1,8-Diazabicyclo[5.4.0]undec-7-ene: A remarkable base in the debromination of 4- or 5-substituted N-benzyl α-bromo-α-p- toluenesulfonylglutarimide

Article abstract of DOI:10.1002/jccs.200200145

Debromination of N-benzyl 4- or 5-substituted α-bromo-α-p- toluenesulfonylglutarimides is achieved with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give the N-benzyl 4- or 5-substituted α-p- toluenesulfonylglutarimides. The DBU/THF system is applied to a new methodology for the synthesis of bicyclic glutarimide skeleton in moderate yields.

Full text of DOI:10.1002/jccs.200200145

Journal of the Chinese Chemical Society, 2002, 49, 1015-1024
1015
1,8-Diazabicyclo[5.4.0]undec-7-ene: A Remarkable Base in the
Debromination of 4- or 5-Substituted N-Benzyl
-Bromo- -p-toluenesulfonylglutarimide
Meng-Yang Changa (
Shui-Tein Chen*a (
), John, Yi-Chung Lina (
) and Nein-Chen Changb (
),
)
aInstitute of Bio l o g i c a l Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan, R.O.C.
bDepartment of Chemistry, National Sun Yat-Sen University, Kaohsiung 804, Taiwan, R.O.C.
Debromination of N-benzyl 4- or 5-substituted -bromo- -p-toluenesulfonylglutarimides is achieved
with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give the N-benzyl 4- or 5-substituted -p-toluenesul-
fonylglutarimides. The DBU/THF system is applied to a new methodology for the synthesis of bicyclic
glutarimide skeleton in moderate yields.
INTRODUCTION
DBU is a bicyclic amidine that has become of particular
bromination of -p-toluenesulfonylglutarimides A as sum-
marized in Scheme I and Table 1.
interest as a reagent in synthetic organic chemi s t r y. The ex-
tinction coefficient ( ) of this bicyclic amidine (DBU) is
greater than for other bases.1 It is widely used as an organic
base in dehydrohalogenation to olefins.1-3 Some important
applications are esterification of carboxylic acid with alkyl
halides,4 alkylation and acylation of active methylene com-
pounds,5 epoxidation of , -unsaturated -lactones and other
enones by t-butyl hydroperoxide,6 ring-opening of epoxide
by titanium (IV) chloride to give chlorohydrins,7 synthesis of
acylurea and carbamate from amide by Bu4NBr3-DBU re-
agent system,8 and DBU-promoted addition of chloroform to
carbonyl compounds.9 In order to investigate the other app l i -
cations of DBU, we find that DBU can abstract the bromide
ion in the -p-toluenesulfonylglutarimide.
Scheme I
Y
Y
Br
SO2Tol
X
SO2Tol
X
o
NaHCO , NBS, CH CN, 30 min, 25
C
4
3
3
5
O
N
O
O
N
O
o
DBU, THF, 10 min, 65
C
Bn
A
Bn
B
This is a facile, mild and high yield (82~97%) method
for the bromination on -p-toluenesulfonylpiperidine-2,6-
dione. But, the bromination was unsuccessful on the -p-
toluenesulfonylpiperidine-2-one and pyrrolidine-2-one. The
difference between -p-toluenesulfonylpiperidine-2,6-dione
and piperidine-2-one was not clear. We also attempted to use
the Br2/CHCl3 reagent system, but the yield (40~71%) was
less than for the NBS/NaHCO3/CH3CN system. All bromides
B have the expected two isomers except No. 1 (R=H) in Table 1.
RESULTS AND DISCUSSION
Debromination using DBU/THF system in the skele t o n
of N-benzyl 4- or 5-substituted -bromo- -p-toluenesul-
fonylglutarimides
Bromination using NBS/NaHCO3/CH3CN system in the
skeleton of N-benzyl 4- or 5-substituted -p-toluenesul-
fonylglutarimides
With this result in hand, the next focus was to examine
the elimination of these bromides from B. Bromides B when
treated with DBU yielded debrominated products A as shown
in Scheme I. The reactions yielded purified products in the
range of 53~89%. Two isomers of bromides B were con-
verted to compounds A by the DBU/THF system. The stereo-
chemistry of compounds A at C-3 and C-4 retained its trans
form (reactions No. 2~17)10 and at the relatively positions of
C-3 and C-5 (reactions 18~20)11 maintained the mixed iso-
First, N-benzyl -p-toluenesulfonylacetamide was pre-
pared from acylation and substitution of chloroacetyl chlo-
ride. The starti n g materials A10-12 of the debromination rea c -
tion in turn were prepared by the formal [3+3] cycloaddition
reactions of N-benzyl -p-toluenesulfonylacetamide with
various , -unsaturated esters. Then, bromination reaction is
the next step. However, there have been few reports13-15 on
the halogenation of -p-toluenesulfonylacetamide. The
NBS/NaHCO3/CH3CN system is an efficient method for the

1016 J. Chin. Chem. Soc., Vol. 49, No. 6, 2002
Chang et al.
Table 1. Representative Examples of NBS Mediated Bromination of N-Benzyl 4- or 5-
Substituted -p-Toluenesulfonylglutarimides and DBU/THF Mediated Debromination
of N-Benzyl 4- or 5-Substituted -Bromo- -p-toluenesulfonylglutarimides
Reaction
No.
Yield (%)
B (bromination)
Yield (%)
A (debromination)
X, Y
1
2
3
4
5
6
7
8
H, H
H, C10H21
92
93
96
90
91
90
95
97
95
90
89
94
92
89
84
84
85
91
82
85
81
79
70
89
83
88
79
76
80
68
72
66
56
61
53
59
64
72
64
58
H, CH(OCH3)2
H, C3H6OH
H, C4H8OH
H, C5H10OH
H, C3H6Obn
H, C4H8Obn
H, C5H10Obn
H, CH2CH2CH(OH)CH3
H, CH2CH2CH(OTBS)CH3
H, CH2CH2CH=CH2
H, C6H5
9
10
11
12
13
14
15
16
17
18
19
20
H, 4-F-C6H4
H, 4-NO2-C6H4
H, 4-OMe-C6H4
H, 3,4-(OMe)2-C6H3
Me, H
NHBoc, H
Phthalimido, H
mer forms.
debromination. Therefore, the debromination process re-
quired DBU as an assistant. The quenched water supplied the
proton in the intermediate state to give compounds A. The re-
action must be heated to increase reaction rate. If the reaction
was refluxed over 30 min, the desired product disappeared
and a complex mixture resulted. Therefore, the best condition
for debromination reaction is 65 C within 10 min. DBU was
recognized as an efficient promoter in these debrominations
since other bases such as triethylamine and diisopropylethyl-
amine were not useful to deliver the same products.
How is the bromide removed from the compounds B?
Our hypothesis is that DBU functions as a promoter for the
debromination in the skeleton of N-benzyl 4- or 5-substituted
-p-toluenesulfonylglutarimides. This hypothesis has not
usually been reported in the literature. The p-toluenesulfonyl
group is the important factor in the debromination process
(Fig. 1). Hydrogen bondi n g between the lone pair of electrons
of p-toluenesulfonyl oxy g e n atom and the proton of the C-4
position fastens this proton into two rigid conformations of
bromides B. The second factor is the 1,3-repulsion force be-
tween the nitrogen lone pair of electrons and bromide, and
which may promote the release of the bromide group.
DBU promoted debromination process in the intra-
molecular cyclization and elimination of the skeleton of
N-benzyl 4- or 5-substituted -p-toluenesulfonylglutar-
imides
Furthermore, a reaction of bromides B in tetrahydro-
furan without DBU at refluxed temperature did not cause
With these results in hand, the DBU/THF system was
applied to synthesize the bicyclic glutarimide skeletons C1,
C2 from chloro-substituted glutarimides B1, B2 (as shown in
Scheme II). Chlorides B1, B2, B3 were converted from alc o -
hols (reaction No. 4~6) by chlorination of triphenylphos-
phine and carbon tetrachloride in 50~61% yield. When chlo-
rides B1 and B2 were treated with DBU in tetrahydrofuran,
the desired bicyclic glutarimides C1 and C2 were obtained.
When the chloride B3 was treated with DBU in tetrahydro-
furan, only the debrominated compound C3 was obtained.
Y
H
O
O
X
X
O
S
O
S
H
Y
N
N
O
O
O
O
Br
Br
DBU
DBU
Fig. 1.

1,8-Diazabicyclo[5.4.0]undec-7-ene in Debromination of
J. Chin. Chem. Soc., Vol. 49, No. 6, 2002 1017
-Bromo- -p-toluenesulfonylglutarimide
Scheme II
R1
R2
Cl
n
n
n
Br
SO2Tol
DBU, THF
SO2Tol
SO2Tol
SO2Tol
+
+
o
10-15 min, 65 C
O
N
Bn
O
O
N
O
O
N
O
O
N
O
Bn
Bn
C3 n = 3 (52%)
Bn
B1 n = 1, R1=H, R2=Cl
B2 n = 2, R1=H, R2=Cl
B3 n = 3, R1=H, R2=Cl
B4 n = 1, R1=Me, R2=OMs
C1 n = 1 (57%)
C2 n = 2 (66%)
C4 (51%)
This structure of C3 was confirmed by X-ray analysis. 6,7-
Fused bicyclic glutarimide was not easily formed, because
the ring size was too large to cyclize. Mesylate B4 was con-
verted from alcohol (reaction No. 10) by mesylation of meth-
anesulfonyl chloride and pyridinein 48% yield. The mesylate
B4 was treated with DBU in tetrahydrofuran to obtain the
elimination compound C4 as a mixture of exo and endo ole-
fins. This reaction revealed that the secondary mesylate
group was not attacked by the intramolecular anion interme-
diate, but it was easily eliminated by DBU. These results rep-
resented the interesting reaction types of different functional
groups of 4- or 5-substituted -p-toluenesulfonylglutar-
imides using DBU.
magnetic stirring. Organic layers were dried with anhydrous
magnesium sulfate before concentration in vacuo. Crude
products were purified using preparative TLC or column
chromatography on silica gel. All reported melting points
were uncorrected.
N-Benzyl-2-p-toluenesulfonylacetamide
Chloroacetyl chloride (5.99 g, 53.0 mmol) in tetra-
hydrofuran (40 mL) was added to a solution of benzylamine
(5.35 g, 50.0 mmol) and triethylamine (5.57 g, 55.0 mmol) in
tetrahydrofuran (100 mL) over a period of 1 h at 0 C. Stirring
continued at room temperature for 4 h. The mixture was con-
centrated und e r reduced pressure. Water (30 mL) was added
to the residue and extracted with ethyl acetate (3 100 mL).
The combined organic layers were washed with brine (2 50
mL), dried over anhydrous magnesium sulfate, filtered and
evaporated. Without further purification, the crude product
was refluxed with sodium salt of p-toluenesulfinic acid
(TolSO2Na-2H2O, 16.05 g, 75.0 mmol) in dioxane (150 mL)
and water (150 mL) for 10 h. Then the mixture was concen-
trated und e r reduced pressure, and the residue was extracted
with ethyl acetate (3 150 mL). The combined organic laye r s
were washed with brine (2 50 mL), dried over anhydrous
magnesium sulfate, filtered and evaporated. Recrystalliza-
tion on hexane and ethyl acetate (100 mL and 50 mL) pro-
duced 12.88 g (85%, two steps) of -p-toluenesulfonyl-
acetamide: mp 157-159 C; IR (CHCl3) 2361, 1664, 1528,
1290, 1147 cm-1; ESI-MS: C16H18NO3S m/z (%) = 91 (100),
154 (65), 304 (M++1, 85); HRMS (EI, M+) calcd for
C16H17NO3S 303.0930, found 303.0925; 1H NMR (400 MHz,
CDCl3) 7.65 (d, J = 8.2 Hz, 2H), 7.33-7.24 (m, 7H), 7.06 (br
s, 1H), 4.42 (d, J = 5.9 Hz, 2H), 3.99 (s, 2H), 2.42 (s, 3H); 13C
NMR (100 MHz, CDCl3): 160.64, 145.58, 137.35, 135.12,
130.04, 128.74, 128.16 (4 ), 127.97 (2 ), 127.70, 62.01,
44.02, 21.70; Anal. Calcd for C16H17NO3S C, 63.34; H, 5.65.
CONCLUSION
In summary, we demonstrate two methodologies: (1)
bromination using NBS/NaHCO3/CH3CN system and (2)
debromination using DBU/THF system in the skeleton of N-
benzyl 4- or 5-substituted -p-toluenesulfonylglutarimides.
We propose that DBU is a promoter in the debromination pro-
cess of the skeleton of N-benzyl 4- or 5-substituted -p-
toluenesulfonylglutarimides, and it also promotes the intra-
molecular cyclization and elimination.
EXPERIMENTAL
General
Tetrahydrofuran (THF) was distilled prior to use from a
deep-blue solution of sodium-benzophenone ketyl. All other
reagents and solvents were obtained from commercial sources
and used without further purification. Reactions were rou-
tinely carried out under an atmosphere of dry nitrogen with

1018 J. Chin. Chem. Soc., Vol. 49, No. 6, 2002
Chang et al.
Found C, 63.14; H, 5.44.
mmol) and sodium bicarbonate (4.0 mmol) in dry acetonitrile
(10 mL). The mixture was stirred under nitrogen atmosphere
at room temperature for 30 min, and the reaction was
quenched with water (1 mL). Evapo r a t i o n of solvent fol-
lowed by purification of the crude product by colu m n chro-
matography on silica gel with hexane/ethyl acetate (8/1~4/1)
produced pure bromides B as an isomeric mixture (reaction,
No. 1 is a pure compound).
Preparation of various , -unsaturated ethyl esters
No. 2~17 in Table 1, Wittig reaction
A solution of aldehyde (3.0 mmol) in methylene chlo-
ride (10 mL) was added to a rapidly stirred solution of
Ph3P=CHCO2Et (3.1 mmol) in methylene chloride (20 mL),
then stirred at room temperature for 2 h. The resulting mix-
ture was concentrated und e r reduced pressure. Water (20 mL)
was added to the residue and extracted with ethyl acetate (3
50 mL). The combined organic layers were washed with
brine (2 20 mL), dried over anhydrous magnesium sulfate,
filtered and evaporated. Purification of the crude product by
column chromatography on silica gel with hexane/ethyl ace -
tate (20/1~15/1) produced various , -unsaturated ethyl es-
ters.
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)piperidine-
2,6-dione
Gum; IR (CHCl3) 1731, 1691 cm-1; HRMS (EI, M+)
calcd for C19H18BrNO4S 435.0146, found 435.0138;1H NMR
(300 MHz, CDCl3): 7.74 (d, J = 8.7 Hz, 2H), 7.31-7.25 (m,
7H), 5.06 (d, J = 13.8 Hz, 1H), 4.87 (d, J = 13.8 Hz, 1H),
3.22-3.00 (m, 2H), 2.92-2.82 (m, 1H), 2.76-2.66 (m, 1H),
2.45 (s, 3H); 13C NMR (75 MHz, CDCl3): 169.47, 164.25,
146.40, 135.70, 132.17 (2 ), 131.09, 129.02 (2 ), 128.47
(2 ), 128.35 (2 ), 127.58, 71.97, 44.19, 30.14, 27.87, 21.81.
No. 19 in Table 1, Jackson’s method11,16
No. 20 in Table 1, Trost’s method: 2-Phthalimidoacrylic
acid methyl ester17,18
Formal [3+3] cycloaddition reaction of N-benzyl
-p-toluenesulfonylacetamide with vari o u s , -unsatu-
rated ethyl esters
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-n-decyl-
piperidine-2,6-dione
1
Gum; H NMR (400 MHz, CDCl3): 7.41-7.14 (m,
A solution of N-benzyl -p-toluenesulfonylacetamide
(1.0 mmol) in tetrahydrofuran (30 mL) was carefully added
to a rapidly stirred suspension of sodium hydride (2.1 mmol,
60%) in tetrahydrofuran (30 mL). After the reaction mixture
was stirred at room temperature for 15 min, a solution of ethyl
ester (1.0 mmol) in tetrahydrofuran (30 mL) was added. The
resulting mixture was heated at reflux for 30 min (for reaction
No. 1, at room temperature for over 2 h), quenched with satu -
rated ammonium chloride solution (2 mL) in an ice bath, and
concentrated under reduced pressure. Water (20 mL) was
added to the crude product and extracted with ethyl acetate (3
50 mL). The combined organic laye r s were washed with
brine (2 20 mL), dried over anhydrous magnesium sulfate,
filtered and evaporated. Purification of the crude product by
column chromatography on silica gel with hexane/ethyl ace -
tate (4/1~2/1~1/1) produced starting materials A in 68~92%
yield.
9H), 5.24-5.17 (m, 1H), 4.83-4.73 (m, 1H), 3.65-2.77 (m,
2H), 2.40 (s, 3H), 2.15-1.80 (m, 1H), 1.25 (br s, 18H),
0.92-0.82 (m, 3H).
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-dimethoxy-
methylpiperidine-2,6-dione
1
Gum; H NMR (400 MHz, CDCl3): 8.16 (d, J = 8.3
Hz, 4/5H), 7.44-7.16 (m, 41/5H), 5.19-5.15 (m, 1H), 4.97-
4.67 (m, 2H), 3.51-2.91 (m, 2H), 3.40 (s, 3H), 3.13 (s, 3H),
3.01-2.92 (m, 1H), 2.46 (s, 6/5H), 2.40 (s, 9/5H).
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-(3-
hydroxypropyl)piperidine-2,6-dione
1
Gum; H NMR (400 MHz, CDCl3): 7.39-7.12 (m,
9H), 5.20 (d, J = 13.9 Hz, 1/2H), 5.19 (d, J = 13.8 Hz, 1/2H),
4.81 (d, J = 13.9 Hz, 1/2H), 4.74 (d, J = 13.8 Hz, 1/2H), 3.68
(t, J = 6.3 Hz, 3/2H), 3.63 (t, J = 6.1 Hz, 3/2H), 3.57 (ddd, J =
0.8, 5.3, 17.8 Hz, 1/2H), 3.35 (dd, J = 10.5, 18.4 Hz, 1/2H),
3.11 (J = 5.8, 18.3 Hz, 1/2H), 3.04-2.98 (m, 1/2H), 2.89-2.81
(m, 1H), 2.57-2.49 (m, 1/2H), 2.40 (s, 3/2H), 2.39 (3/2H),
2.30-2.22 (m, 1/2H), 2.01-1.22 (m, 3H).
Bromination from N-benzyl 4- or 5-substituted
-p-toluenesulfonylglutarimides A to N-benzyl 4- or
5-substituted -bromo- -p-toluenesulfonylglutarimides B
using NBS/NaHCO3/CH3CN system
The typical procedure is as follows: N-benzyl 4- or
5-substituted -p-toluenesulfonylglutarimide (1.0 mmol)
was added to a solution of N-bromosuccinimide (NBS, 1.2
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-(4-
hydroxybutyl)piperidine-2,6-dione
1
Gum; H NMR (400 MHz, CDCl3): 7.40-7.13 (m,

1,8-Diazabicyclo[5.4.0]undec-7-ene in Debromination of
J. Chin. Chem. Soc., Vol. 49, No. 6, 2002 1019
-Bromo- -p-toluenesulfonylglutarimide
9H), 5.20 (d, J = 13.8 Hz, 3/5H), 5.18 (d, J = 13.7 Hz, 2/5H),
4.82 (d, J = 13.8 Hz, 3/5H), 4.75 (d, J = 13.7 Hz, 2/5H),
3.65-3.57 (m, 2H), 3.41-2.75 (m, 2H), 2.40 (br s, 3H),
2.18-1.85 (m, 1H), 1.62-1.23 (m, 7H).
(dd, J = 7.4, 18.5 Hz, 2/7H), 3.65 (dd, J = 7.0, 18.3 Hz, 5/7H),
3.40 (dd, J = 6.2, 18.3 Hz, 5/7H), 3.12 (dd, J = 1.5, 18.5 Hz,
2/7H), 2.41 (s, 6/7H), 2.39 (s, 15/7H).
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-(4-fluoro-
phenyl)piperidine-2,6-dione
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-(5-
hydroxypentyl)piperidine-2,6-dione
1
Gum; H NMR (400 MHz, CDCl3): 7.53-6.80 (m,
1
Gum; H NMR (400 MHz, CDCl3): 7.40-7.13 (m,
13H), 5.35 (d, J = 13.5 Hz, 2/9H), 5.20 (d, J = 13.6 Hz, 7/9H),
5.02 (d, J = 13.5 Hz, 2/9H), 4.88 (d, J = 13.6 Hz, 7/9H), 4.35
(dd, J = 1.9, 7.2 Hz, 2/9H), 4.10 (dd, J = 6.1, 7.8 Hz, 7/9H),
3.93 (dd, J = 7.2, 18.5 Hz, 2/9H), 3.66 (dd, J = 7.8, 18.4 Hz,
7/9H), 3.37 (dd, J = 6.1, 18.4 Hz, 7/9H), 3.08 (dd, J = 1.9,
18.5 Hz, 2/9H), 2.41 (s, 2/3H), 2.39 (s, 7/3H).
9H), 5.22 (d, J = 13.8 Hz, 1/2H), 5.18 (d, J = 13.7 Hz, 1/2H),
4.82 (d, J = 13.8 Hz, 1/2H), 4.75 (d, J = 13.7 Hz, 1/2H),
3.65-3.58 (m, 2H), 3.30-2.74 (m, 2H), 2.41 (br s, 3H), 2.16-
1.88 (m, 1H), 1.59-1.23 (m, 9H).
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-(3-benzyl-
oxypropyl)piperidine-2,6-dione
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-(4-nitro-
phenyl)piperidine-2,6-dione
1
Gum; H NMR (400 MHz, CDCl3): 7.42-7.11 (m,
1
14H), 5.23 (d, J = 13.9 Hz, 1/2H), 5.21 (d, J = 13.8 Hz, 1/2H),
4.82 (d, J = 13.9 Hz, 1/2H), 4.74 (d, J = 13.8 Hz, 1/2H), 4.50
(s, 1H), 4.47 (s, 1H), 3.62 (dd, J = 5.5, 18.1 Hz, 1/2H), 3.52 (t,
J = 6.2 Hz, 1H), 3.50 (t, J = 6.1 Hz, 1H), 3.38 (dd, J = 11.9,
18.4 Hz, 1/2H), 3.11 (dd, J = 5.8, 18.4 Hz, 1/2H), 3.08-3.00
(m, 1/2H), 2.90-2.81 (m, 1H), 2.60-2.50 (m, 1/2H), 2.41 (s,
3/2H), 2.39 (s, 3/2H), 2.30-2.20 (m, 1/2H), 2.05-1.92 (m
,1/2H), 1.88-1.69 (m, 1H), 1.68-1.51 (m, 1H), 1.43-1.32 (m,
1/2H).
Gum; H NMR (400 MHz, CDCl3): 8.06 (d, J = 8.8
Hz, 4/3H), 8.00 (d, J = 8.8 Hz, 2/3H), 7.52-7.11 (m, 11H),
5.34 (d, J = 13.5 Hz, 1/3H), 5.22 (d, J = 13.6 Hz, 2/3H), 5.05
(d, J = 13.5 Hz, 1/3H), 4.89 (d, J = 13.6 Hz, 2/3H), 4.51 (dd, J
= 2.3, 7.1 Hz, 1/3H), 4.22 (dd, J = 6.2, 8.1 Hz, 2/3H), 3.93
(dd, J = 7.1, 18.5 Hz, 1/3H), 3.72 (dd, J = 8.1, 18.1 Hz, 2/3H),
3.38 (dd, J = 6.1, 18.1 Hz, 2/3H), 3.07 (dd, J = 2.3, 18.5 Hz,
1/3H), 2.45 (s, 1H), 2.40 (s, 2H).
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-(4-meth-
oxyphenyl)piperidine-2,6-dione
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-(4-benzyl-
oxybutyl)piperidine-2,6-dione
1
Gum; H NMR (400 MHz, CDCl3): 7.53-7.12 (m,
1
Gum; H NMR (400 MHz, CDCl3): 7.41-7.12 (m,
11H), 6.86-6.67 (m, 2H), 5.37 (d, J = 13.5 Hz, 1/4H), 5.20 (d,
J = 13.6 Hz, 3/4H), 5.00 (d, J = 13.5 Hz, 1/4H), 4.89 (d, J =
13.6 Hz, 3/4H), 4.31-3.08 (m, 3H), 3.81 (s, 9/4H), 3.76 (s,
3/4H), 2.42 (br s, 3H).
14H), 5.22 (d, J = 13.8 Hz, 1/2H), 5.20 (d, J = 13.8 Hz, 1/2H),
4.80 (d, J = 13.8 Hz, 1/2H), 4.74 (d, J = 13.8 Hz, 1/2H), 4.49
(s, 1H), 4.47 (s, 1H), 3.60-3.32 (m, 3H), 3.11-2.84 (m, 2H),
2.40 (br s, 3H), 2.17-1.86 (m, 1H), 1.69-1.24 (m, 5H).
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-(3,4-
dimethoxyphenyl)piperidine-2,6-dione
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-(5-benzyl-
oxypentyl)piperidine-2,6-dione
1
Gum; H NMR (400 MHz, CDCl3): 7.53-7.11 (m,
1
Gum; H NMR (400 MHz, CDCl3): 7.43-7.13 (m,
9H), 6.82-6.47 (m, 3H), 5.35 (d, J = 13.5 Hz, 1/4H), 5.18 (d, J
= 13.6 Hz, 3/4H), 4.99 (d, J = 13.5 Hz, 1/4H), 4.87 (d, J = 13.6
Hz, 3/4H), 4.30-3.09 (m, 3H), 3.88 (s, 9/4H), 3.84 (s, 3/4H),
3.79 (s, 9/4H), 3.64 (s, 3/4H), 2.40 (br s, 3H).
14H), 5.23 (d, J = 13.8 Hz, 1/2H), 5.20 (d, J = 13.8 Hz, 1/2H),
4.83 (d, J = 13.8 Hz, 1/2H), 4.76 (d, J = 13.8 Hz, 1/2H), 4.50
(s, 1H), 4.49 (s, 1H), 3.64-3.31 (m, 3H), 3.11-2.73 (m, 2H),
2.40 (br s, 3H), 2.19-1.80 (m, 1H), 1.65-1.25 (m, 7H).
Debromination from N-benzyl 4- or 5-substituted
-bromo- -p-toluenesulfonylglutarimides B to N-benzyl
4- or 5-substituted -p-toluenesulfonylglutarimides A
using DBU/THF system
1-Benzyl-3-bromo-3-(4-methylphenylsulfonyl)-4-phenyl-
piperidine-2,6-dione
1
Gum; H NMR (400 MHz, CDCl3): 7.55-6.90 (m,
14H), 5.39 (d, J = 13.6 Hz, 2/7H), 5.21 (d, J = 13.6 Hz, 5/7H),
5.02 (d, J = 13.6 Hz, 2/7H), 4.90 (d, J = 13.6 Hz, 5/7H), 4.36
(dd, J = 1.5, 7.4 Hz, 2/7H), 4.11 (br t, J = 7.0 Hz, 5/7H), 3.96
The typical experiment procedure is as follows: DBU
(0.3 mmol) was added to a solution of N-benzyl 4- or 5-sub-
stituted -bromo- -sulfonylglutarimide (0.1 mmol) in tetra-

1020 J. Chin. Chem. Soc., Vol. 49, No. 6, 2002
Chang et al.
hydrofuran (5 mL). The mixture was stirred at refluxed tem-
perature for 10 min, and the reaction was quenched with wa-
ter (1 mL) at room temperature. Evaporation of solvent fol-
lowed by purification of the crude product by colu m n chro-
matography on silica gel with hexane/ethyl acetate produced
pure compound A.
1679, 1383, 1148, 744 cm-1; ESI-MS: C22H26NO5S m/z (%) =
91 (100), 137 (19), 154 (18), 260 (10), 416 (M++1, 50);
HRMS (ESI, M++1) calcd for C22H26NO5S 416.1533, found
416.1536; 1H NMR (400 MHz, CDCl3): 7.45 (d, J = 8.3 Hz,
2H), 7.37-7.15 (m, 7H), 5.06 (d, J = 14.0 Hz, 1H), 4.85 (d, J =
14.0 Hz, 1H), 3.94 (br s, 1H), 3.67 (t, J = 5.7 Hz, 2H), 3.49
(dd, J = 6.1, 18.1 Hz, 1H), 3.03-2.95 (m, 1H), 2.70 (d, J = 18.1
Hz, 1H), 2.42 (s, 3H), 1.75-1.23 (m, 5H); Anal. Calcd for
C22H25NO5S C, 63.59; H, 6.06. Found C, 63.16; H, 6.21.
1-Benzyl-3-(4-methylphenylsulfonyl)piperidine-2,6-dione
Mp 66-69 C; IR (CHCl3) 2936, 2858, 1728, 1677,
1382, 736 cm-1; HRMS (EI, M+) calcd for C19H19NO4S
357.1036, found 357.1032; 1H NMR (300 MHz, CDCl3):
7.52 (d, J = 8.1 Hz, 2H), 7.32-7.25 (m, 7H), 5.03 (d, J = 13.8
Hz, 1H), 4.86 (d, J = 13.8 Hz, 1H), 4.06 (br s, 1H), 3.38-3.20
(m, 1H), 2.82-2.68 (m, 2H), 2.43 (s, 3H), 2.40-2.20 (m, 1H);
13C NMR (75 MHz, CDCl3): 170.66, 164.65, 145.59,
135.28, 134.36, 129.69 (2 ), 128.94 (2 ), 128.57 (2 ),
128.24 (2 ), 127.40, 65.62, 43.38, 29.15, 21.71, 17.62.
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(4-hydroxybutyl)-
piperidine-2,6-dione
Mp 80-83 C; IR (CHCl3) 3390, 2938, 2863, 1727,
1681, 1386, 753 cm-1; ESI-MS: C23H28NO5S m/z (%) = 91
(100), 430 (M++1, 22); HRMS (ESI, M++1) calcd for
C23H28NO5S 430.1689, found 430.1690; 1H NMR (400 MHz,
CDCl3): 7.45 (d, J = 8.1 Hz, 2H), 7.35-7.23 (m, 7H), 5.05
(d, J = 14.0 Hz, 1H), 4.85 (d, J = 14.0 Hz, 1H), 3.92 (br s, 1H),
3.54 (t, J = 5.3 Hz, 2H), 3.47 (dd, J = 6.0, 18.1 Hz, 1H),
3.00-2.95 (m, 1H), 2.69 (d, J = 18.1 Hz, 1H), 2.41 (s, 3H),
1.75-1.23 (m, 7H); 13C NMR (100 MHz, CDCl3): 170.47,
164.33, 145.74, 136.40, 134.50, 129.83 (2 ), 128.94 (2 ),
128.69 (2 ), 128.34 (2 ), 127.53, 70.70, 62.13, 43.34, 34.31,
33.80, 31.92, 28.80, 22.95, 21.74; Anal. Calcd for C23H27NO5S
C, 64.31; H, 6.34. Found C, 64.21; H, 6.40.
1-Benzyl-3-(4-methylphenylsulfonyl)-4-n-decylpiperidine-
2,6-dione
Mp 49-51 C; IR (CHCl3) 2926, 2855, 1728, 1676,
1382, 754 cm-1; HRMS (EI, M+) calcd for C29H39NO4S
497.2602, found 497.2610; 1H NMR (400 MHz, CDCl3):
7.45 (d, J = 8.3 Hz, 2H), 7.33-7.24 (m, 7H), 5.06 (d, J = 14.0
Hz, 1H), 4.85 (d, J = 14.0 Hz, 1H), 3.90 (br s, 1H), 3.47 (dd, J
= 6.1, 18.1 Hz, 1H), 3.00-2.95 (m, 1H), 2.69 (d, J = 18.1 Hz,
1H), 2.42 (s, 3H), 1.40-1.10 (m, 18H), 0.87 (t, J = 6.7 Hz,
3H); 13C NMR (100 MHz, CDCl3): 170.50, 164.39, 145.66,
136.43, 134.61, 129.80 (2 ), 128.93 (2 ), 128.64 (2 ),
128.33 (2 ), 127.48, 70.85, 43.31, 34.32, 34.02, 31.86, 29.49
(2x), 29.44, 29.24, 29.06, 28.76, 26.57, 22.65, 21.73, 14.09.
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(5-hydroxypentyl)-
piperidine-2,6-dione
Mp 60-62 C; IR (CHCl3) 3391, 2935, 2860, 1727,
1679, 1383, 751 cm-1; HRMS (EI, M+) calcd for C24H29NO5S
443.1768, found 443.1761; 1H NMR (400 MHz, CDCl3):
7.45 (d, J = 8.2 Hz, 2H), 7.32-7.23 (m, 7H), 5.05 (d, J = 14.0
Hz, 1H), 4.85 (d, J = 14.0 Hz, 1H), 3.90 (br s, 1H), 3.55 (t, J =
6.4 Hz, 2H), 3.46 (dd, J = 6.1, 18.1 Hz, 1H), 2.99-2.95 (m,
1H), 2.68 (d, J = 18.1 Hz, 1H), 2.41 (s, 3H), 1.62-1.29 (m,
9H); 13C NMR (100 MHz, CDCl3): 170.49, 164.37, 145.74,
136.42, 134.50, 129.83 (2 ), 129.18 (2 ), 128.94 (2 ),
128.69 (2 ), 127.53, 70.81, 62.47, 43.34, 34.30, 33.95,
32.18, 28.73, 26.33, 25.29, 21.75.
1-Benzyl-3-(4-methylphenylsulfonyl)-4-dimethoxymethyl-
piperidine-2,6-dione
Mp 151-154 C; IR (CHCl3) 2940, 2837, 1727, 1676,
1388, 765 cm-1; HRMS (EI, M+) calcd for C22H25NO6S
431.1404, found 431.1411; 1H NMR (400 MHz, CDCl3):
7.54 (d, J = 8.3 Hz, 2H), 7.33-7.20 (m, 7H), 4.98 (d, J = 14.0
Hz, 1H), 4.84 (d, J = 14.0 Hz, 1H), 4.22 (br s, 1H), 4.17 (br s,
1H), 3.34-3.14 (m, 2H), 3.27 (s, 3H), 3.14 (s, 3H), 2.75 (d, J =
17.5 Hz, 1H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3):
170.38, 164.43, 145.64, 136.65, 134.35, 129.78 (2 ), 129.03
(2 ), 128.96 (2 ), 128.12 (2 ), 127.26, 106.67, 65.79, 56.36,
55.94, 43.30, 32.00, 30.55, 21.75.
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(3-benzyloxypropyl)-
piperidine-2,6-dione
Mp 79-82 C; IR (CHCl3) 2938, 2860, 1727, 1680,
1382, 1148, 737 cm-1; ESI-MS: C29H32NO5S m/z (%) = 91
(100), 181 (19), 398 (4), 506 (M++1, 18); HRMS (ESI, M++1)
1
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(3-hydroxypropyl)-
piperidine-2,6-dione
calcd for C29H32NO5S 506.2002, found 506.2001; H NMR
(400 MHz, CDCl3): 7.43 (d, J = 8.3 Hz, 2H), 7.35-7.23 (m,
12H), 5.06 (d, J = 14.0 Hz, 1H), 4.85 (d, J = 14.0 Hz, 1H),
Mp 97-100 C; IR (CHCl3) 3390, 2941, 2868, 1727,

1,8-Diazabicyclo[5.4.0]undec-7-ene in Debromination of
J. Chin. Chem. Soc., Vol. 49, No. 6, 2002 1021
-Bromo- -p-toluenesulfonylglutarimide
4.43 (s, 2H), 3.94 (br s, 1H), 3.48 (dd, J = 6.0, 18.1 Hz, 1H),
3.46-3.37 (m, 2H), 3.02-2.98 (m, 1H), 2.70 (d, J = 18.1 Hz,
1H), 2.42 (s, 3H), 1.55-1.35 (m, 4H); 13C NMR (100 MHz,
CDCl3): 170.39, 164.32, 145.68, 138.13, 136.42, 134.59,
129.81 (3 ), 128.94 (4 ), 128.63 (2 ), 128.44 (2 ), 128.35,
127.71, 127.48, 73.09, 70.75, 69.12, 43.36, 34.33, 30.99,
28.75, 26.94, 21.76; Anal. Calcd for C29H31NO5S C, 68.89;
H, 6.18. Found C, 69.16; H, 6.03.
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(2-t-butyldimethyl-
silyloxybutyl)piperidine-2,6-dione
Mp 58-60 C; IR (CHCl3) 2954, 2929, 1728, 1682,
1382, 775 cm-1; HRMS (EI, M+) calcd for C29H41NO5SSi
543.2476, found 543.2481; 1H NMR (400 MHz, CDCl3):
7.47-7.43 (m, 2H), 7.33-7.24 (m, 7H), 5.06 (dd, J = 4.6, 14.0
Hz, 1H), 4.84 (dd, J = 3.2, 14.0 Hz, 1H), 3.89 (br s, 1H),
3.73-3.69 (m, 1H), 3.50-3.44 (m, 1H), 3.02-2.94 (m, 1H),
2.69 (d, J = 18.1 Hz, 1H), 2.42 (s, 3H), 1.38-1.31 (m, 4H),
1.08-1.02 (m, 3H), 0.87-0.82 (m, 9H), 0.02-0.50 (m, 6H).
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(4-benzyloxybutyl)-
piperidine-2,6-dione
Mp 67-70 C; IR (CHCl3) 2938, 2860, 1728, 1682,
1383, 750 cm-1; ESI-MS: C30H34NO5S m/z (%) = 91 (100),
181 (11), 520 (M++1, 5); HRMS (ESI, M++1) calcd for
C30H34NO5S 520.2159, found 520.2158; 1H NMR (400 MHz,
CDCl3): 7.45 (d, J = 8.3 Hz, 2H), 7.34-7.23 (m, 12H), 5.06
(d, J = 14.0 Hz, 1H), 4.85 (d, J = 14.0 Hz, 1H), 4.44 (s, 2H),
3.90 (br s, 1H), 3.47 (dd, J = 6.1, 18.1 Hz, 1H), 3.39 (t, J = 5.9
Hz, 2H), 2.97-2.95 (m, 1H), 2.69 (d, J = 18.1 Hz, 1H), 2.42 (s,
3H), 1.55-1.35 (m, 6H); 13C NMR (100 MHz, CDCl3):
170.41, 164.32, 145.68, 138.39, 136.44, 134.58, 129.81 (3 ),
128.94, 128.66 (3 ), 128.40 (2 ), 128.35, 127.67 (2 ),
127.61, 127.50, 72.95, 70.73, 69.54, 43.32, 34.31, 33.80,
29.16, 28.80, 23.47, 21.74; Anal. Calcd for C30H33NO5S C,
69.34; H, 6.40. Found C, 69.39; H, 6.38.
1-Benzyl-3-(4-methylphenylsulfonyl)-4-phenylpiperidine-
2,6-dione
Mp 166-168 C; IR (CHCl3) 2977, 2361, 1724, 1678,
1382, 751 cm-1; HRMS (EI, M+) calcd for C25H23NO4S
433.1349, found 433.1359; 1H NMR (400 MHz, CDCl3):
7.53 (d, J = 8.3 Hz, 2H), 7.28-7.15 (m, 10H), 6.96-6.94 (m,
2H), 5.09 (d, J = 13.9 Hz, 1H), 4.91 (d, J = 13.9 Hz, 1H), 4.32
(d, J = 6.8 Hz, 1H), 4.20 (t, J = 1.5 Hz, 1H), 3.74 (dd, J = 6.9,
18.3 Hz, 1H), 3.05 (dt, J = 1.8, 18.3 Hz, 1H), 2.43 (s, 3H); 13C
NMR (100 MHz, CDCl3): 170.34, 164.12, 145.89, 139.51,
136.05, 134.32, 129.88 (2 ), 129.34 (3 ), 129.04 (3 ),
128.92, 128.28 (2 ), 127.93, 127.55, 126.62, 71.66, 43.44,
34.95, 33.55, 21.76.
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(4-fluorophenyl)-
piperidine-2,6-dione
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(5-benzyloxypentyl)-
piperidine-2,6-dione
Mp 185-187 C; IR (CHCl3) 2976, 2362, 1721, 1676,
1380, 744 cm-1; HRMS (EI, M+) calcd for C25H22NO4SF
451.1255, found 451.1249; 1H NMR (400 MHz, CDCl3):
7.54 (d, J = 8.3 Hz, 2H), 7.30-7.24 (m, 7H), 6.92-6.82 (m,
4H), 5.08 (d, J = 13.8 Hz, 1H), 4.92 (d, J = 13.8 Hz, 1H), 4.31
(d, J = 6.7 Hz, 1H), 4.17 (br s, 1H), 3.74 (dd, J = 6.9, 18.2 Hz,
1H), 3.01 (d, J = 18.2 Hz, 1H), 2.43 (s, 3H); 13C NMR (100
MHz, CDCl3): 170.10, 164.00, 160.87, 146.00, 135.99,
135.31, 134.24, 129.92 (2 ), 129.05 (3 ), 129.04 (3 ),
128.40, 128.32 (2 ), 127.68, 127.68, 71.64, 43.45, 35.07,
33.02, 21.77.
Mp 51-53 C; IR (CHCl3) 2936, 2858, 1727, 1681,
1382, 736 cm-1; HRMS (EI, M+) calcd for C31H35NO5S
533.2238, found 533.2239; 1H NMR (400 MHz, CDCl3):
7.44 (d, J = 8.3 Hz, 2H), 7.33-7.23 (m, 12H), 5.06 (d, J = 14.0
Hz, 1H), 4.85 (d, J = 14.0 Hz, 1H), 4.46 (s, 2H), 3.88 (br s,
1H), 3.47 (dd, J = 6.1, 18.1 Hz, 1H), 3.40 (t, J = 6.4 Hz, 2H),
2.98-2.95 (m, 1H), 2.68 (d, J = 18.1 Hz, 1H), 2.42 (s, 3H),
1.54-1.27 (m, 8H).
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(2-hydroxybutyl)-
piperidine-2,6-dione
Viscous gum; IR (CHCl3) 3353, 2944, 2354, 1715,
1681, 1381, 764 cm-1; HRMS (EI, M+) calcd for C23H27NO5S
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(4-nitrophenyl)-
piperidine-2,6-dione
1
429.1611, found 429.1613; H NMR (400 MHz, CDCl3):
IR (CHCl3) 2930, 1724, 1680, 1380, 754 cm-1; HRMS
(EI, M+) calcd for C25H22N2O6S 478.1200, found 478.1203;
1H NMR (400 MHz, CDCl3): 8.00 (dd, J = 1.9, 6.9 Hz, 2H),
7.55 (d, J = 8.4 Hz, 2H), 7.33-7.23 (m, 7H), 7.09 (dd, J = 1.9,
6.9 Hz, 2H), 5.08 (d, J = 13.7 Hz, 1H), 4.93 (d, J = 13.7 Hz,
1H), 4.43 (d, J = 6.8 Hz, 1H), 4.17 (t, J = 1.8 Hz, 1H), 3.79
7.45 (d, J = 8.2 Hz, 2H), 7.35-7.24 (m, 7H), 5.06 (dd, J = 2.2,
14.0 Hz, 1H), 4.85 (dd, J = 2.5, 14.0 Hz, 1H), 3.94-3.90 (m,
1H), 3.73-3.67 (m, 1H), 3.48 (dd, J = 6.1, 18.1 Hz, 1H), 3.02-
2.90 (m, 1H), 2.70 (d, J = 18.1 Hz, 1H), 2.42 (s, 3H), 1.65-
1.34 (m, 5H), 1.18 (d, J = 6.2 Hz, 3H).

1022 J. Chin. Chem. Soc., Vol. 49, No. 6, 2002
Chang et al.
(dd, J = 6.9, 18.3 Hz, 1H), 3.04 (dt, J = 1.8, 18.3 Hz, 1H), 2.44
(s, 3H); 13C NMR (100 MHz, CDCl3): 169.39, 163.58,
147.44, 146.48, 146.32, 135.82, 133.93, 130.02, 129.16,
129.11 (3 ), 128.39 (3 ), 127.92, 127.78 (3 ), 124.46, 70.91,
43.55, 34.71, 33.71, 21.80.
1386, 756 cm-1; HRMS (EI, M+) calcd for C24H28N2O6S
472.1670, found 472.1672; 1H NMR (400 MHz, CDCl3):
7.73 (d, J = 8.2 Hz, 4/5H), 7.51 (J = 8.1 Hz, 6/5H), 7.33-7.20
(m, 7H), 5.54-5.50 (m, 1H), 5.02 (d, J = 14.0 Hz, 1H), 4.91-
4.77 (m, 2H), 4.39-4.32 (m, 3/5H), 4.13-4.11 (m, 2/5H),
3.07-2.92 (m, 1H), 2.41 (s, 3H), 2.28-2.18 (m, 1H), 1.44 (br s,
9H).
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(4-methoxyphenyl)-
piperidine-2,6-dione
Mp 138-140 C; IR (CHCl3) 2958, 1727, 1678, 1382,
756 cm-1; HRMS (EI, M+) calcd for C26H25NO5S 463.1455,
found 463.1461; 1H NMR (400 MHz, CDCl3): 7.53 (d, J =
8.2 Hz, 2H), 7.28-7.24 (m, 7H), 6.85 (d, J = 8.7 Hz, 2H), 6.69
(d, J = 8.5 Hz, 2H), 5.09 (d, J = 13.9 Hz, 1H), 4.90 (d, J = 13.9
Hz, 1H), 4.27 (d, J = 6.6 Hz, 1H), 4.18 (br s, 1H), 3.77-3.69
(m, 1H), 3.72 (s, 3H), 3.02 (d, J = 18.2 Hz, 1H), 2.43 (s, 3H);
13C NMR (100 MHz, CDCl3): 170.48, 164.20, 159.10,
145.85, 136.12, 134.41, 131.39, 129.88 (3 ), 129.03 (3 ),
128.96 (3 ), 128.29, 127.74 (2 ), 127.54, 71.86, 55.29,
43.41, 35.15, 32.88, 21.76.
1-Benzyl-3-(4-methylphenylsulfonyl)-5-phthalimidopiper-
idine-2,6-dione
Mp 238-240 C; IR (CHCl3) 2927, 2360, 1720, 1686,
1390, 754 cm-1; HRMS (EI, M+) calcd for C27H22N2O6S
502.1200, found 502.1211; 1H NMR (400 MHz, CDCl3)
7.90-7.74 (m, 14/3H), 7.50 (d, J = 8.2 Hz, 4/3H), 7.34-7.21
(m, 7H), 5.82 (dd, J = 6.4, 13.1 Hz, 2/3H), 5.05-4.97 (m,
1/3H), 5.05 (d, J = 14.1 Hz, 2/3H), 4.97 (d, J = 14.1 Hz,
2/3H), 4.95 (d, J = 14.1 Hz, 1/3H), 4.85 (d, J = 14.1 Hz,
1/3H), 4.33 (dd, J = 5.2, 13.7 Hz, 1/3H), 4.21 (dd, J = 1.3, 6.0
Hz, 2/3H), 3.25-2.74 (m, 2H), 2.44 (br s, 3H).
1-Benzyl-3-(4-methylphenylsulfonyl)-4-(3,4-dimethoxy-
phenyl)piperidine-2,6-dione
Chlorination from N-benzyl 4-hydroxy-substituted
-bromo- -p-toluenesulfonylglutarimides B to N-benzyl
4-chloro-substituted -bromo- -p-toluenesulfonylglutar-
imide B1, B2 and B3 using PPh3/CCl4 system (entry 4,
5, 6 in Table 1)
Mp 170-172 C; IR (CHCl3) 2927, 2361, 1726, 1678,
1320, 754 cm-1; HRMS (EI, M+) calcd for C27H27NO6S
493.1560, found 493.1571; 1H NMR (400 MHz, CDCl3):
7.54 (d, J = 8.2 Hz, 2H), 7.32-7.24 (m, 7H), 6.61 (d, J = 7.9
Hz, 1H), 6.45 (s, 1H), 6.43 (d, J = 7.9 Hz, 1H), 5.07 (d, J =
13.8 Hz, 1H), 4.90 (d, J = 13.8 Hz, 1H), 4.27 (d, J = 6.7 Hz,
1H), 4.21 (br s, 1H), 3.79 (s, 3H), 3.73 (dd, J = 6.9, 18.2 Hz,
1H), 3.59 (s, 3H), 3.04 (d, J = 18.2 Hz, 1H), 2.43 (s, 3H); 13C
NMR (100 MHz, CDCl3): 170.47, 164.20, 149.53, 145.91,
136.09, 134.33, 131.99, 129.89 (3 ), 129.07, 129.04 (2 ),
128.31 (3 ), 127.59, 118.54, 111.63, 109.84, 71.78, 55.92,
55.76, 43.48, 35.32, 33.20, 21.77.
Alcohol (1.0 mmol) was added to a solution of
triphenylphosphine (1.5 mmol) and carbon tetrabromide (1.3
mmol) in methylene chloride (20 mL). The reaction mixture
was stirred at room temperature for 4 h, then quenched with
saturated aqueous ammonium chloride solution (5 mL) and
concentrated. The residue was diluted with water (15 mL)
and extracted with ethyl acetate (3 30 mL). The combined
organic layers were washed with brine (2 20 mL), dried
over anhydrous magnesium sulfate, filtered and evaporated.
Purification of the crude product by column chromatography
on silica gel with hexane/ethyl acetate produced B1, B2 and
B3 in 50-61% yield.
1-Benzyl-3-(4-methylphenylsulfonyl)-5-methylpiperidine-
2,6-dione
IR (CHCl3) 3033, 1726, 1677, 1320, 755 cm-1; HRMS
(EI, M+) calcd for C20H21NO4S 371.1192, found 371.1185; 1H
NMR (300 MHz, CDCl3): 7.83 (d, J = 8.4 Hz, 1/2H), 7.54 (J
= 8.1 Hz, 3/2H), 7.35-7.22 (m, 7H), 5.03 (d, J = 14.1 Hz,
3/4H), 4.90 (d, J = 14.1 Hz, 1H), 4.83 (d, J = 14.1 Hz, 1/4H),
4.23 (dd, J = 5.1, 12.3 Hz, 1/4H), 4.10 (dd, J = 2.1, 6.0 Hz,
3/4H), 3.42-3.18 (m, 1H), 2.95-2.87 (m, 1H), 2.44 (s, 3H),
2.13-2.00 (m, 1H), 1.36 (d, J = 6.6 Hz, 3H).
Mesylation from N-benzyl 4-hydroxy-substituted
-bromo- -p-toluenesulfonyl glutarimide B to N-benzyl
4-mesylate-substituted -bromo- -p-toluenesulfonyl
glutarimide B4 (No. 10 in Table 1)
Methanesulfonyl chloride (1 mL) was added to a sol u -
tion of secondary alcohol (1.0 mmol) in pyridine (5 mL) and
stirred for 5 h at room temperature. The resulting mixture was
poured into 0.1N hydrogen chloride (10 mL) and extracted
with ethyl acetate (3 20 mL). The combined organic laye r s
were dried by magnesium sulfate, filtered and evaporated.
Purification of the crude product by column chromatography
1-Benzyl- -(4-methylphenylsulfonyl)-5-t-butoxycarbonyl-
aminopiperidine-2,6-dione
Viscous gum; IR (CHCl3) 2930, 2362, 1729, 1667,

1,8-Diazabicyclo[5.4.0]undec-7-ene in Debromination of
J. Chin. Chem. Soc., Vol. 49, No. 6, 2002 1023
-Bromo- -p-toluenesulfonylglutarimide
on silica gel with hexane/ethyl acetate produced B4 in 48%
2.97-2.94 (m, 1H), 2.68 (dd, J = 1.5, 18.1 Hz, 1H), 2.42 (s,
3H), 1.70-1.20 (m, 8H); 13C NMR (100 MHz, CDCl3):
170.36, 164.31, 145.76, 136.41, 134.55, 129.85 (2 ), 128.96
(2 ), 128.71 (2 ), 128.37 (2 ), 127.56, 70.79, 44.64, 43.35,
34.28, 33.87, 32.07, 28.72, 26.32, 25.87, 21.77. The structure
of chloride C3 was also determined by single-crystal X-ray
analysis.
yield.
Debromination (then cyclization or elimination) from
N-benzyl 4-substituted -bromo- -p-toluenesulfonyl-
glutarimides B1, B2, B3, B4 to N-benzyl bicyclic
-p-toluenesulfonylglutarimides C1, C2, C3, C4 using
DBU/THF system
The procedure was the same as mentioned above for the
procedure of debromination.
C4: 1-Benzyl-3-(4-methylphenylsulfonyl)-4-(exo 1- or
endo 2-butenyl)piperidine-2,6-dione
Spectral data of C1~C4:
Yield 51%; viscous oil; IR (CHCl3) 1729, 1677 cm-1;
HRMS (EI, M+) calcd for C23H25NO4S 411.1506, found
411.1510; 1H NMR (400 MHz, CDCl3): 7.46-7.43 (m, 2H),
7.33-7.24 (m, 7H), 5.07 (d, J = 14.1 Hz, 1H), 4.85 (d, J = 14.0
Hz, 1H), 3.92 (br s, 1H), 3.50-3.44 (m, 1H), 2.99-2.97 (m,
1H), 2.71-2.66 (m, 1H), 2.42 (br s, 3H), 2.03-1.98 (m, 2H),
1.63-1.55 (m, 3H), 1.45-1.35 (m, 2H).
C1: 1-Benzyl-7a-(4-methylphenylsulfonyl)hexahydro[2]-
pyridine-1,3-dione
Yield 57%; viscous oil; IR (CHCl3) 2960, 1725, 1681,
1315, 758 cm-1; HRMS (EI, M+) calcd for C22H23NO4S
397.1349, found 397.1348; 1H NMR (400 MHz, CDCl3):
7.35-7.24 (m, 7H), 7.18 (d, J = 8.3 Hz, 2H), 5.16 (d, J = 14.0
Hz, 1H), 4.85 (d, J = 14.0 Hz, 1H), 3.41 (dd, J = 6.4, 18.1 Hz,
1H), 3.24-3.21 (m, 1H), 2.81 (dd, J = 1.6, 18.1 Hz, 1H), 2.39
(s, 3H), 2.24-2.14 (m, 3H), 1.71-1.40 (m, 3H); 13C NMR (100
MHz, CDCl3): 170.61, 168.02, 145.51, 136.67, 133.18,
130.09, 129.33 (2 ), 128.63 (2 ), 128.36 (2 ), 127.45 (2 ),
75.67, 43.93, 34.96, 34.76, 33.79, 31.77, 21.73, 21.03; Anal.
Calcd for C22H23NO4S: C, 66.48; H, 5.83. Found: C, 66.52; H,
5.88.
ACKNOWLEDGEMENT
The authors would like to thank the National Science
Council of the Republic of China for financial support.
Received May 8, 2002.
C2: 1-Benzyl-8a-(4-methylphenylsulfonyl)hexahydroiso-
quinoline-1,3-dione
Key Words
1,8-Diazabicyclo[5.4.0]undec-7-ene;
Debromination; N-Bromosuccinimide;
Bromination; Glutarimide.
Yield 66%; mp 46-48 C; IR (CHCl3) 2938, 1725, 1674,
1380, 1180, 756 cm-1; HRMS (EI, M+) calcd for C23H25NO4S
411.1506, found 411.1514; 1H NMR (400 MHz, CDCl3):
7.43-7.15 (m, 9H), 5.25 (d, J = 13.9 Hz, 1H), 4.86 (d, J = 13.9
Hz, 1H), 3.76 (dd, J = 6.0, 18.3 Hz, 1H), 2.80-2.77 (m, 1H),
2.56 (d, J = 18.3 Hz, 1H), 2.38 (s, 3H), 1.90-1.80 (m, 2H),
1.62-1.48 (m, 3H), 1.27-1.13 (m, 2H), 0.96-0.91 (m, 1H); 13C
NMR (100 MHz, CDCl3): 171.10, 166.99, 145.58, 136.70,
131.48, 130.56 (3 ), 129.24 (2 ), 129.06 (2 ), 128.29,
127.44, 72.03, 43.89, 37.64, 31.99, 31.02, 30.49, 24.06,
22.28, 21.68.
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