Synthesis and applications of sulfur-substituted cis-hexahydro-2- quinolinones

Article abstract of DOI:10.1016/j.tet.2010.11.096

An efficient synthesis of sulfur-substituted cis-hexahydro-2-quinolinones has been achieved by an aza-Diels^-Alder reaction of p-toluenesulfonyl isocyanate with a diene precursor derived from a bicyclic 3-sulfolene via ring-closing metathesis. S

Full text of DOI:10.1016/j.tet.2010.11.096

Tetrahedron 67 (2011) 1183e1186
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Synthesis and applications of sulfur-substituted cis-hexahydro-2-quinolinones
*
Shang-Shing P. Chou , Yi-Lin Cai
Department of Chemistry, Fu Jen Catholic University, Taipei County 24205, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient synthesis of sulfur-substituted cis-hexahydro-2-quinolinones has been achieved by an aza-
Diels_Alder reaction of p-toluenesulfonyl isocyanate with a diene precursor derived from a bicyclic 3-
sulfolene via ring-closing metathesis. Some synthetic tranformations have also been carried out.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 8 September 2010
Received in revised form 26 November 2010
Accepted 30 November 2010
Available online 13 December 2010
Keywords:
2-Quinolinones
Aza-Diels_Alder reaction
Ring-closing metathesis
Spiro bicyclic lactones
1. Introduction
SPh
1) BuLi (1.7 eq), HMPA (4 eq)
THF, -78 oC, 40 min
SPh
Grubbs' I (5 mol%)
CH2Cl2, rt, 24 h
Br
Quinolinone alkaloids have been isolated from various sources,
and some of them show interesting biological activities.1 The
quinoline or quinolinone moieties are also important part of other
more complex natural products.2 There are many different strate-
gies for constructing these alkaloids,3 but we are more interested in
developing a method for constructing the heretofore unknown
hexahydro-2-quinolinone structures. We have previously de-
veloped a new aza-Diels_Alder reaction of thio-substituted 3-sul-
folenes with p-toluenesulfonyl isocyanate (PTSI) to synthesize
piperidine derivatives.4 We have also used this method to prepare
some indolizidines and quinolizidines,5 and other heterocyclic
compounds.6 We now report our successful synthesis of sulfur-
substituted hexahydro-2-quinolinones and some of their reactions.
S
2)
(4 eq)
S
O2
O2
-78 oC, 2 h
1
2 (54%)
SPh
SPh
H
SPh
Et3N/EtOAc (1:3)
PTSI (3 eq)
sealed tube
110 oC, 24 h
p-xyl /CH3CN (3:1)
NaHCO3 (1 eq), HQ (cat.)
reflux, 5 h
N
Ts
O
N
Ts
O
S
H
O2
4 (76%)
5 (82%)
3 (89%)
Scheme 1.
equatorial position. Using the Hyperchem AM1 method, we cal-
culated the heat of formation for both the cis and trans isomers of
compound 5, and found that the trans isomer is more stable by
1.2 kcal/mol. Thus we propose that deprotonation of compound 4 at
C-3 followed by reprotonation at C-4a occurred under kinetic
control; the proton is added from the less hindered side (the same
side as the H8a) to give cis-product 5.
2. Results and discussion
Deprotonation of 3-allyl-4-(phenylthio)-3-sulfolene (1)7 in THF
with BuLi at ꢀ78 ꢁC in presence of hexamethylphosphoric amide
(HMPA), followed by reaction with allyl bromide gave the bis-allyl
product 2 (Scheme 1). Ring-closing metathesis of 2 with Grubbs’
catalyst-I yielded the bicyclic 3-sulfolene 3. Heating compound 3
with p-toluenesulfonyl isocyanate (PTSI)2 gave the aza-Diels_Alder
product 4. Isomerization of the double bond under basic condition
yielded mostly the conjugated product cis-5. The stereochemistry
of compound 5 is proven by its X-ray crystal structure (Fig. 1),8
which also shows that H8a is at the axial position and H4a at the
Removal of the tosyl group of compound 5 with Bu3SnH/AIBN9
yielded the hexahydro-2-quinolinone 6. Deprotonation by BuLi at
low temperature followed by reaction with an alkyl or an acyl halide
produced the N-substituted derivatives 7e11 in fair to good yields.
* Corresponding author. Fax: þ886 2 29023209; e-mail address: chem1004@
mails.fju.edu.tw (S.-S.P. Chou).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.11.096

1184
S.-S.P. Chou, Y.-L. Cai / Tetrahedron 67 (2011) 1183e1186
Scheme 2.
Fig. 1. X-ray crystal structure of compound 5.
Reaction of compound 4 with NBS (1.2 equiv) in refluxing
CH3CN gave the allylic bromide 12. Its cis-stereochemistry is shown
by the X-ray crystal structure (Fig. 2).8 We propose that NBS ap-
proaches from the less hindered side of compound 4 (the same side
as the H8a) to give the cis-product 12.
Fig. 3. X-ray crystal structure of compound 13.
Fig. 2. X-ray crystal structure of compound 12.
yields a carboxylate anion C, which attacks the aziridine from the
back side. After protonation, the retention product 13 would be
obtained after two inversions.
3. Conclusions
The aza-Diels_Alder reaction of p-toluenesulfonyl isocyanate
with bicyclic 3-sulfolene 3 gave the cycloaddition product 4, which
upon isomerization of the double bond yielded the sulfur-
substituted cis-hexahydro-2-quinolinone 5. The tosyl group of
compound 5 was efficiently cleaved by Bu3SnH/AIBN to give the
secondary amide 6, which was readily converted to the N-
substitution products 7e11. Compound 4 also reacted efficiently
with NBS to give the cis-allylic bromide 12. The reaction of com-
pound 12 with NaOH/MeOH provided a novel spiro bicyclic lactone
13 with complete stereospecificity in excellent yield.
Treatment of compound 12 with NaOH/MeOH under reflux did
not lead to the expected elimination product, but gave a novel spiro
bicyclic lactone 13 in excellent yield (Scheme 2). The stereochem-
istry of compound 13 is proven by its X-ray crystal structure
(Fig. 3),8 which shows clearly that the carbon bearing the bromine
atom in compound 12 was converted to the CeO bond in product 13
with retention of configuration. We propose that sodium hydroxide
first attacks the amide group of compound 12 to give an amide
anion A, which then undergoes an intramolecular cyclization to
give an aziridine intermediate B. Deprotonation of intermediate B

S.-S.P. Chou, Y.-L. Cai / Tetrahedron 67 (2011) 1183e1186
1185
4. Experimental section
4.1. General
129.2, 127.6, 126.5, 124.5, 117.7, 59.1, 38.3, 37.5, 32.9, 21.7; FAB-MS
(rel intensity) m/z 412 (MþþH, 35), 154 (57), 136 (80), 91 (100), 89
(53), 77 (68), 69 (64), 57 (71), 55 (89), 43 (75), 41 (74); FABeHRMS
m/z calcd for C22H21NO3S2 [M]þ 411.0963, found 411.0961.
Melting points were determined with a SMP3 melting appara-
tus. Infrared spectra were recorded with a PerkineElmer 100 series
FTIR spectrometer. 1H and 13C NMR spectra were recorded on
a Bruker Avance 300 spectrometer operating at 300 and at 75 MHz,
4.1.4. cis-4-(Phenylthio)-1-tosyl-4a,5,8,8a-tetrahydroquinolin-2-one
(5). A mixture of compound 4 (500.0 mg,1.21 mmol) in Et3N (2 mL)
and ethyl acetate (6 mL) was heated in a sealed tube at 110 ꢁC for
24 h. The solvent was then removed under vacuum, and the residue
was purified by flash chromatography using ethyl acetate/hexanes
(1:5) as eluent to give, besides recovered starting material 4
(73.0 mg, 15%), product 5 (412.0 mg, 82%) as a white solid: mp
respectively. Chemical shifts (d) are reported in parts per million
(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 Enraf-Nonius FR-590 diffrac-
tometer (CAD4, Kappa CCD). Elemental analyses were carried out
with Heraeus Vario III-NCSH, Heraeus CHNeOeS-Rapid Analyzer or
Elementar Vario EL III. Flash column chromatographic purifications
were performed using Merck 60H silica gel.
160e161 ꢁC (recryst from CH2Cl2/hexanes); 1H NMR (CDCl3)
d 7.94
(2H, d, J¼8.4 Hz), 7.43e7.36 (5H, m), 7.27 (2H, d, J¼8.4 Hz), 5.78e5.64
(2H, m), 5.02 (1H, d, J¼2.4 Hz), 4.95 (1H, ddd, J¼10.7, 6.3, 4.8 Hz),
3.43e3.40 (1H, m), 2.83 (1H, dd, J¼18.6, 4.8 Hz), 2.63 (1H, br d,
J¼18.6 Hz), 2.51e2.33 (5H, m); 13C NMR (CDCl3)
d 163.7,160.8,144.6,
136.8, 135.7, 130.4, 130.1, 129.2, 129.0, 127.6, 125.5, 124.5, 114.4, 54.0,
38.3, 28.1, 26.5, 21.7; FAB-MS (rel intensity) m/z 412 (MþþH, 100),
149 (45), 69 (54), 57 (58), 55 (71), 43 (49), 41 (56); FABeHRMS m/z
calcd for C22H21NO3S2 [M]þ 411.0963, found 411.0956.
4.1.1. 2,3-Diallyl-4-(phenylthio)-3-sulfolene (2). To
a solution of
compound 1 (1.6 g, 6.01 mmol) and HMPA (4.19 mL, 24.1 mmol) in
THF (40 mL) at ꢀ78 ꢁC under nitrogenwas added dropwise a solution
of BuLi (2.5 M in hexane, 4.09 mL,10.2 mmol). After stirring at ꢀ78 ꢁC
for 40 min, allyl bromide (2.08 mL, 24.1 mmol) was added in one
portion, and the reaction mixture was stirred at ꢀ78 ꢁC for another
2 h before it was poured into saturated ammonium chloride solution.
The solvent was removed by rotary evaporation, and the residue was
extracted with ethyl acetate, dried (MgSO4), and evaporated under
vacuum. The crude product was purified by flash chromatography
using ethyl acetate/hexanes (1:7) as eluent to give compound 2 (1.0 g,
4.1.5. cis-4-(Phenylthio)-4a,5,8,8a-tetrahydro-1H-quinolin-2-one
(6). To a refluxing solution of compound 5 (394.0 mg, 0.96 mmol) in
degassed toluene (10 mL) was added in one portion a solution of
Bu3SnH (0.57 mmol, 2.11 mmol) and AIBN (94.3 mg, 0.57 mmol) in
toluene (2 mL). The reaction mixture was refluxed for another 2 h.
The solvent was then evaporated under vacuum, and the crude
product was purified by flash chromatography using ethyl acetate/
hexanes (1:3e1:1) as eluent to give compound 6 (227.0 mg, 92%) as
a white solid: mp 228e229 ꢁC (recryst from CH2Cl2/hexanes); 1H
54%) as a yellow oil: 1H NMR (CDCl3)
d 7.37e7.26 (5H, m), 5.95e5.71
(2H, m), 5.29e5.17 (4H, m), 3.89 (1H, t, J¼6.0 Hz), 3.63e3.56 (3H, m),
2.97 (1H, dd, J¼15.0, 6.9 Hz), 2.69 (2H, t, J¼6.3 Hz); 13C NMR (CDCl3)
NMR (CDCl3)
m), 5.43 (1H, br s), 5.19 (1H, d, J¼0.6 Hz), 3.96 (1H, br s), 2.53e2.43
(3H, m), 2.23e2.04 (2H, m); 13C NMR (CDCl3)
166.5, 162.4, 135.4,
d 7.52e7.42 (5H, m), 5.83e5.80 (1H, m), 5.64e5.61 (1H,
d
140.2, 132.6, 132.3, 131.5, 131.3, 129.7, 128.2, 124.7, 119.6, 118.4, 67.8,
58.0, 33.7, 32.5; FAB-MS (rel intensity) m/z 307 (MþþH,1), 73 (52), 71
(58), 69 (83), 57 (89), 55 (100), 43 (93), 41 (83); FABeHRMS m/z calcd
for C16H18O2S2 [M]þ 306.0748, found 306.0748.
d
130.1,130.0,128.4,126.7,122.3,113.3, 48.5, 37.7, 29.8, 27.1; EI-MS (rel
intensity) m/z 257 (Mþ,10), 203 (66), 202 (100), 91 (37); EI-HRMS m/
z calcd for C15H15NOS [M]þ m/z 257.0874, found 257.0872.
4.1.2. 3-(Phenylthio)-2,4,7,7a-tetrahydrobenzothiophene 1,1-dioxide
(3). A mixture of compound 2 (177.0 mg, 0.58 mmol) and Grubbs’ I
catalyst (24.0 mg, 0.029 mmol) in CH2Cl2 (10 mL) was stirred at
room temperature for 24 h. The solvent was then evaporated under
vacuum, and the residue was purified by flash chromatography
using ethyl acetate/hexanes (1:7) as eluent to give compound 3
4.2. General procedure for the N-substitution of amide 6
To a solution of compound 6 (50.0 mg, 0.19 mmol) and HMPA
(0.14 mL, 0.78 mmol) in THF (5 mL) at ꢀ78 ꢁC under nitrogen was
added dropwise a solution of BuLi (2.5 M in hexane, 0.09 mL,
0.23 mmol). After stirring at ꢀ78 ꢁC for 40 min, the electrophile
(0.78 mmol) was added in one portion, and the reaction mixture
was slowly warmed to room temperature and stirred for another
24 h before it was poured into saturated ammonium chloride so-
lution. The solvent was removed by rotary evaporation, and the
residue was extracted with ethyl acetate, dried (MgSO4), and
evaporated under vacuum. The crude product was purified by flash
chromatography using ethyl acetate/hexanes (1:3) as eluent to give
purified products 7e11.
(144.0 mg, 89%) as a yellow oil: 1H NMR (CDCl3)
d 7.37e7.28 (5H,
m), 5.87e5.74 (2H, m), 3.99 (1H, t, J¼6.0 Hz), 3.76 (1H, dd, J¼15.9,
4.2 Hz), 3.64 (1H, d, J¼15.9 Hz), 3.45 (1H, d, J¼21.6 Hz), 2.95 (1H, d,
J¼21.6 Hz), 2.66e2.63 (2H, m); 13C NMR (CDCl3)
d 137.3, 131.4, 131.3,
129.7, 128.2, 124.3, 123.4, 120.5, 63.5, 58.0, 28.4, 24.6; FAB-MS (rel
intensity) m/z 278 (MþþH, 21), 218 (53), 215 (56), 214 (74),154 (66),
137 (61), 136 (100), 105 (96), 103 (99), 91 (60), 77 (62); FABeHRMS
m/z calcd for C14H14S [MþꢀSO2] 214.0816, found 214.0816.
4.1.3. 4-(Phenylthio)-1-tosyl-3,5,8,8a-tetrahydroquinolin-2-one
(4). A mixture of compound 3 (445.0 mg, 1.60 mmol), NaHCO3
(134.5 mg, 1.60 mmol), hydroquinone (8.8 mg, 0.08 mmol), and
PTSI (0.75 mL, 4.80 mmol) in p-xylene/CH3CN (6 mL:2 mL) was
heated at reflux under nitrogen for 5 h. After cooling in an ice bath,
5% aq NaOH was slowly added to decompose the excess PTSI. The
solvent CH3CN was removed under vacuum, and the residue was
purified by flash chromatography using ethyl acetate/hexanes (1:6)
as eluent to give compound 4 (500.0 mg, 76%) as a white solid: mp
4.2.1. cis-1-Methyl-4-(phenylthio)-4a,5,8,8a-tetrahydroquinolin-2-
one (7). Yellow oil: 1H NMR (CDCl3)
d
7.50e7.40 (5H, m), 5.79e5.68
(2H, m), 5.22 (1H, s), 3.71e3.65 (1H, m), 3.08e3.03 (1H, m), 2.96
(3H, s), 2.60e2.37 (4H, m); 13C NMR (CDCl3)
164.3, 157.7, 135.7,
d
129.95, 129.91, 128.7, 125.8 124.3, 115.5, 55.6, 37.8, 31.1, 26.7, 26.2;
EI-MS (rel intensity) m/z 271 (Mþ, 3), 218 (18), 217 (86), 216 (100),
184 (9), 42(8); EI-HRMS m/z calcd for C16H17NOS [M]þ 271.1031,
found 271.1035.
104e105 ꢁC (recryst from CH2Cl2/hexanes); 1H NMR (CDCl3)
d 7.93
(2H, d, J¼8.4 Hz), 7.31 (2H, d, J¼8.4 Hz), 7.27e7.20 (5H, m),
5.78e5.68 (2H, m), 5.18e5.13 (1H, m), 3.80 (1H, d, J¼18.9 Hz), 3.17
(1H, dt, J¼16.2, 5.1 Hz), 3.07e2.96 (3H, m), 2.42e2.30 (4H, m); 13C
4.2.2. cis-1-Ethyl-4-(phenylthio)-4a,5,8,8a-tetrahydroquinolin-2-one
(8). Yellow oil: 1H NMR (CDCl3)
d 7.51e7.38 (5H, m), 5.79e5.67 (2H,
m), 5.21 (1H, d, J¼1.5 Hz), 3.83 (1H, dq, J¼21, 7.2 Hz), 3.74e3.68 (1H,
NMR (CDCl3)
d 166.8, 145.1, 136.8, 136.2, 132.3, 130.9, 129.4, 129.3,
m), 3.08e2.97 (2H, m), 2.63e2.56 (1H, m), 2.51e2.33 (3H, m), 1.14

1186
S.-S.P. Chou, Y.-L. Cai / Tetrahedron 67 (2011) 1183e1186
(3H, t, J¼7.2 Hz); 13C NMR (CDCl3)
d
163.5, 157.1, 135.6, 129.93,
and NaOH (32.6 mg, 0.82 mmol) in methanol (10 mL) was heated at
reflux under nitrogen for 2 h. The solvent was evaporated under
vacuum, and the crude product was purified by flash chromatog-
raphy using ethyl acetate/hexanes (1:4) as eluent to give product 13
(232 mg, 93%) as a white solid: mp 182e183 ꢁC (recryst from
129.88, 128.7, 125.6, 124.7, 115.9, 53.6, 38.8, 38.2, 26.9, 26.7, 14.2; EI-
MS (rel intensity) m/z 285 (Mþ, 4), 232 (20), 231 (100), 230 (47), 203
(52), 202 (37), 86 (27), 84 (41), 51 (14), 49 (42); EI-HRMS m/z calcd
for C17H19NOS [M]þ 285.1187, found 285.1184.
CH2Cl2/hexanes); 1H NMR (CDCl3)
d
7.76 (2H, d, J¼8.4 Hz),
4.2.3. cis-1-Allyl-4-(phenylthio)-4a,5,8,8a-tetrahydroquinolin-2-one
7.54e7.41 (5H, m), 7.33 (2H, d, J¼8.4 Hz), 5.76e5.61 (2H, m), 5.12
(1H, s), 4.63 (1H, d, J¼10.2 Hz), 3.71 (1H, dt, J¼10.2, 5.1 Hz),
2.75e2.61 (2H, m), 2.48e2.40 (4H, m), 2.04e1.96 (1H, m); 13C NMR
(9). Yellow oil: 1H NMR (CDCl3)
d 7.50e7.41 (5H, m), 5.85e5.67 (3H,
m), 5.23e5.14 (3H, m), 4.53 (1H, dd, J¼15.9, 4.8 Hz), 3.74e3.68 (1H,
m), 3.53 (1H, dd, J¼15.9, 6.6 Hz), 3.09e3.07 (1H, m), 2.61 (1H, br d,
J¼18.9 Hz), 2.50e2.42 (1H, m), 2.32 (2H, br s); 13C NMR (CDCl3)
(CDCl3)
d 175.1, 169.1, 144.1, 137.5, 134.8, 130.6, 130.2, 130.0, 128.9,
127.3, 124.1, 123.7, 112.0, 86.1, 53.3, 33.5, 30.6, 21.7; FAB-MS (rel
intensity) m/z 428 (MþþH, 6), 91 (61), 89 (52), 57 (60), 55 (78), 43
(82), 41 (100), 39 (77), 27 (55); FABeHRMS m/z calcd for
C22H21NO4S2 [M]þ 427.0912, found 427.0919.
d
163.5, 157.8, 135.6, 134.4, 129.9 (ꢂ2), 128.6, 125.5, 124.8, 116.8,
115.5, 53.2, 46.1, 38.0, 26.6, 26.4; EI-MS (rel intensity) m/z 297 (Mþ,
19), 244 (22), 243 (100), 242 (77), 229 (15), 228 (99), 226 (12), 77
(12), 41 (13); EI-HRMS m/z calcd for C18H19NOS [M]þ 297.1187,
found 297.1184.
Acknowledgements
4.2.4. cis-1-Benzyl-4-(phenylthio)-4a,5,8,8a-tetrahydroquinolin-2-
one (10). Yellow oil: 1H NMR (CDCl3)
d 7.57e7.25 (10H, m),
Financial support of this work by the National Science Council of
the Republic of China (NSC 97-2113-M-030-001-MY3) and Fu Jen
Catholic University (9991A15/10973104995-4) is gratefully
acknowledged.
5.73e5.62 (2H, m), 5.29 (1H, d, J¼1.2 Hz), 5.22 (1H, d, J¼15.6 Hz),
4.03 (1H, d, J¼15.6 Hz), 3.69e3.63 (1H, m), 3.05e3.03 (1H, m), 2.58
(1H, br d, J¼19.5 Hz), 2.43e2.28 (2H, m), 2.20e2.14 (1H, m); 13C
NMR (CDCl3)
d 163.8, 158.0, 138.4, 136.1, 135.7, 130.0, 128.7, 128.6,
127.7, 127.3, 125.4, 124.7, 115.3, 53.2, 47.0, 38.0, 26.6, 26.3; EI-MS (rel
intensity) m/z 347 (Mþ, 32), 294 (30), 293 (98), 292 (70), 187 (22),
109 (14), 105 (15), 91 (100), 77 (20), 65 (17); EI-HRMS m/z calcd for
C22H21NOS [M]þ 347.1344, found 347.1339.
References and notes
1. (a) For a review, see: Grundon, M. F. Nat. Prod. Rep. 1990, 7, 131e138; (b) Staerk,
D.; Kesting, J. R.; Sairafianpour, M.; Witt, M.; Asili, J.; Emami, S. A.; Jaroszewski, J.
W. Phytochemistry 2009, 70, 1055e1061; (c) Luo, X. M.; Qi, S. H.; Yin, H.; Gao, C.
H.; Zhang, S. Chem. Pharm. Bull. 2009, 57, 600e602; (d) He, J.; Lion, U.; Sattler, I.;
4.2.5. cis-1-Benzoyl-4-(phenylthio)-4a,5,8,8a-tetrahydroquinolin-2-
€
Gollmick, F. A.; Grabley, S.; Cai, J.; Meiners, M.; Schunke, H.; Schaumann, K.;
one (11). Yellow oil: 1H NMR (CDCl3)
d 7.54e7.33 (10H, m),
Dechert, U.; Krohn, M. J. Nat. Prod. 2005, 68, 1397e1399; (e) Wu, S. J.; Chen, I. S.
Phytochemistry 1993, 34, 1659e1661; (f) Neville, C. F.; Barr, S. A.; Grundon, M. F.
Tetrahedron Lett. 1992, 33, 5995e5998; (g) Campbell, W. E.; Davidowitz, B.;
Jackson, G. E. Phytochemistry 1990, 29, 1303e1306.
5.81e5.72 (2H, m), 5.18 (1H, d, J¼2.1 Hz), 4.80e4.73 (1H, m), 3.47
(1H, br s), 2.87 (1H, br d, J¼18.3 Hz), 2.66e2.61 (2H, m), 2.40e2.30
(1H, m); 13C NMR (CDCl3)
d 173.4, 165.1, 163.2, 136.4, 135.8, 131.4,
2. Dalton, D. R. The Alkaloids: The Fundamental ChemistrydA Biogenetic Approach;
130.4, 130.2, 128.2, 128.0, 127.7, 126.2, 124.2, 115.0, 53.3, 37.9, 27.1,
26.5; EI-MS (rel intensity) m/z 361 (Mþ, 18), 279 (24), 278 (12), 177
(25), 150 (12), 149 (100), 105 (88), 77 (40), 73 (37), 65 (11), 44 (27);
EI-HRMS m/z calcd for C22H19NO2S [M]þ 361.1136, found 361.1133.
Marcel Dekker: New York, NY, 1979.
3. For some recent synthetic work, see: (a) Biechy, A.; Hachisu, S.; Quiclet-Sire, B.;
Ricard, L.; Zard, S. Z. Tetrahedron 2009, 65, 6730e6738; (b) Ken-ichi Yamada, K.;
Mitsuaki Yamashita, M.; Takaaki Sumiyoshi, T.; Katsumi Nishimura, K.; Kiyoshi To-
mioka, K. Org. Lett. 2009, 11, 1631e1633; (c) Biechy, A.; Hachisu, S.; Quiclet-Sire, B.;
Ricard, L.; Zard, S. Z. Angew. Chem., Int. Ed. 2008, 47, 1436e1438; (d) Queiroz, M. J. R.
P.; Abreu, A. S.; Calhelha, R. C.; Carvalho, M. S. D.; Ferreira, P. M. T. Tetrahedron 2008,
4.2.6. cis-4a-Bromo-4-(phenylthio)-1-tosyl-4a,5,8,8a-tetrahy-
ꢀ
64, 5139e5146; (e) Amat, M.; Perez, M.; Minaglia, A. T.; Passarella, D.; Bosch, J. Tet-
droquinolin-2-one (12). A mixture of compound
4 (220 mg,
rahedron: Asymmetry 2008, 19, 2406e2410; (f) Padwa, A.; Zhang, H. J. Org. Chem.
2007, 72, 2570e2582; (g) Crich, D.; Krishnamurthy, V. Tetrahedron 2006, 62,
6830e6840; (h) Binot, G.; Zard, S. Z. Tetrahedron Lett. 2005, 46, 7503e7506; (i)
Barclay, G. L.; Quiclet-Sire, B.; Sabchez-Jimenez, G.; Zard, S. Z. Org. Biomol. Chem.
2005, 3, 823e835; (j) Minter, D. E.; Winslow, C. D. J. Org. Chem. 2004, 69,1603e1606.
4. (a) Chou, S. S. P.; Hung, C. C. Tetrahedron Lett. 2000, 40, 8323e8326; (b) Chou, S.
S. P.; Hung, C. C. Synthesis 2001, 2450e2462.
5. (a) Chou, S. S. P.; Chiu, H. C.; Hung, C. C. Tetrahedron Lett. 2003, 44, 4653e4655;
(b) Chou, S. S. P.; Ho, C. W. Tetrahedron Lett. 2005, 46, 8551e8554; (c) Chou, S. S.
P.; Liang, C. F.; Lee, T. M.; Liu, C. F. Tetrahedron 2007, 63, 8267e8273.
6. (a) Chou, S. S. P.; Hsieh, H. I.; Hung, C. C. J. Chin. Chem. Soc. 2006, 53,
891e900; (b) Chou, S. S. P.; Chen, P. W. Tetrahedron 2008, 64, 1879e1887; (c)
Chou, S. S. P.; Wang, H. C.; Chen, P. W.; Yang, C. H. Tetrahedron 2008, 64,
5291e5297.
0.53 mmol) and NBS (114.0 mg, 0.64 mmol) in CH3CN (15 mL) was
heated at reflux under nitrogen for 2 h. The solvent was evaporated
under vacuum, and the crude product was purified by flash chro-
matography using ethyl acetate/hexanes (1:6) as eluent to give
product 12 (209.0 mg, 80%) as a yellow solid: mp 139e140 ꢁC
(recryst from CH2Cl2/hexanes); 1H NMR (CDCl3)
d 8.03 (2H, d,
J¼8.4 Hz), 7.46e7.36 (5H, m), 7.29 (2H, d, J¼8.4 Hz), 5.78e5.72 (1H,
m), 5.63e5.57 (1H, m), 5.17 (1H, dd, J¼9.0, 7.2 Hz), 5.07 (1H, s), 3.48
(1H, dd, J¼18.0, 5.4 Hz), 3.20 (1H, d, J¼18.0 Hz), 2.89e2.80 (1H, m),
2.51e2.40 (4H, m); 13C NMR (CDCl3)
d 162.4, 159.2, 145.0, 135.8,
7. Chou, S. S. P.; Tai, H. P. J. Chin. Chem. Soc. 1993, 40, 463e467.
135.6, 130.6, 130.3, 129.5, 129.1, 127.0, 126.4, 124.1, 116.7, 61.5, 60.5,
38.9, 33.3, 21.7; FAB-MS (rel intensity) m/z 490 (MþþH, 7), 147 (32),
73 (100); FABeHRMS m/z calcd for C22H2079BrNO3S2 [M]þ
489.0068, found 489.0073.
8. Crystallographic data (excluding structure factors) for compounds 5, 12,
and 13 in this paper have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication CCDC 791734 (com-
pound 5), 791733 (compound 12), 791732 (compound 13). Copies of the
data can be obtained, free of charge, on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (fax: þ44 (0)1223 336033 or e-mail: de-
posit@ccdc.cam.ac.uk).
4.2.7. 2-Oxo-4-(phenylthio)-10
b-tosylamido-1a-oxaspiro[4.5]deca-
3,7-diene (13). A mixture of compound 12 (200.0 mg, 0.41 mmol)
9. Parsons, A. F.; Pettifer, R. M. Tetrahedron Lett. 1996, 37, 1667e1671.