8.18 (m, 1H), 7.58-7.45 (m, 7H), 7.26-7.24 (m, 2H),
7.08-7.05 (m, 2H), 6.48 (s, 1H), 2.31 (s, 3H); IR (KBr, cm-1
)
1
none (5c): white solid, mp 155-156 °C (from hexane); H NMR
3061, 2925, 2854, 1596, 1442, 1376, 1178, 1062, 810, 763, 582,
543; MS (EI) (m/z) 427, 425, 270, 268, 190, 155, 91, 77, 65; 13C
NMR (75 MHz, CDCl3) δ 144.9, 143.4, 137.0, 134.4, 132.2, 131.8,
130.4, 129.4, 129.0, 127.6, 126.8, 126.3, 123.4, 118.1, 117.8, 112.5,
21.6. Anal. Calcd for C21H16BrNO2S: C, 59.16; H, 3.78; N, 3.29.
Found: C, 59.14; H, 3.76; N, 3.04.
(300 MHz, CDCl3) δ 8.02-7.99 (m, 2H), 7.72-7.70 (m, 1H),
7.55-7.49 (m, 3H), 7.32-7.18 (m, 4H), 7.08-7.04 (m, 4H), 6.22-
6.20 (m, 1H), 6.08-6.06 (m, 1H), 2.10 (s, 3H); IR (KBr, cm-1
)
2924, 2852, 1682, 1464, 1367, 1172, 1086, 757, 577; MS (ESI)
(m/z) 442.3 [M + H+]; 13C NMR (75 MHz, CDCl3) δ 175.8, 157.9,
146.1, 146.0, 144.8, 137.9, 136.2, 132.6, 132.4, 131.6, 130.1,130.06
129.8, 129.0, 128.9, 128.6, 127.9, 124.2, 121.9, 118.7, 111.6, 21.4;
HRMS calcd for C26H19NO4S 464.0927 [M + Na+], found
464.0931.
6-Nitro-5-chloro-2-phenyl-1-(toluene-4-sulfonyl)indole (2p):
yellow solid, mp 174-175 °C (EtOAc); 1H NMR (300 MHz,
CDCl3) δ 8.92 (s, 1H), 7.60-7.44 (m, 6H), 7.26-7.09 (m, 4H),
6.54 (s, 1H), 2.33 (s, 3H); IR (KBr, cm-1) 2925, 1738, 1527, 1448,
Cyclopropyl[2-phenyl-1-(toluene-4-sulfonyl)indol-3-yl]metha-
1380, 1177, 1089, 661, 582; MS (ESI) (m/z) 427.0 [M + H+]; 13
C
none (5e): white solid, mp 125-126 °C (from hexane); H NMR
1
NMR (75 MHz, CDCl3) δ 144.8, 137.5, 137.0, 135.9, 134.4, 129.7,
129.1, 127.3, 126.9, 126.4, 124.6, 123.4, 120.9, 117.4, 114.4, 111.0,
21.6. Anal. Calcd for C21H15ClN2O4S: C, 59.09; H, 3.54; N, 6.56.
Found: C, 59.24; H, 3.59; N, 6.40.
(300 MHz, CDCl3) δ 7.80-7.97 (m, 2H), 7.65-7.61 (m, 2H),
7.52-7.44 (m, 2H), 7.30-7.18 (m, 3H), 7.06-7.00 (m, 4H), 2.12
(s, 3H), 1.34-1.28 (m, 1H), 1.18-1.12 (m, 1H), 0.99-0.91 (m,
1H), 0.72-0.68 (m, 2H); IR (KBr, cm-1) 3067, 2923, 1701, 1382,
J. Org. Chem, Vol. 72, No. 15, 2007 5735

Yin et al.
1164, 1087, 666, 577; MS (ESI) (m/z) 416.2 [M + H+]; 13C NMR
(75 MHz, CDCl3) δ 173.8, 144.6, 137.8, 136.5, 132.8, 132.1, 131.6,
129.9, 129.7, 129.3, 128.9, 128.7, 128.0, 124.4, 122.1, 95.4, 85.5,
21.4, 14.8, 11.1, 10.2; HRMS calcd for C25H21NO3S 438.1134 [M
+ Na+], found 438.1149.
2.31 (s, 3H); IR (KBr, cm-1) 3025, 2925, 1445, 1371, 1175, 1090,
813; MS (ESI) (m/z) 426.0 [M + H+]; 13C NMR (75 MHz, CDCl3)
δ 144.8, 137.1, 136.2, 132.8, 131.9, 131.6, 131.2, 129.9, 129.4,
129.0, 128.7, 128.3, 127.9, 124.3, 95.7, 85.1, 21.5; HRMS calcd
for C21H16BrNO2S 426.0158 [M + H+], found 426.0140.
2,2-Dimethyl-1-[2-phenyl-1-(toluene-4-sulfonyl)indol-3-yl]pro-
1
pan-1-one (5f): white solid, mp 161-162 °C (from hexane); H
Acknowledgment. Generous financial support from the
National Natural Science Foundation of China, QT Program,
Shanghai Natural Science Council, and Excellent Young
Scholars Foundation of NNSF is gratefully acknowledged.
NMR (300 MHz, CDCl3) δ 7.90-7.87 (m, 2H), 7.69-7.44 (m,
4H), 7.27-7.01 (m, 7H), 2.10 (s, 3H), 1.04 (s, 9H); IR (KBr, cm-1
)
2970, 2867, 1738, 1362, 1217, 1171, 1086, 758, 579; MS (ESI)
(m/z) 432.2 [M + H+]; 13C NMR (75 MHz, CDCl3) δ 179.4, 144.2,
137.9, 136.9, 133.6, 132.6, 131.5, 130.0, 129.8, 128.8, 128.7, 128.6,
128.0, 125.5, 122.1, 95.4, 85.8, 43.7, 28.4, 21.4. Anal. Calcd for
C26H25NO3S: C, 72.36; H, 5.84; N, 3.25. Found: C, 72.49; H, 5.83;
N, 3.10.
Supporting Information Available: Experimental procedures
and characterization data for all substrates 1a-u, the cyclization
products 2a,c,d,f,k,l,m,o,r,s and 4a,c-e, and acylated product 5d,
and 1H NMR and 13C NMR for selected compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
3-Bromo-2-phenyl-1-(toluene-4-sulfonyl)indole (5g): yellow
1
solid, mp 85-86 °C (from hexane); H NMR (300 MHz, CDCl3)
δ 8.35-8.33 (m, 1H), 7.51-7.24 (m, 10H), 7.12-7.06 (m, 2H),
JO070681H
5736 J. Org. Chem., Vol. 72, No. 15, 2007