Pd(II)-catalyzed oxidative cyclization reaction for the preparation of 2-substituted 1,2,3,4-tetrahydroquinolines with halide functionality

Article abstract of DOI:10.1016/j.tet.2010.12.017

The first Pd(II)-catalyzed oxidative cyclization reaction was developed for preparation of 2-substituted 1,2,3,4-tetrahydroquinolines from olefinic tosylamides. Under the optimized conditions, up to 86% yield was obtained. This reaction provides direct an

Full text of DOI:10.1016/j.tet.2010.12.017

Tetrahedron 67 (2011) 1501e1505
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Tetrahedron
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Pd(II)-catalyzed oxidative cyclization reaction for the preparation of 2-substituted
1,2,3,4-tetrahydroquinolines with halide functionality
y
*
Feng Jiang , Zhengxing Wu, Wanbin Zhang
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 October 2010
Received in revised form 2 December 2010
Accepted 7 December 2010
Available online 10 December 2010
The first Pd(II)-catalyzed oxidative cyclization reaction was developed for preparation of 2-substituted
1,2,3,4-tetrahydroquinolines from olefinic tosylamides. Under the optimized conditions, up to 86% yield
was obtained. This reaction provides direct and easy access to 2-substituted 1,2,3,4-tetrahydroquinolines
with halide functionality.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Oxidative cyclization reaction
Pd(II)
2-Substituted 1,2,3,4-tetrahydroquinolines
Olefinic tosylamides
Halide functionality
1. Introduction
containing heterocycles with catalytic amounts of PdCl2(MeCN)2 or
PdCl2.15 However, the formation of six-membered rings is difficult
In recent years, considerable efforts have been prompted toward
the synthesis of the 1,2,3,4-tetrahydroquinoline derivatives for
their broad range of biological activities,1 such as antibacteric2 and
fungicide.3 Furthermore their inhibiting or antagonist properties to-
ward specific enzymes or receptors involved in human diseases make
them promising compounds in antidepressive4 and antidiabetes5
therapies. Besides pharmaceutical applications, they are also useful
as pesticides,6 antioxidants,7 various types of dyes,8 and charge-
transporting agents for electrophotographic photoconductors
in modern recording technologies.9 Among these derivatives,
2-substituted 1,2,3,4-tetrahydroquinoline is the most important
compound.10 For example, oxamniquine with skeleton of 2-
substituted 1,2,3,4-tetrahydroquinoline has been commonly used in
therapeutics against Schistosoma mansoni.11 Recently, some of these
compounds have been used in finding selective estrogen receptor
modulators12 and inhibitorsof thecholesteryl estertransfer protein.13
Many syntheses of 2-substituted 1,2,3,4-tetrahydroquinolines
have been reported.10 Pd(II)-catalyzed oxidative cyclization reaction
is a powerful tool to construct nitrogen-containing heterocycles un-
der mild conditions.14 A landmark for this reaction was laid by
Hegedus and co-workers, who obtained five-membered nitrogen-
under the same conditions with this reaction.15d The approach
was afterward improved by other groups for the preparation of
six-membered dihydroquinolines and quinolines.16 Recently, 3-
substituted 1,2,3,4-tetrahydroquinolines were prepared with Pd
(II)-catalyzed oxidative cyclization reaction in very low yields and
five-membered dihydroindoles were afforded as predominant
products.17 However, the preparation of 2-substituted 1,2,3,4-tetra-
hydroquinolines with this reaction has not been reported so far.
Recently, we have been interested in the Pd(II)-catalyzed
asymmetric oxidative cyclization reactions for the preparation of
chiral five-membered dihydrobenzofurans18 and dihydroindoles.19
Here we report the first Pd(II)-catalyzed oxidative cyclization re-
action for the preparation of 2-substituted 1,2,3,4-tetrahy-
droquinolines with halide functionality from olefinic tosylamides.
2. Results and discussion
As mentioned above, the 3-substituted tetrahydroquinolines
had been obtained in very low yields from olefinic tosylamides with
a 2-propenyl side chain.17 So if we started from olefinic amides 1
with a 3-butenyl side chain, we anticipated that 2-substituted
tetrahydroquinolines 2 may be afforded in high yields because the
formation of six-membered ring (Scheme 1, path a) is generally
much easier than seven-membered ring (Scheme 1, path b). Then
we prepared a series of p-toluenesulfonamides to probe this re-
action, because p-toluenesulfonamides could be synthesized with
* Corresponding author. Tel./fax: þ86 021 54743265; e-mail address: wanbin@
sjtu.edu.cn (W. Zhang).
y
On leave from Ningbo University.
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.12.017

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F. Jiang et al. / Tetrahedron 67 (2011) 1501e1505
Table 1
Pd(II)
The effect of Pd(II) source on the Pd(II)-catalyzed oxidative cyclization reactiona
Pd(II)
R
a
R
Pd(II)
NHR1
NH
R1
b
Br
N
NHTs
1b
CuBr2
Ts
1
2b
CuBr2
R
R
R
Br
Entry
Pd(II)
Quantity
Time (days)
Yieldb (%)
path a
Pd(II)
N
R1
N
R1
1
2
3
4
5
6
7
8
9
Pd(OCOCF3)2
Pd(OAc)2
PdCl2(MeCN)2
PdCl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
0.2
0.2
0.2
0.2
0.05
0.1
0.15
0.3
0.4
3
3
3
3
3
3
3
3
3
86
85
33
71
34
53
69
89
89
2
path b
CuBr2
R
Pd(II)
Br
N
R1
N
R1
a
All reactions were catalyzed by Pd(II) in the presence of K2CO3 (2 equiv) and
CuBr2 (3 equiv) in THF at 25 ꢀC.
3
b
NMR yield (internal standard¼ethyl acetate).
Scheme1. Pd(II)-catalyzed oxidative cyclization reactions.
ease from primary amines as stable crystalline solids (Scheme 2).
Thus, to a solution of 2-aminobenzylalcohol 4 in dichloromethane
was added 1.3 equiv of pyridine and 1.2 equiv of 4-methylbenzene-
1-sulfonyl chloride, and then the reaction mixture was refluxed for
Table 2
Condition optimization for the Pd(II)-catalyzed oxidative cyclization reactiona
12 h. After purification, intermediate
5 was obtained. Next,
1.5 equiv of SOCl2 was added slowly to the solution of 5 in
dichloromethane at 0 ꢀC and the mixture was refluxed for 12 h.
After the solvent was removed in vacuo, the residue 6 was dissolved
in THF, which was slowly added to a THF solution of 3.0 equiv of 3-
propenyl Grignard reagent. After the mixture was stirred for 12 h,
the substrates 1 were afforded with up to 89% yield from 5.
Entry
Temp (ꢀC)
Solvent
Additive
Time (days)
Yieldb (%)
1
2
3
4
5
6
7
8
25
45
Reflux
0
25
25
25
25
25
25
25
25
THF
THF
THF
THF
THF
THF
THF
THF
K2CO3
K2CO3
K2CO3
3
1
1
3
3
3
3
3
3
3
3
3
85
66
39
Trace
83
80
80
Trace
Trace
80
K2CO3
KOAcc
PhCOOHc
No additive
c
NEt3
9
THF
Pyridinec
K2CO3
10
11
12
DMF
MeOH
MeCN
K2CO3
K2CO3
61
38
a
All reactions were catalyzed by 20% Pd(OAc)2 in the presence of additive
(2 equiv) and CuBr2 (3 equiv).
b
NMR yield (internal standard¼ethyl acetate).
c
Additive (4 equiv).
Scheme 2. Reagents and conditions: (a) TsCl, pyridine, CH2Cl2, reflux; (b) SOCl2,
CH2Cl2, reflux; (c) 3-propenyl Grignard reagent, THF, rt.
temperature to 45 ꢀC, the yield decreased from 85% to 66%. When
the reaction temperature was further increased to reflux, the yield
decreased to 39% and a series of byproducts were produced (entries
1e3). However, when the temperature was decreased to 0 ꢀC, only
trace product was afforded and unreacted substrate was recovered
in good yield (entry 4).
Then substrate 1b was used in the Pd(II)-catalyzed oxidative
cyclization reaction at first (Table 1). As expected, we were pleased
to find that treatment of substrate 1b with 20 mol % Pd(OCOCF3)2,
K2CO3 (2 equiv), and CuBr2 (3 equiv) in THF at 25 ꢀC for 3 days
afforded 2b in 86% yield (entry 1), and seven-membered ring
byproduct 3 was not detected. When we replaced CuBr2 with CuCl2,
only trace product was detected.
The source of the Pd(II) profoundly affected the reaction (Table
1). It was shown that Pd(OCOCF3)2 and Pd(OAc)2 were superior to
PdCl2(MeCN)2 and PdCl2 based on the yields (entries 1e4). Con-
sidering the price and performance, we chose inexpensive Pd
(OAc)2 as the catalyst.
The quantity of the Pd(OAc)2 was also examined (Table 1，entries
2, 5e9). It was shown that when the quantity of the Pd(OAc)2 was
decreased from 0.2 equiv to 0.05 equiv, the catalytic activities de-
creased sharply and the yields decreased from 85% to 34%. However,
when we increased the quantity of the Pd(OAc)2 from 0.2 equiv
to0.3 equivandevento0.4 equiv, theyieldsdidnotincreaseobviously.
Then, the effect of temperature on reaction was examined
(Table 2). When the reaction temperature was increased from room
It was reported that acid and base had some effect on the Pd(II)-
catalyzed oxidative cyclization reaction.16b Therefore, some acids and
bases were selected to examine this reaction (Table 2, entries 5e9). It
was shown that when using KOAc, PhCOOH or no additive, the cata-
lyticactivitiesaswellastheyieldsofthereactiondecreasedcomparing
with that using K2CO3 (entries 1, 5e7). But when using triethylamine
or pyridine, only trace products were afforded (entries 8 and 9).
The effect of solvents on the Pd(II)-catalyzed oxidative cycliza-
tion reaction was examined (Table 2, entries 1, 10e12). Compared
with THF, DMF was also an efficient solvent (entry 10). When the
reaction was carried out in methanol, the reaction could afford 61%
yield (entry 11). However, when the reaction was carried out in
MeCN, only 38% yield was obtained and a byproduct 7b was
detected in 45% yield (entry 12). Toluene, dichloromethane, diethyl
ether, and ethyl acetate were also examined and only trace prod-
ucts were obtained.

F. Jiang et al. / Tetrahedron 67 (2011) 1501e1505
1503
With the optimized reaction conditions in hand, we applied this
methodology to a series of olefinic tosylamides mentioned above to
generalize the scope of the reaction (Table 3). It was observed that
excellent yields were afforded for 4-substituted substrates in THF,
regardless of electron-rich and electron-poor substrates, and 1d
with a 4-Cl group afforded the highest yield of 86% (entries 1, 2, 4,
and 6). The substrate 1e with a 6-Cl group could also afford high
yield of 75% in THF (entry 5). However only 27% yield was afforded
for substrate 1c with a 6-CH3 group in THF (entry 3). Fortunately,
when this reaction was carried out in DMF, the substrate 1c could
afford up to 86% yield (entry 9). 1a, 1b, 1d, and 1e also afforded high
yields in DMF (entries 7, 8, 10, and 11). It was interesting that the
substrate 1f with a 4-OCH3 group afforded in 77% yield in THF
(entry 6), however only 26% yield was given in DMF (entry 12).
(5a). The 2-aminobenzylalcohol 4a (12.3 g, 0.10 mol) was dissolved in
60 mL dichloromethane, and pyridine (10 mL, 0.13 mol) was added to
the solution. Then 4-methylbenzene-1-sulfonyl chloride (22.9 g,
0.12 mol) was added and the solution was refluxed for 12 h. The so-
lution was allowed to cool to room temperature and washed with
dilute hydrochloric acid (50 mL, 1 mol/L), brine (3ꢁ50 mL) and dried
over Na2SO4. After removal of the solvent, the residue was crystallized
from CH2Cl2/toluene to give the intermediate 5a (24.4 g, 88% yield).
Characterization data of the compound agree with reference:16b 1H
NMR (400 MHz, CDCl3)
d
7.85 (s, 1H), 7.65 (d, J¼8 Hz, 2H), 7.42e7.40
(m, 1H), 7.28e7.24 (m, 1H), 7.12e7.06 (m, 2H), 7.22 (d, J¼8 Hz, 2H),
4.39 (s, 2H), 2.37 (s, 3H), 2.08 (s, 1H).
4.2.1.2. N-(2-Hydroxymethyl-4-methyl-phenyl)-4-methyl-benze-
nesulfonamide (5b). Compound 5b was prepared from 4b by
a similar procedure with 5a (25.3 g, 87% yield). Characterization
data of the compound agree with reference:16b 1H NMR (400 MHz,
Table 3
Different substratesa
CDCl3)
d
7.63e7.57 (m, 3H), 7.26e7.19 (m, 3H), 7.04 (d, J¼8 Hz, 1H),
6.93 (s, 1H), 4.33 (d, J¼4 Hz, 2H), 2.39 (s, 3H), 2.27 (s, 3H), 2.05 (t,
J¼8 Hz, 1H).
4.2.1.3. N-(2-Hydroxymethyl-6-methyl-phenyl)-4-methyl-benze-
nesulfonamide (5c). Compound 5c was prepared from 4c by a sim-
ilar procedure with 5a (24.8 g, 85% yield). Characterization data of
the compound agree with reference:16b 1H NMR (400 MHz, CDCl3)
Entry
Substrate
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
1a (R¼H)
THF
THF
THF
THF
THF
THF
DMF
DMF
DMF
DMF
DMF
DMF
84
85
27
86
75
77
75
80
86
83
76
26
1b (R¼4-CH3)
1c (R¼6-CH3)
1d (R¼4-Cl)
1e (R¼6-Cl)
1f (R¼4-OCH3)
1a (R¼H)
d
7.57 (d, J¼8 Hz, 2H), 7.28e7.10 (m, 5H), 6.69(s, 1H), 4.40 (d, J¼6 Hz,
2H), 2.42 (s, 4H), 1.97 (s, 3H).
4.2.1.4. N-(4-Chloro-2-hydroxymethyl-phenyl)-4-methyl-benze-
nesulfonamide (5d). Compound 5d was prepared from 4d by
a similar procedure with 5a (25.9 g, 83% yield). Characterization
data of the compound agree with reference:16b 1H NMR (400 MHz,
1b (R¼4-CH3)
1c (R¼6-CH3)
1d (R¼4-Cl)
1e (R¼6-Cl)
1f (R¼4-OCH3)
9
10
11
12
CDCl3)
d
7.77 (s, 1H), 7.63 (d, J¼8 Hz, 2H), 7.38 (d, J¼8 Hz, 1H),
a
7.27e7.20 (m, 3H), 7.09 (d, J¼6 Hz, 1H), 4.34 (d, J¼6 Hz, 2H), 2.40 (s,
3H), 2.08 (t, J¼6 Hz, 1H).
All reactions were catalyzed by 20% Pd(OAc)2 in the presence of K2CO3 (2 equiv)
and CuBr2 (3 equiv) at 25 ꢀC for 3 days.
b
NMR yield (internal standard¼ethyl acetate).
4.2.1.5. N-(6-Chloro-2-hydroxymethyl-phenyl)-4-methyl-benze-
nesulfonamide (5e). Compound 5e was prepared from 4e by a sim-
ilar procedure with 5a (24.0 g, 77% yield). 1H NMR (400 MHz,
3. Conclusion
In summary, we have demonstrated the first Pd(II)-catalyzed
oxidative cyclization reaction for the preparation of 2-substituted
1,2,3,4-tetrahydroquinolines from olefinic tosylamides. The re-
action result is dependent on the Pd(II) source, reaction tempera-
ture, solvent, and the substituent of substrates. This method
provides a direct access to 2-substituted 1,2,3,4-tetrahydroquino-
lines with halide functionality with up to 86% yield.
CDCl3)
d 7.56e7.44 (m, 3H), 7.28e7.16 (m, 4H), 6.44(s, 1H), 4.86 (d,
J¼8 Hz, 2H), 3.14 (t, J¼8 Hz, 1H), 2.42 (s, 3H); 13C NMR (100 MHz,
CDCl3)
d 144.7, 142.7, 135.9, 132.3, 130.8, 130.2, 129.8, 129.2, 129.1,
127.8, 62.1, 21.9; HRMS calcd for C14H14ClNO3S 311.0383, found
311.0386.
4.2.1.6. N-(2-Hydroxymethyl-4-methoxyl-phenyl)-4-methyl-ben-
zenesulfonamide (5f). Compound 5f was prepared from 4f by
a similar procedure with 5a (28.0 g, 91% yield). Characterization
data of the compound agree with reference:20 1H NMR (400 MHz,
4. Experimental section
4.1. General
CDCl3)
d
7.58 (d, J¼8 Hz, 2H), 7.24e7.18 (m, 3H), 7.13 (d, J¼8 Hz, 1H),
6.77e6.71 (m, 2H), 4.31 (d, J¼4 Hz, 2H), 3.77 (s, 3H), 2.40 (s, 3H),
All air- and moisture-sensitive manipulations were carried out
with standard Schlenk techniques under nitrogen. DMF, MeCN,
methanol, THF, ethyl acetate, Et2O, dichloromethane, and toluene
were dried according to published procedures. The commercially
available reagents were used without further purification. TLC was
run on 2 cmꢁ5 cm silica plate. Column chromatography was run on
silica gel (100e200 mesh). 1H NMR (400 MHz) spectra and 13C NMR
(100 MHz) spectra were obtained on a Varian MERCURY plus-400
spectrometer. HRMS was performed on a Micromass LCT TM at the
Instrumental Analysis Center of Shanghai Jiao Tong University.
2.22 (t, J¼8 Hz, 1H).
4.2.2. Preparation of the substrates 1.
4.2.2.1. N-(2-But-3-enyl-phenyl)-4-methyl-benzenesulfonamide
(1a). The intermediate 5a (2.8 g, 0.010 mol) was dissolved in 20 mL
dichloromethane. To this solution, SOCl2 (1.1 mL, 0.015 mol) was
added slowly at 0 ꢀC and the reaction mixture was refluxed for 12 h.
After the solvent was removed in vacuo, the residue 6a was dis-
solved in 15 mL THF. Then the solution was slowly added to the THF
solution of 3-propenyl Grignard reagent (30 mL, 1 mol/L,
0.030 mol). After the mixture was stirred for 12 h, it was quenched
by the addition of cool water. The mixture was extracted with Et2O
(3ꢁ50 mL) and the combined organic layers were washed with
brine (3ꢁ50 mL) and dried over Na2SO4. After removal of the sol-
vent, the residue was purified by flash column chromatography to
4.2. Procedures and analytical data
4.2.1. Preparation of the intermediates 5.
4.2.1.1. N-(2-Hydroxymethyl-phenyl)-4-methyl-benzenesulfonamide

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F. Jiang et al. / Tetrahedron 67 (2011) 1501e1505
afford the substrates 1a (2.1 g, 70% yield). Rf¼0.27 (10:1 petroleum
ether/ethyl acetate); 1H NMR (400 MHz, CDCl3)
mixture was stirred for 3 days at 25 ꢀC. The mixture was filtered
through SiO2 and washed with Et2O (3ꢁ10 mL). After removal of
the solvent, the residue was purified by flash column chromatog-
raphy to afford the products 2.
Procedure b: 0.10 mmol of the substrates 1, 0.20 mmol of po-
tassium carbonate, and 0.30 mmol of copper bromide were sus-
pended in 5 mL DMF and the reaction mixture was stirred for 1 h at
0 ꢀC. Then 0.02 mmol of palladium acetate was added and the
mixture was stirred for 3 days at 25 ꢀC. The mixture was diluted
with water (10 mL) and extracted with Et2O (3ꢁ10 mL). The com-
bined organic layers were washed with brine (3ꢁ5 mL) and dried
over Na2SO4. After removal of the solvent, the residue was purified
by flash column chromatography to afford the products 2.
d
7.60 (d, J¼8 Hz,
2H), 7.33e7.29 (m, 1H), 7.21 (d, J¼8 Hz, 2H), 7.15e7.09 (m, 3H), 6.33
(s, 1H), 5.78e5.66 (m, 1H), 4.99e4.91 (m, 2H), 2.43e2.37 (m, 5H),
2.16e2.09 (m, 2H); 13C NMR (100 MHz, CDCl3)
d
144.0, 137.4, 136.9,
135.4, 134.2, 130.0, 129.8, 127.4, 127.2, 126.6, 125.0, 116.0, 34.0, 30.3,
21.7; HRMS calcd for C17H19NO2S, 301.1136, found 301.1138.
4.2.2.2. N-(2-But-3-enyl-4-methyl-phenyl)-4-methyl-benzene-
sulfonamide (1b). Compound 1b was prepared from 5b by a similar
procedure with 1a (2.3 g, 73% yield). Rf¼0.27 (10:1 petroleum
ether/ethyl acetate); 1H NMR (400 MHz, CDCl3)
2H), 7.22 (d, J¼8 Hz, 2H), 7.13 (d, J¼8 Hz, 1H), 6.95e6.91 (m, 2H),
6.20 (s, 1H), 5.77e5.66 (m, 1H), 4.99e4.92 (m, 2H), 2.41e2.34 (m,
5H), 2.28 (s, 3H), 2.14e2.07 (m, 2H); 13C NMR (100 MHz, CDCl3)
d
7.59 (d, J¼8 Hz,
4.2.3.1. 2-Bromethyl-1-(toluene-4-sulfonyl)-1,2,3,4-tetrahy-
d
143.9, 137.6, 137.0, 136.7, 136.1, 131.3, 130.7, 129.8, 127.8, 127.4,
droquinoline (2a). Yield 84% (procedure a); Rf¼0.24 (50:1 petro-
125.8, 115.9, 34.3, 30.4, 21.7, 21.2; HRMS calcd for C18H21NO2S,
315.1293, found 315.1294.
leum ether/ethyl acetate); 1H NMR (400 MHz, CDCl3)
d 7.70 (d,
J¼8 Hz, 1H), 7.32 (d, J¼8 Hz, 2H), 7.27e7.22 (m, 1H), 7.17e7.10 (m,
3H), 6.96 (d, J¼8 Hz, 1H), 4.40e4.31 (m, 1H), 3.75e3.71 (m, 1H),
3.40e3.34 (m, 1H), 2.37 (s, 3H), 2.32e2.24 (m, 1H), 2.22e2.12 (m,
4.2.2.3. N-(2-But-3-enyl-6-methyl-phenyl)-4-methyl-benzene-
sulfonamide (1c). Compound 1c was prepared from 5c by a similar
procedure with 1a (1.8 g, 57% yield). Rf¼0.29 (10:1 petroleum ether/
1H), 1.62e1.47 (m, 2H); 13C NMR (100 MHz, CDCl3)
d 144.0, 135.6,
135.3, 134.9, 129.7, 128.1, 127.7, 127.3, 127.2, 126.5, 57.0, 36.5, 28.9,
25.2, 21.8; HRMS calcd for C17H18BrNO2S, 379.0242, found
379.0237.
ethyl acetate); 1H NMR (400 MHz, CDCl3)
d
7.58 (d, J¼8 Hz, 2H), 7.24
(d, J¼8 Hz, 2H), 7.16e7.11 (m, 1H), 7.06e7.01 (m, 2H), 5.95 (s, 1H),
5.75e5.64 (m, 1H), 4.95e4.92 (m, 1H), 4.92e4.88 (m, 1H),
2.50e2.44 (m, 2H), 2.42 (s, 3H), 2.21e2.14 (m, 2H), 2.06 (s, 3H); 13C
4.2.3.2. 2-Bromethyl-6-methyl-1-(toluene-4-sulfonyl)-1,2,3,4-tet-
NMR (100 MHz, CDCl3)
129.8, 129.1, 128.2, 127.7, 127.4, 115.4, 34.6, 30.9, 21.8, 19.2; HRMS
calcd for C18H21NO2S, 315.1293, found 315.1298.
d
143.9, 141.5, 138.2, 138.0, 137.9, 132.3,
rahydroquinoline (2b). Yield 85% (procedure a); Rf¼0.17 (30:1 pe-
troleum ether/ethyl acetate); 1H NMR (400 MHz, CDCl3)
d 7.57 (d,
J¼8 Hz, 1H), 7.33 (d, J¼8 Hz, 2H), 7.17 (d, J¼8 Hz, 2H), 7.07e7.03 (m,
1H), 6.77 (s, 1H), 4.36e4.28 (m, 1H), 3.75e3.71 (m, 1H), 3.38e3.32
(m, 1H), 2.38 (s, 3H), 2.30 (s, 3H), 2.26e2.19 (m, 1H), 2.18e2.10 (m,
4.2.2.4. N-(2-But-3-enyl-4-chloro-phenyl)-4-methyl-benzene-
sulfonamide (1d). Compound 1d was prepared from 5d by a similar
procedure with 1a (2.9 g, 86% yield). Rf¼0.24 (10:1 petroleum
1H), 1.59e1.41 (m, 2H); 13C NMR (100 MHz, CDCl3)
d 143.9, 136.3,
135.6, 134.7, 132.7, 129.7, 128.4, 128.0, 127.9, 127.3, 56.9, 36.6, 29.0,
25.1, 21.8, 21.2; HRMS calcd for C18H20BrNO2S 393.0398, found
393.0392.
ether/ethyl acetate); 1H NMR (400 MHz, CDCl3)
d
7.58 (d, J¼8 Hz,
2H), 7.27e7.22 (m, 3H), 7.14e7.08 (m, 2H), 6.24 (s, 1H), 5.74e5.63
(m, 1H), 5.01e4.92 (m, 2H), 2.40 (s, 3H), 2.38e2.33 (m, 2H),
2.15e2.08 (m, 2H); 13C NMR (100 MHz, CDCl3)
d
144.3, 137.8, 137.0,
4.2.3.3. 2-Bromethyl-8-methyl-1-(toluene-4-sulfonyl)-1,2,3,4-tet-
136.6, 132.8, 132.1, 130.0, 129.9, 127.4, 127.2, 126.6, 116.2, 33.8, 30.2,
21.8; HRMS calcd for C17H18ClNO2S, 335.0747, found 335.0745.
rahydroquinoline (2c). Yield 86% (procedure b); Rf¼0.24 (50:1 pe-
troleum ether/ethyl acetate); 1H NMR (400 MHz, CDCl3)
d 7.42 (d,
J¼8 Hz, 2H), 7.26e7.15 (m, 3H), 7.10 (t, J¼8 Hz, 1H), 6.80 (d, J¼8 Hz,
1H), 4.40e4.31 (m, 1H), 3.69e3.63 (m, 1H), 3.36e3.29 (m, 1H), 2.53
(s, 3H), 2.42 (s, 3H), 2.30e2.22 (m, 1H), 2.10e2.03 (m, 1H), 1.34e1.10
d 144.2, 139.6, 139.2, 136.0,
134.4, 130.2, 129.8, 127.9, 127.3, 124.9, 57.5, 37.3, 31.0, 26.4, 21.8,
19.8; HRMS calcd for C18H20BrNO2S 393.0398, found 393.0379.
4.2.2.5. N-(2-But-3-enyl-6-chloro-phenyl)-4-methyl-benzene-
sulfonamide (1e). Compound 1e was prepared from 5e by a similar
procedure with 1a (3.0 g, 89% yield). Rf¼0.19 (30:1 petroleum
(m, 2H); 13C NMR (100 MHz, CDCl3)
ether/ethyl acetate); 1H NMR (400 MHz, CDCl3)
d
7.54 (d, J¼8 Hz,
2H), 7.25e7.19 (m, 3H), 7.17e7.12 (m, 1H), 7.11e7.08 (m, 1H), 6.19 (s,
1H), 5.88e5.76 (m, 1H), 5.04e4.93 (m, 2H), 3.08e3.03 (m, 2H), 2.41
(s, 3H), 2.39e2.32 (m, 2H); 13C NMR (100 MHz, CDCl3)
d
144.4,144.1,
4.2.3.4. 2-Bromethyl-6-chloro-1-(toluene-4-sulfonyl)-1,2,3,4-tet-
137.9, 136.9, 133.1, 131.3, 129.6, 129.2, 128.7, 127.8, 127.4, 115.4, 34.5,
31.8, 21.8; HRMS calcd for C17H18ClNO2S, 335.0747, found 335.0765.
rahydroquinoline (2d). Yield 86% (procedure a); Rf¼0.24 (50:1 pe-
troleum ether/ethyl acetate); 1H NMR (400 MHz, CDCl3)
d 7.65 (d,
J¼8 Hz, 1H), 7.35 (d, J¼8 Hz, 2H), 7.24e7.17 (m, 3H), 6.97e6.95 (m,
1H), 4.39e4.31 (m, 1H), 3.72e3.67 (m, 1H), 3.41e3.35 (m, 1H), 2.39
(s, 3H), 2.30e2.22 (m, 1H), 2.17e2.08 (m,1H),1.64e1.44 (m, 2H); 13C
4.2.2.6. N-(2-But-3-enyl-4-methoxyl-phenyl)-4-methyl-benzene-
sulfonamide (1f). The 1f was prepared from 5f by a similar pro-
cedure with 1a (2.9 g, 87% yield). Rf¼0.15 (10:1 petroleum ether/
NMR (100 MHz, CDCl3)
d 144.3, 136.4, 135.3, 134.1, 131.9, 129.9,
ethyl acetate); 1H NMR (400 MHz, CDCl3)
d
7.56 (d, J¼8 Hz, 2H),
129.3, 127.7, 127.5, 127.3, 56.8, 36.3, 28.5, 25.0, 21.8; HRMS calcd for
C17H17BrClNO2S, 412.9852, found 412.9850.
7.25e7.21 (m, 2H), 7.11e7.06 (m, 1H), 6.68e6.64 (m, 2H), 6.04 (s,
1H), 5.76e5.65 (m, 1H), 4.99e4.91 (m, 2H), 3.77 (s, 3H), 2.41e2.34
(m, 5H), 2.15e2.08 (m, 2H); 13C NMR (100 MHz, CDCl3)
d
158.7,
4.2.3.5. 2-Bromethyl-8-chloro-1-(toluene-4-sulfonyl)-1,2,3,4-tet-
143.8, 139.5,137.6,137.0,130.0,128.6,127.5,126.6,115.8,115.3,112.0,
55.5, 34.1, 30.5, 21.7; HRMS calcd for C18H21NO3S, 331.1242, found
331.1240.
rahydroquinoline (2e). Yield 76% (procedure b); Rf¼0.17 (30:1 pe-
troleum ether/ethyl acetate); 1H NMR (400 MHz, CDCl3)
d 7.63 (d,
J¼8 Hz, 2H), 7.37 (d, J¼8 Hz, 1H), 7.27 (d, J¼8 Hz, 2H), 7.14 (t, J¼8 Hz,
1H), 6.96 (d, J¼8 Hz, 1H), 4.42e4.32 (m, 1H), 3.59e3.53 (m, 1H),
3.20e3.13 (m, 1H), 2.45e2.36 (m, 4H), 2.26e2.20 (m, 1H), 1.70e1.60
4.2.3. General procedure for Pd(II)-catalyzed oxidative cyclization
reaction. Procedure a: 0.10 mmol of the substrates 1, 0.20 mmol of
potassium carbonate, and 0.30 mmol of copper bromide were
suspended in 5 mL THF and the reaction mixture was stirred for 1 h
at 0 ꢀC. Then 0.02 mmol of palladium acetate was added and the
(m,1H),1.41e1.30 (m,1H); 13C NMR (100 MHz, CDCl3)
d 144.5,141.6,
136.1, 135.1, 133.4, 130.0, 129.4, 128.4, 128.2, 126.0, 57.1, 36.5, 31.1,
26.7, 21.8; HRMS calcd for C17H17BrClNO2S, 412.9852, found
412.9823.

F. Jiang et al. / Tetrahedron 67 (2011) 1501e1505
1505
4. Scott, J. D.; Miller, M. W.; Li, S. W.; Lin, S.-I.; Vaccaro, H. A.; Hong, L.; Mullins, D.
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tetrahydroquinoline (2f). Yield 77% (procedure a); Rf¼0.17 (30:1 pe-
troleum ether/ethyl acetate); 1H NMR (400 MHz, CDCl3)
d 7.59 (d,
5. Parmenon, C.; Guillard, J.; Caignard, D.-H.; Hennuyer, N.; Staels, B.; Audinot-
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J¼8 Hz, 1H), 7.31 (d, J¼8 Hz, 2H), 7.16 (d, J¼8 Hz, 2H), 6.81e6.76 (m,
1H), 6.51e6.48 (m, 1H), 4.33e4.25 (m, 1H), 3.78 (s, 3H), 3.74e3.69
(m,1H), 3.38e3.32 (m,1H), 2.38 (s, 3H), 2.24e2.12 (m, 2H),1.54e1.34
(m, 2H); 13C NMR (100 MHz, CDCl3)
d 158.0, 143.9, 136.8, 135.4, 129.7,
129.5,128.1, 127.3, 113.0,112.2, 56.9, 55.6, 36.7, 29.2, 25.6, 21.8; HRMS
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acetate); 1H NMR (400 MHz, CDCl3)
d
7.60 (d, J¼8 Hz, 2H), 7.23 (d,
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T.; Makino, K.; Kunimune, I.; Namiki, A.; Hamada, Y. Tetrahedron 2007, 63,
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J¼8 Hz, 2H), 7.12 (d, J¼8 Hz, 1H), 6.97e6.94 (m, 2H), 6.30 (s, 1H),
4.10e4.02 (m, 1H), 3.83e3.78 (m, 1H), 3.59e3.53 (m, 1H), 2.60e2.52
(m, 1H), 2.50e2.43 (m, 1H), 2.40 (s, 3H), 2.28 (s, 3H), 2.26e2.17 (m,
1H),1.89e1.77 (m, 1H); 13C NMR (100 MHz, CDCl3)
d 144.0, 137.1, 136.8,
135.0, 131.5, 130.7, 129.8, 128.3, 127.5, 126.2, 52.2, 36.7, 36.0, 28.0, 21.8,
21.2; HRMS calcd for C18H21Br2NO2S, 472.9660, found 472.9662.
Acknowledgements
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This work was supported by the National Nature Science
Foundation of China (No. 20772081), Science and Technology
Commission of Shanghai Municipality (No. 09JC1407800), and
Nippon Chemical Industrial Co., Ltd. We thank Professor T. Imamoto
and Dr. M. Sugiya for the helpful discussion and Instrumental
Analysis Center of Shanghai Jiao Tong University for HRMS analysis.
H. Bioorg. Med. Chem. Lett. 2009, 19, 2456e2460.
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Supplementary data
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2010.12.017.
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