Synthesis of densely substituted 1,3-butadienes through acid-catalyzed alkenylations of α-oxoketene dithioacetals with aldehydes

Article abstract of DOI:10.1021/jo5017234

Aldehydes were proved to be viable reagents for implementing alkenylation of α-oxoketene dithioacetals. AlCl₃ was found to be the best catalyst. The established reaction opened an avenue to access densely substituted 1,3-butadiene derivatives. The obtained product bears multiple reactive sites that can be converted into various valuable molecules. (Chemical Equation Presented).

Full text of DOI:10.1021/jo5017234

Article
pubs.acs.org/joc
Synthesis of Densely Substituted 1,3-Butadienes through Acid-
Catalyzed Alkenylations of α‑Oxoketene Dithioacetals with
Aldehydes
Changhui Liu† and Yanlong Gu*,†,‡
†Key Laboratory for Large-Format Battery Materials and System, Ministry of Education, School of Chemistry and Chemical
Engineering, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China
‡State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Lanzhou 730000, People’s
Republic of China
S
* Supporting Information
ABSTRACT: Aldehydes were proved to be viable reagents for
implementing alkenylation of α-oxoketene dithioacetals. AlCl3
was found to be the best catalyst. The established reaction
opened an avenue to access densely substituted 1,3-butadiene
derivatives. The obtained product bears multiple reactive sites
that can be converted into various valuable molecules.
molecules.6 The reaction was established on the basis of a
INTRODUCTION
■
mechanism involving reversible carbon−carbon or carbon−
heteroatom bond formation, and a good leaving ability of the
nucleophile is the key for rendering the alkenylation protocol
possible. While this is readily accomplished with activated
substrates, such as 2-alkylindole and alkyl carbamates, the use of
unactivated compounds is exceedingly rare and, up to now,
represents a formidable challenge.
α-Oxoketene dithioacetals have recently emerged as valuable
building blocks for organic synthesis.7 The reactions with α-
oxoketene dithioacetals often produced molecules that bear
multiple reactive sites, allowing for further functionalizations.
Because of the unique reactivity that cannot be attained with
other substances, we were attracted to use these molecules in
acid-catalyzed organic synthesis.8 In this paper, some densely
substituted 1,3-butadiene derivatives were synthesized through
an acid-catalyzed alkenylation of α-oxoketene dithioacetal with
some suitable aldehydes. The reaction displayed a fairly good
scope with respect to both components. Remarkably, the
generated compound was proven to be a unique kind of
bifunctional building block that can be used in the synthesis of
some valuable molecules.
The 1,3-diene unit is often found in natural products that have
shown potential biological activities.1 Organic compounds that
have a fragment of conjugated diene have often been used as
key intermediates in the synthesis of pharmaceutically
interesting molecules.2 Because of the great importance of
the 1,3-diene unit, these derivatives are very attractive synthetic
targets in the search for efficient and selective synthetic
methods. Some conjugated dienes can be prepared by Wittig-
type olefination3 or transition-metal-mediated coupling reac-
tions of the deliberately functionalized precursors.4 Recently,
olefin−olefin dehydrogenative coupling methods for the
synthesis of 1,3-butadienes have also been reported.5 Although
there are numerous methods for the preparation of 1,3-
butadiene derivatives, most of these methods suffer from the
use of expensive reagents or catalysts. In some cases, the
reaction was established on the basis of the use of
stoichiometric or overstoichiometric amounts of environ-
mentally unfriendly additives (or sacrificial reagents). Fur-
thermore, some reported reactions were performed under less
favorable reaction conditions and suffered from the lack of
simplicity and also the yields and selectivities reported were far
from satisfactory. Therefore, there is a need to develop general
and efficient routes to the selective synthesis of conjugated
dienes.
Acid-catalyzed alkenylation of a nucleophile with an aldehyde
or its congeners that contains at least one proton in an α
position has proved recently to be an effective method for
introducing a carbon−carbon double bond into the target
Received: July 31, 2014
© XXXX American Chemical Society
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When Fe(OTf)3 was used as catalyst, no significant yield
improvement was observed (entry 6). A moderate yield, 50%,
was obtained when CuBr2 was used (entry 7). An attempt to
use a weak Lewis acid, LiBr·H2O, as catalyst led only to
recovery of unreacted starting materials (entry 8). Brønsted
acids, such as sulfuric acid and toluenesulfonic acid, were also
examined, and the yields obtained were rather poor (entries 9
and 10).
RESULTS AND DISCUSSION
■
Initially, phenylacetaldehyde 1a was treated with the α-
oxoketene dithioacetal 2a. The reaction was performed in
acetonitrile at 80 °C. No reaction was observed in the absence
of catalyst (Table 1, entry 1). When AlCl3 was used as catalyst,
Table 1. Alkenylation of α-Oxoketene Dithioacetal 2a with
a
1a
The effect of solvent was also investigated. Among different
solvents tested in the reaction between 1a and 2a, acetonitrile
clearly stood out, producing the desired product 3a with the
highest yield (88%), with chlorobenzene and nitromethane in a
distant second place (62−72%). Methanol, toluene, and 1,2-
dichloroethane resulted in significantly lower efficiency of the
reaction (entries 11−15). A decrease in the catalyst loading
from 10 to 5 mol % resulted in a significant decrease in the
reaction yield. Only 57% yield was obtained, although the
reaction time was increased to 16 h (entry 16). Further
investigation revealed that the reaction was also affected by
temperature and reaction time, and the optimal conditions are
80 °C and 6 h (entries 17 and 18).
entry
catalyst (10 mol %)
additive
MeOH
solvent
yield (%)
1
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
PhCl
0
2
AlCl3
36
88
73
18
26
50
trace
34
21
72
62
NR
35
23
57
64
67
3
AlCl3
MeOH
EtOH
4
AlCl3
5
FeCl3·6H2O
Fe(OTf)3
CuBr2
LiBr·H2O
H2SO4
PTSA
AlCl3
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
6
7
With the optimized conditions in hand, we probed the scope
of the reaction with respect to both the α-oxoketene
dithioacetal and the aldehyde components. As evidenced by
the results in Figure 1, ketene dithioacetals with different
substituents smoothly reacted with phenylacetaldehyde, pro-
ducing the expected 1,3-butadienes in generally good yield.
Both electron rich and moderately electron poor α-oxoketene
dithioacetals readily participated in the reaction. The moderate
yield obtained with 2-(1,3-dithiolan-2-ylidene)-1-(4-
iodophenyl)ethanone can be ascribed partially to its poor
solubility in the reaction system (3f). Only 58% yield was
obtained with a ketene dithioacetal that contains a strongly
electron-withdrawing group, 2-(1,3-dithiolan-2-ylidene)-1-(4-
nitrophenyl)ethanone (3g). This may result from its low
reactivity.10 A ketene dithioacetal containing a sterically
demanding substituent, such as 3,3-bis(methylthio)-1-phenyl-
2-propen-1-one (3h), can also be used in this type of reaction,
but the yield obtained is inferior as compared with that of 2a.
The scope of the reaction with respect to aldehydes was next
investigated and found to be excellent. We selected a set of
aldehydes spanning a convenient spectrum of reactivity. In all
cases, 2a was used as a benchmark substrate in order to
compare the reactivities of different aldehydes. Results with β-
arylacetaldehydes largely paralleled, in most cases, the yield of
phenylacetaldehyde (3i−t). Remarkably, 3-phenylpropanal and
butyraldehyde can also be used as alkenylation reagents, and
the corresponding products, 3u,x, were obtained in 87% and
90% yields, respectively. Cyclohexanecarbaldehyde and 3-
cyclohexene-1-carboxaldehyde participated readily in the
alkenylation reaction as well (3aa,ab). Only moderate yields
were obtained when methyl 3,3-dimethoxypropanoate and
ethyl 3,3-diethoxypropanoate were used (3ac,ad). In these
cases, the 3,3-dimethoxypropanoate was completely consumed,
whereas nearly half of the 2a can be recovered at the end of the
reaction. We therefore suspected that the susceptibility of 3,3-
dialkoxypropanoate toward the strong acid, AlCl3 catalyst,
might be partially responsible for the embarrassing yields.
It is significant to note that the reaction can also be
effectively scaled up with the similar efficiency (Scheme 2). For
example, the reaction of 2a (20 mmol) with 2,2-diphenylace-
taldehyde (1b; 20 mmol) gave the corresponding product 3j in
92% yield (7.4 g). Significantly, 3j was obtained by filtration as
8
9
10
11
12
AlCl3
CH3NO2
MeOH
toluene
DCE
b
13
AlCl3
b
14
AlCl3
MeOH
MeOH
MeOH
MeOH
MeOH
b
15
AlCl3
c
16
d
AlCl3
CH3CN
CH3CN
CH3CN
17
AlCl3
e
18
AlCl3
a
Conditions unless specified otherwise: 2a, 0.2 mmol; additive, 0.24
b
mmol; catalyst, 0.02 mmol; solvent, 1.0 mL; 80 °C; 6 h. Conditions:
c
d
12 h. Conditions: AlCl3: 0.01 mmol, 16 h. Conditions: 60 °C, 24 h.
e
Conditions: 3 h.
the alkenylation product 3a was obtained in 36% yield after 6 h
of reaction (Table 1, entry 2). The H NMR spectrum of 3a
1
showed that only trans isomer was obtained, indicating that this
reaction is exclusively stereoselective. This is probably a result
of stereo hindrance arising from the existence of bulky groups
on the two sides of the C−C double bond. Intriguingly, the
yield can be improved to 88% by adding 1.2 equiv of methanol
to the reaction system (entry 3). In this case, formation of the
dimethyl acetal of 1a may be responsible for the yield
improvement. This can be verified by the fact that 83% yield
could be obtained by using 4a as substrate (Scheme 1). When
ethanol was used instead of methanol, the yield decreased to
73% (entry 4).
Various Lewis acids were then examined in the reaction of 1a
and 2a. FeCl3·6H2O has been reported by Yu9 to be an efficient
catalyst for the alkenylation of indole with aldehyde. However,
with this catalyst, 3a was obtained only in 18% yield (entry 5).
Scheme 1. Reaction of 2a with 4a Catalyzed by AlCl3
B
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Figure 1. Alkenylation of α-oxoketene dithioacetals with aldehydes or their congeners. Legend to superscripts: (a) the configuration was determined
by 1H NMR; (b) 3ac and 3ad were synthesized with methyl 3,3-dimethoxypropanoate and ethyl 3,3-diethoxypropanoate in the absence of methanol.
reaction times, and harsh conditions.12 The present reaction
Scheme 2. Large-Scale Synthesis of 3j
thus opens an efficient route to synthesize these kinds of
functionalized α-oxoketene dithioacetals. The mechanism of
the alkenylation reaction most likely involves an acid-assisted
carbon cation based nucleophilic substitution. That is,
activation of phenylacetalaldehyde 1a is achieved via the
it precipitated out from the reaction mixture at the end of the
reaction (parts a and b of Figure 2). The structures of 3j have
been unambiguously confirmed by X-ray structural analysis (see
Figure S1 in the Supporting Information).11
It should be noted that the previous methods to access the
similar vinylated α-oxoketene dithioacetal derivatives not only
involved the use of noble-metal-based catalysts but also suffered
from some drawbacks, such as insufficient reactions, long
formation of an acetal or a hemiacetal. A carbon cation (I) was
formed by elimination of either methanol or water. This is
followed by nucleophilic attack of α-oxoketene dithioacetal 2a,
which leads to generation of an intermediate (II) that can be
then converted into 3a (Figure 3).
When aldehyde is used as an alkenylation reagent, the
existence of an α-proton is the key for rendering the reaction
possible. However, we found that, in this reaction, this is not
always the case. An exception was found with cocal (1c) and 4-
methyl-2-phenyl-2-pentenal (1d). These two aldehydes have no
α-proton but were also applicable in this type of alkenylation.
Different from the case for 1a-induced alkenylation, the present
reactions are associated with an elimination of a γ-proton,
which unexpectedly generated 5a,b in 45% and 40% yields,
respectively (Scheme 3). These structures contain a skeleton of
1,3,5-triene which has often occurred in natural products.13
Previous methods to access this scaffold involved the use of
either hazardous reaction conditions14 or metallic reagents.15
This reaction thus provided a convenient way to synthesize this
type of structure.
Figure 2. Large-scale synthesis of 3j: (a) before reaction; (b) after
reaction.
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III, and then (ii) the intermediate III underwent a ring-opening
reaction triggered by an attack of chloride anion in the presence
of a proton donor (presumably methanol), producing 6a.
After establishing the synthetic method, we then investigated
the transformations of the obtained products. The study
commenced from the use of the compound 3z in the synthesis
of some important heterocycles. First, the densely substituted
pyrrole derivative 7a was obtained in 77% yield when 3z was
treated with aniline in the presence of CuBr2 catalyst (Scheme
5). The initial event of the reaction might be the formation of a
Scheme 5. Catalytic Reactions Developed with 3z as Starting
Material
Figure 3. Proposed mechanism.
Scheme 3. Alkenylation of 2a with cocal (1c) and 4-Methyl-
2-phenyl-2-pentenal (1d)
Michael adduct, which then underwent intramolecular
nucleophilic substitution17 and an aromatization reaction to
generate 7a. Interestingly, when aniline was replaced by
anthranilamide, the substituted thiophene derivative 8a was
obtained. Further investigation revealed that a catalytic amount
of anthranilamide (20 mol %) is sufficient to ensure an
excellent yield for this reaction (Scheme 5). In the absence of
anthranilamide, only a trace amount of 8a was detected. No
reaction occurred when CuBr2 was omitted from this catalytic
system. Although the detailed mechanism of the cooperative
catalysis remains to be delineated, the established reaction is
valuable for organic synthesis because many thiophene
derivatives with a methylthio group in a C2 position have
exhibited good bioactivities for antibacterial use.18 Compound
3z was also proved to be susceptible toward basic reagents. For
example, an unexpected product, 9a, was obtained in 55% yield
when it was treated with Cs2CO3 in refluxing ethanol for 3 h
(Scheme 5). The mechanism of this reaction might be
associated with the formation of a carbon anion, which then
triggered an intramolecular migration of both a proton and a
methylthio group.
Alkylidenecyclopropane derivatives have been widely used as
intermediates in organic synthesis over the past few decades.16
On the basis of the aforementioned results, we envisioned that
it is possible to synthesize an alkylidenecyclopropane derivative
by using cyclopropanecarboxaldehyde (1e) as an alkenylation
reagent. Indeed, a product was obtained when 2a was treated
with 1e in the presence of AlCl3 (Scheme 4). However,
Scheme 4. Alkenylation of 2a with 1e
In addition, in the presence of 1.2 equiv of CuBr2, 3u could
be smoothly converted into 10a in nitromethane (Scheme 6).
Compound 10a contains a scaffold of naphthalenone, which is
an important medicinal intermediate.19 The reaction might
proceed according to the following pathways: (i) an intra-
molecular Friedel−Crafts reaction, generating the intermediate
IV and (ii) dehydrogenation of the intermediate IV, which led
to the formation of 10a. CuBr2 acted as a dual Lewis acid
catalyst and an oxidant, thus allowing the reaction to proceed
smoothly. All of these examples demonstrated that the title
reactions of α-oxoketene dithioacetals using aldehyde as an
alkenylation reagent are indeed valuable for organic synthesis.
spectroscopic analysis of the product revealed that the structure
of this product is 6a. Considering the fact that, in this reaction,
AlCl3 acts as a dual catalyst and reagent, we then increased its
loading to 30 mol %. To our delight, 6a was obtained in 85%
yield. The mechanism of the reaction may involve the following
two steps: (i) the alkenylation reaction occurred with the aid of
AlCl3 catalyst, generating alkylidenecyclopropane intermediate
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10.9 mmg) as catalysts. The mixture was stirred at 60 °C for 10 h.
Then, the product was obtained in 95% yield (0.38 mmol, 123.1 mg)
by isolation with preparative TLC (eluent: petroleum ether/ethyl
acetate 10/1 (v/v)).
Scheme 6. Synthesis of 10a from 3u
Procedure for the Synthesis of 9a. A solution of 3z (0.4 mmol,
136.0 mg) in ethanol (2 mL) was mixed with Cs2CO3 (1.0 equiv, 0.4
mmol, 130.0 mg). The mixture was stirred at 80 °C for 3 h. Then, the
product was obtained in 55% yield (0.22 mmol, 74.8 mg) by isolation
with preparative TLC (eluent: petroleum ether/ethyl acetate 10/1 (v/
v)).
Procedure for the Synthesis of 10a. A solution of 3u (0.4 mmol,
135.2 mg) in nitromethane (2 mL) was mixed with CuBr2 (1.2 equiv,
0.48 mmol, 105.6 mg) The mixture was stirred at 60 °C for 4 h. Then,
the product was obtained in 82% yield (0.33 mmol, 110.2 mg) by
isolation with preparative TLC (eluent: petroleum ether/ethyl acetate
10/1 (v/v)).
CONCLUSIONS
Characterization Data of New Compounds. (E)-2-(1,3-
Dithiolan-2-ylidene)-1,4-diphenylbut-3-en-1-one (3a). Yield: 88%,
0.18 mmol, 57.0 mg; yellowish oil. 1H NMR (400 MHz, CDCl3, TMS,
25 °C): δ 7.88−7.80 (m, 2H), 7.50 (dd, J = 11.7, 4.4 Hz, 1H), 7.40 (t,
J = 7.5 Hz, 2H), 7.31−7.15 (m, 5H), 7.02 (d, J = 16.2 Hz, 1H), 6.26
(d, J = 16.2 Hz, 1H), 3.51−3.38 (m, 4H). 13C NMR (100 MHz,
CDCl3, TMS, 25 °C): δ 194.0, 137.9, 137.2, 132.4, 131.2, 129.7, 128.6,
128.3, 127.5, 126.6, 126.2, 38.6, 36.9 ppm. IR (KBr): ν 2961, 2924,
2853, 1724, 1659, 1450, 1262, 1074, 912, 801, 745, 691 cm−1. HRMS
(TOF, ESI): m/z calcd for C19H16NaOS2, [M + Na]+ 347.0540, found
347.0547.
■
In summary, the alkenylation reaction of α-oxoketene
dithioacetal with aldehyde has been established by using
AlCl3 as catalyst. With this reaction, various densely substituted
1,3-butadiene derivatives were synthesized in moderate to
excellent yields. The generated conjugated dienes not only bear
a reactive C−C double bond but also contain a few active sites
from α-oxoketene dithioacetal, which can be used as bifunc-
tional building blocks for the synthesis of some valuable
molecules. Given the large number of commercially available
aldehydes and the easy access to α-oxoketene dithioacetals, the
present method should be able to synthesize a wide range of
conjugated dienes. Considering the unique reactivity of the
products, we believe that this method has a great potential to be
applied extensively in the field of synthetic chemistry.
(E)-2-(1,3-Dithiolan-2-ylidene)-4-phenyl-1-(p-tolyl)but-3-en-1-
1
one (3b). Yield: 72%, 0.14 mmol, 48.7 mg; yellowish oil. H NMR
(600 MHz, CDCl3, TMS, 25 °C): δ 7.77 (d, J = 8.1 Hz, 2H), 7.34−
7.24 (m, 5H), 7.21 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 16.2 Hz, 1H), 6.25
(d, J = 16.2 Hz, 1H), 3.49−3.44 (m, 2H), 3.40 (dd, J = 6.9, 4.7 Hz,
2H), 2.39 (s, 3H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ
194.1, 151.9, 143.4, 137.3, 134.9, 130.6, 130.0, 129.1, 128.6, 127.5,
126.6, 126.2, 125.6, 38.5, 37.0, 21.7 ppm. IR (KBr): ν2955, 2925,
2855, 1745, 1659, 1603, 1456, 1284, 1217, 1173, 952, 751, 694 cm−1.
HRMS (TOF, ESI): m/z calcd for C20H18NaOS2, [M + Na]+
361.0697, found 361.0701.
EXPERIMENTAL SECTION
■
General Information. Chemical shifts are expressed in ppm
relative to Me4Si in solvent. All chemicals used were of reagent grade
and were used as received without further purification. α-Oxoketene
dithioacetals were prepared according to previously reported
methods.20 All reactions were conducted in a 10 mL V-type flask
equipped with triangle magnetic stirring.
(E)-2-(1,3-Dithiolan-2-ylidene)-1-(4-methoxyphenyl)-4-phenyl-
but-3-en-1-one (3c). Yield: 86%, 0.17 mmol, 60.9 mg; yellowish oil.
1H NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.88 (d, J = 8.9 Hz, 2H),
7.31 (d, J = 7.4 Hz, 2H), 7.27 (t, J = 7.6 Hz, 2H), 7.19 (t, J = 7.2 Hz,
1H), 7.05 (d, J = 16.1 Hz, 1H), 6.90 (d, J = 8.9 Hz, 2H), 6.24 (d, J =
16.2 Hz, 1H), 3.84 (s, 3H), 3.46 (t, J = 6.1 Hz, 2H), 3.39 (t, J = 5.9 Hz,
2H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ 193.6, 163.5,
149.5, 137.3, 132.3, 130.1, 129.9, 128.6, 127.5, 126.6, 126.2, 126.0,
113.7, 55.5, 38.5, 37.2 ppm. IR (KBr): ν 2957, 2927, 2842, 1725, 1652,
1595, 1459, 1303, 1256, 1164, 1027, 952, 841, 752 cm−1. HRMS
(TOF, ESI): m/z calcd for C20H18NaO2S2, [M + Na]+ 377.0646,
found 377.0654.
General Procedure for the Reactions of α-Oxoketene Dithioace-
tal and Aldehyde. In a typical reaction, ketene dithioacetal (0.20
mmol) was mixed with the aldehyde (0.20 mmol), MeOH (0.24
mmol), and AlCl3 (10 mol %) in acetonitrile (1.0 mL). The mixture
was then stirred at 80 °C for 6 h. After the reaction, the mixture was
cooled to room temperature, and the product was obtained by
isolation with preparative TLC (elutent: petroleum ether/ethyl acetate
10/1 (v/v)). Tests for substrate scope were all performed with an
analogous procedure.
Large-Scale Synthesis of 3j. A solution of 2a (20 mmol, 4.4 g) in
nitromethane (25 mL) was mixed with 1b (20 mmol, 3.9 g), MeOH
(24 mmol, 768 mg), and AlCl3 (10 mol %, 2.0 mmol, 266 mg). The
mixture was stirred at 80 °C for 10 h. After the reaction, the product
was obtained in 92% yield (18.4 mmol, 7.4 g) by filtration.
Procedure for the Synthesis of 6a. A solution of 2a (0.2 mmol,
44.0 mg) in nitromethane (1 mL) was mixed with 1e (0.2 mmol, 14.0
mg), MeOH (0.24 mmol, 7.7 mg), and AlCl3 (30 mol %, 0.06 mmol,
8.0 mg). The mixture was stirred at 80 °C for 10 h. Then, the product
was obtained in 85% yield (0.17 mmol, 52.7 mg) by isolation with
preparative TLC (eluent: petroleum ether/ethyl acetate 10/1 (v/v)).
Procedure for the Synthesis of 7a. A solution of 3z (0.4 mmol,
136.0 mg) in nitromethane (2 mL) was mixed with aniline (2.0 eq, 0.8
mmol, 74.4 mg) and CuBr2 (20 mol %, 0.08 mmol, 17.6 mg). The
mixture was stirred at 60 °C for 2 h. Then, the product was obtained in
77% yield (0.31 mmol, 118.7 mg) by isolation with preparative TLC
(eluent: petroleum ether/ethyl acetate 10/1 (v/v)).
(E)-1-(4-Chlorophenyl)-2-(1,3-dithiolan-2-ylidene)-4-phenylbut-
1
3-en-1-one (3d). Yield: 68%, 0.14 mmol, 48.7 mg; yellowish oil. H
NMR (400 MHz, CDCl3, TMS, 25 °C): δ 7.77 (d, J = 8.5 Hz, 2H),
7.37 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 3.6 Hz, 4H), 7.24−7.19 (m, 1H),
7.00 (d, J = 16.2 Hz, 1H), 6.25 (d, J = 16.2 Hz, 1H), 3.53−3.35 (m,
4H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ 192.4, 156.2,
138.6, 137.0, 136.3, 131.6, 131.1, 128.7, 128.6, 127.7, 126.4, 126.2,
124.5, 38.6, 36.9 ppm. IR (KBr): ν 3024, 2923, 2852, 1725, 1660,
1586, 1282, 1167, 1088, 1007, 952, 838, 747, 693 cm−1. HRMS (TOF,
ESI): m/z calcd for C19H15ClNaOS2, [M + Na]+ 381.0151, found
381.0130.
(E)-2-(1,3-Dithiolan-2-ylidene)-1-(4-fluorophenyl)-4-phenylbut-3-
1
en-1-one (3e). Yield: 77%, 0.15 mmol, 52.7 mg; yellowish oil. H
NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.87 (dd, J = 8.7, 5.5 Hz,
2H), 7.33−7.25 (m, 5H), 7.23−7.18 (m, 1H), 7.07 (t, J = 8.6 Hz, 2H),
7.02 (d, J = 16.2 Hz, 1H), 6.24 (d, J = 16.2 Hz, 1H), 3.48−3.44 (m,
2H), 3.43−3.39 (m, 2H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C):
δ 192.5, 166.1, 164.4, 154.5, 137.1, 134.0, 134.0, 132.4, 132.3, 131.2,
128.6, 127.7, 126.4, 126.2, 124.8, 115.5, 115.4, 38.6, 37.0 ppm. 19F
NMR (377 MHz, CDCl3, TMS, 25 °C): δ −105.9 ppm. IR (KBr): ν
Procedure for the Synthesis of 8a. A solution of 3z (0.4 mmol,
136.0 mg) in nitromethane (2 mL) was mixed with CuBr2 (20 mol %,
0.08 mmol, 17.6 mg) and 2-aminobenzamide (20 mol %, 0.08 mmol,
E
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Article
3024, 2926, 2854, 1724, 1662, 1595, 1499, 1455, 1284, 1229, 1153,
954, 845, 753, 694, 565 cm−1. HRMS (TOF, ESI): m/z calcd for
C19H16FOS2, [M + H]+ 343.0627, found 343.0621.
(E)-2-(1,3-Dithiolan-2-ylidene)-4-(4-nitrophenyl)-1-phenylbut-3-
en-1-one (3l). Yield: 67%, 0.13 mmol, 49.4 mg; red solid, mp 155−
157 °C. 1H NMR (600 MHz, CDCl3, TMS, 25 °C): δ 8.11 (d, J = 8.7
Hz, 2H), 7.83 (d, J = 7.5 Hz, 2H), 7.54 (t, J = 7.4 Hz, 1H), 7.44 (t, J =
7.7 Hz, 2H), 7.38 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 16.1 Hz, 1H), 6.27
(d, J = 16.1 Hz, 1H), 3.54−3.49 (m, 2H), 3.45 (dd, J = 11.9, 5.3 Hz,
2H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ 193.9, 157.1,
146.5, 143.9, 137.4, 132.9, 130.5, 129.7, 128.5, 127.7, 126.5, 124.1,
38.8, 37.2 ppm. IR (KBr): ν 3070, 2926, 2852, 1660, 1589, 1514, 1450,
1339, 1248, 1179, 1109, 949, 910, 866, 728, 693, 637 cm−1. HRMS
(TOF, ESI): m/z calcd for C19H16NO3S2, [M + H]+ 370.0572, found
370.0572.
(E)-2-(1,3-Dithiolan-2-ylidene)-1-(4-iodophenyl)-4-phenylbut-3-
en-1-one (3f). Yield: 51%, 0.10 mmol, 45.8 mg; yellowish oil. 1H
NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.75 (d, J = 8.4 Hz, 2H),
7.53 (d, J = 8.4 Hz, 2H), 7.32−7.27 (m, 4H), 7.21 (ddd, J = 8.6, 5.7,
2.9 Hz, 1H), 6.99 (d, J = 16.2 Hz, 1H), 6.26 (d, J = 16.2 Hz, 1H),
3.47−3.41 (m, 4H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ
192.6, 156.6, 137. 6, 137.3, 137.0, 131.7, 131.2, 128.7, 127.7, 126.4,
126.3, 124.3, 100.0, 38.7, 36.9 ppm. IR (KBr): ν 2957, 2925, 2854,
1725, 1662, 1611, 1578, 1452, 1389, 1309, 1285, 1252, 1173, 1057,
1001, 953, 835, 746, 694, 507 cm−1. HRMS (TOF, ESI): m/z calcd for
C19H16IOS2, [M + H]+ 450.9687, found 450.9667.
(E)-4-(4-Chlorophenyl)-2-(1,3-dithiolan-2-ylidene)-1-phenylbut-
1
3-en-1-one (3m). Yield: 92%, 0.18 mmol, 65.9 mg; yellowish oil. H
NMR (600 MHz, CDCl3, 25 °C): δ 7.85−7.77 (m, 2H), 7.50 (t, J =
6.8 Hz, 1H), 7.40 (t, J = 7.7 Hz, 2H), 7.21 (q, J = 8.7 Hz, 4H), 6.99 (d,
J = 16.2 Hz, 1H), 6.19 (d, J = 16.2 Hz, 1H), 3.46−3.43 (m, 2H), 3.42−
3.39 (m, 2H). 13C NMR (150 MHz, CDCl3, 25 °C): δ 186.0, 155.0,
137.7, 135.7, 133.1, 132.5, 132.1, 129.7, 129.6, 128.8, 128.8, 128.5,
128.4, 128.3, 127.9, 127.8, 127.4, 127.1, 124.8, 108.3, 38.6, 37.0 ppm.
IR (KBr): ν 3026, 2926, 2854, 1725, 1660, 1614, 1486, 1450, 1279,
1250, 1224, 957, 809, 695, 637 cm−1. HRMS (TOF, ESI): m/z calcd
for C19H15ClOS2, [M + H]+ 359.0331, found 359.0324.
(E)-2-(1,3-Dithiolan-2-ylidene)-1-(4-nitrophenyl)-4-phenylbut-3-
en-1-one (3g). Yield: 58%, 0.12 mmol, 42.8 mg; red solid, mp 110−
112 °C. 1H NMR (600 MHz, CDCl3, TMS, 25 °C): δ 8.22 (d, J = 8.7
Hz, 2H), 7.88 (d, J = 8.7 Hz, 2H), 7.29−7.22 (m, 5H), 6.95 (d, J =
16.2 Hz, 1H), 6.26 (d, J = 16.2 Hz, 1H), 3.48 (s, 4H). 13C NMR (150
MHz, CDCl3, TMS, 25 °C): δ 190.3, 163.3, 149.2, 144.3, 136.6, 133.4,
130.9, 130.6, 130.3, 129.5, 128.8, 128.7, 128.0, 126.3, 125.9, 124.1,
124.0, 123.8, 123.4, 123.1, 38.9, 36.7 ppm. IR (KBr): ν2957, 2926,
2855, 1725, 1672, 1596, 1522, 1452, 1346, 1284, 956, 854, 754, 728,
695 cm−1. HRMS (TOF, ESI): m/z calcd for C19H16NO3S2, [M + H+]
370.0572, found 370.0553.
(E)-4-(4-Bromophenyl)-2-(1,3-dithiolan-2-ylidene)-1-phenylbut-
1
3-en-1-one (3n). Yield: 83%, 0.17 mmol, 66.6 mg; yellowish oil. H
NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.53−7.47 (m, 2H), 7.42
(dd, J = 15.5, 7.6 Hz, 3H), 7.36 (d, J = 5.0 Hz, 2H), 7.13 (d, J = 8.5
Hz, 2H), 7.01 (d, J = 16.2 Hz, 1H), 6.17 (d, J = 16.2 Hz, 1H), 3.47
(dd, J = 7.4, 5.5 Hz, 2H), 3.38 (dt, J = 12.6, 3.7 Hz, 2H). 13C NMR
(150 MHz, CDCl3, TMS, 25 °C): δ 193.9, 155.1, 137.7, 136.2, 132.5,
132.1, 131.7, 129.7, 128.5, 128.4, 127.9, 127.7, 127.2, 124.8, 121.2,
108.3, 38.6, 37.0 ppm. IR (KBr): ν 2959, 2925, 2853, 1742, 1660,
1615, 1575, 1483, 1450, 1280, 1250, 1225, 1175, 1049, 960, 806, 695
cm−1. HRMS (TOF, ESI): m/z calcd for C19H16BrOS2, [M + H]+
402.9826, found 402.9804.
(E)-2-(Bis(methylthio)methylene)-1,4-diphenylbut-3-en-1-one
(3h).21 Yield: 52%, 0.10 mmol, 33.9 mg; yellowish oil. H NMR (600
1
MHz, CDCl3, TMS, 25 °C): δ 7.96 (d, J = 7.2 Hz, 2H), 7.61 (d, J =
16.5 Hz, 1H), 7.56 (t, J = 7.4 Hz, 1H), 7.47 (t, J = 7.7 Hz, 2H), 7.37
(d, J = 7.5 Hz, 2H), 7.27 (t, J = 7.6 Hz, 2H), 7.21 (t, J = 7.3 Hz, 1H),
6.34 (d, J = 16.5 Hz, 1H), 2.42 (s, 3H), 2.12 (s, 3H). 13C NMR (150
MHz, CDCl3, TMS, 25 °C): δ 196.2, 145.4, 136.8, 136.8, 135.7, 133.5,
133.5, 129.3, 128.8, 128.8, 128.8, 128.6, 128.6, 128.3, 126.8, 124.7,
17.4, 16.7 ppm. IR (KBr): ν 3028, 2921, 2852, 1737, 1669, 1596, 1577,
1517, 1492, 1447, 1421, 1314, 1288, 1213, 1170, 1054, 961, 908, 751,
724 cm−1.
(E)-2-(1,3-Dithiolan-2-ylidene)-4-(4-fluorophenyl)-1-phenylbut-3-
1
en-1-one (3o). Yield: 90%, 0.18 mmol, 61.6 mg; yellowish oil. H
(E)-2-(1,3-Dithiolan-2-ylidene)-1,4-diphenylpent-3-en-1-one (3i).
NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.79 (d, J = 7.2 Hz, 2H),
7.51−7.37 (m, 7H), 6.93 (d, J = 16.1 Hz, 1H), 6.66 (d, J = 16.1 Hz,
1H), 3.43 (d, J = 4.6 Hz, 2H), 3.42−3.39 (m, 2H). 13C NMR (151
MHz, CDCl3, TMS, 25 °C): δ 193.6, 158.3, 138.3, 137.2, 133.0, 132.2,
132.1, 130.2, 129.6, 129.2, 128.7, 128.5, 128.3, 127.9, 127.5, 126.4,
124.4, 123.9, 108.3, 38.6, 37.0 ppm. 19F NMR (377 MHz, CDCl3,
TMS, 25 °C): δ −102.9, −102.9, −102.9 ppm. IR (KBr): ν 3057,
2925, 2853, 1659, 1615, 1499, 1451, 1279, 1250, 1224, 1022, 954, 803,
753, 694 cm−1. HRMS (TOF, ESI): m/z calcd for C19H16FOS2, [M +
H]+ 343.0627, found 343.0629.
1
Yield: 60%, 0.12 mmol, 40.6 mg; yellowish oil. H NMR (600 MHz,
CDCl3, TMS, 25 °C): δ 7.50−7.22 (m, 10H), 6.61 (s, 1H), 3.47 (t, J =
6.4 Hz, 2H), 3.40−3.36 (m, 2H), 1.71 (s, 3H). 13C NMR (150 MHz,
CDCl3, TMS, 25 °C): δ 190.9, 165.1, 142.6, 139.5, 139.4, 131.0, 130.3,
128.8, 128.3, 128.3, 127.9, 127.6, 127.4, 127.0, 126.9, 125.9, 125.7,
124.7, 122.5, 39.1, 36.1, 17.9 ppm. IR (KBr): ν 2959, 2925, 2852,
1726, 1616, 1462, 1279, 1021, 914, 727, 695, 635 cm−1. HRMS (TOF,
ESI): m/z calcd for C20H18NaOS2, [M + Na]+ 361.0697, found
361.0703.
2-(1,3-Dithiolan-2-ylidene)-1,4,4-triphenylbut-3-en-1-one (3j).
Yield: 92%, 0.18 mmol, 73.6 mg; light yellow solid, mp 210−212
°C. 1H NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.28 (dt, J = 3.9, 2.1
Hz, 3H), 7.24−7.21 (m, 3H), 7.21−7.17 (m, 2H), 7.15−7.08 (m, 3H),
7.03 (t, J = 7.7 Hz, 2H), 6.77 (s, 1H), 6.58 (dd, J = 8.0, 0.9 Hz, 2H),
3.47−3.41 (m, 4H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ
191.6, 163.2, 144.2, 142.8, 139.6, 138.4, 130.7, 130.3, 128.3, 128.3,
128.1, 127.9, 127.7, 127.3, 127.1, 125.8, 124.2, 38.5, 36.6 ppm. IR
(KBr): ν 3055, 2924, 2853, 1622, 1598, 1458, 1316, 1279, 1247, 1075,
1009, 910, 772, 729, 696 cm−1. HRMS (TOF, ESI): m/z calcd for
C25H20NaOS2, [M + Na]+ 423.0853, found 423.0840.
(E)-4-(3,4-Dimethoxyphenyl)-2-(1,3-dithiolan-2-ylidene)-1-phe-
nylbut-3-en-1-one (3p). Yield: 79%, 0.16 mmol, 60.7 mg; yellowish
oil. 1H NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.84 (d, J = 7.2 Hz,
2H), 7.49 (t, J = 7.4 Hz, 1H), 7.41 (t, J = 7.7 Hz, 2H), 6.88 (d, J = 16.1
Hz, 1H), 6.86−6.81 (m, 2H), 6.77 (d, J = 8.3 Hz, 1H), 6.21 (d, J =
16.2 Hz, 1H), 3.86 (d, J = 2.8 Hz, 6H), 3.45 (dd, J = 6.7, 4.7 Hz, 2H),
3.42−3.38 (m, 2H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ
194.1, 153.0, 149.0, 148.9, 137.8, 132.4, 130.9, 130.4, 129.7, 128.3,
125.2, 125.0, 119.4, 111.2, 108.9, 56.0, 55.9, 38.6, 36.9 ppm. IR (KBr):
ν 2957, 2928, 2837, 1744, 1660, 1598, 1512, 1461, 1261, 1139, 1025,
728 cm−1. HRMS (TOF, ESI): m/z calcd for C21H21O3S2, [M + H]+
385.0932, found 385.0930.
(E)-2-(1,3-Dithiolan-2-ylidene)-4-(4-methoxyphenyl)-1-phenyl-
but-3-en-1-one (3k). Yield: 94%, 0.19 mmol, 66.6 mg; yellowish oil.
1H NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.87−7.79 (m, 2H),
(E)-4-(3-Bromophenyl)-2-(1,3-dithiolan-2-ylidene)-1-phenylbut-
1
3-en-1-one (3q). Yield: 88%, 0.18 mmol, 70.6 mg; yellowish oil. H
7.48 (dd, J = 10.5, 4.3 Hz, 1H), 7.39 (t, J = 7.7 Hz, 2H), 7.22 (d, J =
8.7 Hz, 2H), 6.88 (d, J = 16.2 Hz, 1H), 6.80 (d, J = 8.7 Hz, 2H), 6.21
(d, J = 16.2 Hz, 1H), 3.77 (s, 3H), 3.45−3.42 (m, 2H), 3.41−3.38 (m,
2H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ 194.0, 159.3,
137.9, 132.3, 130.8, 130.0, 129.7, 128.3, 127.8, 127.5, 125.3, 124.7,
114.1, 55.3, 38.6, 36.9 ppm. IR (KBr): ν2999, 2926, 2834, 1739, 1659,
1603, 1507, 1449, 1248, 1174, 1029, 814, 715 cm−1. HRMS (TOF,
ESI): m/z calcd for C20H18NaO2S2, [M + Na]+ 377.0646, found
377.0636.
NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.85−7.79 (m, 2H), 7.50 (t,
J = 7.4 Hz, 1H), 7.41 (t, J = 7.7 Hz, 2H), 7.20 (s, 1H), 7.21−7.09 (m,
3H), 7.03 (d, J = 16.2 Hz, 1H), 6.17 (d, J = 16.2 Hz, 1H), 3.46 (t, J =
5.6 Hz, 2H), 3.44−3.40 (m, 2H). 13C NMR (150 MHz, CDCl3, TMS,
25 °C): δ 193.8, 155.7, 139.1, 137.7, 134.5, 132.5, 129.8, 129.7, 129.5,
128.4, 127.8, 127.4, 126.0, 124.6, 124.5, 38.6, 37.0 ppm. IR (KBr): ν
3060, 2926, 1661, 1615, 1503, 1281, 1250, 1230, 1156, 1049, 961, 815,
700 cm−1. HRMS (TOF, ESI): m/z calcd for C19H16BrOS2, [M + H]+
402.9826, found 402.9853.
F
dx.doi.org/10.1021/jo5017234 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(E)-4-(3-Chlorophenyl)-2-(1,3-dithiolan-2-ylidene)-1-phenylbut-
1010, 853, 749, 700 cm−1. HRMS (TOF, ESI): m/z calcd for
C21H18NOS2, [M + H]+ 364.0830, found 364.0829.
1
3-en-1-one (3r). Yield: 95%, 0.19 mmol, 68.0 mg; yellowish oil. H
NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.74 (d, J = 7.1 Hz, 2H),
7.43 (t, J = 7.4 Hz, 1H), 7.33 (t, J = 7.7 Hz, 2H), 7.19 (s, 1H), 7.14−
7.03 (m, 3H), 6.95 (d, J = 16.2 Hz, 1H), 6.10 (d, J = 16.2 Hz, 1H),
3.36 (ddd, J = 11.1, 7.2, 5.1 Hz, 4H). 13C NMR (150 MHz, CDCl3,
TMS, 25 °C): δ 193.8, 155.6, 139.1, 137.7, 134.4, 132.2, 129.8, 129.7,
129.4, 128.3, 127.9, 127.3, 126.0, 124.6, 124.5, 38.6, 37.0 ppm. IR
(KBr): ν 3059, 2926, 2854, 1662, 1612, 1592, 1451, 1317, 1280, 1248,
1172, 952, 781, 731, 689, 638 cm−1. HRMS (TOF, ESI): m/z calcd for
C19H15ClNaOS2, [M + Na]+ 381.0151, found 381.0130.
(E)-2-(1,3-Dithiolan-2-ylidene)-1-phenylhex-3-en-1-one (3x).
Yield: 90%, 0.18 mmol, 49.7 mg; yellowish oil. H NMR (600 MHz,
1
CDCl3, TMS, 25 °C): δ 7.74 (d, J = 7.5 Hz, 2H), 7.46 (t, J = 7.4 Hz,
1H), 7.38 (t, J = 7.6 Hz, 2H), 6.25 (d, J = 15.8 Hz, 1H), 5.43 (dt, J =
15.7, 6.7 Hz, 1H), 3.41−3.36 (m, 4H), 2.09−2.01 (m, 2H), 0.90 (t, J =
7.4 Hz, 3H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ 193.4,
138.4, 136.8, 131.7, 129.7, 127.9, 127.1, 124.8, 38.5, 36.6, 26.3, 13.3
ppm. IR (KBr): ν 2962, 2927, 2871, 1662, 1616, 1454, 1277, 1173,
962, 804, 720, 692, 633 cm−1. HRMS (TOF, ESI): m/z calcd for
C15H16NaOS2, [M + Na]+ 299.0540, found 299.0551.
(E)-2-(1,3-Dithiolan-2-ylidene)-4-(2-fluorophenyl)-1-phenylbut-3-
1
en-1-one (3s). Yield: 98%, 0.20 mmol, 67.0 mg; yellowish oil. H
(E)-2-(1,3-Dithiolan-2-ylidene)-1-phenylhept-3-en-1-one (3y).
1
NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.82 (d, J = 7.3 Hz, 2H),
7.49 (t, J = 7.4 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H), 7.38−7.35 (m, 1H),
7.15 (dd, J = 13.8, 6.7 Hz, 1H), 7.10 (d, J = 16.4 Hz, 1H), 7.04 (t, J =
7.5 Hz, 1H), 7.01−6.94 (m, 1H), 6.42 (d, J = 16.4 Hz, 1H), 3.43 (td, J
= 11.2, 5.1 Hz, 4H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ
193.8, 161.0, 159.3, 156.2, 137.9, 132.3, 129.7, 128.9, 128.9, 128.7,
128.6, 128.3, 127.0, 126.9, 125.2, 125.1, 125.0, 124.1, 124.1, 123.6,
123.6, 115.8, 115.7, 38.6, 36.9 ppm. 19F NMR (377 MHz, CDCl3,
TMS, 25 °C): δ −117.6, −117.6 ppm. IR (KBr): ν 3059, 2926, 2854,
1661, 1613, 1486, 1315, 1275, 1229, 1174, 957, 756, 691, 637 cm−1.
HRMS (TOF, ESI): m/z calcd for C19H16FOS2, [M + H]+ 343.0627,
found 343.0629.
Yield: 89%, 0.18 mmol, 51.6 mg; yellowish oil. H NMR (400 MHz,
CDCl3,TMS, 25 °C): δ 7.73 (d, J = 7.2 Hz, 2H), 7.45 (t, J = 7.3 Hz,
1H), 7.37 (t, J = 7.5 Hz, 2H), 6.25 (d, J = 15.8 Hz, 1H), 5.39 (dt, J =
15.6, 7.0 Hz, 1H), 3.37 (s, 4H), 2.07−1.95 (m, 2H), 1.29 (dd, J = 14.6,
7.3 Hz, 2H), 0.88 (t, J = 7.2 Hz, 1H), 0.80 (t, J = 7.4 Hz, 3H), 0.69 (td,
J = 7.3, 2.1 Hz, 1H). 13C NMR (100 MHz, CDCl3, TMS, 25 °C): δ
193.4, 138.4, 135.3, 131.7, 129.6, 128.2, 128.0, 38.5, 36.6, 35.3, 22.2,
13.6 ppm. IR (KBr): ν 2958, 2926, 2867, 1659, 1615, 1455, 1314,
1278, 1248, 1175, 964, 693, 633 cm−1. HRMS (TOF, ESI): m/z calcd
for C16H18NaOS2, [M + Na]+ 313.0697, found 313.0703.
(E)-2-(Bis(methylthio)methylene)-1,5-diphenylpent-3-en-1-one
1
(3z). Yield: 78%, 0.16 mmol, 53.0 mg; yellowish oil. H NMR (600
MHz, CDCl3, TMS, 25 °C): δ 7.90 (d, J = 7.8 Hz, 2H), 7.55 (t, J = 7.4
Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 7.29 (t, J = 7.5 Hz, 1H), 7.24−7.18
(m, 4H), 6.93 (d, J = 16.0 Hz, 1H), 5.67 (dt, J = 15.9, 7.0 Hz, 1H),
3.43 (d, J = 7.0 Hz, 2H), 2.37 (s, 3H), 2.09 (s, 3H). 13C NMR (150
MHz, CDCl3, TMS, 25 °C): δ 196.2, 154.8, 145.4, 139.2, 136.7, 135.2,
133.4, 129.4, 128.7, 128.6, 128.4, 127.9, 126.2, 39.6, 17.3, 16.5 ppm. IR
(KBr): ν 3026, 2923, 2855, 1726, 1670, 1598, 1494, 1450, 1283, 1171,
1073, 964, 698 cm−1. HRMS (TOF, ESI): m/z calcd for
C20H20NaOS2, [M + Na]+ 363.0853, found 363.0837.
3-Cyclohexylidene-2-(1,3-dithiolan-2-ylidene)-1-phenylpropan-1-
one (3aa). Yield: 81%, 0.16 mmol, 51.2 mg; yellowish solid, mp 122−
124 °C. 1H NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.68 (d, J = 7.3
Hz, 2H), 7.40 (t, J = 7.4 Hz, 1H), 7.33 (t, J = 7.6 Hz, 2H), 5.96 (s,
1H), 3.43 (t, J = 6.4 Hz, 2H), 3.35 (t, J = 6.4 Hz, 2H), 2.13−2.06 (m,
2H), 1.80−1.74 (m, 2H), 1.42 (dt, J = 11.9, 5.8 Hz, 2H), 1.35 (dt, J =
11.4, 5.7 Hz, 2H), 1.01 (dt, J = 11.9, 6.1 Hz, 2H). 13C NMR (150
MHz, CDCl3, TMS, 25 °C): δ 191.2, 163.8, 144.9, 139.3, 130.8, 129.3,
127.4, 122.4, 120.3, 39.1, 36.4, 35.9, 30.6, 27.7, 26.2, 26.2 ppm. IR
(KBr): ν 2927, 2852, 1614, 1574, 1452, 1278, 1014, 839, 727, 634
cm−1. HRMS (TOF, ESI): m/z calcd for C18H20NaOS2, [M + Na]+
339.0853, found 339.0854.
3-(Cyclohex-3-en-1-ylidene)-2-(1,3-dithiolan-2-ylidene)-1-phenyl-
propan-1-one (E/Z = 3/2) (3ab). Yield: 85%, 0.17 mmol, 53.4 mg;
yellowish oil. 1H NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.67 (dd, J
= 15.6, 7.5 Hz, 2H), 7.39 (t, J = 7.3 Hz, 1H), 7.31 (q, J = 7.4 Hz, 2H),
6.08 (d, J = 54.4 Hz, 1H), 5.58 (d, J = 9.6 Hz, 0.5H), 5.55 (s, 1H), 5.40
(d, J = 9.7 Hz, 0.5H), 3.44 (t, J = 6.3 Hz, 2H), 3.38−3.32 (m, 2H),
2.73 (s, 1H), 2.41 (s, 1H), 2.25 (t, J = 6.3 Hz, 1H), 2.10 (s, 1H), 1.93
(t, J = 6.4 Hz, 1H), 1.69 (s, 1H). 13C NMR (150 MHz, CDCl3, TMS,
25 °C): δ 191.1, 191.0, 164.3, 164.2, 141.6, 141.1, 139.5, 139.2, 130.9,
130.8, 129.1, 128.9, 127.5, 127.5, 126.7, 126.7, 125.5, 125.2, 122.1,
122.0, 121.6, 121.1, 39.1, 39.1, 36.0, 35.9, 34.2, 32.4, 30.0, 27.2, 27.0,
25.6 ppm. IR (KBr): ν 3024, 2924, 2847, 1721, 1613, 1454, 1277,
1176, 1011, 843, 726, 634 cm−1. HRMS (TOF, ESI): m/z calcd for
C18H18NaOS2, [M + Na]+ 337.0697, found 337.0698.
(E)-Methyl 4-(1,3-Dithiolan-2-ylidene)-5-oxo-5-phenylpent-2-
enoate (3ac). Yield: 48%, 0.10 mmol, 29.4 mg; yellowish oil. 1H
NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.74 (d, J = 8.0 Hz, 2H),
7.71 (d, J = 15.8 Hz, 1H), 7.54 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.6 Hz,
2H), 5.57 (d, J = 15.8 Hz, 1H), 3.69 (s, 3H), 3.52 (t, J = 6.2 Hz, 2H),
3.47−3.44 (m, 2H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ
193.6, 167.5, 140.8, 137.2, 132.9, 129.5, 128.5, 122.8, 117.8, 51.6, 38.6,
37.4 ppm. IR (KBr): ν 2953, 2927, 2854, 1710, 1663, 1601, 1434,
1281, 1168, 975, 705, 642 cm−1. HRMS (TOF, ESI): m/z calcd for
C15H14NaO3S2, [M + Na]+ 329.0282, found 329.0265.
(E)-2-(1,3-Dithiolan-2-ylidene)-4-(naphthalen-2-yl)-1-phenylbut-
1
3-en-1-one (3t). Yield: 99%, 0.20 mmol, 74.1 mg; yellowish oil. H
NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.93 (d, J = 7.6 Hz, 1H),
7.85 (d, J = 8.1 Hz, 2H), 7.77 (d, J = 8.1 Hz, 1H), 7.71 (d, J = 8.2 Hz,
1H), 7.55 (dd, J = 11.9, 7.9 Hz, 2H), 7.49 (dd, J = 8.4, 6.3 Hz, 1H),
7.46−7.38 (m, 4H), 7.34 (t, J = 7.6 Hz, 1H), 7.02 (d, J = 10.1 Hz, 1H),
3.47−3.37 (m, 4H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ
193.6, 157.7, 138.6, 135.0, 133.6, 132.1, 132.0, 131.2, 129.7, 129.5,
128.6, 128.5, 128.4, 121.0, 127.9, 126.0, 125.9, 125.7, 124.9, 123.7,
123.2, 108.3, 38.6, 36.9 ppm. IR (KBr): ν 3056, 2925, 2854, 1657,
1617, 1482, 1280, 1226, 1174, 1152, 953, 776, 695 cm−1. HRMS
(TOF, ESI): m/z calcd for C23H18NaOS2, [M + Na]+ 397.0697, found
397.0684.
(E)-2-(1,3-Dithiolan-2-ylidene)-1,5-diphenylpent-3-en-1-one (3u).
1
Yield: 87%, 0.17 mmol, 58.8 mg; yellowish oil. H NMR (600 MHz,
CDCl3, TMS, 25 °C): δ 7.70 (dd, J = 8.1, 1.0 Hz, 2H), 7.44 (t, J = 7.2
Hz, 1H), 7.35 (t, J = 7.7 Hz, 2H), 7.21 (t, J = 7.4 Hz, 2H), 7.15 (t, J =
7.4 Hz, 1H), 7.01 (d, J = 7.1 Hz, 2H), 6.33 (d, J = 15.7 Hz, 1H), 5.56
(dt, J = 15.7, 7.0 Hz, 1H), 3.38 (dt, J = 5.3, 2.6 Hz, 6H). 13C NMR
(150 MHz, CDCl3, TMS, 25 °C): δ 193.17, 156.78, 139.67, 138.50,
133.27, 131.60, 129.55, 129.34, 128.49, 128.35, 128.27, 128.02, 126.05,
124.33, 39.40, 38.56, 36.59 ppm. IR (KBr): ν 3058, 3025, 2925, 1723,
1661, 1601, 1452, 1280, 1174, 962, 697 cm−1. HRMS (TOF, ESI): m/
z calcd for C20H18NaOS2, [M + Na]+ 361.0697, found 361.0700.
(E)-4-(2-(1,3-Dithiolan-2-ylidene)-5-phenylpent-3-enoyl)benzoic
1
acid (3v). Yield: 68%, 0.14 mmol, 52.0 mg; yellowish oil. H NMR
(400 MHz, CDCl3, TMS, 25 °C): δ 8.02 (d, J = 8.0 Hz, 2H), 7.67 (d, J
= 8.1 Hz, 2H), 7.21 (t, J = 7.2 Hz, 2H), 7.16 (d, J = 7.0 Hz, 1H), 6.98
(d, J = 7.2 Hz, 2H), 6.28 (d, J = 15.8 Hz, 1H), 5.53 (dt, J = 15.6, 7.0
Hz, 1H), 3.42 (s, 4H), 3.35 (d, J = 6.8 Hz, 2H). 13C NMR (100 MHz,
CDCl3, TMS, 25 °C): δ 191.5, 143.6, 139.3, 134.7, 129.7, 129.2, 128.7,
128.4, 128.4, 126.2, 123.4, 39.4, 38.8, 36.4 ppm. IR (KBr): ν 3025,
2925, 2627, 1703, 1610, 1449, 1279, 1248, 1108, 1010, 965, 911, 870,
738, 700 cm−1. HRMS (TOF, ESI): m/z calcd for C21H18NaO3S2, [M
+ Na]+ 405.0595, found 405.0606.
(E)-4-(2-(1,3-Dithiolan-2-ylidene)-5-phenylpent-3-enoyl)-
1
benzonitrile (3w). Yield: 73%, 0.15 mmol, 53.0 mg; yellowish oil. H
NMR (400 MHz, CDCl3, TMS, 25 °C): δ 7.63 (d, J = 8.2 Hz, 2H),
7.53 (d, J = 8.2 Hz, 2H), 7.22 (t, J = 7.9 Hz, 3H), 6.96 (d, J = 6.6 Hz,
2H), 6.26 (d, J = 15.8 Hz, 1H), 5.46 (dt, J = 15.5, 7.1 Hz, 1H), 3.43 (s,
4H), 3.34 (d, J = 7.0 Hz, 2H). 13C NMR (100 MHz, CDCl3, TMS, 25
°C): δ 190.1, 143.0, 139.1, 135.4, 131.7, 129.7, 128.5, 128.4, 128.3,
126.3, 122.8, 118.3, 114.1, 77.4, 77.1, 76.8, 39.5, 38.9, 36.5 ppm. IR
(KBr): ν 3024, 2924, 2852, 2228, 1612, 1451, 1312, 1279, 1251, 1175,
G
dx.doi.org/10.1021/jo5017234 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(E)-Ethyl 4-(1,3-Dithiolan-2-ylidene)-5-oxo-5-phenylpent-2-
136.6, 132.9, 131.1, 129.2, 129.1, 129.0, 128.3, 127.8, 117.0, 28.8, 16.1,
15.9 ppm. IR (KBr): ν 2956, 2923, 2852, 1734, 1636, 1589, 1443,
1263, 1092, 913, 697, 639 cm−1. HRMS (TOF, ESI): m/z calcd for
C20H20NaOS2, [M + Na]+ 363.0853, found 363.0852.
enoate (3ad).12a Yield: 46%, 0.09 mmol, 29.4 mg; yellowish oil. H
1
NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.75 (d, J = 8.2 Hz, 2H),
7.70 (d, J = 15.8 Hz, 1H), 7.54 (t, J = 7.2 Hz, 1H), 7.43 (t, J = 7.7 Hz,
2H), 5.58 (d, J = 15.8 Hz, 1H), 4.15 (q, J = 7.2 Hz, 2H), 3.54−3.49
(m, 2H), 3.47−3.42 (m, 2H), 1.24 (t, J = 7.2 Hz, 3H). 13C NMR (150
MHz, CDCl3, TMS, 25 °C): δ 193.7, 167.1, 140.6, 137.2, 132.9, 129.6,
128.5, 122.9, 118.3, 60.4, 38.6, 37.4, 14.3 ppm. IR (KBr): ν 2957, 2927,
2855, 1706, 1662, 1600, 1448, 1368, 1280, 1169, 1037, 974, 704, 642
cm−1.
(5E)-2-(1,3-Dithiolan-2-ylidene)-7-methyl-1,4-diphenylocta-3,5-
dien-1-one (E,E/E,Z = 3/1) (5a). Yield: 45%, 0.09 mmol, 35.3 mg;
yellowish oil. 1H NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.72 (d, J
= 7.4 Hz, 2H), 7.39−7.35 (m, 1H), 7.35−7.28 (m, 5H), 7.20 (d, J =
6.9 Hz, 2H), 6.23 (s, 1H), 5.98 (d, J = 15.7 Hz, 1H), 5.27 (dd, J = 15.7,
6.9 Hz, 1H), 3.49−3.44 (m, 2H), 3.43−3.39 (m, 2H), 2.01 (dd, J =
11.5, 6.2 Hz, 1H), 0.83 (d, J = 6.7 Hz, 6H). 13C NMR (150 MHz,
CDCl3, TMS, 25 °C): δ 190.72, 144.01, 142.22, 141.33, 139.26,
130.95, 129.81, 129.07, 128.66, 127.95, 127.43, 127.27, 126.14, 124.83,
122.59, 108.31, 102.30, 96.80, 38.86, 36.40, 31.64, 30.94, 21.95 ppm.
IR (KBr): ν 2958, 2925, 2854, 1733, 1619, 1500, 1279, 1225, 1049,
969, 911, 808, 733, 696, 619 cm−1. HRMS (TOF, ESI): m/z calcd for
C24H24NaOS2, [M + Na]+ 415.1166, found 415.1169.
4-Benzyl-2-(1,3-dithiolan-2-ylidene)naphthalen-1(2H)-one (10a).
1
Yield: 82%, 0.33 mmol, 110.2 g; yellowish oil. H NMR (600 MHz,
CDCl3, TMS, 25 °C): δ 7.61 (d, J = 7.1 Hz, 2H), 7.46 (t, J = 7.4 Hz,
1H), 7.34 (t, J = 7.7 Hz, 2H), 7.23 (dd, J = 4.9, 2.1 Hz, 2H), 6.99 (dd,
J = 7.1, 2.0 Hz, 2H), 6.70 (s, 1H), 3.73 (s, 2H), 3.48−3.44 (m, 2H),
3.42−3.38 (m, 2H). 13C NMR (100 MHz, CDCl3, TMS, 25 °C): δ
181.6, 139.6, 137.2, 132.2, 130.8, 128.9, 128.6, 128.5, 127.6, 126.9,
121.9, 116.7, 47.4, 39.0, 36.3 ppm. IR (KBr): ν 2957, 2924, 2853,
1730, 1623, 1598, 1490, 1454, 1277, 1013, 910, 729, 697, 639 cm−1.
HRMS (TOF, ESI): m/z calcd for C20H17OS2, [M + H]+ 337.0721,
found 337.0719.
ASSOCIATED CONTENT
* Supporting Information
■
S
Text, figures, tables, and a CIF file giving details of the synthesis
of starting materials, 1H and 13C NMR spectra of the products,
and X-ray crystallographic data for compound 3j. This material
is available free of charge via the Internet at http://pubs.acs.org.
2-(1,3-Dithiolan-2-ylidene)-6-methyl-1,4-diphenylhepta-3,5-
dien-1-one (5b). Yield: 40%, 0.08 mmol, 30.2 mg; yellowish oil. H
1
AUTHOR INFORMATION
Corresponding Author
*Y.G.: fax, (0)86-(0)27-87 54 45 32; e-mail, klgyl@hust.edu.cn.
■
NMR (600 MHz, CDCl3, TMS, 25 °C): δ 7.69 (d, J = 7.2 Hz, 2H),
7.36−7.27 (m, 7H), 7.26−7.22 (m, 1H), 6.67 (s, 1H), 5.02 (s, 1H),
3.47−3.39 (m, 4H), 1.66 (s, 3H), 1.16 (s, 3H). 13C NMR (150 MHz,
CDCl3, TMS, 25 °C): δ 187.5, 160.1, 141.2, 140.1, 140.0, 139.1, 131.1,
128.6, 128.2, 127.4, 127.3, 126.8, 125.9, 125.0, 124.1, 38.3, 36.9, 25.4,
19.4 ppm. IR (KBr): ν 2957, 2924, 2852, 1732, 1633, 1464, 1277,
1016, 912, 799, 695 cm−1. HRMS (TOF, ESI): m/z calcd for
C23H22NaOS2, [M + Na]+ 401.1010, found 401.1015.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank the National Natural Science Foundation of
China for financial support (21173089 and 21373093). The
authors are also grateful to the Analytical and Testing Centre of
HUST and Prof. Aiwen Lei, Wuhan University, for his kind
help in using an instrument for in situ IR. The Chutian Scholar
Program of the Hubei Provincial Government and the
Cooperative Innovation Center of Hubei Province are also
acknowledged. This work has also been supported by the
fundamental research funds for the central universities in China
(2014ZZGH019).
(E)-6-Chloro-2-(1,3-dithiolan-2-ylidene)-1-phenylhex-3-en-1-one
1
(6a). Yield: 85%, 0.17 mmol, 49.0 mg; yellowish oil. H NMR (400
MHz, CDCl3, TMS, 25 °C): δ 7.73 (d, J = 7.0 Hz, 2H), 7.48 (t, J = 7.4
Hz, 1H), 7.39 (t, J = 7.4 Hz, 2H), 6.38 (d, J = 15.8 Hz, 1H), 5.38 (dt, J
= 15.8, 7.1 Hz, 1H), 3.45−3.36 (m, 6H), 2.50 (qd, J = 7.0, 1.3 Hz,
2H). 13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ 193.0, 157.3,
138.3, 131.8, 130.9, 129.8, 129.6, 128.0, 124.0, 43.6, 38.6, 36.6, 36.4
ppm. IR (KBr): ν 2956, 2924, 2853, 1735, 1659, 1627, 1452, 1277,
1173, 1009, 960, 804, 691 cm−1. HRMS (TOF, ESI): m/z calcd for
C15H16ClOS2, [M + H]+ 311.0331, found 311.0322.
(5-Benzyl-2-(methylthio)-1-phenyl-1H-pyrrol-3-yl)(phenyl)-
1
methanone (7a). Yield: 77%, 0.31 mmol, 118.7 mg; brown oil. H
REFERENCES
NMR (400 MHz, CDCl3, TMS, 25 °C): δ 7.91 (d, J = 7.1 Hz, 2H),
7.57−7.51 (m, 1H), 7.45 (dd, J = 14.7, 7.6 Hz, 5H), 7.21−7.09 (m,
5H), 6.90 (d, J = 6.4 Hz, 2H), 6.34 (s, 1H), 3.73 (s, 2H), 2.17 (s, 3H).
13C NMR (150 MHz, CDCl3, TMS, 25 °C): δ 191.6, 139.8, 138.3,
137.4, 135.0, 132.1, 131.7, 130.4, 129.6, 128.9, 128.8, 128.8, 128.6,
128.5, 128.4, 128.3, 128.1, 128.0, 126.1, 112.1, 33.7, 20.4 ppm. IR
(KBr): ν 2956, 2923, 2853, 1710, 1641, 1597, 1493, 1458, 1242, 1071,
907, 763, 698 cm−1. HRMS (TOF, ESI): m/z calcd for
C25H21NNaOS, [M + Na]+ 406.1242, found 406.1245.
■
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Yield: 95%, 0.38 mmol, 123.1 mg; deep yellow oil. H NMR (600
MHz, CDCl3, TMS, 25 °C): δ 7.75 (d, J = 8.0 Hz, 2H), 7.53 (t, J = 7.8
Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.32 (t, J = 7.6 Hz, 2H), 7.24 (dd, J
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