Ring opening of dihydro-2-pyridones and intramolecular Diels-Alder reactions

Article abstract of DOI:10.1016/j.tet.2011.11.060

A new ring-opening reaction of 5,6-dihydro-2-pyridones was discovered. Compounds 1 and 7 were converted to the dienoic amides 2 and 8 by reaction with sodium hydride at room temperature. N-Allylation of compounds 2 and 8 followed by IMDA reaction provided

Full text of DOI:10.1016/j.tet.2011.11.060

Tetrahedron 68 (2012) 1185e1191
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Ring opening of dihydro-2-pyridones and intramolecular DielseAlder reactions
*
Shang-Shing P. Chou , Chien-Jung J. Wu
Department of Chemistry, Fu Jen Catholic University, 510 Chung-Cheng Rd., Hsin-Chuang, New Taipei City 24205, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 August 2011
Received in revised form 11 October 2011
Accepted 22 November 2011
Available online 27 November 2011
A new ring-opening reaction of 5,6-dihydro-2-pyridones was discovered. Compounds 1 and 7 were
converted to the dienoic amides 2 and 8 by reaction with sodium hydride at room temperature. N-Al-
lylation of compounds 2 and 8 followed by IMDA reaction provided the cis-fused hexahydro-1-indolones
5 and 10, respectively. Treatment of compounds 5 and 10 with DBU in refluxing ethyl acetate gave the
conjugated products 6 and 11, which were further transformed to the amides 12e15. The phenylthio
group of compound 11 was substituted by a methyl group to give product 16.
Keywords:
Ó 2011 Elsevier Ltd. All rights reserved.
Dihydro-2-pyridones
Aza-DielseAlder reaction
Intramolecular DielseAlder reactions
Isoindolones
SPh
SPh
SPh
3
1. Introduction
SPh
_
_
R
O
5
base
R-X
Piperidine derivatives are widely present in many natural and
synthetic compounds with various biological activities.1 Many
synthetic methods have been developed,2 among them the aza-
DielseAlder reaction is one of the most versatile routes.3 We have
previously developed a new aza-DielseAlder reaction of thio-
substituted 3-sulfolenes with p-toluenesulfonyl isocyanate (PTSI)
to synthesize sulfur-substituted piperidine derivatives,4 and have
reported some of their synthetic applications.5
In continuation with our previous studies, we intended to
deprotonate compound 1 at C-5 to generate a carbanion, which
could then react with an electrophile at C-3 (Scheme 1, path A).
However, the carbanion underwent an unexpected ring-opening
reaction (path B) and then reacted with the electrophile at the ni-
trogen atom. To the best of knowledge, this ring-opening process
has never been reported for the 5,6-dihydro-2-pyridones. We now
describe the use of this method in combination with the intra-
molecular DielseAlder reaction (IMDA)6 to construct the hexahy-
dro-1-isoindolones.7 Muironolide A, isolated from the Phorbas sp.
of marine sponge, has an uncommon isoindolone polyketide
macrolide,8 and the isoindolone core has very recently been con-
structed by IMDA.9 Isoindolones have also been reported as im-
portant intermediates for the synthesis of natural products
jamtine10 and kainic acids.11
path A
N
Ts
O
N
Ts
O
N
Ts
N
Ts
O
1
path B
SPh
SPh
R-X
_
N
Ts
RN
Ts
O
O
Scheme 1.
2. Results and discussion
Treatment of compound 14 with NaH (3 equiv) in CH2Cl2 at room
temperature followed by workup with saturated ammonium
chloride provided the ring-opening product 2 in good yield (Table 1,
entry 1). However, the reaction was quite slow, requiring 3 days to
complete, probably due to the low solubility of NaH in CH2Cl2. So
we carried out the reaction in refluxing CH2Cl2 (entry 2), and the
reaction was complete in one day giving a similar yield of product 2.
The reaction of compound 1 with NaH in THF at reflux (entry 3) or
at room temperature (entry 4) only gave unidentified mixture of
products. The reaction in CH2Cl2 proceeded much faster if 20 equiv
of NaH was used (entry 5). Furthermore, the reaction was even
faster when carried out with NaH (3 equiv) in N,N-dime-
thylformamide (DMF) at room temperature to give very good yield
* Corresponding author. Tel.: þ886 2 29052474; fax: þ886 2 29023209; e-mail
address: chem1004@mails.fju.edu.tw (S.-S.P. Chou).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.060

1186
S.-S.P. Chou, C.-J.J. Wu / Tetrahedron 68 (2012) 1185e1191
Table 1
Ring-opening of compound 1 to give product 2
SPh
SPh
1) NaH
2) sat'd NH4Cl
N
Ts
O
HN
Ts
O
(Table 1)
2
1
Entry
NaH (equiv)
Reaction conditions
Yield (%)
1
2
3
4
5
6
7
3
3
3
3
20
3
CH2Cl2, rt, 3 days
CH2Cl2, reflux, 1 days
THF, reflux, 3 days
THF, rt, 3 days
CH2Cl2, rt, 3 h
DMF, rt, 2 h
70
67
NDa
NDa
70
Fig. 2. X-ray crystal structure of compound 5.
85
87
3
CH2Cl2/DMF (4:1), rt, 2 h
a
shows the cis ring fusion. It was reported in the literature that the
IMDA of N-allyl 2(E),4-hexadienoic amides in toluene usually gave
a mixture of cis- and trans-fused products.14 However, the specific
An unidentified mixture of products was obtained.
of product 2 (entry 6). Since DMF was rather difficult to remove, we
found that a mixture of CH2Cl2 and DMF (4:1) was the best solvent
system for the reaction, and an excellent yield of product 2 was
obtained (entry 7). The structure of compound 2 was proven by X-
ray crystallography (Fig. 1).12 Some 2,4-hexadienoic amides were
found to exhibit potent antimicrobial activities.13
formation of the E-configuration around the
a,b-double bond of
compound 4 (cis configuration based on the carbon skeleton)
strongly favors the exo transition state,6 which led only to the cis
product 5. This is a very important improvement over the literature
methods.9,14
SPh
SPh
SPh
O
H
Br (3 eq)
NaHCO3 (1.2 eq)
tol, reflux
N
Ts
K2CO3 (3 eq)
DMF, rt, 18 h
HN
Ts
O
N
O
H
Ts
5 (91%)
4 (65%)
2
We then investigated the reaction conditions for converting
compound 5 to the conjugated product 6. Using Et3N as the base
and ethyl acetate as the solvent, the reaction did not proceed either
at room temperature or at reflux. A very good yield of the conju-
gated product 6 was obtained when compound 5 was refluxed with
5 equiv of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in ethyl ace-
tate for 24 h. The structure of compound 6 was proven by X-ray
crystallography (Fig. 3).12
SPh
SPh
O
O
H
H
Fig. 1. X-ray crystal structure of compound 2.
DBU (5 eq)
N
Ts
N
Ts
EtOAc, reflux, 24 h
We then investigated the reaction conditions for N-methylation
of compound 2. Treatment of a mixture of compound 2 and methyl
iodide (3 equiv) in CH2Cl2 with NaH (3 equiv) at room temperature
for 18 h only gave the recovered starting material 2. We thought
this might be due to the low solubility of NaH in CH2Cl2, so we used
a mixture of CH2Cl2 and DMF (4:1) as the solvent, but an un-
identified mixture of products was obtained. Since the NeH of
compound 2 is rather acidic, we then used K2CO3 as the base, and
the reaction proceed well in DMF at room temperature to give a fair
yield of product 3.
6 (89%)
5
SPh
SPh
K2CO3 (3 eq), MeI (3 eq)
DMF, rt, 4 h
HN
Ts
O
MeN
Ts
3 (63%)
O
2
Compound 2 was similarly N-allylated to give product 4, which
underwent the intramolecular DielseAlder reaction by refluxing in
toluene in the presence of 1.2 equiv of NaHCO3 to afford the bicyclic
product 5 in excellent yield. It should be noted that without the
NaHCO3 the yield was lowered, probably because the diene moiety
in compound 4 was quite sensitive to acid. The structure of com-
pound 5 was proven by X-ray crystallography (Fig. 2),12 which
Fig. 3. X-ray crystal structure of compound 6.

S.-S.P. Chou, C.-J.J. Wu / Tetrahedron 68 (2012) 1185e1191
1187
We have also carried out similar transformations of the C-6
methylated dihydropyridone to the bicyclic compound 11
7
(Scheme 2). Treatment of compound 7 with NaH (3 equiv) in
CH2Cl2/DMF (4:1) at room temperature for 1 h gave the ring-
opening product 8, the 1H NMR of which showed that the C]C
bond at the g,d-position has the trans configuration. Reaction of
compound 8 with allyl bromide and K2CO3 afforded the N-allyla-
tion product 9. Intramolecular DielseAlder reaction of compound 9
proceeded well in refluxing toluene in the presence of K2CO3 to give
the bicyclic product 10 in good yield. The structure of compound 10
was proven by X-ray crystallography (Fig. 4).12 Apparently, the
IMDA reaction proceeded through the exo transition state and with
retention of configuration of the C]C bond of the diene moiety of
compound 9. Compound 10 was further converted to its conjugated
isomer 11 by treatment with DBU in refluxing ethyl acetate. The
structure of compound 11 was also confirmed by X-ray crystallog-
raphy (Fig. 5).12
SPh
SPh
SPh
Fig. 5. X-ray crystal structure of compound 11.
Br (3 eq)
NaH (3 eq)
K2CO3 (3 eq)
DMF, rt, 18 h
CH2Cl2/DMF
(4:1), rt, 1 h
N
Ts
O
HN
Ts
O
N
O
Ts
Table 2
Synthesis of compounds 14 and 15 from compounds 12 and 13
8 (89%)
9 (70%)
7
Entry
R0eX
R0
Product (% yield)
SPh
SPh
O
O
H
NaHCO3 (1.2 eq)
tol, reflux, 18 h
DBU (5 eq)
1
2
3
4
5
MeI
EtI
AllyleBr
BnBr
BzCl
CH3
14a (82)
14b (60)
14c (66)
14d (54)
14e (75)
15a (92)
N
Ts
N
Ts
CH3CH2
CH2]CHCH2
PhCH2
15b (81)
15c (68)
15d (64)
15e (79)
EtOAc, reflux, 24 h
H
H
10 (85%)
11 (78%)
PhCO
Scheme 2.
Compound 11 was effectively converted to the methyl-
substituted product 16 by treatment with Me2CuLi in the pres-
ence of BF3$Et2O in THF.5f
SPh
O
O
MeLi (7 eq), CuI (3.5 eq), THF
N
Ts
N
Ts
BF3 Et2O (5.5 eq), -78 oC to rt, 4 h
.
H
H
16 (69%)
11
3. Conclusions
Fig. 4. X-ray crystal structure of compound 10.
We have discovered a new ring-opening reaction of 5,6-dihydro-
2-pyridones 1 and 7 to the corresponding dienoic amides 2 and 8 by
reaction with sodium hydride in a mixture of CH2Cl2 and DMF at
room temperature. N-Allylation of compounds 2 and 8 followed by
IMDA reaction provided the cis-fused hexahydro-1-indolones 5 and
10, respectively. Compounds 5 and 10 upon treatment with DBU in
refluxing ethyl acetate were further converted to the conjugated
The tosyl group of compounds 6 and 11 were cleaved by
Bu3SnH/AIBN15 to give the secondary amides 12 and 13, re-
spectively. Deprotonation of amides 12 and 13 with NaH in THF
followed by the reaction with an electrophile gave the tertiary
amides 14 and 15, respectively (Table 2).
SPh
SPh
SPh
O
Bu3SnH (1.2 eq)
AIBN (0.6 eq)
O
O
1) NaH (1.5 eq), THF
rt, 30 min
N
Ts
NH
N
R'
tol, reflux, 30 min
2) R'X (3 eq), rt, 2 h
R
R
R
H
H
H
6, R = H
11, R = Me
12, R = H (74%)
13, R = Me (70%)
14, R = H
15, R = Me

1188
S.-S.P. Chou, C.-J.J. Wu / Tetrahedron 68 (2012) 1185e1191
products 6 and 11, which could be transformed to the amides 12e15.
The phenylthio group of compound 11 was also successfully
substituted by a methyl group to give product 16.
(50 mL) and water (30 mL). The organic solution was washed with
water (3ꢀ30 mL) and dried (MgSO4). The solvent was removed
under vacuum and the residue was purified by column chroma-
tography using ethyl acetate/hexane (1:4) as eluent to give crude
product 4, which was further recrystallized from CH2Cl2/hexane to
give purified product 4 (360 mg, 65%) as a white solid: mp
4. Experimental section
4.1. General
93.8e94.4 ꢁC; 1H NMR (CDCl3)
d
7.57 (2H, d, J¼8.4 Hz), 7.54e7.44
(5H, m), 7.31 (1H, dd, J¼17.4, 10.8 Hz), 7.23 (2H, d, J¼8.4 Hz), 5.98
(1H, d, J¼17.4 Hz), 5.74 (1H, s), 5.72e5.61 (1H, m), 5.47 (1H, d,
J¼10.8 Hz), 5.06e4.99 (2H, m), 4.27 (2H, d, J¼5.4 Hz), 2.40 (3H, s);
Melting points were determined with a SMP3 melting appara-
tus. Infrared spectra were recorded with a PerkineElmer 1600 or
100 series FTIR spectrometer using the ATR (attenuated total re-
flectance) mode. 1H and 13C NMR spectra were recorded on a Bruker
Avance 300 spectrometer operating at 300 and at 75 MHz, re-
13C NMR (CDCl3)
d 163.9, 157.2, 144.3, 136.7, 135.7, 132.7, 132.5,
129.9, 129.4 (ꢀ2), 129.1, 127.8, 121.5, 117.8, 113.2, 48.5, 21.5; IR (ATR,
film) v: 3058, 3022, 2925, 2851, 1738, 1669, 1356, 1169, 1089 cmꢂ1
;
spectively. Chemical shifts (
d
) are reported in parts per million
FABMS (rel intensity) m/z 400 (MþH, 13), 244 (13), 190 (14), 189
(100), 155 (17), 128 (11), 91 (52), 81 (37), 69 (59); Exact mass calcd
for C21H22NO3S2 m/z 400.1041; FABeHRMS m/z 400.1039.
(ppm) and the coupling constants (J) are given in Hertz. High res-
olution mass spectra (HRMS) were measured with a mass spec-
trometer Finnigan/Thermo Quest MAT 95XL. X-ray crystal
structures were obtained with an EnrafeNonius FR-590 diffrac-
tometer (CAD4, Kappa CCD). Column chromatographic purifica-
4.1.4. cis-7-(Phenylthio)-2-tosyl-2,3,3a,4,5,7a-hexahydro-1H-iso-
indol-1-one (5). A mixture of compound 4 (100 mg, 0.25 mmol)
and NaHCO3 (25 mg, 0.3 mmol) in toluene (10 mL) was heated
under nitrogen at reflux for 18 h. The solvent was then evaporated
under vacuum, and the residue was purified by column chroma-
tography using ethyl acetate/hexane (1:4) as eluent to give crude
product 5, which was further recrystallized from CH2Cl2/hexane to
give purified product 5 (91 mg, 91%) as a white solid: mp
tions were performed using Merck silica gel 60 (40e60 mm).
4.1.1. (E)-3-(Phenylthio)-N-tosylpenta-2,4-dienamide (2). To a solu-
tion of compound 1 (500 mg, 1.39 mmol) in CH2Cl2 (8 mL) and DMF
(2 mL) at room temperature under nitrogen was added NaH (50% in
oil dispersion, 100 mg, 4.17 mmol). The mixture was stirred for 2 h,
and was then poured into saturated ammonium chloride (50 mL)
and CH2Cl2 (20 mL). The aqueous solution was extracted with
CH2Cl2 (3ꢀ20 mL), and the organic layers were combined and dried
(MgSO4). The solvent was removed under vacuum and the residue
was purified by column chromatography using ethyl acetate/hex-
ane (1:3) as eluent to give crude product 2, which was further
recrystallized from CH2Cl2/hexane to give purified product 2
(0.435 g, 87%) as a white solid: mp 134.3e135.6 ꢁC; 1H NMR (CDCl3)
130.4e131.6 ꢁC; 1H NMR (CDCl3)
(7H, m), 6.09 (1H, t, J¼3.6 Hz), 3.87 (1H, dd, J¼10.2, 6.0 Hz), 3.65
(1H, d, J¼10.2 Hz), 3.09 (1H, d, J¼6.6 Hz), 2.55e2.40 (4H, m),
2.21e2.11 (2H, m), 1.81e1.60 (1H, m), 1.40e1.21 (1H, m); 13C NMR
d
7.92 (2H, d, J¼8.1 Hz), 7.38e7.20
(CDCl3)
d 170.5, 145.0, 135.0, 134.1, 133.9, 131.2, 129.6, 129.0, 128.1,
127.1, 126.9, 50.4, 46.2, 32.1, 24.8, 23.2, 21.6; IR (ATR, film) v: 3061,
2956, 2923, 2871, 2855, 1733, 1597, 1334, 1164, 1091 cmꢂ1; FABMS
(rel intensity) m/z 400 (MþH, 12), 252 (12), 167 (20), 154 (32), 136
(58), 89 (76), 77 (100); Exact mass calcd for C21H22NO3S2 m/z
400.1041; FABeHRMS m/z 400.1046.
d
8.28 (1H, br s), 7.81 (2H, d, J¼8.4 Hz), 7.64 (1H, dd, J¼17.4, 10.8 Hz),
7.46 (2H, d, J¼8.4 Hz), 7.33e7.28 (5H, m), 6.02 (1H, d, J¼17.4 Hz),
5.52 (1H, d, J¼10.8 Hz), 5.00 (1H, s), 2.45 (3H, s); 13C NMR (CDCl3)
d
161.0, 159.9, 144.8, 135.6, 132.0, 130.1, 130.0, 129.5, 128.4, 128.2,
4.1.5. 7-(Phenylthio)-2-tosyl-2,3,3a,4,5,6-hexahydro-1H-isoindol-1-
one (6). A solution of compound 5 (0.5 g, 1.25 mmol) and DBU
(0.93 mL, 6.25 mmol) in ethyl acetate (30 mL) was stirred at room
temperature for 24 h, and was then poured into 10% H2SO4 (20 mL).
The aqueous solution was extracted with ethyl acetate (3ꢀ25 mL),
and the combined organic layer was dried (MgSO4) and evaporated
under vacuum. The residue was purified by column chromatography
using ethyl acetate/hexane (1:1) as eluent to give crude product 6,
which was further recrystallized from CH2Cl2/hexane to give purified
product 6 (445 mg, 89%) as a white solid: mp 176.1e177.2 ꢁC; 1H
122.2, 110.8, 21.6; IR (ATR, film) v: 3229, 3060, 2923, 2868, 1685,
1555, 1440, 1345, 1147, 1084 cmꢂ1; FABMS (rel intensity) m/z 360
(MþH, 100), 341 (13), 209 (17), 189 (26), 184 (35); Exact mass calcd
for C18H18O3NS2 m/z 360.0728; FABeHRMS m/z 360.0725.
4.1.2. (E)-N-Methyl-3-(phenylthio)-N-tosylpenta-2,4-dienamide
(3). To a mixture of compound 2 (100 mg, 0.28 mmol) and anhy-
drous K2CO3 (90 mg, 0.84 mmol) in DMF (2 mL) at room tempera-
ture under nitrogen was added methyl iodide (0.053 mL,
0.84 mmol). After stirring for 4 h, the reaction mixture was poured
into ethyl acetate (50 mL) and water (30 mL). The organic solution
was washed with water (3ꢀ30 mL), dried (MgSO4), and concen-
trated. The crude product was purified by column chromatography
using ethyl acetate/hexane (1:6) as eluent to give compound 3
NMR (CDCl3)
d
7.99 (2H, d, J¼8.1 Hz), 7.47 (2H, d, J¼6.9 Hz), 7.40e7.26
(5H, m), 4.18 (1H, t, J¼8.7 Hz), 3.27 (1H, t, J¼9.5 Hz), 2.91e2.77 (1H,
m), 2.43 (3H, s), 2.02e1.70 (4H, m), 1.59e1.35 (1H, m), 1.19e1.05 (1H,
m); 13C NMR (CDCl3)
d
165.0, 149.2, 144.7, 136.2, 135.5, 129.5, 129.4,
129.1, 128.9, 128.2, 122.0, 51.4, 36.2, 30.0, 25.8, 22.4, 21.6; IR (ATR,
film) v: 3055, 2956, 2925, 2868, 1709, 1610, 1356, 1169, 1084 cmꢂ1
;
(65.3 mg, 63%) as a yellow liquid: 1H NMR (CDCl3)
d
7.59e7.56 (2H,
m), 7.51e7.49 (3H, m), 7.42 (2H, d, J¼8.4 Hz), 7.25e7.21 (3H, m),
FABMS (rel intensity) m/z 400 (MþH, 6), 252 (12), 167 (20), 154 (32),
136(58), 89 (76), 77 (100); Exact mass calcd for C21H22NO3S2 m/z
400.1041; FABeHRMS m/z 400.1049.
6.00 (1H, d, J¼17.4 Hz), 5.99 (1H, s), 5.48 (1H, d, J¼11.1 Hz), 3.15 (3H,
s), 2.42 (3H, s); 13C NMR (CDCl3)
d 164.3, 156.2, 144.4, 136.2, 135.8,
132.5, 129.8 (ꢀ2), 129.7, 129.2, 127.0, 121.4, 114.1, 32.7, 21.5; IR (ATR,
film) v: 3061, 2989, 2952, 2918, 1667, 1551, 1359, 1210, 1163,
1088 cmꢂ1; EI-MS (rel intensity) m/z 373 (Mþ, 8), 252 (14), 218 (22),
202 (14), 189 (100), 128 (18), 109 (15), 91 (31); Exact mass calcd for
C19H19NO3S2 m/z 373.0806; HRMS m/z 373.0807.
4.1.6. (2E,4E)-3-(Phenylthio)-N-tosylhexa-2,4-dienamide
(8). To
a solution of compound 7 (500 mg, 1.34 mmol) in CH2Cl2 (8 mL)
and DMF (2 mL) at room temperature under nitrogen was added
NaH (50% in oil dispersion, 100 mg, 4.17 mmol). The mixture was
stirred for 1 h, and was then poured into saturated ammonium
chloride (50 mL) and CH2Cl2 (20 mL). The aqueous solution was
extracted with CH2Cl2 (3ꢀ20 mL), and the organic layers were
combined and dried (MgSO4). The solvent was removed under
vacuum and the residue was purified by column chromatography
using ethyl acetate/hexane (1:3) as eluent to give crude product 8,
4.1.3. (E)-N-Allyl-3-(phenylthio)-N-tosylpenta-2,4-dienamide (4). To
a mixture of compound 2 (500 mg, 1.39 mmol) and anhydrous
K2CO3 (450 mg, 4.17 mmol) in DMF (10 mL) at room temperature
under nitrogen was added allyl bromide (0.40 mL, 4.17 mmol). After
stirring for 18 h, the reaction mixture was poured into ethyl acetate

S.-S.P. Chou, C.-J.J. Wu / Tetrahedron 68 (2012) 1185e1191
1189
which was further recrystallized from CH2Cl2/hexane to give pu-
136.2, 135.7, 129.7, 129.5, 129.4, 129.1, 128.4, 121.5, 51.7, 36.9, 31.7,
26.9, 26.8, 21.7, 19.6; IR (ATR, film) v: 3055, 2957, 2918, 2874, 1710,
1609, 1359, 1169, 1084 cmꢂ1; EI-MS (rel intensity) m/z 413 (Mþ, 55),
349 (13), 348 (8), 258 (32), 240 (67), 216 (25), 201 (41),160 (53),109
(14), 91 (100), 84 (90), 65 (28); Exact mass calcd for C22H23NO3S2 m/
z 413.1119; EI-HRMS m/z 413.1128.
rified product 8 (44.5 mg, 89%) as a white solid: mp 160.1e161.4 ꢁC;
1H NMR (CDCl3)
d
7.85 (1H, br s), 7.79 (2H, d, J¼8.4 Hz), 7.46e7.34
(6H, m), 7.28 (2H, d, J¼8.4 Hz), 6.62 (1H, dq, J¼15.6, 6.9 Hz), 4.82
(1H, s), 2.41 (3H, s), 1.87 (3H, dd, J¼6.9, 1.5 Hz); 13C NMR (CDCl3)
d
161.1, 160.1, 144.7, 136.1, 135.9, 135.6, 130.0, 129.9, 129.4, 128.8,
128.2, 126.8, 108.7, 21.6, 18.8; IR (ATR, film) v: 3261, 3061, 2924,
2855, 1717, 1688, 1553, 1441, 1339, 1161, 1085 cmꢂ1; FABMS (rel
intensity) m/z 374 (MþH, 67), 341 (9), 203 (51), 172 (23), 155 (36),
147 (35), 137 (68); Exact mass calcd for C19H20O3NS2 m/z 374.0885;
FABeHRMS m/z 374.0890.
4.1.10. 7-(Phenylthio)-2,3,3a,4,5,6-hexahydro-1H-isoindol-1-one
(12). To a refluxing solution of compound 6 (500 mg, 1.25 mmol)
and Bu3SnH (0.40 mL, 1.50 mmol) in degassed toluene (50 mL) was
added in three portions of AIBN (123 mg, 0.75 mmol) every 30 min.
The reaction mixture was refluxed for another 30 min. The solvent
was then evaporated under vacuum, and the crude product was
purified by flash chromatography using ethyl acetate/hexane (1:1)
containing 5% Et3N as eluent to give compound 12 (227 mg, 74%) as
4.1.7. (2E,4E)-N-Allyl-3-(phenylthio)-N-tosylhexa-2,4-dienamide
(9). To a mixture of compound 8 (500 mg, 1.34 mmol) and anhy-
drous K2CO3 (435 mg, 4.02 mmol) in DMF (10 mL) at room tem-
perature under nitrogen was added allyl bromide (0.34 mL,
4.02 mmol). After stirring for 18 h, the reaction mixture was poured
into ethyl acetate (50 mL) and water (30 mL). The organic solution
was washed with water (3ꢀ30 mL), dried (MgSO4) and concen-
trated to give compound 9 (387 mg, 70%) as a light yellow solid: mp
a
d
white solid: 176.5e178.2 ꢁC (decomp.); 1H NMR (CDCl3)
7.60e7.51 (2H, m), 7.38e7.30 (3H, m), 6.75e6.60 (1H, m), 3.55 (1H,
t, J¼8.3 Hz), 3.02 (1H, t, J¼8.3 Hz), 2.98e2.85 (1H, m), 2.07e1.89
(3H, m), 1.88e1.73 (1H, m), 1.59e1.44 (1H, m), 1.27e1.14 (1H, m);
13C NMR (CDCl3)
d 171.3, 140.5, 136.1, 130.3, 128.8, 128.7, 124.9, 46.9,
93.7e94.2 ꢁC; 1H NMR (CDCl3)
d
7.57 (2H, d, J¼8.4 Hz), 7.52e7.44
39.2, 29.7, 26.3, 22.8; IR (ATR, film) v: 3210, 3066, 2930, 2863, 1683,
1626, 1439, 1248 cmꢂ1; EI-MS (rel intensity) m/z 245 (Mþ, 23), 203
(13), 149 (30), 136 (21), 129 (46), 125 (42), 91 (66), 77 (68), 71 (48),
57 (100); Exact mass calcd for C14H15NOS m/z 245.0874; EI-HRMS
m/z 245.0868.
(5H, m), 7.23 (2H, d, J¼8.4 Hz), 7.16 (1H, d, J¼15.8 Hz), 6.59 (1H, dq,
J¼15.8, 6.8 Hz), 5.73e5.60 (1H, m), 5.64 (1H, s), 5.06e5.00 (2H, m),
4.27 (2H, d, J¼5.4 Hz), 2.41 (3H, s), 1.88 (3H, dd, J¼1.2, 6.8 Hz); 13C
NMR (CDCl3)
d 164.1, 157.8, 144.3, 136.9, 135.8, 135.5, 132.9, 129.9
(ꢀ2), 129.6, 129.5, 127.9, 127.3, 117.8, 111.1, 48.5, 21.6, 18.9; IR (ATR,
film) v: 3057, 2959, 2918, 2874, 1741, 1668, 1548, 1354, 1167,
1088 cmꢂ1; FABMS (rel intensity) m/z 414 (MþH, 16), 258 (21), 203
(100), 191 (12), 155 (15), 147 (57), 91 (46); Exact mass calcd for
C22H24NO3S2 m/z 414.1197; FABeHRMS m/z 414.1209.
4.1.11. (3aR*,5R*)-5-Methyl-7-(phenylthio)-2,3,3a,4,5,6-hexahydro-
1H-isoindol-1-one (13). Using a procedure similar to that for the
preparation of compound 12, compound 11 (500 mg, 1.21 mmol)
gave product 13 (220 mg, 70%) as a white solid: 178.1e179.5 ꢁC
(decomp.); 1H NMR (CDCl3)
d 7.56e7.52 (2H, m), 7.38e7.32 (3H, m),
4.1.8. (3aR*,5R*,7aS*)-5-Methyl-7-(phenylthio)-2-tosyl-
2,3,3a,4,5,7a-hexahydro-1H-isoindol-1-one (10). A mixture of com-
pound 9 (100 mg, 0.24 mmol) and NaHCO3 (25 mg, 0.29 mmol) in
toluene (10 mL) was heated under nitrogen at reflux for 18 h. The
solvent was then evaporated under vacuum, and the residue was
purified by column chromatography using ethyl acetate/hexane
(1:4) as eluent to give crude product 10, which was further
recrystallized from CH2Cl2/hexane to give purified product 10
(85 mg, 85%) as a white solid: mp 133.4e135.0 ꢁC; 1H NMR (CDCl3)
6.22 (1H, s), 3.60e3.51 (1H, m), 3.13e2.98 (2H, m), 2.21e2.02 (2H, m),
1.80e1.71 (2H, m),1.43e1.32 (1H, m), 0.94 (3H, d, J¼6.9 Hz); 13C NMR
(CDCl3) d 171.3, 139.7, 135.9, 130.8, 128.9, 128.8, 124.5, 47.3, 36.7, 34.5,
32.2, 27.2, 19.6; IR (ATR, film) v: 3276, 3066, 2955, 2922, 2870, 1683,
1626,1340,1239,1069 cmꢂ1; EI-MS (rel intensity) m/z 259 (Mþ,100),
244 (4), 230 (23), 216 (29), 201 (40),160 (49),147 (10),109 (11); Exact
mass calcd for C15H17NOS m/z 259.1031; EI-HRMS m/z 259.1024.
4.2. General procedure for the N-substitution of amides 12
and 13
d
7.92 (2H, d, J¼8.4 Hz), 7.34e7.20 (7H, m), 6.05 (1H, dd, J¼4.5,
1.5 Hz), 3.90 (1H, dd, J¼10.0, 6.6 Hz), 3.61 (1H, dd, J¼10.0, 2.4 Hz),
3.06 (1H, d, J¼7.2 Hz), 2.66e2.56 (1H, m), 2.44 (3H, s), 2.40e2.32
(1H, m), 1.50e1.48 (2H, m), 1.07 (3H, d, J¼7.2 Hz); 13C NMR (CDCl3)
To a solution of compound 12 (50 mg, 0.20 mmol) in THF (5 mL)
at room temperature under nitrogen was added NaH (50% in oil
dispersion, 30 mg, 0.61 mmol). After stirring for 30 min, the elec-
trophile (0.61 mmol) was added in one portion. The reaction mixture
was stirred for 2 h, and was then poured into saturated ammonium
chloride (20 mL) and CH2Cl2 (20 mL). The aqueous solution was
extracted with CH2Cl2 (3ꢀ20 mL), and the organic layers were
combined and dried (MgSO4). The solvent was removed under
vacuum and the residue was purified by column chromatography
using ethyl acetate/hexane as eluent to give products 14 and 15.
d
170.4, 145.0, 139.9, 135.0, 134.0, 131.0, 129.6, 129.0, 128.1, 127.0,
126.0, 50.0, 46.2, 30.1, 29.2, 28.9, 21.6, 20.4; IR (ATR, film) v: 3060,
2959, 2925, 2868, 1740, 1357,1171,1091 cmꢂ1; FABMS (rel intensity)
m/z 414 (MþH, 22), 258 (51), 203 (47), 155 (38), 115 (36), 91 (100),
77 (79), 39 (51), 28 (32); Exact mass calcd for C22H24NO3S2 m/z
414.1197; FABeHRMS m/z 414.1204.
4.1.9. (3aR*,5R*)-5-Methyl-7-(phenylthio)-2-tosyl-2,3,3a,4,5,6-
hexahydro-1H-isoindol-1-one (11). A solution of compound 10
(500 mg,1.21 mmol) and DBU (0.90 mL, 6.05 mmol) in ethyl acetate
(30 mL) was stirred at room temperature for 24 h, and was then
poured into 10% H2SO4 (20 mL). The aqueous solution was extracted
with ethyl acetate (3ꢀ25 mL), and the combined organic layer was
dried (MgSO4) and evaporated under vacuum. The residue was
purified by column chromatography using ethyl acetate/hexane
(1:1) as eluent to give crude product 11, which was further
recrystallized from CH2Cl2/hexane to give purified product 11
(390 mg, 78%) as a white solid: mp 158.4e160.1 ꢁC; 1H NMR (CDCl3)
4.2.1. 2-Methyl-7-(phenylthio)-2,3,3a,4,5,6-hexahydro-1H-isoindol-
1-one (14a). Yellow oil; 1H NMR (CDCl3)
d 7.57e7.53 (2H, m),
7.38e7.30 (3H, m), 3.47 (1H, t, J¼8.6 Hz), 2.99 (1H, t, J¼8.6 Hz), 2.92
(3H, s), 2.90e2.75 (1H, m), 2.07e1.76 (4H, m), 1.61e1.43 (1H, m),
1.24e1.10 (1H, m); 13C NMR (CDCl3)
d 168.3, 138.8, 136.1, 130.7,128.6
(ꢀ2), 125.7, 53.8, 36.6, 29.8, 29.6, 26.3, 22.9; IR (ATR, film) v: 3056,
2933, 2862, 1675, 1632, 1439, 1398, 1274 cmꢂ1; EI-MS (rel intensity)
m/z 259 (M, 61), 218 (100), 187 (27), 160 (26), 147 (63), 146 (45), 118
(37), 109 (84), 91 (31), 86 (45), 84 (55); Exact mass calcd for
C15H17NOS m/z 259.1031; EI-HRMS m/z 259.1040.
d
8.01 (2H, d, J¼8.1 Hz), 7.47 (2H, d, J¼7.2 Hz), 7.42e7.33 (5H, m),
4.20 (1H, t, J¼8.7 Hz), 3.20 (1H, t, J¼9.0 Hz), 3.03e2.89 (1H, m), 2.44
(3H, s), 2.14e2.02 (2H, m), 1.79e1.63 (2H, m), 1.30 (1H, dt, J¼3.6,
4.2.2. 2-Ethyl-7-(phenylthio)-2,3,3a,4,5,6-hexahydro-1H-isoindol-1-
9.0 Hz), 0.89 (3H, d, J¼6.9 Hz); 13C NMR (CDCl3)
d
165.1, 148.5,144.8,
one (14b). Yellow oil; 1H NMR (CDCl3)
d 7.52e7.48 (2H, m),

1190
S.-S.P. Chou, C.-J.J. Wu / Tetrahedron 68 (2012) 1185e1191
7.36e7.25 (3H, m), 3.50e3.25 (3H, m), 2.96 (1H, t, J¼8.6 Hz),
2.83e2.72 (1H, m), 2.02e1.75 (4H, m), 1.58e1.41 (1H, m), 1.22e1.10
287 (22), 286 (17); Exact mass calcd for C17H22NOS m/z 288.1422;
FABeHRMS m/z 288.1412.
(1H, m), 1.12 (3H, t, J¼7.2 Hz); 13C NMR (CDCl3)
d 167.9, 138.8, 136.2,
130.9, 128.8 (ꢀ2), 126.3, 50.9, 37.2, 36.9, 29.7, 26.5, 23.1, 12.7; IR
(ATR, film) v: 3060, 2973, 2932, 2863, 1674, 1631, 1424, 1271,
1067 cmꢂ1; FABMS (rel intensity) m/z 274 (MþH,100), 273 (30), 272
(16), 69 (13); Exact mass calcd for C16H20NOS m/z 274.1265;
FABeHRMS m/z 274.1256.
4.2.8. (3aR*,5R*)-2-Allyl-5-methyl-7-(phenylthio)-2,3,3a,4,5,6-
hexahydro-1H-isoindol-1-one (15c). Yellow oil; 1H NMR (CDCl3)
d
7.52e7.48 (2H, m), 7.33e7.26 (3H, m), 5.75 (1H, tdd, J¼6.3, 10.2,
16.2 Hz), 5.22e5.12 (2H, m), 4.11 (1H, tdd, J¼1.5, 6.0, 15.0 Hz), 3.76
(1H, dd, J¼6.0, 15.0 Hz), 3.50e3.39 (1H, m), 2.97e2.82 (2H, m),
2.17e2.00 (2H, m), 1.87e1.65 (2H, m), 1.38e1.23 (1H, m), 0.89 (3H,
4.2.3. 2-Allyl-7-(phenylthio)-2,3,3a,4,5,6-hexahydro-1H-isoindol-1-
d, J¼7.2 Hz); 13C NMR (CDCl3)
d 167.7, 138.5, 135.8, 132.9, 130.9,
one (14c). Yellow oil; 1H NMR (CDCl3)
d
7.56e7.53 (2H, m),
128.7, 128.5, 125.2, 117.7, 51.2, 45.3, 36.4, 32.0, 31.8, 27.0, 19.5; IR
(ATR, film) v: 3073, 3055, 2956, 2920, 2870, 1678, 1630, 1438, 1412,
1251, 1239 cmꢂ1; FABMS (rel intensity) m/z 300 (MþH, 100), 299
(28), 298 (13), 281 (14), 221 (26), 207 (29), 147 (17), 136 (13), 97
(10), 95 (14), 91 (18), 81 (17); Exact mass calcd for C18H22NOS m/z
300.1422; FABeHRMS m/z 300.1435.
7.36e7.29 (3H, m), 5.78 (1H, tdd, J¼6.3, 9.9, 16.2 Hz), 5.25e5.16 (2H,
m), 4.11 (1H, tdd, J¼1.2, 6.0, 15.0 Hz), 3.79 (1H, tdd, J¼1.2, 5.7,
15.0 Hz), 3.46 (1H, t, J¼8.6 Hz), 2.93 (1H, t, J¼8.6 Hz), 2.87e2.73
(1H, m), 2.05e1.74 (4H, m), 1.58e1.41 (1H, m), 1.25e1.09 (1H, m);
13C NMR (CDCl3)
d
167.9, 139.5, 136.2, 133.0, 130.8, 128.8 (ꢀ2), 125.9,
117.9, 51.1, 45.4, 36.8, 29.7, 26.4, 23.0; IR (ATR, film) v: 3066, 2925,
2855, 1677, 1631, 1435, 1411, 1269 cmꢂ1; FABMS (rel intensity) m/z
286 (MþH, 15), 123 (12), 119 (11), 111 (11), 109 (25), 97 (25), 95 (45),
81 (53), 55 (100); Exact mass calcd for C17H20NOS m/z 286.1265;
FABeHRMS m/z 286.1252.
4.2.9. (3aR*,5R*)-2-Benzyl-5-methyl-7-(phenylthio)-2,3,3a,4,5,6-
hexahydro-1H-isoindol-1-one (15d). Yellow oil; 1H NMR (CDCl3)
d
7.57e7.53 (2H, m), 7.38e7.25 (8H, m), 4.80 (1H, d, J¼14.4 Hz), 4.27
(1H, d, J¼14.4 Hz), 3.42e3.32 (1H, m), 2.98e2.83 (2H, m),
2.20e2.00 (2H, m), 1.73e1.61 (2H, m), 1.38e1.25 (1H, m), 0.92 (3H,
4.2.4. 2-Benzyl-7-(phenylthio)-2,3,3a,4,5,6-hexahydro-1H-isoindol-
d, J¼7.2 Hz); 13C NMR (CDCl3)
d 168.0, 138.9, 137.0, 135.9, 131.0,
1-one (14d). Yellow oil; 1H NMR (CDCl3)
d
7.59e7.45 (2H, m),
128.8, 128.7 (ꢀ2), 128.4, 127.5, 125.2, 51.2, 46.8, 36.6, 32.1, 32.0, 27.1,
19.7; IR (ATR, film) v: 3060, 3029, 2951, 2923, 2855, 1677, 1418,
1239, 1251, 1077 cmꢂ1; FABMS (rel intensity) m/z 350 (MþH, 37),
131 (10), 123 (11), 119 (13), 117 (11), 109 (21), 105 (25), 91 (60), 81
(46), 55 (100); Exact mass calcd for C22H24NOS m/z 350.1578;
FABeHRMS m/z 350.1581.
7.41e7.27 (8H, m), 4.76 (1H, d, J¼14.7 Hz), 4.28 (1H, d, J¼14.7 Hz),
3.37 (1H, t, J¼8.3 Hz), 2.89 (1H, t, J¼8.3 Hz), 2.88e2.71 (1H, m),
2.01e1.79 (4H, m), 1.59e1.40 (1H, m), 1.22e1.13 (1H, m); 13C NMR
(CDCl3)
d
167.9, 139.7, 136.9, 136.1, 130.7, 128.7 (ꢀ2), 128.5, 128.3,
127.4, 125.6, 50.9, 46.6, 36.7, 29.6, 26.2, 22.9; IR (ATR, film) v: 3055,
3022, 2925, 2857, 1674, 1415, 1267, 1248 cmꢂ1; FABMS (rel in-
tensity) m/z 336 (MþH, 100), 335 (26), 334 (17), 102 (11), 91 (92), 77
(10); Exact mass calcd for C21H22NOS m/z 336.1422; FABeHRMS m/z
336.1407.
4.2.10. (3aR*,5R*)-2-Benzoyl-5-methyl-7-(phenylthio)-2,3,3a,4,5,6-
hexahydro-1H-isoindol-1-one (15e). Yellow oil; 1H NMR (CDCl3)
d
7.70e7.66 (2H, m), 7.55e7.49 (3H, m), 7.45e7.33 (5H, m), 4.14 (1H,
dd, J¼8.1, 10.5 Hz), 3.45 (1H, t, J¼10.7 Hz), 3.10e2.98 (1H, m),
2.26e2.18 (2H, m), 1.89 (1H, td, J¼3.6, 12.3 Hz), 1.75 (1H, dd, J¼2.4,
17.5 Hz), 1.40 (1H, dt, J¼2.4, 12.3 Hz), 0.99 (3H, d, J¼6.9 Hz); 13C
4.2.5. 2-Benzoyl-7-(phenylthio)-2,3,3a,4,5,6-hexahydro-1H-isoindol-
1-one (14e). Yellow oil; 1H NMR (CDCl3)
d 7.70e7.66 (2H, m),
7.55e7.47 (3H, m), 7.44e7.33 (5H, m), 4.13 (1H, dd, J¼10.6, 8.2 Hz),
NMR (CDCl3) d 171.0, 166.3, 149.5, 136.2, 134.7, 131.7, 129.4, 129.3,
3.44 (1H, t, J¼10.4 Hz), 3.00e2.86 (1H, m), 2.15e1.87 (4H, m),
129.03, 128.97, 127.7, 122.6, 51.1, 37.0, 31.8, 30.5, 26.9, 19.5; IR (ATR,
film) v: 3058, 2957, 2923, 2896, 1716, 1667, 1608, 1319, 1306, 1223,
1149 cmꢂ1; FABMS (rel intensity) m/z 364 (MþH, 26), 105 (100), 91
(24), 81 (27); Exact mass calcd for C22H22NO2S m/z 364.1371;
FABeHRMS m/z 364.1373.
1.64e1.50 (1H, m), 1.29e1.15 (1H, m); 13C NMR (CDCl3)
d 171.2,
166.5, 150.5, 136.5, 134.8, 131.8, 129.6, 129.3, 129.1 (ꢀ2) 127.9,
123.6, 51.1, 35.5, 30.4, 26.3, 22.7; IR (ATR, film) v: 3059, 2937, 2860,
1714, 1667, 1605, 1308, 1192, 1150 cmꢂ1; FABMS (rel intensity) m/z
350 (MþH, 51), 349 (11), 348 (10), 109 (14), 105 (100), 81 (33);
Exact mass calcd for C21H20NO2S m/z 350.1214; FABeHRMS m/z
350.1211.
4.2.11. (3aR*,5R*)-5,7-Dimethyl-2-tosyl-2,3,3a,4,5,6-hexahydro-1H-
isoindol-1-one (16). To a mixture of CuI (33 mg, 0.172 mmol) in THF
(1 mL) at 0 ꢁC was added dropwise a solution of MeLi (2.2 M in THF,
0.156 mL, 0.343 mmol). After stirring at 0 ꢁC for 30 min, the mixture
was cooled to ꢂ78 ꢁC, and BF3$OEt2 (d¼1.12, 0.034 mL, 0.264 mmol)
was added and stirred for 5 min. Then a solution of compound 11
(20 mg, 0.048 mmol) in THF (1 mL) precooled at ꢂ78 ꢁC was added
dropwise. The reaction mixture was slowly warmed to room tem-
perature, stirred for another 4 h, and quenched with saturated
ammonium chloride. The aqueous solution was extracted with
ethyl acetate (3ꢀ20 mL), combined with the organic layer, dried
(MgSO4), and concentrated under vacuum. The crude product was
purified by chromatography using ethyl acetate/hexane (1:5) and
then recrystallized with CH2Cl2/hexane to give product 16 (10.6 mg,
4.2.6. (3aR*,5R*)-2,5-Dimethyl-7-(phenylthio)-2,3,3a,4,5,6-
hexahydro-1H-isoindol-1-one (15a). Yellow oil; 1H NMR (CDCl3)
d
7.52e7.45 (2H, m), 7.33e7.26 (3H, m), 3.44 (1H, t, J¼7.8 Hz), 2.96
(1H, t, J¼8.2 Hz), 2.96e2.87 (1H, m), 2.89 (3H, s), 2.15e1.99 (2H, m),
1.76e1.59 (2H, m), 1.35e1.26 (1H, m), 0.89 (3H, d, J¼6.9 Hz); 13C
NMR (CDCl3)
d 168.3, 138.0, 135.9, 131.1, 128.8, 128.6, 125.4, 54.1,
36.5, 32.1, 31.9, 30.0, 27.1, 19.6; IR (ATR, film) v: 3055, 2955, 2920,
2871, 1679, 1631, 1424, 1397, 1286, 1253, 1072 cmꢂ1; FABMS (rel
intensity) m/z 274 (MþH, 100), 273 (22), 272 (15); Exact mass calcd
for C16H20NOS m/z 274.1265; FABeHRMS m/z 274.1273.
4.2.7. (3aR*,5R*)-2-Ethyl-5-methyl-7-(phenylthio)-2,3,3a,4,5,6-
69%) as a white solid, mp 129.7e130.8 ꢁC: 1H NMR (CDCl3)
d 7.96
hexahydro-1H-isoindol-1-one (15b). Yellow oil; 1H NMR (CDCl3)
(2H, d, J¼8.2 Hz), 7.34 (2H, d, J¼8.2 Hz), 4.15 (1H, t, J¼8.7 Hz), 3.23
(1H, t, J¼9.3 Hz), 2.92e2.77 (1H, m), 2.44 (3H, s), 2.37e2.25 (1H, m),
2.21e2.09 (1H, m), 2.05 (3H, d, J¼2.4 Hz), 1.92e1.75 (2H, m), 1.29
(1H, dt, J¼3.6, 12.0 Hz), 0.95 (3H, d, J¼7.2 Hz); 13C NMR (CDCl3)
d
7.52e7.49 (2H, m), 7.33e7.26 (3H, m), 3.52e3.40 (2H, m),
3.38e3.24 (1H, m), 2.96 (1H, t, J¼8.1 Hz), 2.96e2.83 (1H, m),
2.15e1.99 (2H, m), 1.76e1.59 (2H, m), 1.36e1.27 (1H, m), 1.13 (3H, t,
J¼7.4 Hz), 0.89 (3H, d, J¼7.2 Hz); 13C NMR (CDCl3)
d
167.8, 137.8,
d 166.5, 148.2, 144.8, 135.9, 129.6, 128.2, 124.2, 51.3, 39.7, 32.1, 30.3,
135.9, 131.2, 128.8, 128.6, 125.8, 51.1, 37.3, 36.5, 32.2, 32.1, 27.2, 19.7,
12.8; IR (ATR, film) v: 3055, 2957, 2925, 2870, 1676, 1632, 1422,
1240, 1252, 1068 cmꢂ1; FABMS (rel intensity) m/z 288 (MþH, 100),
25.74, 25.65, 21.7, 19.8; IR (ATR, film) v: 2956, 2920, 2868, 1720,
1669, 1358, 1170, 1048 cmꢂ1; EI-MS (rel intensity) m/z 319 (Mþ, 10),
256 (21), 255 (22), 199 (12), 198 (100), 155 (48), 137 (13), 136 (19),

S.-S.P. Chou, C.-J.J. Wu / Tetrahedron 68 (2012) 1185e1191
1191
6. For some reviews, see: (a) Ciganek, E. Org. React. 1984, 32, 1e374; (b) Takao, K.-
I.; Munakata, Y.; Tadano, K.-I. Chem. Rev. 2005, 105, 4779e4807; (c) Juhl, M.;
Tanner, D. Chem. Soc. Rev. 2009, 38, 2983e2992.
94 (12), 93 (14), 91 (55); Exact mass calcd for C17H21NO3S m/z
319.1242; EI-HRMS m/z 319.1241.
7. For some selected syntheses, see: (a) Crisp, G. T.; Meyer, A. G. Tetrahedron 1995,
51, 5585e5596; (b) Csende, F.; Stajer, G. Curr. Org. Chem. 2005, 9, 1261e1276; (c)
Stajer, G.; Csende, F. Curr. Org. Chem. 2005, 9, 1277e1286; (d) Steinhardt, S. E.;
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Acknowledgements
Financial support of this work by the National Science Council of
the Republic of China (NSC 97-2113-M-030-001-MY3) is gratefully
acknowledged.
8. Dalisay, D. S.; Morinaka, B. I.; Skepper, C. K.; Molinski, T. F. J. Am. Chem. Soc.
2009, 131, 7552e7553.
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