Novel synthesis of tetrahydro-2(1H)-quinolones using Diels-Alder reactions of 1-arylsulfonyl-2(1H)-pyridones having an electron-withdrawing group

Article abstract of DOI:10.1016/S0040-4020(01)00893-6

A novel synthetic methodology of preparing tetrahydro-2(1H)-quinolones by Diels-Alder reactions between 2-methyl- and 2,3-dimethyl-1,3-butadienes and 1-arylsulfonyl-2(1H)-pyridones having an electron-withdrawing group at the 5-position is presented. Furthermore, the site-selectivity analyses based on MO calculations of the 5-substituted 2(1H)-pyridones acting as the dienophiles are described.

Full text of DOI:10.1016/S0040-4020(01)00893-6

TETRAHEDRON
Pergamon
Tetrahedron 57 ,2001) 8841±8850
Novel synthesis of tetrahydro-2ꢀ1H)-quinolones using Diels±Alder
reactions of 1-arylsulfonyl-2ꢀ1H)-pyridones having an
electron-withdrawing group
Reiko Fujita,a,p Kazuhiro Watanabe,a Wakako Ikeura,a Yohsuke Ohtake,a Hiroshi Hongo,a
Yosihiro Harigayab and Hisao Matsuzakia
aTohoku Pharmaceutical University, Komatsushima, Aoba-ku, Sendai 981-8558, Japan
bKitasato University School of Pharmaceutical Science, Shirokane Minato-ku, Tokyo 108-8642, Japan
Received 4 June 2001; accepted 4 September 2001
AbstractÐA novel synthetic methodology of preparing tetrahydro-2,1H)-quinolones by Diels±Alder reactions between 2-methyl- and 2,3-
dimethyl-1,3-butadienes and 1-arylsulfonyl-2,1H)-pyridones having an electron-withdrawing group at the 5-position is presented. Further-
more, the site-selectivity analyses based on MO calculations of the 5-substituted 2,1H)-pyridones acting as the dienophiles are described.
q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
between the 1-arylsulfonyl-2,1H)-pyridones having an
electron-withdrawing group at the 5-position and a diene,4
and examinations of the site-selectivity of 1,5-substituted
2,1H)-pyridones in terms of activation energy ,Ea) using
ab initio MO calculations.
There have been many reports describing the Diels±Alder
,DA) reactions of 2,1H)-pyridones, which are aromatic, as
dienes.1 In contrast, we have previously reported on the
DA reactions of 2,1H)-pyridones that have an electron-
withdrawing group at the 4- or 6-position, acting as dieno-
philes, to give tetrahydro-1,2H)-isoquinolones.2 To the best
of our knowledge, there are not many reports on the
syntheses of tetrahydro-2,1H)-quinolones using DA
reactions of 2,1H)-pyridones. Recently, we have reported
on the DA reactions of 1-methyl-5-nitro-2,1H)-pyridones to
yield the aromatic 2,1H)-quinolones in 22±30% yields
,Scheme 1).3 From these results, we can assume that
2,1H)-pyridones that have two electron-withdrawing
groups, at the 1- and 5-positions, would have higher
reactivities as dienophiles than 2,1H)-pyridones with one
group at the 5-position, since the additional electron-
withdrawing group at the 1-position may actually decrease
the delocalization of the unshared electrons on the nitrogen
atom, and thus enhance the dienophilic character of the
pyridone ring. Herein, we wish to report a novel method
of preparing tetrahydro-2,1H)-quinolones by DA reactions
2. Results and discussion
2.1. Arylsulfonylations of 2ꢀ1H)-pyridones
The reactions of 2,1H)-pyridones 1a±d with arylsulfonyl
chlorides 2a±h ,1.5 equiv.) using NaH ,1.5 equiv.) as a
base in THF were carried out at 30 or 608C for 5 h, to
yield the desired 1-arylsulfonyl-2,1H)-pyridones 3a±k and
2-arylsulfonyloxypyridines 4i,j, as shown in Table 1 and
Scheme 2. Results showed that the yields of 3a ,94%), 3b
,60%), and 3c ,57%) from the reactions of 5-methoxy-
carbonyl-, 5-acetyl-, and 5-nitro-2,1H)-pyridones 1a±c,
with p-tosyl chloride 2a decreased in the order of the
electron-attracting properties of the R1 substituents of 1
,entries 1±3).5 The reactions of 1a with 4-methoxy-,
4-chloro-, 2-methyl-, and unsubstituted ,R1ˆR2ˆR3ˆH)
Scheme 1.
Keywords: 1-arylsulfonyl-2,1H)-pyridone; tetrahydro-2,1H)-quinolone; Diels±Alder reaction; MO calculation.
Corresponding author. Fax: 181-22-275-2013; e-mail: refujita@tohoku-pharm.ac.jp
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020,01)00893-6

8842
R. Fujita et al. / Tetrahedron 57 12001) 8841±8850
Table 1. Reactions of 2,1H)-pyridones 1a±e with arylsulfonyl chlorides 2a±h in the presence of NaH in THF
Entry
Compound 1
Compound 2
Temperature ,8C)
Time ,h)
Pyridone 3
Yield ,%)
Product 4
Yield ,%)
1
2
3
4
5
6
7
8
a
b
c
a
a
a
b
c
d
e
f
g
h
a
a
30
60
60
60
60
60
60
30
30
30
30
30
5
5
5
5
5
5
5
5
5
5
5
5
a
b
c
d
e
f
g
h
i
94
60
57
91
93
43
92
90
33
34
82
69
a
a
a
a
a
a
a
d
e
9
i
j
33
64
10
11
12
j
k
l
Scheme 2.
benzenesulfonyl chlorides 2b,c,f,e afforded 3d ,91%), 3e
,93%), 3h ,90%), and 3g ,92%) in excellent yields ,entries
4, 5, 8, and 7), whereas the reactions with 4-nitro-, 2,4,6-
trimethyl-, and 2,4,6-triisopropylbenzene-sulfonyl chlorides
,2d,g,h) afforded 3f ,43%), mixture of 3i ,33%) and 4i
,33%), and mixture of 3j ,34%) and 4j ,64%) in moderate
to good total yields ,entries 6,9, and 10). The reaction of 1d
,3-brominated 1a) with 2a gave 3k ,82%) in a high yield
,entry 11). The reaction of 2,1H)-pyridones 1e, which has
an electron-withdrawing group at the 4-position, with 2a
gave 1-arylsulfonyl-2,1H)-pyridone 3l in 69% yield ,entry
12). These results indicate that arylsulfonyl chlorides
bearing an electron-releasing group afford 1-arylsulfonyl-
pyridones in higher yields than those bearing an electron-
withdrawing group at the 4-position or alkyl groups at the
2,6-positions. Furthermore, a bromo substituent ,R3) at the
3-position on the pyridone ring of 1 was also found to be
effective in providing good yield of 3k ,82%, entry 11).
2days in a sealed tube to afford the desired tetrahydro-
2,1H)-quinolones 6a±k stereoselectively, and in some
cases, the undesired 2-sulfonyloxypyridines 4a,b,d,g,h, as
shown in Table 2and Scheme 3. The DA reactions of 3a±c
with 5a afforded nearly identical yields [6a ,46%), 6b
,43%), and 6c ,39%); entries 1±3], differences in the
reactivities of 3a and 3b appear insigni®cant. The reactions
of 3g,i,k with 5a gave 6g ,67%), 6i ,70%), and 6k ,81%),
respectively ,entries 7, 9, and 11) in satisfactory yields,
whereas the reactions of 3d±f,h,j produced 6d ,52%), 6e
,43%), 6f ,43%), 6h ,46%), and 6j ,53%) in moderate yields
,entries 4±6, 8, and 10). In some cases, we were also able to
isolate the corresponding byproducts, 4a,b,d,g,h ,entries 1,
2, 4, 7, and 8). Subsequently, the DA reaction between 3k
and 5a, which afforded the adduct with the highest yield, as
described above, was further studied using an unsymmetri-
cal diene. The reaction of 3k with 2-methyl-1,3-butadiene
5b afforded the regio- and stereoselectively desired tetra-
hydro-2,1H)-quinolone 6l in 35% yield. From these results,
we presume that steric in¯uences of the substituents at the
nitrogen and at the 3-position of the pyridone ring of 3 play
important roles in slowing down the migration. In view of
the report by Afarinkia et al.6 4a,b,d,g, and h seem to be the
2.2. DA reactions
DA reactions of 3a±k with 2,3-dimethyl-1,3-butadiene 5a
,5 equiv.) in o-xylene were carried out at 120±1808C for

R. Fujita et al. / Tetrahedron 57 12001) 8841±8850
8843
Table 2. Diels±Alder reactions of 1-arylsulfonylpyridones 3a±k with dienes 5a,b in o-xylene
Entry
Pyridone 3
Temperature ,8C)
Time ,d)
Adduct 6
Yield ,%)
Product 4
Yield ,%)
1
2
3
4
5
6
7
8
a
b
c
d
e
f
g
h
i
180
180
120
180
140
140
180
140
160
140
160
160
2
2
2
2
2
2
2
2
2
2
4
4
a
b
c
d
e
f
g
h
i
46
43
39
52
43
43
67
46
70
53
81
35
a
b
43
48
d
35
g
h
31
44
9
10
11
12
j
k
k
j
k
l
Scheme 3.
products of intramolecular rearrangement of the arylsul-
fonyl group of 3a,b,d,g,h. To investigate the site-selectivity
of 1-arylsulfonyl-2,1H)-pyridones 3a±k, we carried out the
reaction of 1-arylsulfonyl-2,1H)-pyridone 3l, which has an
electron-withdrawing group at the 4-position. The reaction
of 3l with 5a afforded tetrahydro-1,2H)-isoquinolone 7a
,38%) and 7b ,22%), site-selectively ,Scheme 4). Assign-
ment of the stereochemistry of the ring juncture in 6a±l and
7a,b were carried out as follow, the cis-stereochemistry of
the ring juncture in 6a±l was determined by NOE measure-
ments and con®rmed by X-ray analysis ,Fig. 1) of 6a. For
6a,b, when H-8a was irradiated in each case, an NOE was
observed between H-8a and CH3OOC-4a ,ca. 3.6%) in 6a,
and between H-8a and CH3OC-4a ,ca. 6.4%) in 6b. The cis-
stereochemistry of the ring juncture in 6c±l was deduced by
1
comparing their H NMR spectra with those of 6a,b. In a
previous paper, we reported that the 1H NMR signals
produced by the proton of the ring juncture in the cis-iso-
quinolone adducts ,d 2.84±2.97) is located at a lower range
than those of the corresponding trans-isoquinolone adducts
,d 2.00±2.80).3 The signals assigned to the proton of the ring
juncture in 7a,b appeared at d 2.95 and 2.72, and therefore,
Scheme 4.

8844
R. Fujita et al. / Tetrahedron 57 12001) 8841±8850
X-ray crystallograpy ,Fig. 1). The root mean square error
Ê
of these structures was 0.04 A for the ten heavy atoms ,N1,
C1±C9) in the two rings.
In the DA reaction of 3a with 5a, for example, the calculated
energies of the quinolone-type product was 28.74 kcal
mol21 lower than that of the initial state, and 4.57 kcal
mol21 higher than that of the isoquinolone-type product.
The energy values of the other reactions in Table 3 showed
the identical behavior. Therefore, we can assume that the
retro-DA reactions do not occur and that these DA reactions
are kinetically controlled, and therefore their activation
energies ,Ea) can be used as reaction indices.
Table 3 summarizes the calculated Ea values together with
the experimental yields of adducts. For the DA reactions
1±7 in Table 3, where the dienophiles have an electron-
withdrawing group at the 5-position, in each case, the calcu-
lated Ea value for 5,6-addition is much smaller than that for
3,4-addition. These results are consistent with the experi-
mental ®ndings that only the quinolone-type adducts were
formed in these DA reactions. However, in the reaction 7,
for dienophile 3m, which has a methoxycarbonyl group at
the 5-position and a methyl group at the 1-position but no
arylsulfonyl group, quinolone-type adduct 6m was
produced in a poor yield.8 This experimental result is
supported by theoretical calculations, since the value of Ea
for producting 6m was 1.51 kcal mol21 smaller than that for
Figure 1. ORTEP drawing of 6a.
the structure of the ring juncture in 7a was con®rmed as the
cis- and 7b as the trans-structure. Next, to assign the
position of the methyl group in 3l, 1H±1H correlation
spectroscopy experiment for 3l was carried out. Since corre-
lation between the methylene protons at C-8 and the ole®nic
proton in their cyclohexene moiety was not observed, the
methyl group in 3l is located at C-7.
Table 3. Experimental yields of adducts and activation energies ,Ea) for the DA reactions calculated at the RHF/3-21G level
Reaction
Diene
Dienophile
Temperature ,8C) ,Time)
,3,4)-Addition
Ea ,kcal mol21
,5,6)-Addition
Ea ,kcal mol21
Adduct ,Yield %)
)
Adduct ,yield %)
)
1
2
3
4
5
6
7
8
5a
5a
5a
5a
5a
5b
5a
5a
3a
3b
3c
180,2 d)
140,2 d)
120,2 d)
160,2d)
160,4 d)
160,4 d)
160,6 d)
180,2 d)
31.27
31.64
28.66
31.59
30.66
32.80
35.25b
27.29
±
±
±
±
±
28.79
29.20
19.55
28.05
26.78
27.71
33.74b
33.72±
6a,46)
6bꢀ43)
6c,39)
6i,70)
6k,81)
6l,35)
6m,3)a
3l
3k
3k
3ma
3l
±
±
7a,b,60%)
a
3mˆ1-Methyl-5-methoxcarbonyl-2,1H)-pyridone; 6mˆ4a,5,8,8a-Tetrahydro-cis4a-methoxcarbonyl-1,6,7-trimethyl-2,1H)-quinone.8
Calculated at the RHF/3-211G level.
b
2.3. Site-selectivity
It should be stressed that the quinolone derivatives 6a±l
were produced with high site-selectively via the DA
reactions in which the dienes 5a,b were cycloadded to the
dienophiles 3a±k on the 5,6-position. To study whether the
quinolone or isoquinolone derivatives would be produced
by way of the 5,6-addition or by 3,4-addition, we carried
theoretical studies on the DA reactions listed in Table 3,
searching and optimizing the structures of the transition
states ,TS) using Gaussian 98 at the RHF/3-21G level.7
The optimized structures of the TS of the DA reaction of
3a with 5a are shown in Fig. 2. Furthermore, we also
optimized the structures of the quinolone-type and the
isoquinolone-type products. The optimized structures of
the quinolone-type product from the 5,6-addition in the
DA reaction of 3a with 5a coincide with the structure of
adduct 6a, which was experimentally determined using the
Figure 2. Calculated Structures of TS for 3,4-addition ,left) and for 5,6-
addition ,right) in the DA reaction of 3a with 5. The calculated relevant
Ê
Ê
interatomic distances are: C1±C3ˆ2.258 A, C4±C4ˆ2.105 A, ,left); C1±
Ê
Ê
C5ˆ2.641 A, C4±C6ˆ1.848 A, ,right).

R. Fujita et al. / Tetrahedron 57 12001) 8841±8850
8845
the isoquinolone-type adduct, and over 4.5 kcal mol21
higher than those of the other reactions leading to the
experimentally formed compounds in Table 3.
68 mmol) and acetic anhydride ,110 ml) was re¯uxed for
14 h. After concentrating the reaction mixture in vacuo, the
residue was puri®ed using column chromatography
,acetone±diisopropyl etherˆ2:1). The ®rst fraction was
evaporated to give 3-acetyl-2,1H)-pyridone ,2.60 g, 28%)
as pale yellow needles ,CHCl3), mp 1608C. IR ,KBr): n
In contrast, in the reaction 8, for dienophile 3l, which has a
methoxycarbonyl group at the 4-position and arylsulfonyl
group at the 1-position, the calculated Ea value for the 3,4-
addition is much smaller than that for the 5,6-addition.
These calculated values explain the experimental results,
which show the formation of the isoquinolone-type adduct.
We can conclude from above that the electron-withdrawing
group at the 5-position and the arylsulfonyl group at the
1-position in the pyridone ring are important substituents
that result in producing the quinolone-type adducts in
these DA reactions.
1
1674, 1650, 1359, 774. H NMR ,CDCl3) d: 2.72 ,3H, s,
COMe), 6.46 ,1H, dd, Jˆ6.3, 7.3 Hz, H-5), 7.66 ,1H, dd,
Jˆ2.3, 6.3 Hz, H-6), 8.25 ,1H, dd, Jˆ2.3, 7.3 Hz, H-4). 13C
NMR ,CDCl3) d: 30.83, 107.05, 127.16, 140.28, 144.70,
163.68, 197.25. LMS m/z: 137 ,M1), 122, 94. HRMS
Calcd for C7H7NO2: 137.0477. Found: 137.0466. The
solvent of the second fraction was evaporated to give
5-acetyl-2,1H)-pyridone ,1b, 2.40 g, 15%) as pale yellow
plates ,CHCl3), mp 203±2058C. IR ,KBr): n 1648, 1368,
833. 1H NMR ,CDCl3) d: 2.46 ,3H, s, COMe), 6.60 ,3H, s,
dd, Jˆ0.7, 9.6 Hz, H-3), 8.06 ,1H, dd, Jˆ2.7, 9.6 Hz, H-4),
8.13 ,1H, dd, Jˆ0.7, 2.7 Hz, H-6). 13C NMR ,CDCl3) d:
25.68, 118.98, 119.95, 139.06, 139.76, 165.24, 192.63. LMS
m/z: 137 ,M1), 122, 94. HRMS Calcd for C7H7NO2:
137.0477. Found: 137.0514.
In conclusion, we have developed a novel synthetic method-
ology of preparing tetrahydro-2,1H)-quinolones through
DA reactions of 2,1H)-pyridones, that have electron-
withdrawing groups at the 1- and 5-positions, acting as
dienophiles. Furthermore, site-selectivity of 1,5-substituted
2,1H)-pyridones was explained by their activation energies
,Ea) using ab initio MO calculations.
3.2. General procedures for sulfonylations of 2ꢀ1H)-
pyridones 1a±e with 2a±h
3. Experimental
3.1. General
A solution of sulfonyl chloride 2a ,0.572g, 3 mmol) in THF
,10 ml) at 2788C was added to a stirred suspension of 1a
,0.306 g, 2mmol) and NaH ,0.072g, 3 mmol) in THF
,20 ml) at 2788C. After 1 h, the reaction mixture was
allowed to warm to 608C, and then was stirred for 5 h.
The mixture was poured into ice water ,10 ml), neutralized
with K2CO3, then extracted with CHCl3 ,200 ml). The
CHCl3 extract was dried over Na2SO4 and concentrated in
vacuo. The residue was puri®ed by ¯ash column chromato-
graphy ,diethyl ether±hexaneˆ2:1) to give sulfonyl-
pyridone 3a ,0.866 g, 94%). Reactions of 1b±e ,2mmol)
with 2b±h ,5 mmol) were carried out under similar condi-
tions, as listed in Table 1. The yields of 3a±l and 4i,j are
summarized in Table 1.
The following instruments were used to obtain physical
data: melting points, Yanaco micromelting point apparatus
,values are uncorrected); IR spectra, Perkin Elmer ET-IR
1725X spectrometer; MS, JEOLJMN-DX 303/JMA-
DA5000spectrometer; NMR spectra, JNM-GSX400 ,1H
NMR, 400 MHz; 13C NMR, 100 MHz), JNM-EX270 ,1H
NMR, 270 MHz; 13C NMR, 67.8 MHz) and JEOLJN-
PMX 60SI spectrometer with tetramethylsilane ,TMS) as
an internal standard; elemental analyses, Perkin Elmer
2400 CHN Elemental Analyzer. The following experi-
mental conditions were used for chromatography; column
chromatography, Merk Kieselgel silica gel 60 ,230±400
mesh); TLC, pre-coated TLC plates with 60F254 ,2mm,
Merck).
3.2.1. 5-Methoxycarbonyl-1-ꢀ4-methylbenzenesulfonyl)-
2ꢀ1H)-pyridone ꢀ3a). Colorless needles ,benzene), mp
130±1328C. IR ,KBr): n 1730, 1697, 1593, 1376, 1185,
1
839. H NMR ,CDCl3) d: 2.45 ,3H, s, PhMe), 3.91 ,3H, s,
3.1.1. Synthesis of 3-acetylpyridine 1-oxide. A suspension
of 3-acetylpyridine ,10.4 g, 85 mmol) and m-chloroperoxy-
benzoic acid ,25.9 g, 150 mmol) in CH2Cl2 ,50 ml) was
stirred at room temperature for 3 days. The reaction mixture
was diluted with CHCl3 ,200 ml), and treated with K2CO3
,138 g, 1 mol) and H2O ,45 ml). The organic layer was
separated, dried over Na2SO4, and evaporated in vacuo to
give 3-acetylpyridine 1-oxide ,10.5 g, 90%) as colorless
needles ,CHCl3), mp 140±1428C. IR ,KBr): n 1683, 1372,
OMe), 6.42,1H, dd, Jˆ0.5, 9.7 Hz, 3-H), 7.36 ,2H, d,
Jˆ8.5 Hz, H-Ph), 7.81 ,1H, dd, Jˆ2.4, 9.7 Hz, H-4), 8.00
,2H, d, Jˆ8.5 Hz, H-Ph), 8.93 ,1H, dd, Jˆ0.5, 2.4 Hz, H-6).
13C NMR ,CDC13) d: 21.81, 52.38, 110.34, 122.34, 129.46,
129.98 ,C2), 132.42, 137.03, 139.66, 146.63, 159.33 ,C-2),
163.74. LMS m/z: 307 ,M1), 276, 244, 185, 122. HRMS
Calcd for C14H13NO5S: 307.0514. Found: 307.0494.
3.2.2. 5-Acetyl-1-ꢀ4-methylbenzenesulfonyl)-2ꢀ1H)-pyri-
done ꢀ3b). Pale yellow powder ,CHCl3), mp 161±1638C.
IR ,KBr): n 1707, 1670, 1603, 1376, 1183, 1360, 821. H
1
1292, 916, 804, 719. H NMR ,CDCl3) d: 2.61 ,3H, s,
1
COMe), 7.41 ,1H, dd, Jˆ6.5, 7.9 Hz, H-5), 7.77 ,1H, ddd,
Jˆ1.2, 1.5, 7.9 Hz, H-6), 8.35 ,1H, ddd, Jˆ1.2, 1.5, 6.5 Hz,
H-4), 8.71,1H, dd, Jˆ1.5, 1.5 Hz, H-2). 13C NMR ,CDCl3)
d: 26.76, 124.44, 125.86, 135.47, 139.22, 142.11, 193.37.
LMS m/z: 137 ,M1), 122, 95, 78. HRMS Calcd for
C7H7NO2: 137.0477. Found: 137.0500.
NMR ,CDCl3) d: 2.46 ,3H, s, COMe), 2.53 ,3H, s, PhMe),
6.43 ,1H, dd, Jˆ0.7, 9.7 Hz, H-3), 7.38 ,2H, d, Jˆ8.7 Hz,
H-Ph), 7.87 ,1H, dd, Jˆ2.5, 9.7 Hz, H-4), 8.02 ,2H, d,
Jˆ8.6 Hz, H-Ph), 8.83 ,1H, dd, Jˆ0.7, 2.5 Hz, H-6). 13C
NMR ,CDCl3) d: 21.93, 25.61, 118.2, 122.79, 129.61
,C2), 130.10 ,C2), 132.41, 136.56, 138.57, 146.86,
159.35, 192.43. LMS m/z: 291 ,M1), 227, 91. HRMS
Calcd for C14H13NO4S: 291.0565. Found: 291.0522.
3.1.2. Reaction of 3-acetylpyridine 1-oxide with acetic
anhydride. A solution of 3-acetylpyridine 1-oxide ,9.3 g,

8846
R. Fujita et al. / Tetrahedron 57 12001) 8841±8850
3.2.3. 1-ꢀ4-Methylbenzenesulfonyl)-5-nitro-2ꢀ1H)-pyri-
done ꢀ3c). Colorless plates ,benzene), mp 1828C. IR
,KBr): n 1696, 1619, 1563, 1380, 1186, 814. H NMR
,CDCl3) d: 2.48 ,3H, s, PhMe), 6.47 ,1H, dd, Jˆ0.5,
10.0 Hz, H-3), 7.40 ,2H, d, Jˆ8.5 Hz, H-Ph), 8.02±8.08
,3H, m, H-4, Ph), 9.34 ,1H, dd, Jˆ0.5, 3.1 Hz, H-6). 13C
NMR ,CDC13) d: 22.00, 122.63, 129.83 ,C2), 130.39 ,C2),
131.55 ,C2), 134.07, 134.30, 147.59, 158.33. LMS m/z: 2 94
,M1), 231, 155. HRMS Calcd for C12H10N2O5S: 294.0310.
Found: 294.0351.
1H NMR ,CDCl3) d: 2.47 ,3H, s, PhMe), 3.92 ,3H, s,
OMe), 6.40 ,1H, dd, Jˆ0.5, 9.6 Hz, 3-H), 7.29 ,1H, d,
Jˆ7.4 Hz, H-Ph), 7.42±7.47 ,1H, m, H-Ph), 7.57±7.60
,1H, m, H-Ph), 7.85 ,1H, dd, Jˆ0.5, 9.6 Hz, 4-H), 8.28
,1H, m, H-Ph), 8.96 ,1H, dd, Jˆ0.5, 2.4 Hz, 6-H). 13C
NMR ,CDC13) d: 20.29, 52.45, 110.30, 122.38, 126.38,
132.36, 132.93, 134.22, 134.96, 137.10, 137.97, 139.75,
159.21, 163.67. LMS m/z; 307 ,M1), 276, 226, 91. HRMS
Calcd for C14H13NO5S: 307.0514. Found: 307.0478.
1
3.2.9. 5-Methoxycarbonyl-1-ꢀ2,4,6-trimethylbenzenesul-
fonyl)-2ꢀ1H)-pyridone ꢀ3i). Colorless needles ,ether), mp
3.2.4.
1-ꢀ4-Methoxylbenzenesulfonyl)-5-methoxycar-
1
1958C. IR ,CHCl3): n 1726, 1689, 1602, 1367, 839. H
bonyl-2ꢀ1H)-pyridone ꢀ3d). Colorless needles ,benzene),
mp 139±1418C. IR ,KBr): n 1728, 1616, 1591, 1382,
1171, 846. H NMR ,CDCl3) d: 3.89 ,3H, s, OMe), 3.90
,3H, s, OMe), 6.42,1H, dd, Jˆ0.5, 9.6 Hz, H-3), 7.00 ,2H,
d, Jˆ10.0 Hz, H-Ph), 7.81 ,1H, dd, Jˆ2.5, 9.6 Hz, H-4),
8.08 ,2H, d, Jˆ10.0 Hz, H-Ph), 8.93 ,1H, dd, Jˆ0.5,
2.5 Hz, H-6). 13C NMR ,CDC13) d: 52.46, 55.88, 110.41,
114.17 ,C2), 122.40, 126.32, 132.68 ,C2), 137.17, 139.73,
NMR ,CDCl3) d: 2,31 ,3H, s, PhMe), 2.58 ,6H, s, PhMe,
PhMe), 3.91 ,3H, s, OMe), 6.41 ,1H, dd, Jˆ0.4, 9.8 Hz,
3-H), 6.98 ,2H, s, H-Ph), 7.85 ,1H, dd, Jˆ2.5, 9.8 Hz,
4-H), 8.95 ,1H, dd, Jˆ0.4, 2.5 Hz, H-6). 13C NMR
,CDCl3) d: 21.22, 22.66 ,C2), 52.51, 109.86, 116.01,
122.46, 130.32, 132.13 ,C2), 137.10, 139.69, 141.20,
145.15, 160.02, 163.91. LMS m/z: 336 ,M111), 271, 254,
119, 91. HRMS Calcd for C16H17NO5S: 335.0828. Found:
335.0771.
1
1
159.50, 163.88, 164.94. LMS m/z: 32 3 ,M), 292, 259.
HRMS Calcd for C14H13NO6S: 323.0464. Found: 323.0448.
3.2.5. 1-ꢀ4-Chlorobenzenesulfonyl)-5-methoxycarbonyl-
2ꢀ1H)-pyridone ꢀ3e). Colorless needles ,acetone), mp
1588C. IR ,KBr): n 1727, 1694, 1619, 1381, 1176, 830.
1H NMR ,CDCl3) d: 3.91 ,3H, s, OMe), 6.45 ,1H, dd,
Jˆ0.6, 9.6 Hz, H-3), 7.55 ,2H, d, Jˆ8.9 Hz, H-Ph), 7.83
,1H, dd, Jˆ2.4, 9.6 Hz, H-4), 8.08 ,2H, d, Jˆ8.9 Hz,
H-Ph), 8.89 ,1H, dd, Jˆ0.6, 2.4 Hz, H-6). 13C NMR
,CDC13) d: 52.46, 110.80, 122.35, 129.20 ,C2), 131.41
,C2), 133.81, 136.77, 139.89, 142.16, 159.23, 163.56.
3.2.10. 5-Methoxycarbonyl-1-ꢀ2,4,6-triisopropylbenze-
nesulfonyl)-2ꢀ1H)-pyridone ꢀ3j). Colorless needles
,ether), mp 151±1528C. IR ,CHCl3): n 1728, 1693, 1599,
1
1379, 883, 839. H NMR ,CDCl3) d: 1.18±1.26 ,18H, m,
Jˆ6.9 Hz, Me£6), 2.91 ,1H, m, Jˆ6.9 Hz, CH), 3.93 ,3H, s,
OMe), 3.93±4.05 ,2H, m, Jˆ6.9 Hz, CH£2), 6.42 ,1H, d,
Jˆ9.6 Hz, H-3), 7.19 ,2H, s, H-Ph), 7.85 ,1H, dd, Jˆ2.3,
9.6 Hz, H-4), 8.95 ,1H, dd, Jˆ2.3 Hz, H-6). 13C NMR
,CDCl3) d: 23.3, 24.27 ,C4), 219.43 ,C2), 34.24, 52.42,
110.22, 122.15, 124.07 ,C2), 129.36, 136.12, 139.48,
151.71 ,C2), 155.04, 159.92, 163.78, 172.82. LMS m/z:
420 ,M111), 355, 338, 312, 203, 91. HRMS Calcd for
C22H29NO5S: 419.1767. Found: 419.1744.
1
LMS m/z: 32 9 ,M12), 327 ,M1), 297, 295, 265, 263.
HRMS Calcd for C13H10ClNO5S: 326.9968. Found:
326.9931.
3.2.6. 5-Methoxycarbonyl-1-ꢀ4-nitrobenzenesulfonyl)-
2ꢀ1H)-pyridone ꢀ3f). Colorless plates ,benzene), mp 135±
1378C. IR ,KBr): n 1731, 1684, 1606, 1526, 1348, 1189,
3.2.11. 3-Bromo-5-methoxycarbonyl-1-ꢀ4-methylbenz-
enesulfonyl)-2ꢀ1H)-pyridone ꢀ3k). Colorless plates
,ether), mp 1478C. IR ,KBr): n 1722, 1697, 1593, 1536,
1
846. H NMR ,CDCl3) d: 3.91 ,3H, s, OMe), 6.45 ,1H, d,
1
Jˆ0.6, 9.6 Hz, H-3), 7.55 ,2H, d, Jˆ8.9 Hz, H-Ph), 7.83
,1H, dd, Jˆ2.4, 9.6 Hz, H-4), 8.08 ,2H, d, Jˆ8.9 Hz,
H-Ph), 8.89 ,1H, dd, Jˆ0.6, 2.4 Hz, H-6). 13C NMR
,CDCl3): 52.46, 110.80, 122.35 ,C2), 129.20 ,C2), 133.81,
136.77, 139.89, 142.16, 148.38, 159.23, 163.56. LMS m/z:
338 ,M1), 307, 274, 215, 122. HRMS Calcd for
C13H10N2O7S: 338.0209. Found: 338.0181.
1374, 1175, 740. H NMR ,CDCl3) d: 2.46 ,3H, s, PhMe),
3.92,3H, s, OMe), 7.37 ,2H, d, Jˆ8.1 Hz, H-Ph), 8.03 ,2H,
d, Jˆ8.1 Hz, H-Ph), 8.23 ,1H, d, Jˆ2.2 Hz, H-4), 8.93 ,1H,
d, Jˆ2.2 Hz, H-6). 13C NMR ,CDCl3) d: 21.97, 52.75,
110.65, 117.92, 129.76 ,C2), 130.37 ,C2), 131.83, 136.12,
141.35, 147.18, 155.77, 162.92. LMS m/z: 387 ,M112),
385 ,M1), 323, 301, 155, 91. HRMS Calcd for
C14H12BrNO5S: 384.9620. Found: 384.9652.
3.2.7. 1-Benzenesulfonyl-5-methoxycarbonyl-2ꢀ1H)-pyri-
done ꢀ3g). Colorless columns ,acetone), mp 129±1318C.
IR ,KBr): n 1728, 1683, 1619, 1581, 1341, 1186, 737. H
3.2.12. 4-Methoxycarbonyl-1-ꢀ4-methylbenzenesulfonyl)-
2ꢀ1H)-pyridone ꢀ3l). Colorless needles ,ether), mp 120±
1218C. IR ,CHCl3): n 1734, 1682, 1614, 1334, 1122, 815.
1H NMR ,CDCl3) d: 2.45 ,3H, s, C-Me), 3.95 ,3H, s, OMe),
6.71 ,1H, dd, Jˆ1.7, 7.3 Hz, H-5), 7.03 ,1H, d, Jˆ1.7 Hz, H-
3), 7.35 ,2H, d, Jˆ8.1 Hz, H-30,50), 7.99 ,2H, d, Jˆ8.1 Hz,
H-20,60), 8.14 ,1H, d, Jˆ7.3 Hz, H-6). 13C NMR ,CDCl3) d:
21.79, 53.08, 104.56, 125.53, 129.59 ,C2), 130.03 ,C2),
132.06, 132.87, 141.86, 146.61, 159.87, 164.11. LMS m/z:
308 ,M111), 276, 243, 184, 91. HRMS Calcd for
C14H13NO5S: 307.0562. Found: 307.0610.
1
NMR ,CDCl3) d: 3.91 ,3H, s, OMe), 6.43 ,1H, dd, Jˆ0.6,
9.7 Hz, H-3), 7.55±7.62,2H, m, H-Ph), 7.69±7.75 ,1H, m,
H-Ph), 7.82,1H, dd, Jˆ2.5, 9.7 Hz, H-4), 8.12±8.16 ,2H,
m, H-Ph), 8.93 ,1H, dd, Jˆ0.6, 2.5 Hz, H-6). 13C NMR
,CDC13) d: 52.41, 110.59, 122.35, 128.83 ,C2), 129.89
,C2), 135.06, 135.56, 136.98, 139.75, 159.26, 163.67.
LMSm/z: 293 ,M1), 262, 229, 170. HRMS Calcd for
C13H11NO5S: 293.0358. Found: 293.0310.
3.2.8. 5-Methoxycarbonyl-1-ꢀ2-methylbenzenesulfonyl)-
2ꢀ1H)-pyridone ꢀ3h). Colorless plates ,ether), mp 99±
1008C. IR ,KBr): n 1727, 1697, 1594, 1366, 1183, 767.
3.2.13. 5-Methoxycarbonylpyridin-2yl-2,4,6-trimethyl-
benzenesulfonate ꢀ4i). Colorless needles ,ether), mp

R. Fujita et al. / Tetrahedron 57 12001) 8841±8850
8847
1
73±748C. IR ,CHCl3): n 1730, 1595, 1369, 1175, 823. H
NMR ,CDCl3) d: 2.32 ,3H, s, PhMe), 2.68 ,6H, s, PhMe),
3.92,3H, s, OMe), 6.98 ,2H, s, H-Ph), 7.12,1H, dd, Jˆ0.5,
8.5 Hz, H-3), 8.32,1H, dd, Jˆ2.4, 8.5 Hz, H-4), 8.80 ,1H,
dd, Jˆ0.5, 2.4 Hz, H-6). 13C NMR ,CDCl3) d: 21.21, 22.77
,C2), 52.52, 114.25, 124.43, 131.63 ,C2), 140.15 ,C3),
141.05, 143.83, 150.03, 159.89, 164.57. LMS m/z: 335
,M1), 271, 254, 119, 91. HRMS Calcd for C16H17NO5S:
335.0828. Found: 335.0792.
3.3.2. cis-4a-Acetyl-4a,5,8,8a-tetrahydro-6,7-dimethyl-1-
ꢀ4-methylbenzenesulfonyl)-2ꢀ1H)-quinolone ꢀ6b). Color-
less powder ,CHCl3), mp 197±1988C. IR ,KBr): n 1710,
1
1689, 1597, 1381, 1345, 1170, 831. H NMR ,CDCl3) d:
1.61 ,3H, s, CMe), 1.66 ,3H, s, CMe), 2.12 ,3H, s, COMe),
2.12, 2.27 ,2H, m, H-5,8), 2.38 ,1H, dd, Jˆ7.1, 7.1 Hz,
H-5), 2.41 ,3H, s, PhMe), 2.70 ,1H, dd, Jˆ7.1, 17.1 Hz,
H-8), 5.25 ,1H, ddd, Jˆ2.0, 7.1, 7.1 Hz, H-8a), 5.92 ,1H,
d, Jˆ9.7 Hz, H-3), 6.55 ,1H, dd, Jˆ2.0, 9.7 Hz, H-4), 7.30
,2H, d, Jˆ8.1 Hz, H-Ph), 7.98 ,2H, d, Jˆ8.4 Hz, H-Ph). 13C
NMR ,CDCl3) d: 18.67, 18.75, 21.75, 27.18, 36.95, 40.03,
53.37, 54.68, 121.88, 126.41, 126.46, 128.97 ,C2), 129.32
,C2), 135.89, 144.57, 146.63, 160.90, 204.79. LMS m/z: 373
,M1), 330, 266, 176, 227. HRMS Calcd for C20H23NO4S:
373.1348. Found: 373.1305.
3.2.14. 5-Methoxycarbonylpyridin-2yl-2,4,6-triisopropyl-
benzenesulfonate ꢀ4j). Colorless needles ,ether), mp
1
1158C. IR ,CHCl3): n 1725, 1595, 1383, 1116, 825. H
NMR ,CDCl3) d:1.25 ,12H, d, Jˆ6.9 Hz, CMe£4), 1.26
,6H, d, Jˆ6.9 Hz, CMe£2), 2.92 ,1H, m, Jˆ6.9 Hz, CH),
3.9 2 ,3H, s, OMe), 4.24 ,2H, m, Jˆ6.9 Hz, PhCH£2), 7.09
,1H, dd, Jˆ0.8, 8.6 Hz, H-3), 7.20 ,2H, s, PhCH), 8.32 ,1H,
dd, Jˆ2.5, 8.6 Hz, H-4), 8.80 ,1H, dd, Jˆ0.8, 2.5 Hz, H-6).
13C NMR ,CDCl3) d: 23.58 ,C2), 24.60 ,C4), 29.82 ,C2),
34.32, 52.51, 114.09, 123.79 ,C2), 124.36, 130.78, 141.02,
150.02 ,C2), 150.74, 154.13, 160.10, 164.62. LMS m/z: 42 0
,M111), 355, 338, 312, 203, 91. HRMS Calcd for
C22H29NO5S: 419.1767. Found: 419.1766.
3.3.3. 4a,5,8,8a-Tetrahydro-6,7-dimethyl-1-ꢀ4-methyl-
benzenesulfonyl)-cis-4a-nitro-2ꢀ1H)-quinolone ꢀ6c). Brown
powder ,CHCl3), mp 1808C. IR ,KBr): n 1672, 1620, 1594,
1
816. H NMR ,CDCl3) d: 1.57 ,3H, s, CMe), 1.65 ,3H, s,
CMe), 1.97 ,1H, dd, Jˆ9.7, 17.4 Hz, H-8), 2.30 ,1H, d,
Jˆ17.2 Hz, H-5), 2.42 ,3H, s, PhMe), 2.57 ,1H, d,
Jˆ17.2Hz, H-5), 2.75 ,1H, dd, Jˆ7.2, 17.4 Hz, H-8), 4.77
,1H, ddd, Jˆ1.8, 7.2 , 9.7 Hz, H-8a), 5.86 ,1H, d,Jˆ9.5 Hz,
H-3), 6.50 ,1H, dd, Jˆ1.8, 9.5 Hz, H-4), 7.30 ,2H, d,
Jˆ8.4 Hz, H-Ph), 7.97 ,2H, d, Jˆ8.4 Hz, H-Ph). 13C NMR
,CDCl3) d: 18.18, 18.90, 21.74, 40.44, 43.78, 60.69, 67.27,
122.91, 125.65, 126.40, 128.80 ,C2), 129.19 ,C2), 136.00,
144.70, 147.69, 161.17. MS m/z: 376 ,M1), 330, 266, 174,
159, 91. HRMS Calcd for C18H20N2O5S: 376.1093. Found:
376.1121.
3.3. General procedures for DA reactions of 1-aryl-
sulfonylpyridones 3a±l with 5a,b
A solution of 3a ,0.307 g, 1 mmol) and 5a ,0.410 g,
5 mmol) in o-xylene ,3 ml) was heated at 1808C for
2days in a sealed tube. The reaction mixture was concen-
trated in vacuo, and then puri®ed by column chromato-
graphy ,acetone±hexaneˆ1:2). The ®rst fraction was
evaporated to give 4a ,0.200 g, 43%). The second fraction
was evaporated, then further puri®ed by preparative TLC
over silica gel ,ether±hexaneˆ3:1) to afford 6a ,0.268 g,
46%). Reactions of 3b±l ,1 mmol) with 5a,b ,5 mmol)
were carried out under similar the conditions, as listed in
Table 2, to afford 6b±l, respectively. Yields of 6a±l and
4a,b,d,g,h are summarized in Table 2.
3.3.4.
4a,5,8,8a-Tetrahydro-1-ꢀ4-methoxybenzenesul-
fonyl)-cis-4a-methoxycarbonyl-6,7-dimethyl-2ꢀ1H)-quino-
lone ꢀ6d). Colorless plates ,benzene), mp 1678C. IR ,KBr):
n 1733, 1624, 1594, 1343, 1163, 834. 1H NMR ,CDCl3) d:
1.59 ,3H, s, CMe), 1.60 ,3H, s, CMe), 2.19 ,1H, d, Jˆ7.1,
11.5 Hz, 8-H), 2.32 ,1H, d, Jˆ17.2 Hz, 5-H), 2.62±2.68
,2H, m, 5,8-H), 3.64 ,3H, s, OMe), 3.86 ,3H, s, PhOMe),
5.22 ,1H, ddd, Jˆ2.0, 7.1, 9.1 Hz, 8a-H), 5.87 ,1H, d,
Jˆ9.7 Hz, 3-H), 6.43 ,1H, dd, Jˆ2.0, 9.7 Hz, 4-H), 6.93±
6.98 ,2H, m, H-Ph), 8.00±8.06 ,2H, m, H-Ph). 13C NMR
,CDCl3): 18.63, 18.65, 36.77, 40.67, 47.78, 52.89, 55.46,
55.65, 113.48 ,C2), 122.02 ,C2), 125.61, 126.00, 130.50,
131.52, 146.03, 161.12, 163.52, 172.68. LMS m/z: 405
,M1), 341, 259. HRMS Calcd for C20H23NO6S: 405.1246.
Found: 405.1230.
3.3.1. 4a,5,8,8a-Tetrahydro-cis-4a-methoxycarbonyl-6,7-
dimethyl-1-ꢀ4-methylbenzene-sulfonyl)-2ꢀ1H)-quinolone
ꢀ6a). Colorless plates ,benzene), mp 172±1738C. IR ,KBr):
1
n 1734, 1687, 1596, 1344, 1169, 831. H NMR ,CDCl3)
d:1.60 ,3H, s, CMe), 1.65 ,3H, s, CMe), 2.16 ,1H, d,
Jˆ17.0 Hz, H-8), 2.33 ,1H, d, Jˆ17.5 Hz, H-5), 2.63±
2.70 ,2H, m, H-5,8), 3.65 ,3H, s, OMe), 5.23 ,1H, ddd,
Jˆ2.1, 7.2, 9.3 Hz, H-8a), 5.88 ,1H, d, Jˆ9.6 Hz, H-3),
6.45 ,1H, dd, Jˆ2.1, 9.6 Hz, H-4), 7.29 ,2H, d, Jˆ8.6 Hz,
H-Ph), 7.97 ,2H, d, Jˆ8.6 Hz, H-Ph). 13C NMR ,CDCl3):
18.51, 18.53, 21.63, 36.70, 40.59, 47.74, 52.84, 55.41,
122.12, 125.67, 126.06, 129.03 ,C2), 129.26 ,C2), 136.28,
144.64, 146.24, 161.27, 172.82. LMS m/z: 389 ,M1), 243,
159, 91. HRMS Calcd for C20H23NO5S: 389.1297. Found:
389.1314. X-Ray analytical data ,Fig. 1): 2u range ,23.2±
30.0), crystal system: monoclinic, temperature: 238C, space
3.3.5. 1-ꢀ4-Chlorobenzenesulfonyl)-4a,5,8,8a-tetrahydro-
cis-4a-methoxycarbonyl-6,7-dimethyl-2ꢀ1H)-quinolone
ꢀ6e). Colorless plates ,ether±hexane), mp 1738C. IR ,KBr):
n 1734, 1696, 1598, 1538, 1357, 1131, 826. 1H NMR
,CDCl3) d: 1.61 ,3H, s, CMe), 1.66 ,3H, s, CMe), 2.14±
2.24 ,1H, brm, H-8), 2.34 ,1H, d, Jˆ17.0 Hz, H-5), 2.61±
2.67 ,2H, brd, H-5, 8), 3.65 ,3H, s, OMe), 5.22 ,1H, ddd,
Jˆ2.0, 7.2, 9.4 Hz, H-8a), 5.89 ,1H, d, Jˆ9.6 Hz, H-3), 6.48
,1H, dd, Jˆ2.0, 9.6 Hz, H-4), 7.47 ,2H, d, Jˆ9.2Hz, H-Ph),
8.04 ,2H, d, Jˆ9.2Hz, H-Ph). 13C NMR ,CDCl3) d: 18.62,
18.65, 36.82, 40.64, 47.74, 53.02, 55.66, 122.10, 125.27,
125.94, 127.44, 128.95, 129.53, 133.64, 134.45, 140.67,
146.56, 161.05, 172.59. LMS m/z: 411 ,M112), 409
,M1), 350, 263. HRMS Calcd for C19H20ClNO5S:
409.0751. Found: 409.0699.
Ê
group: P21/c, Dcalc ,g/cm): 1.311, lattice parameters ,A):
aˆ15.257 ,3), bˆ8.380 ,2), cˆ15.439 ,2), Vˆ1973.8
21
Ê
,5) A3, bˆ90.99 ,1)8. Zˆ4. m ,Cu Ka): 16.73 cm
.
Further details have been deposited with the Cambridge
Crystallographic Data Center, University Chemical
Laboratory, Lens®eld Road, Cambrige CB21EW, UK.

8848
R. Fujita et al. / Tetrahedron 57 12001) 8841±8850
3.3.6. 4a,5,8,8a-Tetrahydro-cis-4a-methoxycarbonyl-6,7-
dimethyl-1-ꢀ4-nitrobenzenesul-fonyl)-2ꢀ1H)-quinolone
ꢀ6f). Colorless needles ,benzene), mp 181±1828C. IR
3.3.10. 4a,5,8,8a-Tetrahydro-cis-4a-methoxycarbonyl-
6,7-dimethyl-1-ꢀ2,4,6-triisopropylbenzene-sulfonyl)-
2ꢀ1H)-quinolone ꢀ6j). Colorless needles ,ether±CHCl3),
mp 181±1828C. IR ,CHCl3): n 1741, 1693, 1599, 1331,
883, 825. H NMR ,CDCl3) d: 1.29 ,12H, d, Jˆ6.9 Hz,
1
,KBr): n 1724, 1696, 1607, 1530, 1357, 1168, 829. H
1
NMR ,CDCl3) d:1.62,3H, s, CMe), 1.66 ,3H, s, CMe),
2.20 ,1H, d, Jˆ17.6 Hz, H-8), 2.38 ,1H, d, Jˆ17.6 Hz, H-
5), 2.60±2.72 ,2H, m, H-5,8), 3.66 ,3H, s, OMe), 5.24 ,1H,
ddd, Jˆ2.1, 7.2, 9.2 Hz, H-8a), 5.87 ,1H, d, Jˆ9.7 Hz, H-3),
6.51 ,1H, dd, Jˆ2.1, 9.7 Hz, H-4), 8.32 ,4H, s, H-Ph). 13C
NMR ,CDCl3): 18.63, 18.64, 36.81, 40.57, 47.58, 53.04,
55.62, 122.22 ,C2), 123.46 ,C2), 124.95, 126.88, 130.71,
144.46, 146.98, 150.41, 161.02, 172.31. LMS m/z: 42 0
,M1), 388, 361, 274. HRMS Calcd for C19H20N2O7S:
420.0991. Found: 420.0976.
CMe£4), 1.32,6H, d, Jˆ6.9 Hz, CMe£2), 1.61 ,3H, s,
CMe), 1.65 ,3H, s, CMe), 2.28±2.35 ,2H, brd, H-5,8),
2.70 ,1H, d, Jˆ16.6 Hz, H-5), 2.83±2.93 ,2H, m, H-8,
CH), 3.74 ,3H, s, OMe), 4.10 ,2H, m, Jˆ6.9 Hz, CH£2),
5.30 ,1H, m, Jˆ2.0, 7.4, 9.4 Hz, H-8a), 5.92 ,1H, d,
Jˆ9.6 Hz, H-3), 6.49 ,1H, dd, Jˆ2.0, 9.6 Hz, H-4), 7.16
,2H, s, H-Ph). 13C NMR ,CDCl3) d: 18.59, 18.63, 23.56
,C2), 23.60 ,C2), 24.52 ,C2), 29.63 ,C2), 34.22, 37.10,
41.65, 47.99, 52.93, 54.90, 121.51, 123.95 ,C2), 125.16,
126.36, 133.23, 146.10, 152.03 ,C2), 153.44, 163.48,
172.82. LMS m/z: 502,M 111), 437, 355, 338, 312,
203. HRMS Calcd for C28H39NO5S: 501.2519. Found:
501.2175.
3.3.7.
methoxycarbonyl-6,7-dimethyl-2ꢀ1H)-quinolone
1-Benzenesulfonyl-4a,5,8,8a-tetrahydro-cis-4a-
ꢀ6g).
Colorless plates ,acetone), mp 1588C. IR ,KBr): n 1732,
1687, 1585, 1344, 1173, 758. H NMR ,CDCl3) d:1.60
1
,3H, s, CMe), 1.65 ,3H, s, CMe), 2.15 ,1H, dd, Jˆ7.3,
17.0 Hz, H-8), 2.33 ,1H, d, Jˆ17.0 Hz, H-5), 2.63±2.69
,2H, m, H-5,8), 3.63 ,3H, s, OMe), 5.20±5.24 ,1H, ddd,
Jˆ2.0, 7.3, 7.3 Hz, H-8a), 5.88 ,1H, d, Jˆ9.5 Hz, H-3),
6.46 ,1H, dd, Jˆ2.0, 9.5 Hz, H-4), 7.47±7.63 ,3H, m,
H-Ph), 8.09 ,2H, d, Jˆ8.4 Hz, H-Ph). 13C NMR ,CDCl3):
18.51, 18.54, 36.70, 40.55, 47.07, 52.80, 55.46, 121.96,
125.42, 125.86, 128.21 ,C2), 129.00, 133.40, 139.01,
146.13, 161.00, 172.53. LMS m/z: 375 ,M1), 316, 229,
159. HRMS Calcd for C19H21NO5S: 375.1141. Found:
375.1171.
3.3.11. 3-Bromo-4a,5,8,8a-tetrahydro-cis-4a-methoxy-
carbonyl-6,7-dimethyl-1-ꢀ4-methylbenzene-sulfonyl)-
1ꢀ2H)-quinolone ꢀ6k). Colorless plates ,CHCl3). IR
1
,CHCl3): n 1736, 1697, 1597, 1356, 815, 750. H NMR
,CDCl3) d: 1.62,3H, s, C-Me), 1.65 ,3H, s, C-Me), 2.17
,1H, dd, Jˆ7.3, 17.1 Hz, 8-H), 2.31 ,1H, d, Jˆ17.1 Hz,
5-H), 2.42 ,3H, s, Ph-Me), 2.63±2.73 ,2H, m, Jˆ17.1 Hz,
5, 8-H), 3.65 ,3H, s, OMe), 5.22 ,1H, m, Jˆ2.0, 7.3, 9.3 Hz,
8a-H), 6.83 ,1H, d, Jˆ2.0 Hz, 4-H), 7.30 ,2H, d, Jˆ8.4 Hz,
30,50-H), 7.97 ,2H, d, Jˆ8.4 Hz, 20,60-H). 13C NMR ,CDCl3)
d: 18.57, 18.65, 21.73, 36.78, 40.57, 49.69, 53.13, 55.81,
118.38, 121.97, 125.99, 129.06, 129.34, 135.38, 144.93,
145.76, 156.73, 171.77. LMS m/z: 469 ,M112), 467
,M1), 403, 388, 321, 91. HRMS Calcd for C20H22BrNO5S:
467.0402. Found: 467.0366.
3.3.8. 4a,5,8,8a-Tetrahydro-cis-4a-methoxycarbonyl-6,7-
dimethyl-1-ꢀ2-methylbenzene-sulfonyl)-2ꢀ1H)-quinolone
ꢀ6h). Colorless needles ,ether), mp 137±1398C. IR ,KBr): n
1
1729, 1652, 1596, 1341, 1168, 749. H NMR ,CDCl3) d:
1.62 ,3H, s, CMe), 1.66 ,3H, s,CMe), 2.21 ,1H, brm, H-8),
2.33 ,1H, d, Jˆ17.0 Hz, H-5), 2.70 ,3H, s, PhMe), 2.74±
2.87 ,2H, brm, H-5,8), 3.68 ,3H, s, OMe), 5.22 ,1H, ddd,
Jˆ2.2, 7.4, 9.6 Hz, H-8a), 5.91 ,1H, d, Jˆ9.7 Hz, H-3), 6.47
,1H, dd, Jˆ2.2, 9.7 Hz, H-4), 7.26 ,1H, dd, Jˆ0.8, 7.6 Hz,
H-Ph), 7.32,1H, ddd, Jˆ0.8, 7.6, 18.0 Hz, H-Ph), 7.45 ,1H,
ddd, Jˆ1.2, 7.6, 7.6 Hz, H-Ph), 8.04 ,1H, dd, Jˆ1.2, 8.0 Hz,
H-Ph). 13C NMR ,CDCl3): 18.50, 18.55, 20.76, 36.97,
40.85, 47.88, 52.91, 55.44, 121.99, 125.71, 126.02,
126.17, 131.14, 132.29, 133.46, 137.87, 139.39, 146.35,
162.28, 173.06. LMS m/z: 389 ,M1), 358. HRMS Calcd
for C20H23NO5S: 389.1297. Found: 389.1337.
3.3.12. 3-Bromo-4a,5,8,8a-tetrahydro-cis-4a-methoxy-
carbonyl-7-methyl-1-ꢀ4-methylbenzenesulfonyl)-1ꢀ2H)-
quinolone ꢀ6l). Colorless needles ,Et2O), mp 1988C. IR
1
,CHCl3): n 1736, 1697, 1620, 1597, 1358, 1143, 814. H
NMR ,CDCl3) d: 1.69 ,3H, s, C-Me), 2.00 ,1H, dd, Jˆ3.4,
16.0 Hz, 8-H), 2.02±2.16 ,2H, m, 5, 5-H), 2.19 ,1H, d,
Jˆ16.0 Hz, H-8), 2.42 ,3H, s, Ph-Me), 3.71 ,3H, s, OMe),
5.37 ,1H, brs, H-6), 5.76 ,1H, dd, Jˆ1.7, 3.4 Hz, H-8a), 6.90
,1H, d, Jˆ1.7 Hz, 4-H), 7.30 ,2H, d, Jˆ8.1 Hz, 30,50-H),
7.98 ,2H, d, Jˆ8.4 Hz, 20,60-H). 13C NMR ,CDCl3) d:
21.65 ,C-Me), 22.69 ,C-Me), 26.00, 31.24 ,C-8), 48.68
,C-5), 53.13 ,O-Me), 57.56 ,C-8a), 119.08 ,C-3), 120.56
,C-6 or 7), 129.21 ,C2), 129.43 ,C2), 135.77, 136.52,
143.15, 145.05, 156.75, 171.50. LMS m/z: 455 ,M112),
453 ,M1). HRMS Calcd for C19H20BrNO5S: 453.0246.
Found: 453.0215.
3.3.9. 4a,5,8,8a-Tetrahydro-cis-4a-methoxycarbonl-6,7-
dimethyl-1-ꢀ2,4,6-trimethylben-zenesulfonyl)-2ꢀ1H)-
quinolone ꢀ6i). Colorless needles ,ether±CHCl3), mp 158±
1598C. IR ,CHCl3): n 1736, 1695, 1602, 1336, 887, 825. 1H
NMR ,CDCl3) d: 1.61 ,3H, s, CMe), 1.66 ,3H, s, CMe),
2.24±2.30 ,5H, m, PhMe, H-5,8), 2.63 ,6H, s, PhMe£2),
2.76±2.90 ,2H, m, H-5,8), 3.74 ,3H, s, OMe), 5.18 ,1H,
ddd, Jˆ2.0, 5.3, 7.3 Hz, H-8a), 5.92 ,1H, d, Jˆ9.8 Hz,
H-3), 6.44 ,1H, dd, Jˆ2.0, 9.8 Hz, H-4), 6.93 ,2H, s,
H-Ph). 13C NMR ,CDCl3) d: 18.4, 18.55, 21.01, 22.64
,C2), 37.25, 41.13, 47.87, 52.83, 55.36, 121.46, 125.65,
126.05, 131.56 ,C2), 133.35, 140.86 ,C2), 143.24, 145.81,
163.33, 173.07. LMS m/z: 418 ,M111), 353, 321, 294, 271,
261, 139, 91. HRMS Calcd for C22H27NO5S: 417.1610.
Found: 417.1559.
3.3.13.
5-Methoxycarbonylpyridin-2yl-4-methylbenz-
enesulfonate ꢀ4a). Colorless needles ,acetone), mp 71±
738C. IR ,KBr): n 1724, 1597, 1375, 1302, 1130, 881,
817. H NMR ,CDCl3) d: 2.46 ,3H, s, PhMe), 3.93 ,3H, s,
1
OMe), 7.15 ,1H, dd, Jˆ0.7, 8.4 Hz, H-3), 7.35 ,2H, d,
Jˆ8.6 Hz, H-Ph), 7.92,2H, d, Jˆ8.6 Hz, H-Ph), 8.34 ,1H,
dd, Jˆ2.3, 8.4 Hz, H-4), 8.86,1H, dd, Jˆ0.7, 2.3 Hz, H-6).
13C NMR ,CDCl3) d: 21.77, 52.58, 114.99, 124.97, 128.78
,C2), 129.78 ,C2), 133.46, 141.35, 145.68, 150.23, 159.71,
164.70. LMS m/z: 306 ,M121), 243. HRMS Calcd for
C14H13NO5S: 307.0515. Found: 307.0531.

R. Fujita et al. / Tetrahedron 57 12001) 8841±8850
8849
3.3.14. 5-Acetylpyridin-2yl-4-methylbenzenesulfonate
ꢀ4b). Colorless powder ,CHCl3), mp 103±1058C. IR
168.64, 172.34. LMS m/z: 389 ,M1), 330, 174, 91. HRMS
Calcd for C20H23NO5S: 389.1297. Found: 389.1307.
1
,KBr): n 1686, 1587, 1371, 1316, 819. H NMR ,CDCl3)
3.3.19. 4a,5,8,8a-Tetrahydro-trans-4a-methoxycarbonyl-
6,7-dimethyl-1-ꢀ4-methylbenzenesulfonyl)-2ꢀ1H)-iso-
quinolone ꢀ7b). Colorless plates ,ether), mp 1558C. IR
d: 2.46 ,3H, s, COMe), 2.60 ,3H, s, PhMe), 7.16 ,1H, d,
Jˆ8.6 Hz, H-3), 7.36 ,2H, d, Jˆ8.4 Hz, H-Ph), 7.93 ,2H, d,
Jˆ8.4 Hz, H-Ph), 8.29 ,1H, dd, Jˆ2.5, 8.6 Hz, H-4), 8.80
,1H, d, Jˆ2.5 Hz, H-6). 13C NMR ,CDCl3) d: 21.93, 25.61,
118.25, 122.79, 129.61 ,C2), 130.10 ,C2), 132.41, 136.56,
138.57, 146.86, 159.35, 192.43. LMS m/z: 291 ,M1), 227,
91. HRMS Calcd for C14H13NO4S: 291.0565. Found:
291.0522.
1
,KBr): n 1732, 1597, 1359, 1172, 814. H NMR ,CDCl3)
d: 1.56 ,3H, s, C-Me), 1.61 ,3H, s, C-Me), 2.11 ,1H, d,
Jˆ16.8 Hz, 5-H), 2.17±2.24 ,1H, m, 8-H), 2.27±2.33 ,1H,
m, 8-H), 2.44 ,3H, s, Ph-Me), 2.67 ,1H, d, Jˆ16.8 Hz, 5-H),
2.72 ,1H, dd, Jˆ5.1, 11.2Hz, 8a-H), 3.50 ,3H, s, OMe),
5.16 ,1H, d, Jˆ8.1 Hz, 4-H), 7.09 ,1H, d, Jˆ8.1 Hz, 3-H),
7.33 ,2H, d, Jˆ8.3 Hz, 30,50-H), 7.91 ,2H, d, Jˆ8.3 Hz,
20,60-H). 13C NMR ,CDCl3) d: 18.72, 18.73, 21.66, 29.29,
39.54, 44.79, 45.84, 52.05, 112.08, 123.46, 124.35, 125.69,
128.72 ,C2), 129.32 ,C2), 135.47, 145.00, 168.94, 171.74.
LMS m/z: 389 ,M1), 330, 174, 91. HRMS Calcd for
C20H23NO5S: 389.1297. Found: 389.1283.
3.3.15.
5-Methoxycarbonylpyridin-2yl-4-methoxyl-
benzenesulfonate ꢀ4d). Colorless needles ,ether±hexane),
mp 89±928C. IR ,KBr): n 1739, 1596, 1371, 1300, 1175,
1129, 843, 832, 807. H NMR ,CDCl3) d: 3.89 ,3H, s,
1
PhOMe), 3.93 ,3H, s, COOMe), 7.00 ,2H, d, Jˆ9.1 Hz,
H-Ph), 7.15 ,1H, dd, Jˆ0.7, 8.4 Hz, H-3), 7.97 ,2H, d,
Jˆ9.1 Hz, H-Ph), 8.34 ,1H, dd, Jˆ2.5, 8.4 Hz, H-4), 8.86
,1H, dd, Jˆ0.7, 2.5 Hz, H-6). 13C NMR ,CDCl3) d: 52.57,
55.76, 114.97, 114.33 ,C2), 124.88, 127.65, 131.16 ,C2),
141.32, 150.22, 159.79, 164.34, 164.73. LMS m/z: 32 3
,M1), 259. HRMS Calcd for C14H13NO6S: 323.0464.
Found: 323.0442.
3.4. Calculation of activation energy
The structures of the initial and the transition states ,TS)
were optimized using the restricted Hartree±Fock ,RHF)
method at the 3-21G level in the Gaussian 98 program
package.7 Solvent effects were not considered. Assuming
that the diene and the dienophile were signi®cantly sepa-
rated at the initial state, the activation energy was calculated
as the energy difference between the TS and the initial state.
After optimizing the TS structure, vibrational calculations
were performed to con®rm that the TS has exactly one
imaginary vibrational frequency. Intrinsic reaction coordi-
nate calculations were also carried out to con®rm that the TS
connected the initial with the intended ®nal state.
3.3.16. 5-Methoxycarbonylpyridin-2yl-benzenesulfonate
ꢀ4g). Colorless needles ,ether±hexane), mp 508C. IR ,KBr):
1
n 1728, 1590, 1386, 1182, 1133, 830, 794, 746. H NMR
,CDCl3) d: 3.93 ,3H, s, OMe), 7.16 ,1H, dd, Jˆ0.7, 8.4 Hz,
H-3), 7.45±7.60 ,2H, m, H-Ph), 7.66±7.72 ,1H, m, H-Ph),
7.92±8.08 ,2H, m, H-Ph), 8.35 ,1H, dd, Jˆ2.4, 8.4 Hz,
H-4), 8.86 ,1H, dd, Jˆ0.7, 2.4 Hz, H-6). 13C NMR
,CDCl3) d: 52.60, 114.95, 125.07, 128.74 ,C2), 129.14
,C2), 134.44, 136.54, 141.42, 150.21, 159.47, 164.66.
LMS m/z: 294 ,M111), 293 ,M1), 229. HRMS Calcd for
C13H11NO5S: 293.0358. Found: 293.0358.
References
3.3.17. 5-Methoxycarbonylpyridin-2yl-2-methylbenz-
enesulfonate ꢀ4h). Colorless oil ,acetone). IR ,KBr): n
1. Review for Diels±Alder reactions of 2,1H)-pyridones:
Afarinkia, K.; Vinader, V.; Nelson, T. D.; Posner, G. H.
Tetrahedron 1992, 48, 9111±9171.
1
1730, 1594, 1319, 1176,748. H NMR ,CDCl3) d: 2.78
,3H, s, PhMe), 3.92,3H, s, OMe), 7.18 ,1H, dd, Jˆ0.7,
8.5 Hz, H-3), 7.30±7.40 ,2H, m, H-Ph), 7.54 ,1H, ddd,
Jˆ1.3, 8.1, 8.1 Hz, H-Ph), 8.99 ,1H, dd, Jˆ1.3, 8.1 Hz,
H-Ph), 8.34 ,1H, dd, Jˆ2.5, 8.5 Hz, H-4), 8.81,1H, dd,
Jˆ0.7, 2.5 Hz, H-6). 13C NMR ,CDCl3) d: 21.77, 52.58,
114.99, 124.97, 128.78 ,C2), 129.78 ,C2), 133.46, 141.35,
145.68, 150.23, 159.71, 164.70. LMS m/z: 307 ,M1),
243. HRMS Calcd for C14H13NO5S: 307.0515. Found:
307.0549.
2. ,a) Kato, H.; Fujita, R.; Hongo, H.; Tomisawa, H. Heterocycles
1979, 12, 1±4. ,b) Tomisawa, H.; Kato, H.; Fujita, R.; Hongo,
H. Chem. Pharm. Bull. 1979, 27, 810±812. ,c) Tomisawa, H.;
Fujita, R.; Kato, H.; Hayasaka, K.; Kamimura, T.; Hongo, H.
Chem. Pharm. Bull. 1988, 36, 1882±1885. ,d) Nakano, H.;
Date, T.; Okamura, K.; Tomisawa, H.; Hongo, H. Chem.
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3. Fujita, R.; Watanabe, K.; Nisiuchi, Y.; Honda, R.; Matsuzaki,
H.; Hongo, H. Chem. Pharm. Bull. 2001, 49, 601±605.
4. Preliminary communication for this paper: Fujita, R.;
Watanabe, K.; Ikeura, W.; Ohtake, Y.; Hongo, H. Heterocycles
2000, 53, 2607±2610.
3.3.18. 4a,5,8,8a-Tetrahydro-6,7-dimethyl-cis-4a-methoxy-
carbonyl-1-ꢀ4-methylbenzenesulfonyl)-2ꢀ1H)-isoquinolone
ꢀ7a). Colorless needles ,ether), mp 708C. IR ,KBr): n 1736,
11359, 1172, 754. 1H NMR ,CDCl3) d: 1.56 ,6H, s, C-Me),
1.96 ,1H, d, Jˆ17.4 Hz, 5-H), 2.14 ,1H, dd, Jˆ6.9, 17.0 Hz,
8-H), 2.26 ,1H, dd, Jˆ6.9, 17.0 Hz, 8-H), 2.37 ,1H, d,
Jˆ17.4 Hz, 5-H), 2.44 ,3H, s, Ph-Me), 2.95 ,1H, ddd,
Jˆ1.0, 6.9, 6.9 Hz, 8a-H), 3.50 ,3H, s, OMe), 5.16 ,1H,
dd, Jˆ1.0, 8.1 Hz, 4-H), 7.03 ,1H, d, Jˆ8.1 Hz, 3-H),
5. Dean, J. A. Lange's Handbook of Chemistry; Mc Graw-Hill:
New York, 1972; Section 3, pp 133±134.
6. Afarinkia, K.; Mahmood, F. Tetrahedron Lett. 1998, 39, 493±
496.
7. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgom-
ery, Jr., J. A.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.;
Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.;
Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.;
Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski,
J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.;
7.32,H2, dd,
Jˆ1.8, 6.8 Hz, 30,50-H), 7.86 ,2H, dd,
Jˆ1.8, 6.8 Hz, 20,60-H). 13C NMR ,CDCl3) d: 17.41,
17.90, 20.68, 28.39, 35.75, 42.43, 43.92, 51.50, 111.30,
121.17, 122.86, 124.11, 127.54, 128.42, 134.24, 144.14,

8850
R. Fujita et al. / Tetrahedron 57 12001) 8841±8850
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