Synthesis of substituted 2-pyridones via the Pummerer cyclization- deprotonation-cycloaddition cascade of imidosulfoxides

Article abstract of DOI:10.1021/jo982315r

1-Ethanesulfinylacetylpiperidin-2-one was prepared from δ-valerolactam in two steps by heating with ethylsulfenylacetyl chloride followed by sodium periodate oxidation. Slow addition of the imidosulfoxide to a refluxing mixture of toluene, acetic anhydride (10 equiv), andp-toluenesulfonic acid (1 mol%) resulted in the formation of an isomunchnone dipole which underwent bimolecular trapping in good yield. The stereochemical assignment of the cycloadduct was made on the basis of X-ray crystallography and is the consequence of an endo cycloaddition with respect to the dipole. The regiochemistry of the cycloaddition is consistent with a HOMO-dipole controlled process. Several related imidosulfoxides containing a tethered alkenyl group were prepared and subjected to the Pummerer reaction conditions. The resulting mesoionic dipoles formed by the cyclizationdeprotonation sequence undergo ready dipolar cycloaddition across the pendant olefin to afford intramolecular cycloadducts in high yield. Exposure of these cycloadducts to acetic anhydride in the presence of a trace of p-toluenesulfonic acid results in ring opening to give 5-acetoxy- substituted 2-pyridones. The lone pair of electrons on the amide nitrogen assists in opening the oxy bridge to generate a transient N-acyliminium ion, which subsequently loses a proton. In certain cases, the amide electron pair with the oxy bridge is partially twisted from an antiperiplanar arrangement and a competive ring cleavage also occurs to give 5-thioethyl-substituted 2- pyridones.

Full text of DOI:10.1021/jo982315r

2038
J . Org. Chem. 1999, 64, 2038-2049
Syn th esis of Su bstitu ted 2-P yr id on es via th e P u m m er er
Cycliza tion -Dep r oton a tion -Cycloa d d ition Ca sca d e of
Im id osu lfoxid es†
Albert Padwa,* Todd M. Heidelbaugh, and J effrey T. Kuethe
Department of Chemistry, Emory University, Atlanta, Georgia 30322
Received November 24, 1998
1-Ethanesulfinylacetylpiperidin-2-one was prepared from δ-valerolactam in two steps by heating
with ethylsulfenylacetyl chloride followed by sodium periodate oxidation. Slow addition of the
imidosulfoxide to a refluxing mixture of toluene, acetic anhydride (10 equiv), and p-toluenesulfonic
acid (1 mol %) resulted in the formation of an isomu¨nchnone dipole which underwent bimolecular
trapping in good yield. The stereochemical assignment of the cycloadduct was made on the basis
of X-ray crystallography and is the consequence of an endo cycloaddition with respect to the dipole.
The regiochemistry of the cycloaddition is consistent with a HOMO-dipole controlled process. Several
related imidosulfoxides containing a tethered alkenyl group were prepared and subjected to the
Pummerer reaction conditions. The resulting mesoionic dipoles formed by the cyclization-
deprotonation sequence undergo ready dipolar cycloaddition across the pendant olefin to afford
intramolecular cycloadducts in high yield. Exposure of these cycloadducts to acetic anhydride in
the presence of a trace of p-toluenesulfonic acid results in ring opening to give 5-acetoxy-substituted
2-pyridones. The lone pair of electrons on the amide nitrogen assists in opening the oxy bridge to
generate a transient N-acyliminium ion, which subsequently loses a proton. In certain cases, the
amide electron pair with the oxy bridge is partially twisted from an antiperiplanar arrangement
and a competive ring cleavage also occurs to give 5-thioethyl-substituted 2-pyridones.
Due to their common occurrence in nature,1 oxygen-
containing heterocycles are frequent and important
targets for synthesis either as final products or as useful
synthetic intermediates. Of particular importance is the
tetrahydrofuran ring2 since this structural unit is found
in many naturally occurring compounds.3 Although the
synthesis of tetrahydrofurans commonly proceeds via
C-O bond formation,3 the application of C-C bond
forming reactions to construct this ring has also been
used in recent years.4 Conceptually, the 1,3-dipolar
cycloaddition of carbonyl ylides with π-bonds represents
an attractive strategy for the construction of tetrahydro-
furans.5
Sch em e 1. Va r iou s Meth od s Utilized to Gen er a te
th e Ca r bon yl Ylid e Dip ole
Common methods for carbonyl ylide formation (Scheme
1) involve the thermolysis or photolysis of epoxides
† This paper is dedicated to Henk van der Plas on the occasion of
his 70th birthday, for his significant contributions to the field of
heterocyclic chemistry.
(1) Moore, R. E. Marine Natural Products: Chemical and Biological
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Vol. 2.
possessing electron-withdrawing substituents,6-9 the ther-
mal extrusion of nitrogen from 1,3,4-oxadiazolines,10-12
and the loss of carbon dioxide from 1,3-dioxolan-4-ones.13
(2) Boiuin, T. L. B. Tetrahedron 1987, 43, 3309. Rao, A. S.; Paknikar,
S. K. K.; Kirtane, J . G. Tetrahedron 1983, 39, 2323.
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and Benzo Derivatives. In Progress in Heterocyclic Chemistry; Gribble,
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pp 117-147.
(4) For some recent examples of C-C bond forming reactions leading
to THFs, see: Broka, C. A.; Shen, T. J . Am. Chem. Soc. 1989, 111,
2981. Feldman, K. S.; Fisher, T. E. Tetrahedron 1989, 45, 2969.
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10.1021/jo982315r CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/03/1999

Synthesis of Substituted 2-Pyridones
J . Org. Chem., Vol. 64, No. 6, 1999 2039
Sch em e 2
More recently, Hosomi and co-workers demonstrated that
simple carbonyl ylides may be expediently produced by
a silicon-based 1,3-elimination under mild and neutral
conditions.14 Nonstabilized carbonyl ylides were also
generated by treating 1-iodoalkyl trialkylsilyl ethers with
15
both SmI2 and a manganese-PbCl2-Me3SiCl combina-
tion.16
Sch em e 3
The creation of carbonyl ylides from the reaction of
diazo compounds with ketones in the presence of Rh(II)
catalysts,17,18 especially in intramolecular reactions,19 has
significantly broadened their applicability for natural
product synthesis.20-22 Subsequent studies have demon-
strated that both carbonyl ylides as well as oxonium
ylides, derived from the reaction of metallo carbenoids
with carbonyl and ethereal oxygens, can be used as
intermediates in a wide variety of subsequent transfor-
mations, including dipolar cycloadditions,17-19 Steven’s
1,2-shifts,23,24 2,3-sigmatropic rearrangements,25,26 and
simple â-eliminations.27 While the generation of carbonyl
ylides from diazo precursors is quite common, the base-
induced deprotonation of an oxonium ion such as 9 as a
method for dipole formation has largely been ignored.
This is somewhat surprising since the removal of a proton
from various onium salts is a well-recognized process that
has been extensively used to form ammonium28 and
sulfonium ylides.29 The absence of this method for car-
bonyl ylide formation is undoubtedly due to the inherent
difficulty in forming the dipole by deprotonation. The
problem stems from a competitive deprotonation at the
â-site, which ultimately leads to a substituted enol ether
(i.e., 10) (Scheme 2).
In an attempt to clarify the factors that might influence
carbonyl ylide formation by the deprotonation approach
(i.e., 9 f 1), we eventually were led to study the
Pummerer reaction of imidosulfoxides.30 Our interest in
this particular reaction was stimulated by our continuing
involvement with the cycloaddition chemistry of me-
soionic compounds.31 Mesoionic betaines are five-mem-
bered heterocyclic ring systems that cannot be repre-
sented by normal covalent structures and are best
described as a hybrid of all possible forms.32 The iso-
mu¨nchnone class of mesoionics can easily be generated
from the Rh(II)-catalyzed reaction of R-diazo imides
(Scheme 3).33,34 The facility with which this mesoionic
system was formed can be attributed to the dipolar
aromatic resonance structure 12, which helps stabilize
the dipole.33,34 Since isomu¨nchnones contain a carbonyl
ylide dipole within their framework, they are willing
participants in 1,3-dipolar cycloaddition chemistry. R-A-
cyl thionium ions generated from R-acyl sulfoxides under
Pummerer conditions are powerful electrophiles, reacting
efficiently with a variety of nucleophilic species.35-37 We
reasoned that the initially formed thionium ion 15
(10) Shimizu, N.; Bartlett, P. D. J . Am. Chem. Soc. 1978, 100, 4260.
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Bekhazi, M.; Smith, P. J . Warkentin, J . Can. J . Chem. 1983, 61, 619.
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Lett. 1993, 37, 5943. Hojo, M.; Ishibashi, N.; Hosomi, A. Synlett 1996,
234.
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A.; Krumpe, K. E. Tetrahedron 1992, 48, 5385. Padwa, A.; Weingarten,
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(30) For a preliminary report of this work, see: Kuethe, J . T.; Padwa,
A. J . Org. Chem. 1997, 62, 774.
(31) Padwa, A.; Harring, S. R.; Semones, M. A. J . Org. Chem. 1998,
63, 44, and references therein.
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1994, 123.
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184.

2040 J . Org. Chem., Vol. 64, No. 6, 1999
Padwa et al.
Sch em e 4
Sch em e 5
derived from imidosulfoxide 14 would rapidly cyclize with
the neighboring imido group, and the resulting oxonium
ion 16 should undergo ready deprotonation to produce
the highly stabilized carbonyl ylide 17 (Scheme 4).
Indeed, under the proper experimental conditions (vide
infra), this tandem Pummerer cyclization-deprotonation
sequence works extremely well and represents a highly
efficient method for generating isomu¨nchnone dipoles. In
this paper, we report a full account of our efforts in this
field.
the ethylsulfenylmethyl carbamoyl ester 24. This com-
pound is formed by the addition of adventitious water to
the isomu¨nchnone dipole followed by ring opening of the
transient hemiaminal 23. When water was deliberately
added to the reaction mixture, a high yield (88%) of 24
was isolated.
Resu lts a n d Discu ssion
The required imidosulfoxides necessary for the Pum-
merer-induced cyclization-deprotonation sequence were
easily obtained by heating the appropriate amide with
(ethylsulfenyl)acetyl chloride (18)38 followed by sodium
periodate oxidation. The classical Pummerer reaction can
be initiated by a variety of electrophilic reagents (Pum-
merer promoters).35-37 Acetic anhydride is by far the most
commonly used reagent and is often utilized as the
solvent at reflux temperature or in combination with
other solvents or cocatalysts. The more electrophilic
trifluoroacetic anhydride (TFAA) has also been exten-
sively employed since it allows the reaction to proceed
under very mild conditions in the presence of basic (e.g.,
pyridine, triethylamine) or Lewis acid catalysts (e.g.,
SnCl4). We opted to conduct our initial set of experiments
using TFAA as the Pummerer promoter. The first system
investigated involved the reaction of N-acetyl-2-ethane-
sulfinyl-N-methylacetamide (19) with excess TFAA at 0
°C in the presence of triethylamine. Even though this
reaction was carried out in the presence of various
trapping agents (i.e., DMAD, N-phenylmaleimide, methyl
acrylate, etc.), no signs of an isomu¨nchnone cycloadduct
could be detected. The only product isolated corresponded
to the trifluoroacetyl-substituted oxazolidone 21 (Scheme
5).
Our inability to isolate an isomu¨nchnone cycloadduct
from these TFAA-promoted reactions suggested that a
modified triggering protocol had to be developed in order
to trap the mesoionic betaine intermediate. After con-
siderable experimentation with a variety of Pummerer
promoters and cocatalysts, we found that dipole forma-
tion/trapping occurred in high yield when a mixture of
toluene and acetic anhydride which also contained a
catalytic quantity of p-toluenesulfonic acid (p-TSOH) was
used.39 These conditions, whereby the sulfoxide is slowly
added to a refluxing mixture of toluene, acetic anhydride
(10 equiv), p-TsOH (catalyst), and the appropriate di-
enophile (1.5 equiv), gave consistently the best results
(>80% yields), for both the inter- and intramolecular
cycloaddition reactions (vide infra). Thus, the reaction
Apparently, the initially formed betaine is unstable to
the reaction conditions and reacts further with excess
TFAA followed by a subsequent deprotonation to give 21.
When the related isobutyramide 22 was treated under
similar experimental conditions, the only product ob-
tained (even with added dipolarophiles) corresponded to
of imidosulfoxide 19 under the above conditions with
added N-phenylmaleimide led, after column chromatog-
raphy, to cycloadduct 25 in 85% yield as a single
diastereomer. Its spectroscopic properties support the
stereochemical assignment of 25 as being the result of
endo cycloaddition with respect to the dipole, and this
(36) Grierson, D. S.; Husson, H. P. In Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 6, pp 909-
947.
(37) Kennedy, M.; McKervey, M. A. In Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 7, pp 193-
216.
(38) Mooradian, A.; Cavallito, C. J .; Bergman, A. J .; Lawson, E. J .;
Suter, C. M. J . Am. Chem. Soc. 1949, 71, 3372.
(39) Watanabe, M.; Nakamori, S.; Hasegawa, H.; Shirai, K.; Kuma-
moto, T. Bull. Chem. Soc. J pn. 1981, 54, 817.

Synthesis of Substituted 2-Pyridones
J . Org. Chem., Vol. 64, No. 6, 1999 2041
Sch em e 6
Sch em e 7
HOMO.43 It is well-known that the Câ coefficient of the
LUMO of an electron-deficient dipolarophile is larger
than the CR coefficient,44 and consequently cycloadduct
31 (or furan 29) is predicted to be the major regioisomer
formed.
During the course of our studies, we found that the
isomu¨nchnone cycloadducts underwent ready rearrange-
ment to give 2-hydroxy pyridones when treated with a
Lewis acid such as BF3‚OEt2. Typically, the ring-opened
2-hydroxy pyridones were converted to the corresponding
acetoxy derivatives for characterization purposes. The
major product is derived by oxybridge cleavage promoted
by the nitrogen atom lone pair. In a typical example,
treatment of cycloadduct 27 with BF3‚OEt2 at 80 °C
afforded a 5:1 mixture of pyridones 33 and 34 (96%
combined yield). Formation of pyridone 34 as the minor
product (16%) is a consequence of oxybridge cleavage in
the alternate direction.
was confirmed by X-ray crystallography.40 An analogous
cycloaddition process occurred when the related pheny-
lacetamide sulfoxide 26 (R ) Ph) was used with N-
phenylmaleimide as the trapping agent (i.e., 26 f 27 in
72% yield).
Several types of dipolarophiles were examined to
establish the scope and generality of the process. The
tandem Pummerer-cyclization-deprotonation-cycload-
dition sequence using imidosulfoxide 19 proceeded
smoothly with 1,4-naphthoquinone, dimethyl acetylene-
dicarboxylate, methyl propiolate, and phenyl vinyl sul-
fone (Scheme 6). In all cases the initially formed iso-
mu¨nchnone dipole was trapped by the added dipolarophile,
and good yields of the expected dipolar cycloadduct were
obtained. When acetylenic dipolarophiles were employed,
the initially formed cycloadducts were not isolated, as
they readily lost methyl isocyanate41 to give R-thioethyl-
substituted furans (i.e., 29 and 30). When phenyl vinyl
sulfone was used as the dipolarophile, a 2:1 mixture of
the exo and endo isomers of the mesoionic cycloadduct
31 was isolated in addition to the acetoxy-substituted
pyridone 32. Compound 32 was shown to be derived from
an acetic acid induced rearrangement of cycloadduct 31.
The regiochemistry of the cycloaddition is consistent with
an FMO analysis of the reaction. MNDO calculations
indicate that the dominant interaction of an isomu¨nch-
none dipole with an electron-deficient dipolarophile is
between the HOMO-dipole LUMO-dipolarophile (type
I).42 This correlates with the exclusive formation of both
cycloadduct 31 and furan 29. The calculations indicate
that the atomic coefficient at the C3 carbon of the
isomu¨nchnone is larger than the C5 carbon for the
To access synthetically more valuable targets, we
focused our attention on the Pummerer-cycloaddition
reaction of several cyclic imidosulfoxides. When the five-
membered ring cyclic imide 35 was subjected to the
Pummerer-deprotonation conditions, R-acetoxy sulfide 36
was the only product isolated from the reaction mixture.
In this case, the initially generated thionium ion is
reluctant to undergo cyclization with the adjacent car-
bonyl group, and instead, it reacts with an external
nucleophile (i.e., AcO-) to furnish the normal Pummerer
product 36. This behavior may be related to the ring
strain present in the fused five-membered-ring mesoionic
intermediate, which causes a significant suppression in
the cyclization rate. In contrast to the five-membered-
ring system, the six- (37) and seven- (38) membered
imido-sulfoxides afforded good yields of cycloadducts 39-
41 when treated with Ac2O and N-phenylmaleimide (or
maleic anhydride) (Scheme 7). Further treatment of 39
with BF3‚OEt2 followed by reaction with Ac2O furnished
pyridone 42 in 98% yield. The facility with which iso-
(40) The authors have deposited coordinates for structure 25 with
the Cambridge Crystallographic Data Centre. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K.
(41) Ibata, T.; Hamaguchi, M.; Kiyohara, H. Chem. Lett. 1975, 21.
(42) Sustmann, R. Tetrahedron Lett. 1971, 2717. Sustmann, R.; Trill,
H. Angew. Chem., Int. Ed. Engl. 1972, 11, 838.
(43) Padwa, A.; Hertzog, D. L. Tetrahedron 1993, 49, 2589.
(44) Houk, K. N. Acc. Chem. Res. 1975, 8, 361.

2042 J . Org. Chem., Vol. 64, No. 6, 1999
Padwa et al.
Sch em e 8
mu¨nchnone formation occurs with these larger ring
lactams is undoubtedly associated with the faster rate
of thionium ion cyclization with the adjacent carbonyl
group. With these systems, intramolecular attack by the
neighboring imido group onto the thionium ion is faster
than the bimolecular reaction with an acetoxy anion.
Ring strain is clearly not an issue in the cyclization of
the six- and seven-membered lactams but is a significant
factor with the five-membered-ring system.
The complexity of the resulting products could be
significantly increased by generating isomu¨nchnones
where the peripheral substituents are part of a cyclic
system. With this in mind, we decided to examine the
Pummerer behavior of a series of cyclic imidosulfoxides
containing tethered π-bonds. Treatment of the 3-butenyl-
substituted imidosulfoxide 43 with excess acetic anhy-
dride provided pyridone 44 in 85% yield as a crystalline
solid. The formation of 44 is consistent with the sequence
Sch em e 9
of events proposed in Scheme 6. The critical steps involve
(a) isomu¨nchnone formation, (b) intramolecular dipolar
cycloaddition, and (c) oxabicyclic ring cleavage. Interest-
ingly, imidosulfoxide 45, where the length of the alkenyl
tether was increased by one methylene unit, was ob-
served to undergo exclusive intramolecular cycloaddition
across the isomu¨nchnone dipole without further ring
opening taking place under the reaction conditions. Thus,
treatment of 45 with Ac2O gave cycloadduct 46 as the
only observable product in 73% yield. The assignment of
Pummerer conditions. In this case, the oxabicyclic ring
of 48 was quite stable toward ring opening and could be
isolated in 83% yield (Scheme 8). In a related fashion,
imidosulfoxide 49 produced primarily cycloadduct 50
(58%) together with lesser quantities of pyridone 51
(15%). This result demonstrates that a tethered alkene
attached to the sulfoxide can also be used in these
Pummerer-induced cycloadditions. Further heating of 50
in toluene with a trace of p-toluenesulfonic acid resulted
in a dehydration producing pyridone 51 in quantitative
yield.
Another substitution variant that was investigated
corresponded to the placement of an alkenyl tether on
the imido carbonyl group of an acyclic imide. Thus,
treatment of imidosulfoxides 52 and 55 with acetic
anhydride afforded the acetoxy-substituted pyridones 54
and 56. In these cases, the initially formed cycloadduct
(e.g., 53) undergoes rapid ring opening of the oxybridge
with ejection of the thioethyl group to furnish the
pyridones in 78% and 70% yield, respectively (Scheme
9).
In a further investigation of the sequential cyclization-
deprotonation-cycloaddition cascade, we also examined
the Pummerer reaction of imidosulfoxides 57 and 60.
Interestingly, with these systems, significant quantities
(ca. 25%) of the 5-thioethyl-substituted pyridone system
(i.e., 59 and 62) were isolated in addition to their acetoxy
counterparts (i.e., 58 and 61 (70% yield)). One rationale
that may account for why these two particular imidosul-
foxides produce a mixture of pyridones in contrast to the
other systems may be related to the stereoelectronic
the stereochemistry of 46 was based on a comparison of
its NMR signals with related substrates for which X-ray
crystallographic data exist. The formation of the endo-
cycloadduct with respect to the carbonyl ylide dipole is
in full accord with molecular mechanics calculations
which show a large ground-state energy difference be-
tween the two diastereomers. We assume that the
transient cycloadduct derived from 43 undergoes an acid-
assisted ring opening at a much faster rate than the
homologous pentenyl adduct as a consequence of relief
of ring strain. Cycloadduct 46 is sufficiently stable to the
acidic conditions used to trigger the Pummerer reaction
and can be isolated prior to rearrangement.
So that a cross section of additional information could
be obtained in regard to the tandem Pummerer cycliza-
tion-deprotonation-cycloaddition protocol, a series of
imidosulfoxides was needed representing a variety of
different permutations. Ultimately, substrates 47, 49, 52,
and 55 were studied, as they contain a range of syntheti-
cally interesting and easily attainable functionality. High
yields of an intramolecular cycloadduct were obtained
upon treating imidosulfoxide 47 under the standard

Synthesis of Substituted 2-Pyridones
J . Org. Chem., Vol. 64, No. 6, 1999 2043
Sch em e 10
factors associated with opening of the oxybridge of the
initially formed cycloadduct. Acetoxy-substituted pyri-
dones are formed when the amide lone pair of electrons
and the oxy-bridge are antiperiplanar, as is typical for
most 1,2-elimination reactions. Examination of molecular
models suggests that cycloadduct 53 (n ) 1) has the
proper stereoelectronic alignment, and thus preferential
cleavage of bond b occurs (Scheme 10). With the homolo-
gous cycloadduct 57 (n ) 2), the geometry is slightly
twisted away from an antiperiplanar arrangement. Con-
sequently, participation of the lone pair of electrons from
the sulfur atom can compete with the amido lone pair,
thereby leading to thioethyl-substituted pyridones by
bond a cleavage. A related explanation can be invoked
to rationalize the mixture of pyridones obtained from
imidosulfoxide 60.
In conclusion, our studies have demonstrated that the
Pummerer reaction of imidosulfoxides represents a highly
efficient method for the synthesis of azapolycyclic ring
systems. The subsequent ring cleavage reaction of the
initially formed isomu¨nchnone cycloadduct appears to be
dependent upon stereoelectronic factors associated with
the amide lone pair of electrons and the oxygen bridge.
We are continuing to explore the scope and mechanistic
details of these Pummerer-induced cycloaddition reac-
tions and will report additional findings at a later date.
Further utilization of this cyclization-deprotonation-
cycloaddition sequence for the stereocontrolled synthesis
of alkaloids is under current investigation.
ate imido sulfide. The resulting mixture was stirred for 3 h at
room temperature, diluted with water, extracted with chloro-
form, and dried over MgSO4. The solvent was removed under
reduced pressure, and the residue was subjected to silica gel
chromatography to afford the pure imido sulfoxide.
N-Acetyl-2-eth ylsu lfen yl-N-m eth yla ceta m id e. Follow-
ing the general procedure, the reaction of 2.0 g (27 mmol) of
N-methylacetamide with 4.9 g (36 mmol) of acid chloride 18
afforded 4.6 g (96%) of N-acetyl-2-ethylsulfenyl-N-methylac-
etamide as a colorless liquid: bp 110-112 °C; IR (neat) 2968,
1694, 1303, and 1139 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.26
(t, 3H, J ) 7.4 Hz), 2.41 (s, 3H), 2.61 (q, 2H, J ) 7.4 Hz), 3.28
(s, 3H), and 3.72 (s, 2H); 13C NMR (CDCl3, 75 MHz) δ 13.9,
25.7, 25.8, 31.5, 37.1, 171.7, and 172.7. HRMS Calcd for C7H13
NO2S: 175.0667. Found: 175.0665.
-
N-Acetyl-2-eth an esu lfin yl-N-m eth ylacetam ide (19). The
reaction of 2.3 g (13 mmol) of the above sulfide with 3.1 g (14
mmol) of sodium periodate gave 2.1 g (84%) of 19 as a clear
oil: IR (neat) 2932, 1687, 1303, and 1047 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 1.39 (m, 3H), 2.40 (s, 3H), 2.80-3.37 (m,
2H), 3.80 (s, 3H), 4.31 (d, 1H, J ) 4.8 Hz), and 4.36 (d, 1H, J
) 4.8 Hz); 13C NMR (CDCl3, 75 MHz) δ 6.5, 25.5, 32.0, 46.2,
60.5, 167.9, and 173.3. Anal. Calcd for C7H13NO3S: C, 43.96;
H, 6.86; N, 7.33. Found: C, 43.84; H, 6.73; N, 7.19.
5-Eth ylsu lfen yl-3-m eth yl-2-m eth ylen e-5-tr iflu or oacetyl-
oxa zolid in -4-on e (21). To a solution containing 0.5 g (2.6
mmol) of acetamide 19 and 0.3 g (2.8 mmol) of triethylamine
in 45 mL of CH2Cl2 at 0 °C was added dropwise 1.4 g (6.5
mmol) of trifluoroacetic anhydride. After stirring at room
temperature for 0.5 h, the mixture was diluted with water,
extracted with CH2Cl2, and dried over MgSO4. The solvent was
removed under reduced pressure, and the residue was chro-
matographed on silica gel to give 0.2 g (30%) of 21 as a colorless
oil: IR (neat) 1766, 1694, 1581, 1452, and 1075 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 1.36 (t, 3H, J ) 7.6 Hz), 2.79 (q, 2H, J )
7.6 Hz), 3.18 (s, 3H), 5.30 (s, 1H), and 6.10 (s, 1H); 13C NMR
(CDCl3, 75 MHz) δ 14.3, 25.0, 26.8, 75.5, 84.4, 116.1 (q, J )
289 Hz), 165.9, 167.6, and 175.6 (d, J ) 35 Hz). HRMS Calcd
for C9H10F3NO3S: 269.0333. Found: 269.0335.
Exp er im en ta l Section
Melting points are uncorrected. Mass spectra were deter-
mined at an ionizing voltage of 70 eV. Unless otherwise noted,
all reactions were performed in flame-dried glassware under
an atmosphere of dry argon. Solutions were evaporated under
reduced pressure with a rotary evaporator, and the residue
was chromatographed on a silica gel column using an ethyl
acetate-hexane mixture as the eluent unless specified other-
wise.
Gen er a l P r oced u r e for th e P r ep a r a tion of Im id o
Su lfoxid es. A solution containing 10 mmol of the appropriate
amide and 13 mmol of ethylsulfenylacetyl chloride (18)38 in
100 mL of benzene was heated at reflux for 12 h. The reaction
mixture was cooled, diluted with ether, and washed with 10%
NaOH. The organic layer was dried over MgSO4 and concen-
trated under reduced pressure. The residue was purified by
flash silica gel chromatography.
N-E t h ylsu lfen yla cet yl-N-m et h ylisob u t yr a m id e. Fol-
lowing the general procedure, treatment of 2.0 g (20 mmol) of
the methyl amide of isobutyric acid with 3.6 g (26 mmol) of
acid chloride 18 afforded 3.5 g (86%) of N-ethylsulfenylacetyl-
N-methylisobutyramide as a colorless oil; IR (neat) 1689, 1297,
1
and 1063 cm-1, H NMR (CDCl3, 300 MHz) δ 1.20 (d, 6H, J )
6.7 Hz), 1.27 (t, 3H, J ) 7.4 Hz), 2.62 (q, 2H, J ) 7.4 Hz), 3.18
(m, 1H), 3.28 (s, 3H), and 3.74 (s, 2H); 13C NMR (CDCl3, 75
MHz) δ 14.3, 19.1, 26.2, 31.6, 34.4, 37.7, 172.7, and 180.4.
HRMS Calcd for C9H17NO2S: 203.0980. Found: 203.0982.
N-Eth a n esu lfin yla cetyl-N-m eth ylisobu tyr a m id e (22).
Treatment of 3.4 g (17 mmol) of the above sulfide with 3.9 g
(19 mmol) of sodium periodate gave 3.0 g (80%) of 22 as a clear
oil; IR (neat) 1689, 1305, and 1056 cm-1; 1H NMR (CDCl3, 300
To a solution of 5.5 mmol of sodium periodate in a 2:1
mixture of methanol-H2O was added 5 mmol of the appropri-

2044 J . Org. Chem., Vol. 64, No. 6, 1999
Padwa et al.
MHz) δ 1.21 (d, 6H, J ) 6.7 Hz), 1.38 (t, 3H, J ) 7.4 Hz), 2.88
(m, 2H), 3.06 (m, 1H), 3.31 (s, 3H), 4.12 (d, 1H, J ) 14.7 Hz),
and 4.34 (d, 1H, J ) 14.7 Hz); 13C NMR (CDCl3, 75 MHz) δ
6.5, 18.8, 18.9, 31.3, 33.9, 46.1, 60.8, 168.3, and 180.3. Anal.
Calcd for C9H17NO3S: C, 49.29; H, 7.82; N, 6.39. Found: C,
49.15; H, 7.75; N, 6.27.
4-E t h ylsu lfen yl-4,10a -ep oxy-1,2-d im et h yl-1,4,4a ,10a -
tetr a h yd r o-2H-ben zo[g]isoqu in olin e-3,5,10-tr ion e (28).
To a refluxing solution of 2.5 g (25 mmol) of acetic anhydride,
0.5 g (3.2 mmol) of 1,4-naphthoquinone, and 2 mg of p-
toluenesulfonic acid in 40 mL of toluene was added dropwise
0.47 g (2.4 mmol) of acetamide 19 in 2 mL of toluene. After
heating at reflux for 1 h, the reaction mixture was concentrated
under reduced pressure, and the residue was subjected to silica
gel chromatography to furnish 28 (73%) as a white solid: mp
Isobu tyr ic Acid Eth ylsu lfen ylm eth ylca r ba m oyl Meth -
yl Ester (24). To a solution containing 0.6 g (2.7 mmol) of 22
and 0.3 g (3.0 mmol) of triethylamine in 45 mL of CH2Cl2 at 0
°C was added dropwise 1.4 g (6.7 mmol) of trifluoroacetic
anhydride. After stirring for 1 h at room temperature, the
mixture was diluted with water, extracted with CH2Cl2, and
dried over MgSO4. The solvent was removed under reduced
pressure, and the residue was chromatographed on silica gel
to give 0.5 g (88%) of 24 as a colorless oil; IR (neat) 1742, 1667,
and 1139 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.24 (d, 6H, J )
7.0 Hz), 1.29 (t, 3H, J ) 7.3 Hz), 2.73 (m, 3H), 2.88 (d, 3H, J
) 4.9 Hz), 6.19 (s, 1H), and 6.45 (brs, 1H); 13C NMR (CDCl3,
75 MHz) δ 14.8, 18.6, 18.8, 24.9, 26.4, 33.9, 75.9, 166.8, and
175.3. HRMS Calcd for C9H17NO3S: 219.0929. Found: 219.0927.
1-E t h ylsu lfen yl-7,8-d im et h yl-4-p h en yl-10-oxa -4,8-d i-
a za tr icyclo[5.2.1.0]d eca n e-3,5,9-tr ion e (25). To a refluxing
solution of 1.8 g (18 mmol) of acetic anhydride, 0.4 g (2.3 mmol)
of N-phenylmaleimide, and 2 mg of p-toluenesulfonic acid in
35 mL of toluene was added dropwise 0.34 g (1.8 mmol) of
acetamide 19 in 2 mL of toluene. After heating at reflux for 1
h, the mixture was concentrated under reduced pressure, and
the residue was subjected to silica gel chromatography to give
0.52 g (85%) of 25 as a white solid: mp 212-213 °C; IR (CCl4)
191-192 °C; IR (CCl4) 1725, 1682, 1590, 1405, and 1259 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 1.22 (t, 3H, J ) 7.5 Hz), 1.64 (s,
3H), 2.75 (m, 2H), 2.90 (s, 3H), 3.38 (s, 2H), 7.78 (m, 2H), 7.97
(m, 1H), and 8.04 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ 14.2,
16.4, 24.4, 25.7, 54.3, 57.6, 95.7, 96.3, 126.6, 127.3, 134.6, 135.0,
135.4, 136.5, 169.7, 191.2, and 192.8. Anal. Calcd for C17H17
-
NO4S: C, 61.62; H, 5.17; N, 4.23. Found: C, 61.63; H, 5.22;
N, 4.19.
5-Eth ylsu lfen yl-2-m eth ylfu r an -3-car boxylic Acid Meth -
yl Ester (29). To a refluxing solution of 3.0 g (30 mmol) of
acetic anhydride, 0.35 g (4.2 mmol) of methyl propiolate, and
2 mg of p-toluenesulfonic acid in 40 mL of toluene was added
dropwise 0.57 g (3.0 mmol) of acetamide 19 in 2 mL of toluene.
After heating at reflux for 1 h, the reaction mixture was
concentrated under reduced pressure, and the residue was
subjected to silica gel chromatography to give 0.09 g (15%) of
29 as a pale yellow oil: IR (neat) 1716, 1595, 1438, 1218, and
1
1111 cm-1; H NMR (CDCl3, 300 MHz) δ 1.26 (t, 3H, J ) 7.4
Hz), 2.58 (s, 3H), 2.76 (q, 2H, J ) 7.4 Hz), 3.82 (s, 3H), and
6.75 (s, 1H); 13C NMR (CDCl3, 75 MHz) δ 14.0, 14.9, 30.0, 51.3,
114.8, 117.8, 144.1, 161.9, and 163.8. Anal. Calcd for
C9H12O3S: C, 53.09; H, 6.05. Found: C, 52.94; H, 5.91.
1
1709, 1396, 1196, 1004, and 755 cm-1; H NMR (CDCl3, 300
MHz) δ 1.27 (t, 3H, J ) 7.4 Hz), 1.80 (s, 3H), 2.80 (q, 2H, J )
7.4 Hz), 2.82 (s, 3H), 3.27 (d, 1H, J ) 6.8 Hz), 3.38 (d, 1H, J
) 6.8 Hz), 7.25 (m, 2H), and 7.39 (m, 3H); 13C NMR (CDCl3,
75 MHz) δ 14.4, 15.1, 23.9, 25.6, 49.7, 53.1, 94.5, 94.9, 126.2,
128.7, 128.9, 131.1, 169.3, 170.6, and 171.9. Anal. Calcd for
2-Eth ylsu lfen yl-5-m eth ylfu r a n -3,4-d ica r boxylic Acid
Dim eth yl Ester (30). To a refluxing solution of 2.5 g (25
mmol) of acetic anhydride, 0.45 g (3.2 mmol) of dimethyl
acetylenedicarboxylate (DMAD), and 2 mg of p-toluenesulfonic
acid was added dropwise 0.47 g (2.5 mmol) of acetamide 19 in
2 mL of toluene. After heating at reflux for 1 h, the reaction
mixture was concentrated under reduced pressure, and the
residue was subjected to silica gel chromatography to give 0.26
g (41%) of 30 as a pale yellow oil: IR (neat) 1723, 1438, 1296,
and 1211 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.30 (t, 3H, J )
7.4 Hz), 2.53 (s, 3H), 2.95 (q, 2H, J ) 7.4 Hz), 3.83 (s, 3H),
and 3.86 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 13.1, 14.6, 27.9,
51.2, 51.5, 113.7, 119.9, 148.5, 159.0, 162.4, and 162.9. Anal.
Calcd for C11H14O5S: C, 51.15; H, 5.47. Found: C, 51.03; H,
5.42.
6-Ben zen esu lfon yl-4-eth ylsu lfen yl-1,2-d im eth yl-7-oxa -
2-a za bicyclo[2.2.1]h ep ta n -3-on e (31). To a refluxing solu-
tion of 2.3 g (22 mmol) of acetic anhydride, 0.48 g (2.8 mmol)
of phenyl vinyl sulfone, and 2 mg of p-toluenesulfonic acid in
35 mL of toluene was added dropwise 0.42 g (2.2 mmol) of
acetamide 19 in 2 mL of toluene. After heating at reflux for 1
h, the reaction mixture was concentrated under reduced
pressure, and the residue was subjected to silica gel chroma-
tography. The first product (0.28 g (38%)) eluted from the
column was the major diastereomer 31a as a clear oil: IR
(neat) 2939, 1723, 1396, 1310, and 1146 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.25 (t, 3H, J ) 7.5 Hz), 1.98 (s, 3H), 2.16 (dd,
1H, J ) 12.7 and 9.7 Hz), 2.29 (dd, 1H, J ) 12.7 and 4.9 Hz),
2.43 (dd, 1H, J ) 9.7 and 4.9 Hz), 2.82 (m, 2H), 3.10 (s, 3H),
7.53 (m, 3H), and 7.87 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ
14.9, 17.8, 23.9, 27.0, 35.4, 69.6, 93.1, 94.4, 127.7, 129.2, 129.5,
134.2, 139.6, and 169.2. Anal. Calcd for C15H19NO4S2: C, 52.77;
H, 5.61; N, 4.11. Found: C, 52.62; H, 5.70; N, 4.08.
C
17H18N2O4S: C, 58.95; H, 5.24; N, 8.09. Found: C, 59.09; H,
5.26; N, 8.03.
N-Acetyl-2-eth ylsu lfon yl-N-p h en yla ceta m id e. Follow-
ing the general procedure, treatment of 2.0 g (15 mmol) of
N-phenylacetamide with 2.9 g (21 mmol) of acid chloride 18
gave 3.2 g (92%) of N-acetyl-2-ethylsulfonyl-N-phenylaceta-
1
mide as a clear oil: IR (neat) 1702, 1595, and 1489 cm-1; H
NMR (CDCl3, 300 MHz) δ 1.22 (t, 3H, J ) 7.1 Hz), 2.16 (s,
3H), 2.58 (q, 2H, J ) 7.1 Hz), 3.59 (s, 2H), 7.15 (d, 2H, J ) 6.3
Hz), and 7.40-7.42 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ 14.1,
26.0, 26.3, 37.0, 128.5, 128.7, 129.5, 138.7, 171.9, and 172.5.
Anal. Calcd for C12H15NO2S: C, 60.73; H, 6.37; N, 5.90.
Found: C, 60.79; H, 6.83; N, 5.84.
N-Acetyl-2-eth an esu lfin yl-N-ph en ylacetam ide (26). The
reaction of 3.2 g (13.6 mmol) of the above sulfide with 5.2 g
(24 mmol) of sodium periodate afforded 2.6 g (80%) of 26 as a
1
colorless oil: IR (neat) 1704, 1592, 1492, and 1362 cm-1; H
NMR (CDCl3, 300 MHz) δ 1.17 (t, 3H, J ) 7.3 Hz), 1.96 (s,
3H), 2.61-2.80 (m, 2H), 3.95 (d, 1H, J ) 14.8 Hz), 4.15 (d,
1H, J ) 14.8 Hz), 7.01-7.10 (m, 2H), and 7.23-7.42 (m, 3H);
13C NMR (CDCl3, 75 MHz) δ 6.1, 25.9, 45.7, 59.3, 128.2, 128.8,
129.5, 137.6, 167.4, and 172.4. Anal. Calcd for C12H15NO3S:
C, 56.90; H, 5.97; N, 5.53. Found: C, 56.75; H, 5.81; N, 5.50.
1-E t h ylsu lfen yl-7-m et h yl-4,8-d ip h en yl-10-oxa -4,8-d i-
a za tr icyclo[5.2.1.0]d eca n e-3,5,9-tr ion e (27). To a refluxing
solution of 1.1 g (10 mmol) of acetic anhydride, 0.19 g (1.1
mmol) of N-phenylmaleimide, and 2 mg of p-toluenesulfonic
acid in 20 mL of toluene was added dropwise 0.24 g (1.0 mmol)
of 26 in 1 mL of toluene. After heating at reflux for 1.5 h, the
reaction mixture was concentrated under reduced pressure,
and the residue was purified by silica gel chromatography to
give 0.32 g (72%) of 27 as a white solid: mp 203-204 °C; IR
(neat) 1712, 1591, 1493, 1372, and 1191 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.31 (t, 3H, J ) 7.6 Hz) 1.84 (s, 3H), 2.87 (q, 2H,
J ) 7.5 Hz), 3.47 (d, 1H, J ) 6.7 Hz), 3.70 (d, 1H, J ) 6.9 Hz),
and 7.17-7.47 (m, 10H); 13C NMR (CDCl3, 75 MHz) δ 14.4,
16.4, 24.0, 49.5, 54.7, 94.7, 96.5, 125.4, 126.2, 127.9, 128.8,
128.9, 129.5, 131.1, 133.6, 168.1, 170.5, and 171.8. Anal. Calcd
for C22H20N2O4S: C, 64.69; H, 4.94; N, 6.86. Found: C, 64.88;
H, 5.00; N, 6.73.
The second product isolated from the column contained 0.15
g (19%) of the minor diastereomer 31b: IR (neat) 2950, 1720,
1396, 1316, and 1150 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.28
(t, 3H, J ) 7.4 Hz), 1.93 (dd, 1H, J ) 13.0 and 8.4 Hz), 2.04 (s,
3H), 2.19 (dd, 1H, J ) 13.0 and 5.0 Hz), 2.70 (m, 5H), 3.50
(dd, 1H, J ) 13.0 and 5.0 Hz), 7.50 (m, 3H), and 7.81 (m, 2H);
13C NMR (CDCl3, 75 MHz) δ 14.7, 16.6, 23.9, 25.0, 36.0, 67.1,
92.0, 95.1, 128.2, 129.4, 134.1, 138.5, and 170.8. Anal. Calcd
for C15H19NO4S2: C, 52.77; H, 5.61; N, 4.11. Found: C, 52.69;
H, 5.78; N, 4.21.

Synthesis of Substituted 2-Pyridones
J . Org. Chem., Vol. 64, No. 6, 1999 2045
The third product eluted from the column contained 0.13 g
(20%) of 5-benzenesulfonyl-1,6-dimethyl-2-oxo-1,2-dihydropy-
ridin-3-yl acetic acid ester (32) as a white solid: mp 167-168
1-Eth a n esu lfin yla cetylp ip er id in -2-on e (37). Following
the general procedure, the reaction of 3.0 g (30 mmol) of
δ-valerolactam with 5.5 g (39 mmol) of acid chloride 18
afforded 5.9 g (97%) of 1-ethylsulfenylacetylpiperidin-2-one as
a colorless liquid: bp 145-147 °C (0.7 mm); IR (neat) 2954,
1687, 1381, 1289, and 1154 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 1.26 (t, 3H, J ) 7.4 Hz), 1.86 (m, 4H), 2.59 (m, 4H), 3.76 (m,
2H), and 3.89 (s, 2H); 13C NMR (CDCl3, 75 MHz) δ 14.2, 19.9,
22.0, 25.9, 34.4, 38.5, 44.0, 172.6, and 172.9.
°C; IR (CCl4) 1773, 1673, 1303, and 1189 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 2.33 (s, 3H), 2.57 (s, 3H), 3.53 (s, 3H),
7.57 (m, 3H), 7.83 (m, 2H), and 7.91 (s, 1H); 13C NMR (CDCl3,
75 MHz) δ 17.7, 20.3, 32.2, 117.5, 126.8, 127.3, 129.3, 133.3,
137.5, 141.5, 149.0, 157.6, and 168.0. Anal. Calcd for C15H15
-
NO5S: C, 56.07; H, 4.71; N, 4.36. Found: C, 56.06; H, 4.76;
N, 4.36.
Treatment of 6.4 g (32 mmol) of the above sulfide with 7.5
4-Meth yl-1,3,6-tr ioxo-2,5-d ip h en yl-2,3,5,6-tetr a h yd r o-
1H-p yr r olo[3,4-c]p yr id in -7-yl Acetic Acid Ester (33). To
a stirred solution containing 0.19 g (0.5 mmol) of cycloadduct
27 in 20 mL of CH2Cl2 was added 0.3 g (2.4 mmol) of boron
trifluoride etherate. The resulting mixture was heated at
reflux for 4 h, quenched with water, and extracted with CHCl3.
The combined extracts were dried over MgSO4 and concen-
trated under reduced pressure. The mixture was dissolved in
20 mL of benzene and 1.3 mL (9.6 mmol) of triethylamine, and
2.2 g (21 mmol) of acetic anhydride was added. The resulting
mixture was heated at reflux for 45 min. The cooled mixture
was diluted with brine and extracted with CHCl3. The mixture
was dried over MgSO4 and concentrated under reduced pres-
sure, and the residue was subjected to silica gel chromatog-
raphy. The major product obtained from the column contained
0.14 g (80%) of 33 as a white solid: mp 279-281 °C; IR (neat)
1787, 1709, 1676, 1487, and 1149 cm-1; 1H NMR (CDCl3, 300
g (35 mmol) of sodium periodate gave 6.1 g (88%) of 37 as a
1
colorless oil: IR (neat) 1680, 1296, 1154, and 1047 cm-1; H
NMR (CDCl3, 300 MHz) δ 1.38 (t, 3H, J ) 7.5 Hz), 1.88 (m,
4H), 2.58 (m, 2H), 2.88 (m, 2H), 3.79 (m, 2H), 4.19 (d, 1H, J )
14.9 Hz), and 4.42 (d, 1H, J ) 14.9 Hz); 13C NMR (CDCl3, 75
MHz) δ 6.5, 20.0, 22.0, 34.5, 44.3, 46.1, 61.3, 168.2, and 173.6.
Anal. Calcd for C9H15NO3S: C, 49.75; H, 6.96; N, 6.45.
Found: C, 49.61; H, 6.85; N, 6.61.
4-E t h ylsu lfen yl-4-10a -ep oxy-2,3,3a ,4,7,8,9,10,10a ,10b-
d eca h yd r o-1,3,5-t r ioxo-2-p h en yl-1H -p yr r olo[3,4-a ]-4H -
qu in olizin e (39). To a refluxing solution of 2.4 g (24 mmol)
of acetic anhydride, 0.53 g (3.1 mmol) of N-phenylmaleimide,
and 2 mg of p-toluenesulfonic acid in 35 mL of toluene was
added dropwise 0.52 g (2.4 mmol) of imide 37 in 2 mL of
toluene. After heating at reflux for 1 h, the reaction mixture
was concentrated under reduced pressure, and the residue was
subjected to silica gel chromatography to give 0.66 g (75%) of
39 as a white solid: mp 222-223 °C; IR (CCl4) 2947, 2868,
1701, 1381, and 1182 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.30
(t, 3H, J ) 7.5 Hz), 1.64 (m, 2H), 1.88 (m, 2H), 2.06 (m, 1H),
2.58 (d, 1H, J ) 13.0 Hz), 2.81 (m, 3H), 3.30 (d, 1H, J ) 6.8
Hz), 3.55 (d, 1H, J ) 6.8 Hz), 3.89 (d, 1H, J ) 13.0 Hz), 7.27
(m, 2H), and 7.38 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ 14.6,
20.2, 23.0, 24.2, 25.8, 39.7, 49.6, 50.7, 93.8, 94.7, 126.3, 128.8,
129.0, 131.3, 168.9, 170.6, and 172.0. Anal. Calcd for
MHz) δ 2.40 (s, 3H), 2.46 (s, 3H), and 7.20-7.68 (m, 10H); 13
C
NMR (CDCl3, 75 MHz) δ 16.9, 20.3, 126.5, 127.5, 128.6, 129.1,
129.9, 130.3, 131.2, 136.5, 148.6, 158.3, 159.6, 162.5, 164.8,
166.4, and 167.7. Anal. Calcd for C22H16N2O5: C, 68.02; H,
4.15; N, 7.22. Found: C, 67.96; H, 4.12; N, 7.08.
The minor product eluted from the column contained 0.03
g (16%) of 7-ethylsulfenyl-4-methyl-2,5-diphenyl-5H-pyrrolo-
[3,4-c]pyridine-1,3,6-trione (34) as a white solid: mp 254-255
°C; IR (neat) 1707, 1664, 1491, and 1379 cm-1 1H NMR
;
C
19H20N2O4S: C, 61.27; H, 5.42; N, 7.53. Found: C, 60.99; H,
(CDCl3, 300 MHz) δ 1.28 (t, 3H, J ) 4.0 Hz), 2.42 (s, 3H), 3.36
(t, 2H, J ) 5.9 Hz), and 7.17-7.60 (m, 10H); 13C NMR (CDCl3,
75 MHz) δ 15.4, 16.8, 27.4, 119.6, 125.5, 126.6, 127.6, 128.3,
129.0, 129.1, 129.7, 130.2, 134.6, 139.5, 147.7, 162.1, 165.0,
and 169.4. Anal. Calcd for C22H18N2O3S: C, 67.67; H, 4.65; N,
7.18. Found: C, 67.54; H, 4.62; N, 7.05.
5.37; N, 7.46.
4-E t h ylsu lfen yl-4-10a -ep oxy-2,3,3a ,4,7,8,9,10,10a ,10b-
d eca h yd r o-1,3,5-tr ioxo-2-oxo-4H-qu in olizin e (40). To a
refluxing solution of 2.1 g (21 mmol) of acetic anhydride, 0.27
g (2.6 mmol) of maleic anhydride, and 2 mg of p-toluenesulfonic
acid in 35 mL of toluene was added dropwise 0.45 g (2.1 mmol)
of imide 37 in 2 mL of toluene. After heating at reflux for 1 h,
the reaction mixture was concentrated under reduced pressure,
and the residue was taken up in 50 mL of chloroform, washed
with a saturated NaCO3 solution, and dried over MgSO4. The
solvent was removed under reduced pressure, and the product
was filtered through a short plug of florsil to give 0.43 g (69%)
of 40 as a light yellow oil: IR (CCl4) 1865, 1780, 1730, and
1-Eth ylsu lfen yla cetylp yr r olid in -2-on e. Following the
general procedure, treatment of 1.3 g (15 mmol) of 2-pyrroli-
dinone with 2.7 g (20 mmol) of acid chloride 18 afforded 2.9 g
(99%) of 1-ethylsulfenylacetylpyrrolidin-2-one as a colorless
oil: IR (neat) 1734, 1682, and 1312 cm-1 1H NMR (CDCl3,
;
300 MHz) δ 1.27 (t, 3H, J ) 7.6 Hz), 2.09 (q, 2H, J ) 7.6 Hz),
2.62 (m, 4H), 3.83 (s, 2H), and 3.84 (m, 2H); 13C NMR (CDCl3,
75 MHz) δ 14.2, 16.9, 25.9, 33.3, 35.2, 45.4, 170.0, and 175.0.
HRMS Calcd for C8H13NO2S: 187.0667. Found: 187.0665.
1-Eth a n esu lfin yla cetylp yr r olid in -2-on e (35). The reac-
tion of 2.8 g (15.3 mmol) of the above sulfide with 3.6 g (17
mmol) of sodium periodate gave 2.6 g (83%) of 35 as a colorless
1
1082 cm-1; H NMR (CDCl3, 300 MHz) δ 1.30 (t, 3H, J ) 7.5
Hz), 1.63 (m, 2H), 1.99 (m, 2H), 2.14 (m, 1H), 2.52 (d, 1H, J )
12.8 Hz), 2.79 (m, 3H), 3.51 (d, 1H, J ) 7.1 Hz), 3.77 (d, 1H,
J ) 7.1 Hz), and 3.86 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ
14.7, 20.0, 22.8, 24.4, 25.6, 39.9, 51.0, 52.2, 94.3, 95.0, 165.7,
167.0, and 168.1; HRMS Calcd for C13H15NO5S: 297.0671.
Found: 297.0670.
oil: IR (neat) 1735, 1682, 1327, and 1048 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 1.38 (t, 3H, J ) 7.4 Hz), 2.10 (m, 2H),
2.65 (t, 2H, J ) 8.1 Hz), 2.91 (m, 2H), 3.87 (t, 2H, J ) 7.2 Hz),
4.23 (d, 1H, J ) 14.0 Hz), and 4.41 (d, 1H, J ) 14.0 Hz); 13C
NMR (CDCl3, 75 MHz) δ 6.4, 16.9, 33.0, 45.2, 46.2, 57.6, 165.1,
and 175.6. Anal. Calcd for C8H13NO3S: C, 47.28; H, 6.45; N,
6.90. Found: C, 47.19; H, 6.39; N, 6.87.
1-Eth ylsu lfen yla cetyla zep a n -2-on e. Following the gen-
eral procedure, treatment of 1.0 g (8.8 mmol) of ꢀ-caprolactam
with 1.6 g (12 mmol) of acid chloride 18 gave 1.9 g (99%) of
1-ethylsulfenylacetylazepan-2-one as a clear oil: IR (neat)
1687, 1381, 1267, and 1147 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 1.26 (t, 3H, J ) 7.3 Hz), 1.75 (m, 6H), 2.58 (q, 2H, J ) 7.3
Hz), 2.74 (m, 2H), 3.88 (s, 2H), and 3.91 (m, 2H); 13C NMR
(CDCl3, 75 MHz) δ 14.3, 23.2, 26.0, 28.2, 29.0, 38.0, 39.5, 43.4,
172.1, and 177.4. Anal. Calcd for C10H17NO2S: C, 55.79; H,
7.97; N, 6.51. Found: C, 55.65; H, 7.91; N, 6.47.
1-Eth ylsu lfin yla cetyla zep a n -2-on e (38). The reaction of
1.9 g (8.6 mmol) of the above sulfide with 2.0 g (9.5 mmol) of
sodium periodate gave 1.9 g (94%) of 38 as a colorless oil: IR
(neat) 1694, 1680, 1381, 1147, and 1047 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.38 (t, 3H, J ) 7.6 Hz), 1.77 (m, 6H), 2.76 (m,
2H), 2.89 (m, 2H), 3.95 (m, 2H), 4.16 (d, 1H, J ) 14.7 Hz), and
4.42 (d, 1H, J ) 14.7 Hz); 13C NMR (CDCl3, 75 MHz) δ 6.3,
23.1, 28.1, 28.7, 39.0, 43.2, 45.9, 60.7, 167.3, and 177.7. Anal.
1-Eth ylsu lfen yl-2-oxo-2-(2-oxo-pyr r olidin -1-yl)eth yl Ace-
tic Acid Ester (36). To a refluxing solution of 2.2 g (22 mmol)
of acetic anhydride and 2 mg of p-toluenesulfonic acid in 15
mL of toluene was added dropwise 0.44 g (2.2 mmol) of
pyrrolidinone 35 in 2 mL of toluene. After heating at reflux
for 1 h, the reaction mixture was concentrated under reduced
pressure, and the residue was subjected to silica gel chroma-
tography to give 0.4 g (73%) of 36 as a colorless oil: IR (neat)
1
1742, 1697, 1357, and 1214 cm-1; H NMR (CDCl, 300 MHz)
δ 1.28 (t, 3H, J ) 7.5 Hz), 2.11 (m, 2H), 2.17 (s, 3H), 2.70 (m,
3H), 3.85 (m, 3H), and 7.01 (s, 1H); 13H NMR (CDCl3, 75 MHz)
δ 14.5, 17.2, 20.5, 24.1, 33.2, 45.4, 74.9, 166.5, 170.2, and 174.7.
Anal. Calcd for C10H15NO4S: C, 48.97; H, 6.17; N, 5.71.
Found: C, 48.82; H, 6.15; N, 5.68.

2046 J . Org. Chem., Vol. 64, No. 6, 1999
Padwa et al.
Calcd for C10H17NO3S: C, 51.93; H, 7.41; N, 6.06. Found: C,
51.82; H, 7.41; N, 5.87.
(neat) 1687, 1388, 1296, 1146, and 1047 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.27 (s, 3H), 1.38 (t, 3H, J ) 7.5 Hz), 1.65 (m,
2H), 1.88 (m, 4H), 2.05 (m, 2H), 2.88 (m, 2H), 3.67 (m, 1H),
3.86 (m, 1H), 4.11 (m, 1H), 4.36 (m, 1H), 5.00 (m, 2H), and
5.79 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ 6.4, 18.9, 19.0, 25.5,
25.8, 28.2, 32.4, 38.6, 38.8, 44.3, 45.7, 46.1, 46.2, 61.4, 114.8,
4-Eth an esu lfen yl-4,11a -epoxy-1,2,2a ,4,5,7,8,9,10,11,11a ,-
11b-d od eca h yd r o-1,3,5-tr ioxo-2-p h en yl-1H-p yr r olo[3,5-a ]-
p yr id o[1,2-a ]a zep in e (41). To a refluxing solution of 3.6 g
(35 mmol) of acetic anhydride, 0.85 g of N-phenylmaleimide,
and 2 mg of p-toluenesulfonic acid in 35 mL of toluene was
added dropwise 0.81 g (3.5 mmol) of azepan-2-one 38 in 2 mL
of toluene. After heating at reflux for 1 h, the reaction mixture
was concentrated under reduced pressure, and the residue was
subjected to silica gel chromatography to give 1.1 g (79%) of
41 as a 1:1 mixture of diastereomers, which were easily
separated by silica gel chromatography.
114.9, 137.6, 137.7, 168.8, and 179.5. Anal. Calcd for C14H23
-
NO3S: C, 58.92; H, 8.13; N, 4.91. Found: C, 58.76; H, 8.05;
N, 4.90.
8a -Meth yl-5-oxo-1,2,6,7,8,8a -h exa h yd r o-5H-5a -a za a ce-
n a p h th ylen -4-yl Acetic Acid Ester (44). To a refluxing
solution of 1.8 g (18 mmol) of acetic anhydride and 2 mg of
p-toluenesulfonic acid in 40 mL of toluene was added 0.5 g
(1.8 mmol) of piperidinone 43 in 2 mL of toluene. After heating
for 1 h at reflux, the reaction mixture was concentrated under
reduced pressure, and the residue was subjected to silica gel
chromatography. The major product isolated from the column
(80%) was identified as pyridone 44: mp 81-82 °C; IR (CCl4)
1766, 1659, 1602, 1552, and 1196 cm-1; 1H NMR (CDCl3, 300
MHz) δ 1.78 (s, 3H), 1.54 (dt, 1H, J ) 12.0 and 5.0 Hz), 1.92
(m, 2H), 2.11 (m, 3H), 2.32 (s, 3H), 2.53 (dd, 1H, J ) 14.9 and
8.3 Hz), 2.83 (m, 1H), 3.88 (m, 1H), 4.04 (m, 1H), and 7.10 (s,
1H); 13C NMR (CDCl3, 75 MHz) δ 19.2, 20.7, 23.2, 26.8, 32.2,
41.1, 41.4, 42.3, 113.8, 127.2, 138.4, 150.8, 157.4, and 169.0.
Anal. Calcd for C14H17NO3: C, 68.00; H, 6.93; N, 5.66. Found:
C, 67.99; H, 6.89; N, 5.67.
One of the diastereomers (41a ) exhibited the following
spectral properties: mp 164-165 °C; IR (CCl4) 1723, 1417,
1
1381, and 1182 cm-1; H NMR (CDCl3, 300 MHz) δ 1.25 (m,
2H), 1.33 (t, 3H, J ) 7.5 Hz), 1.59 (m, 1H), 1.78 (m, 3H), 2.41
(m, 2H), 2.60 (m, 1H), 2.92 (m, 2H), 3.64 (q, 2H, J ) 7.5 Hz),
4.00 (d, 1H, J ) 13.8 Hz), 7.09 (d, 2H, J ) 6.5 Hz), and 7.38
(m, 3H); 13C NMR (CDCl3, 75 MHz) δ 14.9, 23.2, 24.1, 29.6,
30.7, 32.7, 41.2, 51.2, 55.1, 94.8, 97.2, 126.4, 128.7, 129.0, 130.9,
166.4, 170.2, and 171.0. Anal. Calcd for C20H22N2O4S: C, 62.16;
H, 5.74; N, 7.25. Found: C, 62.25; H, 5.73; N, 7.26.
The second diastereomer (41b) exhibited the following
spectral properties: mp 198-199 °C; IR (CCl4) 1716, 1388,
1196, and 748 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.29 (t, 3H,
J ) 7.6 Hz), 1.40 (m, 2H), 1.63 (m, 1H), 1.95 (m, 3H), 2.25 (m,
1H), 2.41 (m, 1H), 2.85 (m, 3H), 3.36 (q, 2H, J ) 7.6 Hz), 3.93
(d, 1H, J ) 14.0 Hz), 7.26 (d, 2H, J ) 8.0 Hz), and 7.43 (m,
3H); 13C NMR (CDCl3, 75 MHz) δ 14.7, 23.0, 24.0, 29.9, 30.2,
31.2, 40.4, 49.6, 54.6, 94.4, 97.9, 126.2, 128.7, 128.9, 131.2,
168.1, 170.7, and 171.8. Anal. Calcd for C20H22N2O4S: C, 62.16;
H, 5.74; N, 7.25. Found: C, 61.95; H, 5.71; 7.14.
1,3,5-Tr ioxo-2-ph en yl-1,2,3,5,7,8,9,10-octah ydr opyr r olo-
[3,4-a ]qu in olizin -4-yl Acetic Acid Ester (42). To a stirred
solution containing 0.53 g (1.4 mmol) of cycloadduct 39 in 35
mL of CH2Cl2 was added 0.9 g (6.4 mmol) of boron trifluoride
etherate. The resulting mixture was stirred at room temper-
ature for 3 h, quenched with water, and extracted with CH2-
Cl2. The combined organic extracts were dried over MgSO4 and
concentrated under reduced pressure. The crude residue was
dissolved in 35 mL of benzene, and 0.72 g (7 mmol) of acetic
anhydride was added. The resulting mixture was heated at
reflux for 1 h, concentrated under reduced pressure, and
subjected to silica gel chromatography to give 0.49 g (98%) of
42 as a bright yellow solid: mp 198-199 °C; IR (CCl4) 1780,
1719, 1667, and 1365 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.92
(m, 2H), 2.03 (m, 2H), 2.42 (s, 3H), 3.39 (m, 2H), 4.04 (m, 2H),
7.37 (m, 3H), and 7.45 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ
17.2, 20.3, 21.6, 25.4, 43.9, 102.3, 126.4, 127.1, 128.3, 128.9,
131.1, 132.9, 149.5, 159.1, 162.6, 164.6, and 167.8. Anal. Calcd
for C19H16N2O5: C, 64.77; H, 4.58; N, 7.95. Found: C, 64.74;
H, 4.59; N, 7.87.
1-Eth ylsu lfen ylacetyl-3-m eth yl-3-pen t-4-en ylpiper idin -
2-on e. Following the general procedure, the reaction of 0.8 g
(4.4 mmol) of 4-pent-4-enyl-3-methylpiperidin-2-one46 with 0.8
g (5.7 mmol) of acid chloride 18 gave 1.2 g (94%) of 1-ethyl-
sulfenylacetyl-3-methyl-3-pent-4-enylpiperidin-2-one as a clear
oil: IR (neat) 1680, 1381, 1296, and 1139 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 1.25 (t, 3H, J ) 7.4 Hz), 1.29-1.63 (m,
9H), 1.80 (m, 3H), 2.05 (m, 2H), 2.59 (q, 2H, J ) 7.4 Hz), 3.70
(m, 1H), 3.85 (s, 2H), 4.99 (m, 2H), and 5.79 (m, 1H); 13C NMR
(CDCl3, 75 MHz) δ 14.4, 19.4, 23.3, 25.7, 26.3, 33.0, 33.9, 38.5,
39.4, 44.6, 45.8, 114.8, 138.2, 173.8, and 179.3. HRMS Calcd
for C15H25NO2S: 283.1606. Found: 283.1600.
1-Eth a n esu lfin yla cetyl-3-m eth yl-3-p en t-4-en ylp ip er i-
d in -2-on e (45). The reaction of 1.1 g (3.8 mmol) of the above
sulfide with 0.9 g (4.2 mmol) of sodium periodate afforded 0.82
g (73%) of 45 as an inseparable mixture of diastereomers: IR
(neat) 1687, 1296, 1146, and 1047 cm-1; 1H NMR (CDCl3, 300
MHz) δ 1.25 (s, 3H), 1.28-1.67 (m, 8H), 1.85 (m, 3H), 2.10 (m,
2H), 2.87 (m, 2H), 3.63 (m, 1H), 3.84 (m, 1H), 4.11 (m, 1H),
4.35 (m, 1H), 5.00 (m, 2H), and 5.78 (m, 1H); 13C NMR (CDCl3,
75 MHz) δ 6.51, 19.0, 19.1, 23.2, 23.3, 25.5, 25.8, 32.6, 32.7,
33.8, 33.9, 39.1, 39.2, 44.5, 45.7, 45.8, 46.1, 46.2, 61.5, 114.9,
115.0, 137.9, 138.0, 168.9, 179.8, and 179.9. Anal. Calcd for
C
15H25NO3S: C, 60.17; H, 8.42; N, 4.68. Found: C, 60.04; H,
8.35; N, 4.51.
Cycloa d d u ct 46. To a refluxing solution of 1.5 g (15 mmol)
of acetic anhydride and 2 mg of p-toluenesulfonic acid in 40
mL of toluene was added dropwise 0.44 g (1.5 mmol) of
imidosulfoxide 45 in 2 mL of toluene. After heating at reflux
for 1 h, the reaction mixture was concentrated under reduced
pressure, and the residue was chromatographed on silica gel
to give 0.3 g (73%) of cycloadduct 46 as a colorless solid: mp
1-Eth ylsu lfen yla cetyl-3-m eth yl-3-bu ten -3-en ylp ip er i-
d in -2-on e. Following the general procedure, treatment of 1.0
g (6 mmol) of 3-buten-3-enyl-3-methylpiperidin-2-one46 with
1.1 g (8 mmol) of acid chloride 18 gave 1.6 g (96%) of
1-ethylsulfenylacetyl-3-methyl-3-buten-3-enylpiperidin-2-
one as a pale yellow oil: IR (neat) 1680, 1388, 1289, and 1139
80-81 °C; IR (CCl4) 1719, 1444, and 1395 cm-1 1H NMR
;
1
cm-1; H NMR (CDCl3, 300 MHz) δ 1.25 (t, 3H, J ) 7.4 Hz),
(CDCl3, 300 MHz) δ 1.11 (s, 3H), 1.31 (m, 5H), 1.48 (m, 4H),
1.66 (m, 2H), 1.93 (m, 4H), 2.14 (m, 1H), 2.70 (m, 2H), 2.90
(m, 1H), and 3.79 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ 15.1,
19.0, 19.9, 22.4, 24.3, 32.1, 32.2, 33.1, 36.7, 38.3, 38.8, 40.0,
92.6, 95.6, and 171.6. Anal. Calcd for C15H23NO2S: C, 64.02;
H, 8.24; N, 4.98. Found: C, 64.07; H, 8.23; N, 4.88.
1.27 (s, 3H), 1.64 (m, 2H), 1.86 (m, 4H), 2.07 (m, 2H), 2.59 (q,
2H, J ) 7.4 Hz), 3.70 (m, 1H), 3.85 (s, 2H), 3.87 (m, 1H), 5.00
(m, 2H), and 5.79 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ 14.4,
19.4, 25.8, 26.4, 28.4, 33.0, 38.5, 39.1, 44.5, 45.9, 114.7, 138.0,
173.8, and 179.1. HRMS Calcd for C14H23NO2S: 269.1449.
Found: 269.1446.
N -Ac e t y l-N -(2-a lly lp h e n y l)-2-e t h y ls u lfe n y la c e t a -
m id e. Following the general procedure, treatment of 0.45 g
(2.6 mmol) of N-(2-allylphenyl)acetamide47 with 0.47 g (3.4
mmol) of acid chloride 18 gave 0.5 g (70%) of N-acetyl-N-(2-
allylphenyl)-2-ethylsulfenylacetamide as a pale yellow oil: IR
(neat) 1713, 1490, 1367, and 1253 cm-1; 1H NMR (CDCl3, 300
1-Eth a n esu lfin yla cetyl-3-m eth yl-3-bu ten -3-en ylp ip er i-
d in -2-on e (43). Treatment of 1.5 g (5.4 mmol) of the above
sulfide with 1.3 g (6 mmol) of sodium periodate afforded 1.4 g
(88%) of 43 as an inseparable mixture of diastereomers; IR
(45) Padwa, A.; Hertzog, D. L.; Nadler, W. R.; Osterhout, M. H.;
Price, A. T. J . Org. Chem. 1994, 59, 1418.
(46) Hertzog, D. L.; Nadler, W. R.; Zhang, Z. J .; Padwa, A. Tetra-
hedron Lett. 1992, 33, 7159.
(47) Padwa, A.; Austin, D. J .; Price, A. T. Tetrahedron Lett. 1994,
35, 7159.

Synthesis of Substituted 2-Pyridones
J . Org. Chem., Vol. 64, No. 6, 1999 2047
MHz) δ 1.26 (t, 3H, J ) 7.4 Hz), 2.16 (s, 3H), 2.62 (q, 2H, J )
7.4 Hz), 3.27 (d, 2H, J ) 6.6 Hz), 3.60 (d, 1H, J ) 14.2 Hz),
3.67 (d, 1H, J ) 14.2 Hz), 5.13 (m, 2H), 5.85 (m, 1H), 7.12 (d,
1H, J ) 7.4 Hz), and 7.34 (m, 3H); 13C NMR (CDCl3, 75 MHz)
δ 14.2, 26.2, 26.6, 35.4, 37.4, 117.2, 127.8, 129.1, 129.4, 130.6,
(CDCl3, 75 MHz) δ 26.2, 31.4, 31.9, 33.3, 37.9, 116.1, 136.2,
172.0, and 173.0. HRMS Calcd for C9H15NO2S: 201.0823.
Found: 201.0822.
N-[(Bu t-3-en ylsu lfin yl)acetyl]-N-m eth ylacetam ide (49).
The reaction of 1.0 g (5.0 mmol) of the above sulfide with 1.2
g (5.5 mmol) of sodium periodate afforded 0.83 g (77%) of 49
135.2, 137.4, 137.9, 171.8, and 172.7. HRMS Calcd for C15H19
NO2S: 277.1136. Found: 277.1134.
-
1
as a clear oil: IR (neat) 1693, 1371, 1311, and 1034 cm-1; H
N -Ace t yl-N -(2-a llylp h e n yl)-2-e t h a n e su lfin yla ce t a -
m id e (47). The reaction of 0.45 g (1.6 mmol) of the above
sulfide with 0.38 g (1.8 mmol) of sodium periodate gave 0.4 g
(84%) of acetamide 47 as a clear oil: IR (neat) 1713, 1367,
NMR (CDCl3, 300 MHz) δ 2.39 (s, 3H), 2.58 (m, 2H), 2.94 (m,
2H), 3.28 (s, 3H), 4.19 (d, 1H, J ) 14.9 Hz), 4.38 (d, 1H, J )
14.9 Hz), 5.16 (m, 2H), and 5.87 (m, 1H); 13C NMR (CDCl3, 75
MHz) δ 25.4, 26.3, 31.9, 51.7, 61.2, 117.0, 134.5, 167.7, and
173.2. Anal. Calcd for C9H15NO3S: C, 49.75; H, 6.96; N, 6.45.
Found: C, 49.52; H, 6.74; N, 6.33.
1258, and 1020 cm-1 1H NMR (CDCl3, 300 MHz) δ 1.36 (t,
;
3H, J ) 7.4 Hz), 2.11 (s, 3H), 2.88 (m, 2H), 3.29 (m, 2H), 4.08
(m, 1H), 4.28 (m, 1H), 5.12 (m, 2H), 5.83 (m, 1H), 7.12 (m,
1H), and 7.36 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ 6.4, 26.2,
35.6, 46.3, 59.8, 117.2, 127.9, 128.9, 129.6, 130.7, 134.8, 136.6,
137.5, 167.5, and 172.8. Anal. Calcd for C15H19NO3S: C, 61.41;
H, 6.53; N, 4.78. Found: C, 61.29; H, 6.44; N, 4.61.
7,8-Dim eth yl-10-oxa-2-th ia-8-azatr icyclo[5.2.1.01,5]decan -
9-on e (50). To a refluxing solution of 2.4 g (24 mmol) of acetic
anhydride and 2 mg of p-toluenesulfonic acid in 40 mL of
toluene was added 0.5 g (2.4 mmol) of amide 49 in 2 mL of
toluene. After heating at reflux for 30 min, the reaction
mixture was concentrated under reduced pressure, and the
residue was subjected to silica gel chromatography. The major
product isolated (58%) was a colorless oil whose structure was
3-Eth ylsu lfen yl-12-oxa -2-oxo-11-p h en yl-3,4,5,6-tetr a h y-
d r o-2H-1,5-m eth a n oben zo[b]a zocin e (48). To a refluxing
solution of 0.6 g (6 mmol) of acetic anhydride and 2 mg of
p-toluenesulfonic acid in 35 mL of toluene was added 0.2 g
(0.6 mmol) of amide 47 in 2 mL of toluene. After heating for 1
h at reflux, the reaction mixture was concentrated under
reduced pressure, and the residue was subjected to silica gel
chromatography to give 0.15 g (83%) of azocine 48 as a
colorless solid: mp 129-130 °C; IR (CCl4) 2933, 1751, 1490,
1390, 1312, and 1062 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.36
(t, 3H, J ) 7.5 Hz), 1.52 (d, 1H, J ) 4.4 Hz), 1.56 (s, 3H), 2.45
(dd, 1H, J ) 13.0 and 10.4 Hz), 2.73 (m, 1H), 2.92 (m, 3H),
3.16 (dd, 1H, J ) 18.7 and 8.0 Hz), 7.23 (m, 4H); 13C NMR
(CDCl3, 75 MHz) δ 15.2, 17.2, 24.3, 28.1, 40.9, 41.6, 92.6, 92.8,
assigned cycloadduct 50: IR (neat) 1724, 1398, and 1002 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 1.68 (s, 3H), 1.70 (m, 1H), 1.84
(m, 1H), 2.07 (dd, 1H, J ) 12.0 and 7.5 Hz), 2.45 (m, 2H), 2.80
(s, 3H), and 3.27 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 17.9,
25.4, 34.4, 37.0, 39.8, 52.2, 96.7, 104.0, and 171.7. Anal. Calcd
for C9H13NO2S: C, 54.25; H, 6.58; N, 7.83. Found: C, 54.13;
H, 6.54; N, 7.72.
5,6-Dim et h yl-2,3-d ih yd r o-6H -t h ien o[2,3-c]p yr id in -7-
on e (51). The minor fraction (15%) from the above column
chromatography was identified as pyridone 51: mp 131-132
°C; IR (CCl4) 1650, 1566, and 1426 cm-1; 1H NMR (CDCl3, 300
MHz) δ 2.32 (s, 3H), 3.21 (m, 2H), 3.30 (m, 2H), 3.52 (s, 3H),
and 6.05 (s, 1H); 13C NMR (CDCl3, 75 MHz) δ 20.6, 30.9, 31.5,
37.4, 104.2, 128.0, 142.0, 147.1, and 158.6. Anal. Calcd for
C9H11NOS: C, 59.64; H, 6.12; N, 7.73. Found: C, 59.65; H,
6.10; N, 7.74. This same compound was obtained in quantita-
tive yield by heating a sample of cycloadduct 50 in toluene at
110 °C for 1 h.
126.2, 127.0, 128.8, 137.4, and 175.6. Anal. Calcd for C15H17
-
NO2S: C, 65.43; H, 6.22; N, 5.09. Found: C, 65.32; H, 6.27;
N, 5.10.
N-[(Bu t-3-en ylsu lfen yl)a cetyl]-N-m eth yla ceta m id e. To
a stirred solution of 5.0 g (47 mmol) of methyl thioglycolate in
100 mL of benzene was added 7.9 g (52 mmol) of DBU followed
by 7.0 g (52 mmol) of 4-bromo-1-butene. The resulting mixture
was stirred for 12 h at room temperature, diluted with water,
extracted with ether, and dried over MgSO4. Removal of the
solvent under reduced pressure gave (but-3-enylsulfenyl)acetic
acid methyl ester as a colorless liquid, which was used in the
next step without further purification: IR (neat) 1738, 1436,
2-Eth ylsu lfen yl-N-h ex-5-en yl-N-m eth yla ceta m id e. Fol-
lowing the general procedure, the reaction of 2.0 g (16 mmol)
of hex-5-enoic acid methylamide with 2.9 g (21 mmol) of acid
chloride 18 gave 2.9 g (80%) of 2-ethylsulfenyl-N-hex-5-enyl-
N-methylacetamide as a clear oil: IR (neat) 1695, 1350, 1140,
1
1
1279, and 1133 cm-1; H NMR (CDCl3, 300 MHz) δ 2.36 (m,
and 971 cm-1; H NMR (CDCl3, 300 MHz) δ 1.27 (t, 3H, J )
2H), 2.71 (m, 2H), 3.25 (s, 3H), 5.08 (m, 2H), and 5.82 (m, 1H);
13C NMR (CDCl3, 75 MHz) δ 31.9, 33.1, 33.3, 52.3, 116.2, 128.2,
136.1, and 170.9.
7.3 Hz), 1.79 (m, 2H), 2.13 (m, 2H), 2.63 (m, 4H), 3.25 (s, 3H),
3.74 (s, 2H), 5.03 (m, 2H), and 5.80 (m, 1H); 13C NMR (CDCl3,
75 MHz) δ 14.3, 23.4, 26.1, 31.4, 32.8, 36.7, 37.7, 115.3, 137.7,
172.2, and 175.6. HRMS Calcd for C11H19NO2S: 229.1136.
Found: 229.1135.
2-Eth an esu lfin yl-N-h ex-5-en yl-N-m eth ylacetam ide (52).
Treatment of 0.9 g (3.9 mmol) of the above sulfide with 0.9 g
(4.3 mmol) of sodium periodate afforded 0.72 g (75%) of 52 as
a colorless oil: IR (neat) 1687, 1374, 1303, and 1047 cm-1; 1H
NMR (CDCl3, 300 MHz) δ 1.39 (m, 3H), 1.79 (m, 2H), 2.13 (m,
2H), 2.62 (m, 2H), 2.79-2.95 (m, 2H), 3.27 (s, 3H), 4.16 (m,
1H), 4.34 (m, 1H), 5.05 (m, 2H), and 5.80 (m, 1H); 13C NMR
(CDCl3, 75 MHz) δ 6.4, 23.0, 31.1, 32.5, 35.9, 46.0, 60.7, 115.4,
137.3, 167.8, and 175.7. Anal. Calcd for C11H19NO3S: C, 53.95;
H, 7.81; N, 5.71. Found: C, 53.72; H, 7.59; N, 5.65.
To a suspension of 2.0 g (15 mmol) of potassium trimeth-
ylsilanolate in 150 mL of ether was added 2.1 g (13 mmol) of
the above ester. After stirring at room temperature for 3 h,
the mixture was diluted with water, washed with ether, and
acidified with a 10% HCl solution. The aqueous layer was
extracted with ether, dried over MgSO4, and concentrated
under reduced pressure to give 1.68 g (89%) of (but-3-
enylsulfenyl)acetic acid, which was used in the next step
without further purification: IR (neat) 1709, 1425, and 1297
cm-1; 1H NMR (CDCl3, 300 MHz) δ 2.35 (m, 2H), 2.71 (m, 2H,
3.24 (s, 2H), 5.05 (m, 2H), 5.79 (m, 1H), and 11.36 (brs, 1H);
13C NMR (CDCl3, 75 MHz) δ 32.0, 33.1, 33.4, 116.4, 136.0, and
177.0.
1-Meth yl-2-oxo-2,5,6,7-tetr a h yd r o-1H-p yr id in -3-yl Ace-
tic Acid Ester (54). To a refluxing solution of 1.8 g (18 mmol)
of acetic anhydride and 2 mg of p-toluenesulfonic acid in 40
mL of toluene was added dropwise 0.44 g (1.8 mmol) of
acetamide 52 in 2 mL of toluene. After heating at reflux for 1
h, the reaction mixture was concentrated under reduced
pressure, and the residue was subjected to silica gel chroma-
tography to give 0.29 g (78%) of pyridone 54: mp 122-123
To a solution of 1.4 g (9.4 mmol) of the above acid was added
9.4 mL of a 2 M solution of oxalyl chloride followed by 1 drop
of DMF. The solution was stirred for 2 h at room temperature
and was then concentrated under reduced pressure. The crude
acid chloride was taken up in 75 mL of toluene, and 0.53 g
(7.2 mmol) of N-methyl acetamide was added. The resulting
mixture was heated at reflux for 12 h, washed with a 10%
NaOH solution, and dried over MgSO4. The solvent was
removed under reduced pressure, and the residue was chro-
matographed on silica gel to give 1.1 g (75%) of N-[(but-3-
enylsulfenyl)acetyl]-N-methylacetamide as a light yellow oil:
°C; IR (CCl4) 1766, 1659, 1602, and 1196 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 2.16 (m, 2H), 2.32 (s, 3H), 2.79 (t, 2H, J
) 7.5 Hz), 2.90 (t, 2H, J ) 7.5 Hz), 3.52 (s, 3H), and 7.09 (s,
1H); 13C NMR (CDCl3, 75 MHz) δ 20.6, 22.4, 30.4, 32.0, 32.9,
116.5, 126.9, 138.8, 146.8, 157.7, and 169.1. Anal. Calcd for
1
IR (neat) 1694, 1369, 1310, and 1139 cm-1; H NMR (CDCl3,
300 MHz) δ 2.36 (m, 2H), 2.41 (s, 3H), 2.67 (m, 2H), 3.27 (s,
C
11H13NO3: C, 63.76; H, 6.32; N, 6.76. Found: C, 63.82; H,
3H), 3.72 (s, 2H), 5.07 (m, 2H), and 5.81 (m, 1H); 13C NMR
6.33; N, 6.73.

2048 J . Org. Chem., Vol. 64, No. 6, 1999
Padwa et al.
2-Allyl-N-eth ylsu lfen yla cetyl-N-m eth ylben za m id e. Fol-
lowing the general procedure, treatment of 1.1 g (6 mmol) of
2-allyl-N-methylbenzamide48 with 1.1 g (7.8 mmol) of acid
chloride 18 afforded 1.2 g (72%) of 2-allyl-N-ethylsulfeny-
lacetyl-N-methylbenzamide as a colorless oil: IR (neat) 1687,
2H), 2.60 (m, 2H), 3.52 (s, 3H), and 6.92 (s, 1H); 13C NMR
(CDCl3, 75 MHz) δ 20.4, 21.4, 22.1, 27.0, 27.2, 30.4, 112.8,
130.5, 138.0, 140.7, 157.5, and 168.8. Anal. Calcd for C12H15
-
NO3: C, 65.14; H, 6.83; N, 6.33. Found: C, 65.50; H, 6.87; N,
6.34.
1417, and 1310 cm-1 1H NMR (CDCl3, 300 MHz) δ 1.28 (t,
;
1-Meth yl-3-eth ylsu lfen yl-5,6,7,8-tetr a h yd r o-1H-qu in o-
lin -2-on e (59). The minor product obtained from the above
column chromatography contained 0.09 g (25%) of quinolin-
2-one 59: mp 98-99 °C; IR (CCl4) 1638, 1583, 1420, and 1213
3H, J ) 7.4 Hz), 2.62 (q, 2H, J ) 7.4 Hz), 3.06 (s, 3H), 3.49 (d,
2H, J ) 6.5 Hz), 3.83 (s, 2H), 5.07 (m, 2H), 5.92 (m, 1H), and
7.35 (m, 4H); 13C NMR (CDCl3, 75 MHz) δ 14.3, 26.3, 34.0,
37.1, 37.5, 116.7, 126.4, 130.5, 135.3, 136.0, 137.6, 173.0,
and 173.2. HRMS Calcd for C15H19NO2S: 277.1136. Found:
277.1140.
2-Allyl-N-eth an esu lfin ylacetyl-N-m eth ylben zam ide (55).
The reaction of 1.1 g (3.8 mmol) of the above sulfide with 0.9
g (4 mmol) of sodium periodate gave 1.0 g (92%) of benzamide
55 as a clear oil: IR (neat) 1687, 1310, and 1047 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 1.40 (t, 3H, J ) 7.4 Hz), 2.94 (m, 2H),
3.07 (s, 3H), 3.47 (d, 2H, J ) 6.6 Hz), 4.16 (d, 1H, J ) 14.5
Hz), 4.45 (d, 1H, J ) 14.5 Hz), 5.06 (m, 2H), 5.90 (m, 1H), and
7.37 (m, 4H); 13C NMR (CDCl3, 75 MHz) δ 6.6, 34.2, 37.2, 46.4,
60.1, 117.0, 126.6, 130.8, 131.0, 134.4, 135.9, 137.8, 168.3, and
173.8. Anal. Calcd for C15H19NO3S: C, 61.41; H, 6.53; N, 4.78.
Found: C, 61.35; H, 6.51; N, 4.66.
1-Meth yl-2-oxo-2,5-d ih yd r o-1H-in d en o[1,2-b]p yr id in -3-
yl Acetic Acid Ester (56). To a refluxing solution of 1.4 g
(14 mmol) of acetic anhydride and 2 mg of p-toluenesulfonic
acid in 40 mL of toluene was added dropwise 0.4 g (1.4 mmol)
of benzamide 55 in 2 mL of toluene. After heating for 1 h at
reflux, the solvent was removed under reduced pressure, and
the residue was chromatographed on silica gel to give 0.24 g
(70%) of 56 as a white solid: mp 149-150 °C; IR (CCl4) 1769,
1649, 1536, and 1197 cm-1; 1H NMR (CDCl3, 300 MHz) δ 2.37
(s, 3H), 3.69 (s, 2H), 4.08 (s, 3H), 7.36 (m, 3H), 7.58 (d, 1H, J
) 6.4 Hz), and 7.92 (d, 1H, J ) 7.9 Hz); 13C NMR (CDCl3, 75
MHz) δ 20.7, 32.5, 34.9, 118.9, 121.9, 125.4, 126.6, 127.2, 127.6,
136.6, 138.8, 144.2, 144.8, 157.8, and 169.0. Anal. Calcd for
1
cm-1; H NMR (CDCl3, 300 MHz) δ 1.32 (t, 3H, J ) 7.3 Hz),
1.71 (m, 2H), 1.83 (m, 2H), 2.52 (m, 2H), 2.61 (m, 2H), 2.86 (q,
2H, J ) 7.3 Hz), 3.52 (s, 3H), and 6.95 (s, 1H); 13C NMR
(CDCl3, 75 MHz) δ 13.6, 21.7, 22.3, 25.0, 27.0, 27.5, 30.6, 114.6,
125.9, 135.0, 139.5, and 160.8. Anal. Calcd for C12H17NOS: C,
64.54; H, 7.67; N, 6.27. Found: C, 64.31; H, 7.55; N, 6.10.
N-Eth ylsu lfen yla cetyl-N-m eth yl-3-(2-vin ylp h en yl)p r o-
p ion a m id e. Following the general procedure, the reaction of
1.1 g (5.8 mmol) of N-methyl-3-(2-vinylphenyl)propionamide49
with 1.1 g (7.6 mmol) of acid chloride 18 afforded 1.5 g (90%)
of N-ethyl-sulfenylacetyl-N-methyl-3-(2-vinylphenyl)propiona-
mide as a clear oil: IR (neat) 1693, 1372, 1288, and 1085 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 1.26 (t, 3H, J ) 7.4 Hz), 2.60 (q,
2H, J ) 7.4 Hz), 2.93 (m, 2H), 3.05 (m, 2H), 3.20 (s, 3H), 3.71
(s, 2H), 5.32 (d, 1H, J ) 11.0 Hz), 5.66 (d, 1H, J ) 17.3 Hz),
6.98 (dd, 1H, J ) 17.3 and 11.0 Hz), 7.22 (m, 3H), and 7.48
(m, 1H); 13C NMR (CDCl3, 75 MHz) δ 14.2, 26.1, 28.1, 31.3,
37.6, 38.8, 116.0, 125.9, 126.7, 127.9, 129.4, 134.0, 136.4, 137.7,
172.0, and 174.9. HRMS Calcd for C16H21NO2S: 291.1293.
Found: 291.1301.
N-E t h a n esu lfin yla cet yl-N-m et h yl-3-(2-vin ylp h en yl)-
p r op ion a m id e (60). The reaction of 1.5 g (5.2 mmol) of the
above sulfide with 1.2 g (5.7 mmol) of sodium periodate gave
1.6 g (99%) of 60 as a colorless oil: IR (neat) 1686, 1302, and
1
1043 cm-1; H NMR (CDCl3, 300 MHz) δ 1.36 (t, 3H, J ) 7.4
Hz), 2.88 (m, 4H), 3.03 (m, 2H), 3.17 (s, 3H), 4.13 (d, 1H, J )
14.9 Hz), 4.31 (d, 1H, J ) 14.9 Hz), 5.34 (d, 1H, J ) 11.0 Hz),
5.67 (d, 1H, J ) 17.3 Hz), 6.96 (dd, 1H, J ) 17.3 and 11.0 Hz),
7.20 (m, 3H), and 7.48 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ
6.3, 27.6, 30.9, 37.8, 45.9, 60.4, 116.1, 125.8, 126.7, 127.7, 129.2,
C
15H13NO3S: C, 70.58; H, 5.13; N, 5.49. Found: C, 70.69; H,
5.19; N, 5.31.
N-Meth yl-2-eth ylsu lfen yl-N-h ept-6-en oylacetam ide. Fol-
lowing the general procedure, the reaction of 1.0 g (7.4 mmol)
of hept-6-enoic acid methylamide with 1.4 g (9.8 mmol) of acid
chloride 18 gave 1.2 g (66%) of N-methyl-2-ethylsulfenyl-N-
hept-6-enoylacetamide as a clear oil: IR (neat) 1695, 1292, and
133.7, 136.2, 137.0, 167.7, and 174.8. Anal. Calcd for C16H21
-
NO3S: C, 62.52; H, 6.89; N, 4.56. Found: C, 62.44; H, 6.72;
N, 4.50.
1
1086 cm-1; H NMR (CDCl3, 300 MHz) δ 1.27 (t, 3H, J ) 7.2
4-Met h yl-3-oxo-3,4,5,6-t et r a h yd r ob en zo[f]q u in olin -2-
yl Acetic Acid Ester (61). To a refluxing solution of 5.2 g
(51 mmol) of acetic anhydride and 2 mg of p-toluenesulfonic
acid in 75 mL of toluene was added dropwise 1.6 g (5.1 mmol)
of propionamide 60 in 2 mL of toluene. After heating at reflux
for 1 h, the reaction mixture was concentrated under reduced
pressure, and the residue was chromatographed on silica gel.
The major product (70%) isolated from the column was
identified as quinolin-2-yl acetic acid ester 61: mp 172-173
Hz), 1.46 (m, 2H), 1.68 (m, 2H), 2.09 (m, 2H), 2.63 (m, 4H),
3.25 (s, 3H), 3.73 (s, 2H), 5.00 (m, 2H), and 5.82 (m, 1H); 13C
NMR (CDCl3, 75 MHz) δ 14.3, 23.9, 26.1, 28.2, 31.4, 33.4, 37.5,
37.8, 114.6, 138.3, 172.2, and 175.7. HRMS Calcd for C12H21
NO2S: 243.1293. Found: 243.1302.
-
N-Met h yl-2-et h a n esu lfin yl-N-h ep t -6-en oyla cet a m id e
(57). The reaction of 1.0 g (4.2 mmol) of the above sulfide with
1.0 g (4.7 mmol) of sodium periodate afforded 1.1 g (99%) of
57 as a colorless oil: IR (neat) 1694, 1456, 1305, and 1048
cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.43 (m, 5H), 1.69 (m, 2H),
2.11 (m, 2H), 2.69 (m, 2H), 2.90 (m, 2H), 3.28 (s, 3H), 4.16 (d,
1H, J ) 14.8 Hz), 4.36 (d, 1H, J ) 14.8 Hz), 5.01 (m, 2H), and
5.81 (m, 1H); 13C NMR (CDCl3, 300 MHz) δ 6.3, 23.4, 27.8,
31.1, 33.1, 36.6, 45.9, 60.6, 114.6, 137.9, 167.8, and 175.7. Anal.
Calcd for C12H21NO3S: C, 55.57; H, 8.17; N, 5.40. Found: C,
55.49; H, 8.08; N, 5.43.
1-Meth yl-2-oxo-1,2,5,6,7,8-h exa h yd r oqu in olin -3-yl Ace-
tic Acid Ester (58). To a refluxing solution of 1.9 g (19 mmol)
of acetic anhydride and 2 mg of p-toluenesulfonic acid in 40
mL of toluene was added dropwise 0.49 g (1.9 mmol) of
acetamide 57 in 2 mL of toluene. After heating at reflux for 1
h, the reaction mixture was concentrated under reduced
pressure, and the residue was chromatographed on silica gel.
The major fraction isolated from the column contained 0.31 g
(70%) of pyridone 58 as a white solid: mp 118-119 °C; IR
(CCl4) 1763, 1664, 1613, 1560, and 1200 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.71 (m, 2H), 1.85 (m, 2H), 2.31 (s, 3H), 2.51 (m,
°C; IR (CCl4) 1770, 1651, 1616, and 1204 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 2.33 (s, 3H), 2.81 (m, 4H), 3.56 (s, 3H),
7.17 (m, 3H), 7.30 (d, 1H, J ) 7.6 Hz), and 7.56 (s, 1H); 13C
NMR (CDCl3, 75 MHz) δ 20.3, 25.0, 27.2, 31.1, 111.9, 121.5,
124.9, 126.4, 126.9, 127.3, 131.3, 132.2, 138.8, 142.7, 157.0,
and 168.4. Anal. Calcd for C16H15NO3: C, 71.36; H, 5.61; N,
5.20. Found: C, 71.30; H, 5.65; N, 5.15.
2-Eth ylsu lfen yl-4-m eth yl-5,6-dih ydr o-4H-ben zo[f]qu in -
olin -3-on e (62). The minor product (25%) obtained from the
above column chromatography was a colorless solid whose
structure was assigned as 2-ethylsulfenyl-4-methyl-5,6-dihy-
dro-4H-benzo[f]quinolin-3-one (62): mp 171-172 °C; IR (CCl4)
1633, 1586, 1534, and 1420 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 1.33 (t, 3H, J ) 7.4 Hz), 2.91 (m, 6H), 3.62 (s, 3H), 7.23 (m,
3H), 7.44 (d, 1H, J ) 7.7 Hz), and 7.61 (s, 1H); 13C NMR
(CDCl3, 75 MHz) δ 13.5, 25.1, 25.2, 27.7, 31.5, 113.7, 121.6,
126.4, 127.0, 127.1, 127.6, 129.9, 132.1, 132.6, 141.9, and 160.4.
Anal. Calcd for C16H17NOS: C, 70.82; H, 6.31; N, 5.16.
Found: C, 70.62; H, 6.30; N, 5.15.
(48) Marino, J . P., J r.; Osterhout, M. H.; Price, A. T.; Semones, M.
A.; Padwa, A. J . Org. Chem. 1994, 59, 5518.
(49) Marino, J . P., J r.; Osterhout, M. H.; Padwa, A. J . Org. Chem.
1995, 60, 2704.

Synthesis of Substituted 2-Pyridones
J . Org. Chem., Vol. 64, No. 6, 1999 2049
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra for new compounds lacking analyses together
with an ORTEP drawing for structure 25. This material is
available free of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. We gratefully acknowledge the
National Cancer Institute for generous support of this
work. Use of high-field NMR spectrometers used in
these studies was made possible through equipment
grants from the NIH and NSF. We also thank Scott M.
Sheehan for determining the X-ray crystal structure of
compound 25.
J O982315R