Multicomponent reactions of β-ketosulfones and formaldehyde in a bio-based binary mixture solvent system composed of meglumine and gluconic acid aqueous solution

Article abstract of DOI:10.1002/adsc.201100799

A mixture of two bio-based chemicals, meglumine and gluconic acid aqueous solution (GAAS, 50 wt%), was demonstrated to be a task-specific bio-based solvent for performing the hydroxymethylation of β-ketosulfones with formaldehyde. The formed hydroxymethylation product could further react with a nucleophile, which allowed us to develop some one-pot, stepwise, three-component reactions of β-ketosulfones and formaldehyde in this binary mixture. Particularly, a one-pot, two-step, sequential four-component reaction of α-bromo ketone, sodium benzenesulfinate, thiophenol and formaldehyde was also developed. These results not only demonstrate that it is possible to develop a new bio-based system by mixing two or more bio-based chemicals together, but also confer us a convenient means for controlling the selectivity of some multicomponent reactions of formaldehyde. Because GAAS and meglumine are both highly hydrophilic, the mixed solvent system could thus be recovered after extraction of organic products. In a three-component reaction of β-ketosulfone, paraformaldehyde and α-methylstyrene, the GAAS/meglumine system could be reused at least four times without significant loss of activity. Copyright

Full text of DOI:10.1002/adsc.201100799

FULL PAPERS
DOI: 10.1002/adsc.201100799
Multicomponent Reactions of b-Ketosulfones and Formaldehyde
in a Bio-Based Binary Mixture Solvent System Composed of
Meglumine and Gluconic Acid Aqueous Solution
Jie Yang,a Haoquan Li,a Minghao Li,a Jiajian Peng,b and Yanlong Gua,*
a
Institute of Physical Chemistry and Industrial Catalysis, School of Chemistry and Chemical Engineering, Hubei Key
Laboratory of Material Chemistry and Service Failure, Huazhong University of Science and Technology (HUST), 1037
Luoyu road, Hongshan District, Wuhan 430074, Peopleꢀs Republic of China
Fax : (+86)-(0)27-8754-4532; e-mail: klgyl@hust.edu.cn
b
Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Hangzhou Normal
University, Hanzhou 310012, Peopleꢀs Republic of China
Received: October 17, 2011; Published online: February 28, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100799.
Abstract: A mixture of two bio-based chemicals, me- chemicals together, but also confer us a convenient
glumine and gluconic acid aqueous solution (GAAS, means for controlling the selectivity of some multi-
50 wt%), was demonstrated to be a task-specific bio- component reactions of formaldehyde. Because
based solvent for performing the hydroxymethyla- GAAS and meglumine are both highly hydrophilic,
tion of b-ketosulfones with formaldehyde. The the mixed solvent system could thus be recovered
formed hydroxymethylation product could further after extraction of organic products. In a three-com-
react with a nucleophile, which allowed us to devel- ponent reaction of b-ketosulfone, paraformaldehyde
op some one-pot, stepwise, three-component reac- and a-methylstyrene, the GAAS/meglumine system
tions of b-ketosulfones and formaldehyde in this could be reused at least four times without signifi-
binary mixture. Particularly, a one-pot, two-step, se- cant loss of activity.
quential four-component reaction of a-bromo
ketone, sodium benzenesulfinate, thiophenol and
formaldehyde was also developed. These results not Keywords: gluconic acid aqueous solution; b-ketosul-
only demonstrate that it is possible to develop a new fones; meglumine; one-pot stepwise multicomponent
bio-based system by mixing two or more bio-based reactions
Introduction
vation that emphasizes the concept of using bio-based
materials as alternatives to conventional organic sol-
The realization of simple and green synthetic proce- vents.[4] Because of the apparent difference of these
dures constitutes an important goal in organic synthe- solvents with all the used systems, remarkable results
sis. To combat the harmful effect of volatile organic that cannot be attained in conventional solvents
solvents frequently used in large quantities for organ- could, sometimes, be obtained by using a bio-based
ic transformations, many green solvent systems have material as solvent. However, the number of bio-
been recently introduced as alternative reaction based solvents is still limited at this stage, which has
media.[1] Among all the green solvents developed so apparently restricted the utilization of this new gener-
far, water and ionic liquids have gained most of the ation of green solvent in organic transformations.[5] In
interests of chemists.[2] Because many remarkable re- order to further improve the development of these
sults have been achieved in recent years, work on the solvent systems, the diversity and functionality of the
replacement of conventional organic solvents with a bio-based solvents certainly need to be extended.
green solvent system has become one of the most im-
Out of these considerations, most of the efforts in
portant topics of green chemistry.[3] In addition, in- this area are focusing on searching for a new bio-
creasing concerns about the sustainability of chemical based material that can act as a solvent. As a basic re-
transformations also open a new area of solvent inno- quirement of a solvent, the candidate for bio-based
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Adv. Synth. Catal. 2012, 354, 688 – 700

Multicomponent Reactions of b-Ketosulfones and Formaldehyde in a Bio-Based Binary Mixture
Table 1. Reaction of 1a and (HCHO)n in different solvents.[a]
solvent should be characterized by the following fac-
tors: (i) a suitable liquid range; (ii) good chemical sta-
bility towards various substrates, and (iii) largely
available in the market. However, bio-based chemi-
cals that have been commercialized are far from
abundant at this moment. All these things put togeth-
er tend to, without doubt, further narrow the possibil-
ity of finding a new bio-based solvent. Therefore, we
have to turn to another route for the exploration of
new bio-based systems.
Recently, some bio-based materials, such as carbo-
hydrates and glycerol, were used in establishing low
melting mixtures that can be used in some organic
transformations.[6] Inspired by this strategy, we envis-
aged that mixing two or more bio-based materials to-
gether might allow us to build up a new solvent
system that possesses a synergistic promoting effect
on a specific class of reactions. Quite recently, we
have reported a concept that uses gluconic acid aque-
Entry
Solvent
Time [h]
Yield [%]
2a
3a
1
2
3
4
5
6
7
water
glycerol
PEG 400
CH3CN
ClCH2CH2Cl
CH3NO2
GAAS
GAAS/meglumine
water/meglumine
glycerol/meglumine
PEG 400/meglumine
GAAS/ethanolamine
GAAS/diethanolamine
GAAS/triethanolamine
GAAS/meglumine
12
12
12
12
12
12
12
24
24
24
24
12
12
12
12
98
10
96
40
15
5
0
0
0
0
0
0
ous solution (GAAS, 50 wt%) as
a promoting
medium for organic transformations.[7] Herein we dis-
close the successful outcome of our recent endeavors
in which a mixture of meglumine and GAAS
(50 wt%) was used as a new bio-based solvent for
promoting some multicomponent reactions of b-keto-
sulfones and formaldehyde. A specific ability of this
binary bio-based solvent for controlling the selectivity
of hydroxymethylation of b-ketosulfones was proved
to be the key for making the three-component reac-
tions possible. Many multicomponent reactions of b-
ketosulfones and formaldehyde were successfully de-
veloped by taking advantage of this new bio-based
solvent system.
5
0
8[b]
9[b]
10[b]
11[b]
12[c]
13[d]
14[e]
15[f]
5
85
0
0
98
90
95
40
10
<5
<5
0
15
72
<5
70
[a]
Solvent: 2.0 mL, 1a: 0.25 mmol, paraformaldehyde:
0.25 mmol.
1a/meglumine: 1.0/1.5.
1a/ethanolamine: 1.0/1.5.
1a/diethanolamine: 1/1.5;
1a/triethanolamine: 1.0/1.5;
1a/meglumine: 1.0/1.0.
[b]
[c]
[d]
[e]
[f]
Results and Discussion
Initially, 2-(phenylsulfonyl)acetophenone (1a), an
À
active C H acid that has been widely used as a nucle-
ophile in many organic transformations,[8] was used to
react with paraformaldehyde in various solvents. We nant (entries 1 to 6). GAAS was also examined, and
are interested in this reaction because of our expecta- not surprisingly, 2a was also formed extensively
tion of forming an a-methylene-b-ketosulfone that (entry 7). However, the reaction selectivity was al-
might be an attractive intermediate for constructing tered significantly when GAAS was used in conjunc-
new multicomponent reactions. Previous methods to tion with the sugar-based organic base, meglumine,
access a-methylene-b-ketosulfones involve (i) oxida- that is a readily available chemical reagent (entry 8).
tion of Baylis–Hillman adduct generated from phenyl In this case, a white solid was formed during the reac-
vinyl sulfone and aldehyde[9] and (ii) decomposition of tion [Figure 1, (a)]. By means of filtration, a hydroxy-
the aminomethylation product of a b-ketosulfone (a methylation product of the b-ketosulfone, 3a, was ob-
Mannich base).[10] Until now, there is no report on tained in high yield. Interestingly, the hydroxymethy-
preparing a-methylene-b-ketosulfones through the lation can only be conducted in the GAAS/meglu-
Knoevenagel reaction of a b-ketosulfone and formal- mine system since combining meglumine with other
dehyde. As shown in Table 1, in water, glycerol, solvents, such as water, glycerol and PEG 400, failed
PEG400 and some common organic solvents, such as to afford 3a (entries 9 to 11). These results manifested
acetonitrile, 1,2-dichloroethane and nitromethane, an that a synergistic effect between GAAS and meglu-
“ABB”-type reaction of formaldehyde and b-ketosul- mine might play a key role in controlling the selectivi-
fone 1a that generates 2a was found to be predomi- ty of hydroxymethylation of 1a with formaldehyde. In
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these results, we speculated that the hydroxymethyla-
tion product, 3a, may be also reactive toward the de-
hydration reaction that could generate an a-methyl-
ene-b-ketosulfone. A literature survey revealed, how-
ever, that the a-methylene-b-ketosulfone is a labile
species.[14] In order to simplify the reaction operation,
and to avoid the possible decomposition of the meth-
ylene intermediate, we therefore designed a one-pot,
stepwise, three-component reaction in which a follow-
ing connected reaction sequence is involved: (i) the
hydroxymethylation of 1a with formaldehyde in
GAAS/meglumine at 608C and (ii) several hours of
reaction after adding a nucleophile into the system.
To ensure a complete consumption of 1a and parafor-
maldehyde, reaction time of the first step was in-
Figure 1. Progress of the model reaction in GAAS/meglu-
mine (a: running of hydroxymethylation reaction of 1a; b:
the end of the hydroxymethylation reaction; c: the end of
the one-pot stepwise reaction).
order to confirm this point, meglumine was then re- creased, on purpose, to 36 h. In order to facilitate the
placed by three organic amines including triethanol- decomposition of 3a and the following trapping of the
ACHTUNGTRENNUNGamine, diethanolamine and ethanolamine (entries 12 methylene intermediate with the nucleophile, the
to 14). In these cases, although 3a could always be ob- second step was performed at an increased tempera-
served, the highest yield was obtained with GAAS/di- ture, 1008C.
ethanolamine system. This result implies that, for the
With this procedure, two nucleophiles were success-
hydroxymethylation of 1a in GAAS, using a secon- fully applied in developing multicomponent reactions.
dary amine as co-solvent is the key for rendering the The first is a styrene derivative that is able to trap the
reaction possible. Although a good performance has generated a-methylene-b-ketosulfone through an
been observed by using the GAAS/diethanolamine oxo-Diels–Alder reaction pathway. As shown in
system, we prefer to use the previous one, the GAAS/ Scheme 1, when a-methylstyrene was used as sub-
meglumine system. The reasons are twofold: (i) me- strate, the expected product, 5a, could be obtained in
glumine is a bio-based chemical reagent that endows 73% yield. This result manifests that 3a is indeed un-
the reaction system with a salient feature in meeting stable at 1008C in the GAAS/meglumine system, and
the sustainability requirement of current organic syn- the generated a-methylene-b-ketosulfone thereby
thesis and (ii) meglumine is a highly hydrophilic spe- could be trapped easily in the presence of an appro-
cies that allows the bio-based solvent system to be re- priate nucleophile. Interestingly, although 3a is insolu-
cyclable. The second point will be verified in the later ble in the GAAS/meglumine system [Figure 1, (b)],
experiments. It should be noted that although after adding a-methylstyrene into the system, the
À
hydroxyACHTUNGTRENNUNGmethylation reactions of active C H acids white solid gradually disappeared. And at the end of
with formaldehyde have been extensively investigat- the reaction, a clear solution was obtained [Figure 1,
ed,[11] a b-ketosulfone has not been examined in this (c)]. An investigation of the substrate scope revealed
type of reaction as substrate. Further investigations that many styrenes and b-ketosulfones could be used
revealed that amount of meglumine plays also a cru- in this reaction, and the corresponding products were
cial role in enhancing the yield of the model reaction, obtained in moderate to good yields. A subtle influ-
and an optimal dosage is 1.5 equivalents of meglu- ence of the substituent functionality in the phenyl
mine with respect to 1a (entry 15). However, despite ring of styrene on the reaction yield was observed.
the observed beneficial effect exerted by the GAAS/ And better yields could be obtained by using styrenes
meglumine system on the model reaction, the exact that possess an electron-donating group as substrates.
nature of this influence cannot be ascribed to a single It should be noted that 5a-type dihydropyrans are
effect such as stabilization of the reaction intermedi- known to be valuable for organic synthesis.[15] Fur-
ate or the solubility of 3a in the solvent, but rather to thermore, a reaction on a 10-mmol scale proceeded
a superposition of several factors. This point deserves also very well, indicating the usefulness of our
further investigation.
method for practical synthesis. The second nucleo-
It is well known that the hydroxymethylation prod- phile we have investigated in the GAAS/meglumine
ucts of 1,3-dicarbonyl compounds could be converted system is 2-methylfuran. The obtained products con-
to 2-methylene-1,3-dicarbonyl compounds through a tain not only a b-ketosulfone fragment but also a
dehydration reaction under mild conditions, which furan ring (Scheme 2). Judging from the structure of
can then be trapped by a suitable nucleophile.[12] On the product, the last step of the reaction mechanism
the basis of this mechanism, we have developed many could be speculated to be a Michael addition of the
multicomponent reactions of 1,3-dicarbonyl com- formed methylene intermediate to 2-methylfuran. It
pounds and formaldehyde recently.[13] Inspired by should be noted that all these one-pot sequential re-
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Multicomponent Reactions of b-Ketosulfones and Formaldehyde in a Bio-Based Binary Mixture
Scheme 1. One-pot, stepwise, three-component reaction of b-ketosulfone, paraformaldehyde and styrene in the GAAS/me-
glumine system.
Scheme 2. One-pot, stepwise, three-component reaction of b-ketosulfone, paraformaldehyde and 2-methylfuran in the
GAAS/meglumine system.
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Jie Yang et al.
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Scheme 3. One-pot, three-component reaction of b-ketosulfone, paraformaldehyde and thiophenol or thiol in the GAAS/me-
glumine system [ratio of b-ketosulfone/(HCHO)n/thiol or thiophenol=1.0/1.0/1.2].
AHCTUNGTRENNUNG
actions have not been reported previously. These re- at least four times without any significant loss of ac-
sults indicated that the GAAS/meglumine system can tivity.
indeed be used as an effective medium for developing
In the course of investigating the above-mentioned
multicomponent reactions of b-ketosulfones and reactions, we have also examined the possibility of as-
formaldehdye. In addition, because both GAAS and sembling all the starting materials together in a
meglumine are highly hydrophilic, they are thus im- single-step reaction. However, this strategy was found
miscible with non-polar organic solvents. Therefore, to be unsuccessful for use with a-methylstyrene and
the GAAS/meglumine system can be easily recovered 2-methylfuran as the nucleophile. Surprisingly, our
after extraction of organic products. In the synthesis idea came to reality when thiols and thiophenols were
of 5a, the GAAS/meglumine system could be reused used. As shown in Scheme 3, a one-pot, three-compo-
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Multicomponent Reactions of b-Ketosulfones and Formaldehyde in a Bio-Based Binary Mixture
Table 2. One-pot, stepwise, four-component reaction of a-
nent reaction of 1a, paraformaldehyde and thiophenol
proceeded very well in the GAAS/meglumine system,
providing a thioether in high yield. It should be noted
that the high yield was obtained in the reaction that
bromo ketone, sodium benzenesulfinate, paraformaldehyde
and thiol or thiophenol in the GAAS/meglumine system.[a]
was conducted under a ratio of 1a/ACTHNUTRGEN(UNG HCHO)n/thiophe-
nol=1.0/1.0/1.2, even though all the starting materials
were added at once. The present approach for the
synthesis of 9a-type thioethers turned out to be quite
general, a variety of b-ketosulfones and a wide range
of thiolACHTUNGTRENNUNG(phenol)s underwent the coupling with formal-
dehyde to furnish the corresponding thioethers in
good to excellent yields. It should be noted that the
present three-component reaction of b-ketosulfone,
formaldehyde and thiol has not been reported previ-
ously. In the reported Mannich-type three-component
Entry
R1
R2
Product
Yield [%]
1
2
3
4
5
6
7
8
9
4-H
4-F
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-ClC6H4
4-i-PrC6H4
Bn
9a
9b
9c
9d
9e
9f
9l
9m
9r
9s
98
92
75
70
90
92
92
90
96
94
4-Cl
4-Me
4-CN
4-NO2
4-H
4-H
4-H
4-H
À
reactions of active C H acids, formaldehyde and thio-
phenol (or amine), it was always necessary to add an
excess amount of thiophenol (or amine) in order to
achieve high yields.[13c] In contrast, in this work, with
the above-mentioned GAAS/meglumine as reaction
medium, high yields were obtained by using nearly
equivalent amounts of substrate, strengthening again
the green property of our method. Although a
method to access 9a-type products has been reported
by Yamauchi,[16]in view of the fact that an N-(methyl-
thiomethyl) piperidine-HCl salt was used in Yama-
10
Cy
[a]
GAAS: 2.0 mL, a-bromo ketone: 0.25 mmol, a-bromo
ketone/sodium benzenesulfinate/(HCHO)n/meglumine/
thiol or thiophenol ratio: 1.0/1.0/1.0/1.5/1.2.
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
All the aforementioned methodologies, however, finate to furnish the corresponding products in good
involve pre-formed b-ketosulfones, for which the use to excellent yields.
of organic solvents and cumbersome product isolation
However, to our disappointment, an attempt to use
are, in general, mandatory. It is well known that b-ke- other nucleophiles in the GAAS/meglumine system
tosulfone could be easily prepared from an SN2 reac- was in vain. Because of the fact that, with GAAS/me-
tion between sodium benzenesulfinate and a-bromo- glumine system, we are able to synthesize 3a in high
ketone.[17] In view of the fact that, for the synthesis of yield from 1a and paraformaldehyde, which cannot be
b-ketosulfone, a protic solvent seems to be preferable, attained in other ways, we were therefore intrigued
we thus explored the possibility of using more funda- by the possibility of using the hydroxymethylation
mental substrates as alternatives to b-ketosulfones product of the b-ketosulfone as substrate for organic
which, being compatible with the standard reaction synthesis. As shown in Scheme 4, by using GAAS as
conditions, could expand the versatility of the GAAS/ medium, 3a could react readily with many carbon-
meglumine system. We undertook this study with the based nucleophiles, such as 2-naphthol, N,N-dimethy-
implementation of the reaction of sodium benzenesul- laniline, pyrrole, 2-phenylindole, antipyrine and resor-
finate and a-bromoacetophenone. As expected, b-ke- cin, providing the corresponding Friedel–Crafts alky-
tosulfone 1a was formed quantitatively after 10 h of lation products in good yields. GAAS might play the
reaction at 808C in the GAAS. From this result, it role of a mild acid catalyst, which not only promotes
can be inferred that combining the SN2 reaction of the decomposition of 3a providing the a-methylene-b-
sodium benzenesulfinate and a-bromoacetophenone ketosulfone intermediate, but also accelerates the Mi-
together with the following condensation of formalde- chael reaction of the intermediate and the nucleo-
hyde and thiophenol might be feasible. As shown in phile. These results imply that Michael reactions of
Table 2, the one-pot, two-step sequential reaction of the a-methylene-b-ketosulfone intermediate and nu-
a-bromo ketone, sodium benzenesulfinate, thiophenol cleophiles are not always compatible with the stan-
and formaldehyde proceeded very well in the binary dard conditions of forming an a-methylene-b-ketosul-
GAAS/meglumine system. Furthermore, the present fone because Michael products cannot be obtained by
four-component reaction turned out to be quite gener- the above-mentioned one-pot sequential methods in
al, various a-bromo ketones and a wide range of GAAS/meglumine system.
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Scheme 4. Reactions of 3a with different nucleophiles in GAAS.
Experimental Section
Conclusions
All the chemicals were used as they were received. Some b-
ketosulfones were prepared from b-bromo ketones and
sodium benzenesulfinate according to a literature method
with slight modification.[18] All reactions were conducted in
a 10-mL V-type flask equipped with triangle magnetic stir-
ring.
The combination of GAAS and meglumine was
proved to be, for the first time, an effective bio-based
solvent for developing multicomponent reactions of
b-ketosulfones and paraformaldehyde. Nucleophiles,
such as thiols, thiophenols, styrenes and 2-methylfur-
an, can all be successfully used in the convergent re-
actions with b-ketosulfone and formaldehyde. While
the desired products were obtained in good yields in
Typical Procedure
the GAAS/meglumine system, the synthesis cannot In a typical reaction, GAAS (2.0 mL) was mixed with me-
glumine (73.2 mg, 0.38 mmol), paraformaldehyde (7.5 mg,
0.25 mmol) and 2-(phenylsulfonyl)acetophenone (1a,
65.1 mg, 0.25 mmol) for 36 h at 608C. Then b-methylstyrene
(44.3 mg, 0.38 mmol) was added into the mixture. The mix-
ture was stirred for 6 h at 1008C. After reaction, the mixture
was extracted with a mixture of ethyl acetate and n-heptane
(v/v=2/1, 6.0 mLꢂ3) at room temperature. The obtained or-
ganic phases were then combined together and dried with
Na2SO4. After concentration under reduced pressure, the or-
ganic solution was then subjected to preparative TLC, and
be performed well in the other solvent systems, indi-
cating the great utility of the present GAAS/meglu-
mine system. The intervention of a solvent effect on
the multicomponent reaction could be speculated in
(i) promoting the hydroxymethylation of b-ketosul-
fone and (ii) stabilizing the formed 3a-type products.
By taking advantage of the GAAS/meglumine system
for the efficient synthesis of 3a, we have a chance to
directly use 3a as a substrate for organic synthesis. In
GAAS, 3a could react readily with many carbon- the product 5a was obtained; yield: 73%. The recovered
aqueous phase can be reused in the next run after a simple
treatment at room temperature under vacuum (20 mmHg
for 30 min).
based nucleophiles, such as 2-naphthol, N,N-dimethyl-
ACHTUNGTRENNUNGaniline, pyrrole, 2-phenylindole, antipyrine and resor-
cin, providing the corresponding Friedel–Crafts alky-
lation products in good yields. In spite of these prom-
ising results, the reasons for the obtained high selec-
tivity for the hydroxymethylation of b-ketosulfone by
using GAAS/meglumine as medium are still unknown
at this stage. This will be the next topic of our study.
The reaction on a 10-mmol scale was performed using an
analogous procedure, but 5a was isolated by silica column
chromatography by using a mixture of ethyl acetate and
petrol ether (60–908C, v/v=1/10) as eluting solvent. The
other reactions were performed with an analogous proce-
dure, and the details are available in the Supporting Infor-
mation. All the products were characterized with 1H and
13C NMR spectroscopy on a Bruker AV-400 instrument.
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Multicomponent Reactions of b-Ketosulfones and Formaldehyde in a Bio-Based Binary Mixture
125.9, 127.4, 127.6, 128.6, 129.3, 129.8, 132.5, 134.2, 136.6,
Characterization Data of Newly Synthesized Products
138.2, 142.1, 162.8; IR: n=3055, 2932, 2854, 1625, 1593,
1442, 1335, 1230, 1262, 1207, 1178, 1143, 1108, 1081, 1060,
1025, 999, 966, 923, 890, 846, 810, 764, 724, 670, 620, 589,
2-Methyl-2,6-diphenyl-5-(phenylsulfonyl)-3,4-dihydro-2H-
1
pyran (5a): white solid; mp 136–1388C; H NMR (CDCl3):
d=1.58 (s, 3H), 2.05–2.13 (m,1H), 2.15–2.25 (m,1H), 2.36–
2.45 (m,1H), 2.56–2.65 (m, 1H), 7.22 (td, Ja =1.6 Hz, Jb =
7.6 Hz, 2H), 7.26–7.32 (m, 4H), 7.32–7.36 (m, 5H), 7.36–
7.42 (m, 4H); 13C NMR (CDCl3): d=21.1, 29.1, 32.6, 80.8,
114.2, 124.3, 126.9, 127.4, 127.7, 128.3, 128.6, 129.7, 129.8,
132.1, 134.3, 142.1, 143.9, 161.5; IR: n=3033, 3001, 2933,
1631, 1494, 1449, 1380, 1350, 1308, 1271, 1203, 1152, 1111,
1084, 1069, 1030, 999, 967, 856, 765, 697, 634 cmÀ1; HR-MS
(ESI): m/z=413.1176, calcd. for C24H22NaO3S [M+Na]+:
413.1187.
567 cmÀ1
;
HR-MS (ESI): m/z=413.1183, calcd. for
C24H22NaO3S [M+Na]+: 413.1187.
6-(4-Fluorophenyl)-2-methyl-2-phenyl-5-(phenylsulfonyl)-
3,4-dihydro-2H-pyran (5f): pale yellow solid; mp 111–
1138C; 1H NMR (CDCl3): d=1.58 (s, 3H), 2.02–2.11 (m,
1H), 2.13–2.23 (m, 1H), 2.36–2.44 (m, 1H), 2.54–2.64 (m,
1H), 7.02 (tt, Ja =2.0 Hz, Jb =8.8 Hz, 2H), 7.23 (dd, Ja =
1.6 Hz, Jb =6.8 Hz, 1H), 7.26 (d, J=1.6 Hz, 1H), 7.27–7.31
(m, 5H), 7.33 (dd, Ja =1.2 Hz, Jb =6.8 Hz, 2H), 7.37–7.43
(m, 3H); 13C NMR (CDCl3): d=21.3, 29.1, 32.6, 81.0, 114.6,
114.7, 114.9, 124.3, 126.9, 127.6, 128.5, 128.7, 131.9, 132.0,
132.4, 142.0, 143.8, 160.5; IR: n=3064, 2932, 2857, 1626,
1505, 1447, 1346, 1303, 1230, 1145, 1110, 1085, 1070, 1028,
964, 911, 861, 935, 800, 762, 724, 694, 633, 577 cmÀ1; HR-MS
(ESI): m/z=431.1086, calcd. for C24H21FNaO3S [M+Na]+:
431.1093.
2-(4-Methoxyphenyl)-6-phenyl-5-(phenylsulfonyl)-3,4-di-
hydro-2H-pyran (5b): green liquid; 1H NMR (CDCl3): d=
2.02–2.13 (m,1H), 2.21–2.30 (m, 1H), 2.57–2.68 (m, 1H),
2.69–2.78 (m, 1H), 3.77 (s, 3H), 4.97 (dd, Ja =2.0 Hz, Jb =
6.0 Hz, 1H), 6.85 (dd, Ja =2.8 Hz, Jb =11.6 Hz, 2H), 7.22
(dd, Ja =2.8 Hz, Jb =11.2 Hz, 2H), 7.28 (t, J=7.2 Hz, 2H),
7.31–7.39 (m, 5H), 7.47 (tt, Ja =1.2 Hz, Jb =7.2 Hz, 1H), 7.54
(dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H); 13C NMR (CDCl3): d=
23.2, 29.3, 55.4, 78.9, 114.0, 114.4, 127.4, 127.4, 127.6, 128.6,
129.7, 129.8, 131.7, 132.5, 134.2, 142.1, 159.6, 162.9; IR: n=
3065, 2935, 2838, 1681, 1605, 1512, 1448, 1309, 1249, 1178,
1150, 1084, 1032, 1000, 970, 939, 838, 805, 750, 688, 596,
6-(4-Chlorophenyl)-2-methyl-2-phenyl-5-(phenylsulfonyl)-
3,4-dihydro-2H-pyran (5g): pale yellow solid; mp 107–
1098C; 1H NMR (CDCl3): d=1.57 (s, 3H), 2.02–2.10 (m,
1H), 2.12–2.22 (m, 1H), 2.34–2.43 (m,1H), 2.53–2.62 (m,
1H), 7.25 (dd, Ja =1.6 Hz, Jb =6.8 Hz, 2H), 7.27–7.30 (m,
3H), 7.30–7.32 (m, 3H), 7.32–7.36 (m, 5H), 7.41 (tt, Ja =
1.2 Hz, Jb =7.6 Hz, 1H); 13C NMR (CDCl3): d=21.2, 29.0,
32.5, 81.1, 114.7, 124.3, 127.0, 127.6, 128.0, 128.5, 128.7,
131.2, 132.1, 132.8, 136.1, 141.9, 143.8, 160.3; IR: n=3063,
2932, 1626, 1591, 1488, 1447, 1397, 1377, 1345, 1306, 1147,
1109, 1087, 1070, 1016, 965, 911, 861, 823, 762, 723, 695, 632,
537 cmÀ1
;
HR-MS (ESI): m/z=429.1138, calcd. for
C24H22NaO4S [M+Na]+: 429.1136.
2-(4-Chlorophenyl)-2-methyl-6-phenyl-5-(phenylsulfonyl)-
3,4-dihydro-2H-pyran (5c): white solid; mp: 120–1228C;
1H NMR (CDCl3): d=1.55 (s, 3H), 2.02–2.11 (m, 1H), 2.14–
2.24 (m, 1H), 2.31–2.38 (m, 1H), 2.57–2.66 (m, 1H), 7.21–
7.24 (m, 2H), 7.25–7.27 (m, 2H), 7.27–7.29 (m, 2H), 7.29–
7.32 (m, 2H), 7.33–7.37 (m, 3H), 7.37–7.40 (m, 1H), 7.40–
7.46 (m, 2H); 13C NMR (CDCl3): d=21.1, 28.9, 32.5, 80.4,
114.5, 126.0, 127.0, 127.8, 128.5, 128.8, 129.7, 130.0, 132.3,
133.3, 134.1, 142.0, 142.6, 161.3; IR: n=3062, 2929, 2862,
1674, 1629, 1593, 1489, 1447, 1395, 1345, 1308, 1272, 1146,
1074, 1008, 966, 922, 855, 831, 768, 747, 723, 688, 632,
570 cmÀ1
;
HR-MS (ESI): m/z=447.0794, calcd. for
C24H21ClNaO3S [M+Na]+: 447.0798.
2-Methyl-6-(4-nitrophenyl)-2-phenyl-5-(phenylsulfonyl)-
3,4-dihydro-2H-pyran (5h): pale yellow liquid; 1H NMR
(CDCl3): d=1.59 (s, 3H), 2.05–2.14 (m, 1H), 2.14–2.24 (m,
1H), 2.37–2.45 (m, 1H), 2.51–2.60 (m, 1H), 7.27–7.31 (m,
3H), 7.31–7.34 (m, 3H), 7.36 (dt, Ja =2.0 Hz, Jb =7.6 Hz,
1H), 7.40 (dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H), 7.47 (tt, Ja =
1.2 Hz, Jb =8.4 Hz, 1H), 7.61 (dt, Ja =2.0 Hz, Jb =8.8 Hz,
2H); 13C NMR (CDCl3): d=21.1, 28.9, 32.3, 81.6, 115.3,
123.0, 124.2, 127.0, 127.8, 128.8, 130.8, 132.9, 140.9, 141.4,
143.5, 148.5, 158.9; IR: n=3066, 2980, 2857, 1632, 1593,
1523, 1447, 1377, 1347, 1309, 1202, 1150, 1109, 1070, 1028,
1000, 967, 911, 865, 759, 724, 695, 634, 569 cmÀ1; HR-MS
(ESI): m/z=458.1031, calcd. for C24H21NNaO5S [M+Na]+:
458.1038.
571 cmÀ1
;
HR-MS (ESI): m/z=447.0789, calcd. for
C24H21ClNaO3S [M+Na]+: 447.0798.
2-(4-Fluorophenyl)-2-methyl-6-phenyl-5-(phenylsulfonyl)-
3,4-dihydro-2H-pyran (5d): white solid; mp 140–1428C;
1H NMR (CDCl3): d=1.55 (s, 3H), 2.03–2.11 (m, 1H), 2.16–
2.27 (m, 1H), 2.31–2.40 (m, 1H), 2.56–2.67 (m, 1H), 7.00 (tt,
Ja =2.4 Hz, Jb =8.8 Hz, 2H), 7.23 (dd, Ja =1.6 Hz, Jb =
6.4 Hz, 1H), 7.25–7.28 (m, 2H), 7.28–7.31 (m, 2H), 7.31–
7.39 (m, 5H), 7.39–7.45 (m, 2H); 13C NMR (CDCl3): d=
21.1, 29.0, 32.6, 80.4, 114.4, 115.4, 115.6, 126.2, 126.3, 127.0,
127.8, 128.5, 129.7, 129.9, 132.3, 134.2, 142.0, 161.4; IR: n=
3062, 2970, 2921, 2844, 1626, 1594, 1502, 1447, 1404, 1382,
1347, 1306, 1273, 1220, 1156, 1140, 1102, 1072, 1011, 998,
966, 920, 904, 861, 840, 812, 766, 751, 724, 701, 687, 632, 572,
6-(4-Chlorophenyl)-2-(4-methoxyphenyl)-5-(phenylsulfon-
yl)-3,4-dihydro-2H-pyran (5i): yellow liquid; 1H NMR
(CDCl3): d=2.00–2.11 (m, 1H), 2.20–2.29 (m, 1H), 2.52–
2.64 (m, 1H), 2.67–2.77 (m, 1H), 3.77 (s, 3H), 4.95 (dd, Ja =
2.0 Hz, Jb =10.0 Hz, 1H), 6.85 (dt, Ja =2.4 Hz, Jb =8.8 Hz,
2H), 7.20 (dt, Ja =2.4 Hz, Jb =8.8 Hz, 2H), 7.28 (q, J=
2.8 Hz, 3H), 7.39 (td, Ja =2.0 Hz, Jb =8.0 Hz, 2H), 7.43–7.54
(m, 2H), 7.58 (dd, Ja =1.6 Hz, Jb =8.8 Hz, 2H), 7.61–7.70
(m, 1H); 13C NMR (CDCl3): d=23.2, 29.2, 55.4, 79.1, 114.1,
114.8, 127.4, 127.4, 127.9, 128.8, 129.3, 131.2, 131.4, 132.7,
135.9, 141.9, 159.7, 161.5; IR: n=3065, 2935, 2838, 1681,
1589, 1513, 1486, 1447, 1401, 1310, 1249, 1206, 1178, 1151,
1087, 1032, 969, 938, 911, 832, 801, 757, 730, 689,569,
519 cmÀ1
;
HR-MS (ESI): m/z=431.1090, calcd. for
C24H21FNaO3S [M+Na]+: 431.1093.
6-Phenyl-5-(phenylsulfonyl)-2-(p-tolyl)-3,4-dihydro-2H-
1
pyran (5e): white solid; mp 125–1278C; H NMR (CDCl3):
d=2.00–2.12 (m, 1H), 2.22–2.30 (m, 1H), 2.31 (s, 3H), 2.57–
2.67 (m, 1H), 2.68–2.76 (m, 1H), 5.00 (dd, Ja =2.0 Hz, Jb =
10.0 Hz, 1H), 7.12 (d, J=8.0 Hz, 2H), 7.17 (d, J=8.0 Hz,
2H), 7.26–7.31 (m, 2H), 7.31–7.39 (m, 5H), 7.46 (tt, Ja =
1.2 Hz, Jb =7.6 Hz, 1H), 7.54 (dd, Ja =1.2 Hz, Jb =8.4 Hz,
2H); 13C NMR (CDCl3): d=21.2, 23.1, 29.4, 79.0, 114.4,
541 cmÀ1
C24H21ClNaO4S [M+Na]+: 463.0747.
;
HR-MS (ESI): m/z=463.0736, calcd. for
Adv. Synth. Catal. 2012, 354, 688 – 700
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asc.wiley-vch.de
695

Jie Yang et al.
FULL PAPERS
6-(4-Fluorophenyl)-2-(4-methoxyphenyl)-5-(phenylsulfon-
yl)-3,4-dihydro-2H-pyran (5j): white solid; mp 89–918C;
1H NMR (CDCl3): d=2.03–2.12 (m, 1H), 2.21–2.30 (m,
1H), 2.54–2.65 (m, 1H), 2.68–2.77 (m, 1H), 3.77 (s, 3H),
4.95 (dd, Ja =2.0 Hz, Jb =10.0 Hz, 1H), 6.86 (dt, Ja =2.4 Hz,
Jb =8.8 Hz, 2H), 6.97 (tt, Ja =2.4 Hz, Jb =8.8 Hz, 2H), 7.11
(dt, Ja =2.4 Hz, Jb =8.4 Hz, 2H), 7.31–7.35 (m, 2H), 7.38 (t,
J=7.6 Hz, 2H), 7.49 (tt, Ja =1.2 Hz, Jb =7.6 Hz, 1H), 7.56
(dd, Ja =1.6 Hz, Jb =8.8 Hz, 2H); 13C NMR (CDCl3): d=
23.3, 29.2, 55.4, 79.0, 114.1, 114.6, 114.7, 114.8, 127.3, 127.4,
128.7, 131.5, 131.8, 131.9, 132.6, 142.0, 159.7, 161.7; IR: n=
3070, 2940, 2841, 1725, 1672, 1638, 1599, 1509, 1447, 1416,
1338, 1310, 1267, 1252, 1174, 1152, 1079, 1029, 1002, 970,
888, 837, 820, 801, 769, 752, 724, 685, 634, 566 cmÀ1; HR-MS
(ESI): m/z=447.1031, calcd. for C24H21FNaO4S [M+Na]+:
447.1042.
Jb =14.4 Hz, 1H), 3.43 (dd, Ja =3.6 Hz, Jb =14.4 Hz, 1H),
5.43 (dd, Ja =3.6 Hz, Jb =10.8 Hz, 1H), 5.69 (dd, Ja =1.2 Hz,
Jb =3.2 Hz, 1H), 5.81 (d, J=3.2 Hz, 1H), 7.54–7.60 (m, 2H),
7.70 (tt, Ja =1.2 Hz, Jb =7.6 Hz, 1H), 7.78–7.84 (m, 2H), 8.02
(dt, Ja =2.0 Hz, Jb =8.8 Hz, 2H), 8.27 (dt, Ja =2.0 Hz, Jb =
8.8 Hz, 2H); 13C NMR (CDCl3): d=13.4, 27.4, 69.1, 106.5,
108.7, 123.9, 129.3, 129.8, 129.9, 134.8, 136.1, 141.5, 146.7,
150.6, 151.8, 191.2; IR: n=3126, 3106, 3060, 2915, 1682,
1604, 1570, 1525, 1446, 1406, 1351, 1314, 1242, 1181, 1147,
1111, 1079, 1026, 942, 853, 791, 763, 721, 686, 640 cmÀ1; HR-
MS (ESI): m/z=422.0662, calcd. for C20H17NNaO6S [M+
Na]+: 422.0674.
3-(5-Methylfuran-2-yl)-2-(phenylsulfonyl)-1-(thiophen-2-
1
yl)propan-1-one (7e): yellow solid; mp 116–1188C; H NMR
(CDCl3): d=2.07 (s, 3H), 3.35 (dd, Ja =10.8 Hz, Jb =14.8 Hz,
1H), 3.43 (dd, Ja =3.6 Hz, Jb =14.8 Hz, 1H), 5.18 (dd, Ja =
3.6 Hz, Jb =10.8 Hz, 1H), 5.69 (dd, Ja =0.8 Hz, Jb =2.8 Hz,
1H), 5.72 (d, J=2.8 Hz, 1H), 7.08 (dd, Ja =4.0 Hz, Jb =
4.8 Hz, 1H), 7.52 (td, Ja =1.6 Hz, Jb =7.6 Hz, 2H), 7.65 (tt,
Ja =1.2 Hz, Jb =7.6 Hz, 1H), 7.66–7.70 (m, 2H), 7.83 (dd,
Ja =1.2 Hz, Jb =8.8 Hz, 2H); 13C NMR (CDCl3): d=13.4,
26.9, 70.3, 106.3, 108.5, 128.5, 129.1, 129.8, 134.2, 134.5,
136.1, 136.4, 144.1, 147.1, 151.6, 183.7; IR: n=3109, 3070,
2965, 2850, 1724, 1659, 1571, 1517, 1480, 1447, 1413, 1354,
1315, 1255, 1218, 1187, 1145, 1080, 1058, 1024, 1000, 953,
892, 851, 785, 750, 722 cmÀ1; HR-MS (ESI): m/z=383.0379,
calcd. for C18H16NaO4S2 [M+Na]+: 383.0388.
3-(5-Methylfuran-2-yl)-1-phenyl-2-(phenylsulfonyl)pro-
1
pan-1-one (7a): brown liquid; H NMR (CDCl3): d=2.03 (s,
3H), 3.37 (dd, Ja =10.8 Hz, Jb =14.8 Hz, 1H), 3.44 (dd, Ja =
4.0 Hz, Jb =14.8 Hz, 1H), 5.46 (dd, Ja =4.0 Hz, Jb =10.8 Hz,
1H), 5.67 (dd, Ja =0.8 Hz, Jb =2.8 Hz, 1H), 5.79 (d, J=
2.8 Hz, 1H), 7.41 (t, J=7.6 Hz, 2H), 7.48–7.57 (m, 3H), 7.63
(tt, Ja =1.6 Hz, Jb =7.6 Hz, 1H), 7.70 (dd, Ja =1.6 Hz, Jb =
8.8 Hz, 2H), 7.84 (dd, Ja =1.6 Hz, Jb =8.8 Hz, 2H);
13C NMR (CDCl3): d=13.4, 27.2, 68.3, 106.3, 108.4, 128.7,
128.9, 129.1, 129.8, 133.9, 134.4, 136.5, 137.0, 147.2, 151.6,
191.9; IR: n=3064, 2923, 1682, 1587, 1448, 1315, 1253, 1215,
1185, 1151, 1083, 1022, 999, 945, 856, 774, 756, 721, 687,
1-Phenyl-2-(phenylsulfonyl)-3-(phenylthio)propan-1-one
536 cmÀ1
;
HR-MS (ESI): m/z=377.0804, calcd. for
(9a): yellow solid; mp 79–818C; H NMR (CDCl3): d=3.45
1
C20H18NaO4S [M+Na]+: 377.0823.
(dd, Ja =11.6 Hz, Jb =13.2 Hz, 1H), 3.67 (dd, Ja =2.8 Hz, Jb =
13.6 Hz, 1H), 5.21 (dd, Ja =2.4 Hz, Jb =11.6 Hz, 1H), 7.15–
7.25 (m, 5H), 7.39 (t, J=8 Hz, 2H), 7.49 (t, J=8 Hz, 2H),
7.56 (t, J=7.6 Hz, 1H), 7.63 (t, J=7.6 Hz, 1H), 7.71–7.77
(m, 4H); 13C NMR (CDCl3): d=31.5, 68.6, 127.6, 128.7,
129.0, 129.2, 129.4, 129.6, 130.8, 133.2, 134.2, 134.6, 136.1,
137.1, 191.2; IR: n=3080, 2927, 1685, 1583, 1480, 1444, 1417,
1330, 1308, 1212, 1137, 1078, 1055, 1022, 999, 972, 916, 838,
781, 764, 735, 689, 655, 562, 535 cmÀ1; HR-MS (ESI): m/z=
405.0583, calcd. for C21H18NaO3S2 [M+Na]+: 405. 0595.
1-(4-Fluorophenyl)-2-(phenylsulfonyl)-3-(phenylthio)pro-
pan-1-one (9b): white solid; mp 99–1018C; 1H NMR
(CDCl3): d=4.20 (dd, Ja =11.6 Hz, Jb =13.6 Hz, 1H), 3.65
(dd, Ja =2.8 Hz, Jb =13.2 Hz, 1H), 5.15 (dd, Ja =2.8 Hz, Jb =
11.6 Hz, 1H), 7.08 (td, Ja =2.0 Hz, Jb =8.4 Hz, 2H), 7.16–
7.21 (m, 2H), 7.22–7.27 (m, 3H), 7.52 (t, J=7.6 Hz, 2H),
7.66 (tt, Ja =1.2 Hz, Jb =7.6 Hz, 1H), 7.73 (dd, Ja =1.2 Hz,
Jb =8.8 Hz, 2H), 7.81 (qd, Ja =2.0 Hz, Jb =5.6 Hz, 2H);
13C NMR (CDCl3): d=31.5, 68.7, 115.9, 116.1, 127.7, 129.2,
129.5, 129.7, 130.9, 131.9, 132.0, 133.1, 134.7, 136.0, 189.6;
IR: n=3074, 2990, 2944, 1672, 1593, 1481, 1447, 1413, 1324,
1308, 1271, 129, 1193, 1160, 1132, 1081, 1052, 1021, 997, 971,
1-(4-Fluorophenyl)-3-(5-methylfuran-2-yl)-2-(phenylsul-
fonyl)propan-1-one (7b): brown solid, mp 82–848C;
1H NMR (CDCl3): d=2.04 (s, 3H), 3.35 (dd, Ja =10.8 Hz,
Jb =14.4 Hz, 1H), 3.42 (dd, Ja =3.6 Hz, Jb =14.4 Hz, 1H),
5.40 (dd, Ja =3.6 Hz, Jb =10.8 Hz, 1H), 5.68 (dd, Ja =0.8 Hz,
Jb =2.8 Hz, 1H), 5.79 (d, J=2.8 Hz, 1H), 7.04–7.14 (m, 2H),
7.53 (td, Ja =1.2 Hz, Jb =7.6 Hz, 2H), 7.66 (tt, Ja =1.2 Hz,
Jb =7.6 Hz, 1H), 7.77–7.83 (m, 2H), 7.87–7.93 (m, 2H);
13C NMR (CDCl3): d=13.4, 27.3, 68.4, 106.3, 108.4, 115.8,
116.1, 129.1, 129.8, 131.7, 131.8, 134.5, 136.4, 147.1, 151.6,
190.4; IR: n=3118, 3073, 2975, 2926, 1723, 1675, 1595, 1509,
1446, 1413, 1370, 1325, 1239, 1190, 1150, 1085, 1025, 1003,
954,866, 822, 786, 739 cmÀ1; HR-MS (ESI): m/z=395.0725,
calcd. for C20H17FNaO4S [M+Na]+: 395.0729.
1-(4-Chlorophenyl)-3-(5-methylfuran-2-yl)-2-(phenylsul-
fonyl)propan-1-one (7c): brown liquid; 1H NMR (CDCl3):
d=2.04 (s, 3H), 3.35 (dd, Ja =10.8 Hz, Jb =14.4 Hz, 1H),
3.42 (dd, Ja =3.6 Hz, Jb =14.4 Hz, 1H), 5.38 (dd, Ja =3.6 Hz,
Jb =10.8 Hz, 1H), 5.68 (dd, Ja =1.2 Hz, Jb =3.2 Hz, 1H), 5.78
(d, J=3.2 Hz, 1H), 7.39 (dt, Ja =2.0 Hz, Jb =8.8 Hz, 2H),
7.53 (td, Ja =1.6 Hz, Jb =7.6 Hz, 2H), 7.66 (tt, Ja =1.2 Hz,
Jb =7.6 Hz, 1H), 7.79 (dd, Ja =1.2 Hz, Jb =3.6 Hz, 2H), 7.80–
7.83 (m, 2H); 13C NMR (CDCl3): d=13.4, 27.3, 68.4, 106.4,
108.5, 129.1, 129.2, 129.8, 130.3, 134.6, 135.4, 136.3, 140.6,
147.1, 151.7, 190.8; IR: n=3098, 3067, 2957, 2924, 1725,
1684, 1587, 1486, 1448, 1402, 1323, 1253, 1216, 1181, 1152,
1136, 1085, 1016, 999, 943, 816, 788 cmÀ1; HR-MS (ESI):
m/z=411.0428, calcd. for C20H17ClNaO4S [M+Na]+:
411.0434.
914, 860, 829, 809, 748, 726, 691, 650, 602, 557, 532 cmÀ1
;
HR-MS (ESI): m/z=423.0485, calcd. for C21H17FNaO3S2
[M+Na]+: 423.0501.
1-(4-Chlorophenyl)-2-(phenylsulfonyl)-3-(phenylthio)pro-
pan-1-one (9c): pale pink solid; mp 93–958C; 1H NMR
(CDCl3): d=3.41 (dd, Ja =11.6 Hz, Jb =13.2 Hz, 1H), 3.64
(dd, Ja =2.4 Hz, Jb =13.2 Hz, 1H), 5.14 (dd, Ja =2.4 Hz, Jb =
11.6 Hz, 1H), 7.16–7.20 (m, 2H), 7.22–7.26 (m, 3H), 7.38
(dt, Ja =2.0 Hz, Jb =8.8 Hz, 2H), 7.51 (td, Ja =2.0 Hz, Jb =
7.6 Hz, 2H), 7.66 (tt, Ja =1.2 Hz, Jb =7.6 Hz, 1H), 7.71 (dd,
Ja =1.6 Hz, Jb =6.8 Hz, 2H), 7.73 (dd, Ja =0.8 Hz, Jb =
3-(5-Methylfuran-2-yl)-1-(4-nitrophenyl)-2-(phenylsul-
fonyl)propan-1-one (7d): pale yellow solid; mp 136–1388C;
1H NMR (CDCl3): d=2.03 (s, 3H), 3.36 (dd, Ja =10.8 Hz,
696
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 688 – 700

Multicomponent Reactions of b-Ketosulfones and Formaldehyde in a Bio-Based Binary Mixture
8.0 Hz, 2H); 13C NMR (CDCl3): d=31.5, 68.7, 127.7, 129.1,
129.1, 129.2, 129.5, 129.7, 130.4, 130.9, 133.0, 134.7, 135.4,
136.0, 140.9, 190.1; IR: n=3010, 3060, 2953, 1676, 1582,
1480, 1443, 1404, 1327, 1307, 1266, 1230, 1146, 1085, 1013,
954, 910, 855, 803, 756, 734, 685, 638, 554, 527 cmÀ1; HR-MS
(ESI): m/z=439.0187, calcd. for C21H17ClNaO3S2 [M+Na]+:
439.0205.
13.6 Hz, 1H), 4.93 (dd, Ja =2.8 Hz, Jb =11.6 Hz, 1H), 7.06
(dd, Ja =3.6 Hz, Jb =4.8 Hz, 1H), 7.22–7.28 (m, 5H), 7.47–
7.54 (m, 3H), 7.65 (tt, Ja =1.2 Hz, Jb =7.6 Hz, 1H), 7.70 (dd,
Ja =1.2 Hz, Jb =4.8 Hz, 1H), 7.76 (dd, Ja =1.2 Hz, Jb =
8.4 Hz, 2H); 13C NMR (CDCl3): d=31.1, 70.8, 127.6, 128.6,
129.2, 129.4, 129.7, 130.9, 133.2, 134.5, 134.7, 136.1, 136.4,
144.4, 182.9; IR: n=3098, 2932, 1722, 1659, 1582, 1515, 1478,
1444, 1412, 1358, 1325, 1273, 1243, 1189, 1151, 1080, 1025,
849, 825, 738, 689, 570, 532 cmÀ1; HR-MS (ESI): m/z=
411.0153, calcd. for C19H16NaO3S3 [M+Na]+: 411.0159.
1-(Furan-2-yl)-2-(phenylsulfonyl)-3-(phenylthio)propan-1-
2-(Phenylsulfonyl)-3-(phenylthio)-1-(p-tolyl)propan-1-one
1
(9d): pale yellow liquid; H NMR (CDCl3): d=2.39 (s, 3H),
3.43 (dd, Ja =11.6 Hz, Jb =13.2 Hz, 1H), 3.65 (dd, Ja =2.8 Hz,
Jb =13.2 Hz, 1H), 5.18 (dd, Ja =2.8 Hz, Jb =11.6 Hz, 1H),
7.18–7.22 (m, 4H), 7.23–7.28 (m, 3H), 7.50 (t, J=8.0 Hz,
2H), 7.63 (d, J=7.6 Hz, 1H), 7.67 (d, J=7.6 Hz, 2H), 7.73
(dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H); 13C NMR (CDCl3): d=
21.9, 31.6, 68.5, 127.6, 129.1, 129.3, 129.4, 129.5, 129.7, 130.9,
133.3, 134.6, 134.7, 136.2, 145.5, 190.5; IR: n=3062, 2928,
1724, 1678, 1605, 1479, 1445, 1412, 1380, 1328, 1272, 1234,
1186, 1152, 1083, 1025, 998, 962, 917, 855, 802, 744, 690, 648,
556, 532 cmÀ1; HR-MS (ESI): m/z=419.0745, calcd. for
C22H20NaO3S2 [M+Na]+: 419.0752.
1
one (9i): pale yellow solid; mp 98–1008C; H NMR (CDCl3):
d=3.43 (dd, Ja =11.6 Hz, Jb =13.2 Hz, 1H), 3.67 (dd, Ja =
2.4 Hz, Jb =13.2 Hz, 1H), 5.00 (dd, Ja =2.4 Hz, Jb =11.6 Hz,
1H), 6.52 (dd, Ja =1.6 Hz, Jb =3.6 Hz, 1H), 7.14 (d, Ja =
3.6 Hz, 1H), 7.21–7.29 (m, 5H), 7.51 (t, J=8.0 Hz, 3H), 7.65
(t, Ja =7.2 Hz, 1H), 7.77 (dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H);
13C NMR (CDCl3): d=30.6, 69.5, 113.2, 120.1, 127.6, 129.2,
129.4, 129.6, 130.9, 133.2, 134.6, 136.3, 148.1, 152.8, 178.5;
IR: n=3159, 3145, 3130, 3063, 2978, 2920, 1724, 1670, 1564,
1462, 1418, 1395, 1324, 1308, 1284, 1256, 1228, 1198, 1171,
1133, 1080, 1068, 1035, 1019, 994, 971, 940, 887, 875, 852,
830, 765, 754, 718, 690, 665, 611, 588, 551, 532 cmÀ1; HR-MS
(ESI): m/z=395.0384, calcd. for C19H16NaO4S2 [M+Na]+:
395.0388.
4-[2-(Phenylsulfonyl)-3-(phenylthio)propanoyl]benzoni-
trile (9e): pale pink solid; mp 118–1208C; 1H NMR
(CDCl3): d=3.40 (dd, Ja =11.6 Hz, Jb =13.6 Hz, 1H), 3.64
(dd, Ja =2.8 Hz, Jb =13.6 Hz, 1H), 5.16 (dd, Ja =2.8 Hz, Jb =
11.6 Hz, 1H), 7.13–7.19 (m, 2H), 7.23–7.27 (m, 3H), 7.55 (t,
J=8.0 Hz, 2H), 7.68–7.75 (m, 5H), 7.85 (d, J=8.4 Hz, 2H);
13C NMR (CDCl3): d=31.5, 69.2, 117.2, 117.7, 127.9, 129.3,
129.4, 129.6, 129.7, 130.8, 132.5, 132.7, 135.0, 135.7, 139.9,
190.5; IR: n=3010, 3069, 2963, 2227, 1727, 1682, 1580, 1480,
1443, 1405, 1336, 1304, 1268, 1230, 1146, 1079, 1021, 999,
3-[(4-Methoxyphenyl)thio]-1-phenyl-2-(phenylsulfonyl)-
1
propan-1-one (9j): pale brown liquid; H NMR (CDCl3): d=
3.36 (dd, Ja =11.6 Hz, Jb =13.2 Hz, 1H), 3.51 (dd, Ja =2.8 Hz,
Jb =13.2 Hz, 1H), 3.78 (s, 3H), 5.16 (dd, Ja =2.8 Hz, Jb =
11.6 Hz, 1H), 6.72–6.77 (m, 2H), 7.10–7.15 (m, 2H), 7.43 (t,
J=7.6 Hz, 2H), 7.49 (t, J=7.6 Hz, 2H), 7.56–7.65 (m, 2H),
7.71 (dd, Ja =1.2 Hz, Jb =7.2 Hz, 2H), 7.81 (dd, Ja =1.2 Hz,
Jb =7.2 Hz, 2H); 13C NMR (CDCl3): d=33.4, 55.4, 68.8,
115.0, 123.1, 128.7, 129.1, 129.7, 134.2, 134.6, 134.6, 136.2,
137.1, 159.9, 191.2; IR: n=3064, 2941, 2838, 1682, 1591,
1494, 1448, 1413, 1326, 1287, 1248, 1181, 1151, 1082, 1028,
963, 917, 830, 742, 686, 556, 532 cmÀ1; HR-MS (ESI): m/z=
435.0685, calcd. for C22H20NaO4S2 [M+Na]+: 435.0701.
3-[(4-Hydroxyphenyl)thio]-1-phenyl-2-(phenylsulfonyl)-
957, 913, 866, 845, 806, 780. 739, 687, 646, 560, 534 cmÀ1
;
HR-MS (ESI): m/z=430.0547, calcd. for C22H17NNaO3S2
[M+Na]+: 430.0548.
1-(4-Nitrophenyl)-2-(phenylsulfonyl)-3-(phenylthio)pro-
1
pan-1-one (9f): pale yellow solid; mp124–1268C; H NMR
(CDCl3): d=3.41 (dd, Ja =11.6 Hz, Jb =13.6 Hz, 1H), 3.65
(dd, Ja =2.8 Hz, Jb =13.6 Hz, 1H), 5.20 (dd, Ja =2.8 Hz, Jb =
11.6 Hz, 1H), 7.14–7.20 (m, 2H), 7.22–7.26 (m, 3H), 7.56 (tt,
Ja =1.6 Hz, Jb =7.6 Hz, 2H), 7.71 (tt, Ja =1.2 Hz, Jb =7.6 Hz,
1H), 7.74 (dd, Ja =1.2 Hz, Jb =8.8 Hz, 2H), 7.92 (dt, Ja =
2.0 Hz, Jb =8.8 Hz, 2H); 13C NMR (CDCl3): d=31.5, 69.4,
123.9, 127.9, 129.4, 129.6, 129.7, 130.0, 130.8, 132.7, 135.0,
135.7, 141.3, 150.7, 190.4; IR: n=3064, 2968, 2928, 1688,
1604, 1527, 1447, 1346, 1326, 1315, 1299, 1269, 1227, 1184,
1149, 1083, 961, 857 cmÀ1; HR-MS (ESI): m/z=450.0439,
calcd. for C21H17NNaO5S2 [M+Na]+: 450.0446.
1
propan-1-one (9k): yellow liquid; H NMR (CDCl3): d=3.37
(dd, Ja =11.6 Hz, Jb =13.2 Hz, 1H), 3.51 (dd, Ja =2.8 Hz, Jb =
13.2 Hz, 1H), 5.19 (dd, Ja =2.8 Hz, Jb =11.2 Hz, 1H), 6.65–
6.70 (m, 2H), 7.02–7.07 (m, 2H), 7.41 (t, J=8.0 Hz, 2H),
7.48 (t, J=8.0 Hz, 2H), 7.58 (t, J=7.6 Hz, 1H), 7.62 (t, J=
7.6 Hz, 1H), 7.71 (dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H), 7.79 (dd,
Ja =1.2 Hz, Jb =8.4 Hz, 2H); 13C NMR (CDCl3): d=31.5,
68.2, 115.8, 127.7, 129.3, 129.4, 129.5, 129.6, 130.9, 131.9,
133.1, 134.8, 135.9, 162.3, 189.2; IR: n=3398, 3184, 3063,
2933, 1668, 1600, 1582, 1514, 1479, 1446, 1440, 1416, 1326,
1308, 1274, 1235, 1172, 1148, 1082, 1025, 999, 916, 823, 742,
1-(4-Hydroxyphenyl)-2-(phenylsulfonyl)-3-(phenylthio)-
1
propan-1-one (9g): yellow solid, mp: 130–1328C; H NMR
(CDCl3): 3.43 (dd, Ja =11.6 Hz, Jb =13.2 Hz, 1H), 3.62 (dd,
Ja =2.8 Hz, Jb =13.2 Hz, 1H), 4.55–5.10 (m, 1H), 5.15 (dd,
Ja =2.8 Hz, Jb =11.6 Hz, 1H), 6.75 (d, J=8.8 Hz, 2H), 7.16–
7.28 (m, 5H), 7.52 (t, J=8.0 Hz, 2H), 7.63–7.66 (m, 1H),
7.71 (d, J=8.8 Hz, 2H), 7.75 (d, J=7.6 Hz,2H); 13C NMR
(CDCl3): 31.6, 68.3, 115.8, 127.7, 129.3, 129.5, 129.7, 129.9,
131.0, 132.0, 133.2, 134.8, 136.0, 162.0, 189.2; IR (cmÀ1):
3403, 3064, 2935, 1666, 1592, 1514, 1478, 1443, 1415, 1327,
1307, 1274, 1234, 1173, 1148, 1081, 1000, 964, 915, 855, 822,
741, 689, 555, 533; HRMS m/z (ESI) calcd for C21H18NaO4S2
[M + Na]+ 421.0544 found 421.0539.
688 cmÀ1
;
HR-MS (ESI): m/z=421.0551, calcd. for
C21H18NaO4S2 [M+Na]+: 421.0544.
3-[(4-Chlorophenyl)thio]-1-phenyl-2-(phenylsulfonyl)pro-
pan-1-one (9l): pale yellow solid; mp 96–988C; 1H NMR
(CDCl3): d=3.46 (dd, Ja =11.2 Hz, Jb =13.2 Hz, 1H), 3.62
(dd, Ja =2.8 Hz, Jb =13.6 Hz, 1H), 5.18 (dd, Ja =2.4 Hz, Jb =
7.2 Hz, 1H), 7.11 (dt, Ja =2.0 Hz, Jb =8.8 Hz, 2H), 7.19 (dt,
Ja =2.0 Hz, Jb =8.8 Hz, 2H), 7.41 (t, J=8.0 Hz, 2H), 7.50 (t,
J=8.0 Hz, 2H), 7.58 (t, J=7.6 Hz, 1H), 7.64 (t, J=7.6 Hz,
1H), 7.70–7.79 (m, 4H); 13C NMR (CDCl3): d=31.8, 68.7,
128.8, 129.0, 129.2, 129.6, 129.7, 131.7, 132.3, 133.8, 134.3,
134.7, 136.1, 137.0, 191.0; IR: n=3057, 2922, 1676, 1585,
2-(Phenylsulfonyl)-3-(phenylthio)-1-(thiophen-2-yl)pro-
pan-1-one (9h): yellow liquid; 1H NMR (CDCl3): d=3.42
(dd, Ja =11.6 Hz, Jb =13.6 Hz, 1H), 3.65 (dd, Ja =2.8 Hz, Jb =
Adv. Synth. Catal. 2012, 354, 688 – 700
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
697

Jie Yang et al.
FULL PAPERS
1477, 1446, 1416, 1390, 1326, 1270, 1233, 1180, 1125, 1080,
1683, 1595, 1479, 1448, 1418, 1326, 1270, 1230, 1186, 1151,
1134, 1083, 1055, 1000, 963, 916, 846, 814, 741, 686, 556,
1004, 958, 912, 842, 813, 773, 741, 685, 622, 553, 530 cmÀ1
;
532 cmÀ1
;
HR-MS (ESI): m/z=433.0897, calcd. for
HR-MS (ESI): m/z=439.0196, calcd. for C21H17ClNaO3S2
[M+Na]+: 439.0205.
C23H22NaO3S2 [M+Na]+: 433.0908.
3-[(4-Isopropylphenyl)thio]-1-phenyl-2-(phenylsulfonyl)-
propan-1-one (9m): brown liquid; 1H NMR (CDCl3): d=
1.22 (s, 3H), 1.24 (s, 3H), 2.87 (sept, J=6.8 Hz, 1H), 3.40
(dd, Ja =11.6 Hz, Jb =13.2 Hz, 1H), 3.61 (dd, Ja =2.8 Hz, Jb =
13.2 Hz, 1H), 5.22 (dd, Ja =2.8 Hz, Jb =11.6 Hz, 1H), 7.09
(dd, Ja =2.0 Hz, Jb =6.4 Hz, 2H), 7.13 (dd, Ja =2.0 Hz, Jb =
6.4 Hz, 2H), 7.40 (t, J=8.0 Hz, 2H), 7.49 (t, J=8.0 Hz, 2H),
7.57 (t, J=7.6 Hz, 1H), 7.63 (t, J=7.6 Hz, 1H), 7.72 (dd,
Ja =1.2 Hz, Jb =8.8 Hz, 2H), 7.78 (dd, Ja =1.2 Hz, Jb =
8.8 Hz, 2H); 13C NMR (CDCl3): d=23.9, 24.0, 32.2, 33.8,
68.8, 127.6, 128.7, 129.1, 129.1, 129.6, 129.7, 131.7, 134.2,
134.6, 136.1, 137.1, 148.9, 191.2; IR: n=3064, 2961, 2870,
1683, 1593, 1490, 1448, 1415, 1326, 1311, 1270, 1229, 1187,
1151, 1134, 1083, 1000, 962, 917, 827, 740, 686, 552,
3-[(3,5-Dimethylphenyl)thio]-1-phenyl-2-(phenylsulfonyl)-
propan-1-one (9q): yellow solid; mp 100–1028C; 1H NMR
(CDCl3): d=2.19 (s, 6H), 3.39 (dd, Ja =11.6 Hz, Jb =13.2 Hz,
1H), 3.60 (dd, Ja =2.8 Hz, Jb =13.2 Hz, 1H), 5.18 (dd, Ja =
2.8 Hz, Jb =11.6 Hz, 1H), 6.78 (s, 2H), 6.86 (s, 1H), 7.41 (t,
J=8.0 Hz, 2H), 7.50 (t, J=8.0 Hz, 2H), 7.57 (tt, Ja =1.2 Hz,
Jb =7.6 Hz, 1H), 7.64 (tt, Ja =1.2 Hz, Jb =7.6 Hz, 1H), 7.74
(dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H), 7.78 (dd, Ja =1.2 Hz, Jb =
8.4 Hz, 2H); 13C NMR (CDCl3): d=21.2, 31.9, 68.6, 128.7,
129.1, 129.1, 129.3, 129.6, 129.7, 132.2, 134.1, 134.6, 136.3,
137.2, 139.1, 191.3; IR: n=3098, 2928, 1674, 1582, 1446,
1419, 1381, 1305, 1259, 1225, 1194, 1130, 1077, 1044, 997,
968, 912, 842, 766, 744, 683, 651, 556, 531 cmÀ1; HR-MS
(ESI): m/z=433.0901, calcd. for C23H22NaO3S2 [M+Na]+:
433.0908.
532 cmÀ1
;
HR-MS (ESI): m/z=447.1060, calcd. for
C24H24NaO3S2 [M+Na]+: 447.1065.
3-(Benzylthio)-1-phenyl-2-(phenylsulfonyl)propan-1-one
(9r): brown liquid; 1H NMR (CDCl3): d=3.11 (dd, Ja =
3.2 Hz, Jb =13.6 Hz, 1H), 3.22 (dd, Ja =11.2 Hz, Jb =13.6 Hz,
1H), 3.63 (s, 2H), 5.00 (dd, Ja =3.2 Hz, Jb =11.6 Hz, 1H),
7.16–7.22 (m, 2H), 7.26–7.31 (m, 2H), 7.39 (t, J=8.0 Hz,
2H), 7.46 (t, J=8.0 Hz, 2H), 7.56 (t, J=7.6 Hz, 1H), 7.60 (t,
J=7.6 Hz, 1H), 7.67 (td, Ja =0.8 Hz, Jb =8.0 Hz, 4H);
13C NMR (CDCl3): d=29.3, 37.8, 69.3, 127.5, 128.7, 128.9,
129.0, 129.1, 129.1, 129.6, 134.1, 134.5, 136.3, 137.0, 138.1,
191.4; IR: n=3062, 2928, 1721, 1681, 1593, 1493, 1449, 1412,
1324, 1274, 1230, 1186, 1150, 1083, 1000, 962, 929, 844, 758,
740, 702, 686, 554, 532 cmÀ1; HR-MS (ESI): m/z=419.0748,
calcd. for C22H20NaO3S2 [M+Na]+: 419.0752.
3-[(2-Methoxyphenyl)thio]-1-phenyl-2-(phenylsulfonyl)-
propan-1-one (9n): white solid; mp 83–858C; 1H NMR
(CDCl3): d=3.38 (dd, Ja =11.6 Hz, Jb =13.2 Hz, 1H), 3.69
(dd, Ja =2.4 Hz, Jb =13.2 Hz, 1H), 3.73 (s, 3H), 5.18 (dd, Ja =
2.4 Hz, Jb =11.2 Hz, 1H), 6.77 (td, Ja =1.2 Hz, Jb =7.6 Hz,
1H), 6.81 (dd, Ja =0.8 Hz, Jb =8.0 Hz, 1H), 7.07 (dd, Ja =
1.2 Hz, Jb =7.6 Hz, 1H), 7.24–7.27 (m, 1H), 7.39 (t, J=
8.0 Hz, 2H), 7.49 (t, J=8.0 Hz, 2H), 7.56 (tt, Ja =1.2 Hz,
Jb =7.2 Hz, 1H), 7.63 (tt, Ja =1.2 Hz, Jb =7.2 Hz, 1H), 7.72
(dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H), 7.78 (dd, Ja =1.2 Hz, Jb =
8.4 Hz, 2H); 13C NMR (CDCl3): d=30.2, 55.7, 69.0, 111.1,
120.1, 121.1, 128.6, 129.1, 129.6, 129.9, 133.7, 134.0, 134.5,
136.3, 137.1, 158.9, 191.1; IR: n=3062, 2936, 2837, 1675,
1579, 1475, 1450, 1431, 1340, 1309, 1276, 1244, 1180, 1127,
1076, 1019, 958, 913, 843, 766, 744, 736, 687, 631, 552,
3-(Cyclohexylthio)-1-phenyl-2-(phenylsulfonyl)propan-1-
1
one (9s): pale yellow solid; mp 88–898C; H NMR (CDCl3):
d=1.13–1.29 (m, 5H), 1.56 (dd, Ja =2.4 Hz, Jb =8.0 Hz, 1H),
1.63–1.75 (m, 2H), 1.78–1.90 (m, 2H), 2.51–2.62 (m, 1H),
3.17 (dd, Ja =11.2 Hz, Jb =12.8 Hz, 1H), 2.24 (dd, Ja =3.2 Hz,
Jb =12.8 Hz, 1H), 3.27 (dd, Ja =3.2 Hz, Jb =11.2 Hz, 1H),
7.46 (t, J=8.0 Hz, 2H), 7.51 (t, J=8.0 Hz, 2H), 7.59 (tt, Ja =
1.2 Hz, Jb =7.6 Hz, 1H), 7.64 (tt, Ja =1.2 Hz, Jb =7.6 Hz,
1H), 7.76 (dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H), 7.94 (dd, Ja =
1.2 Hz, Jb =8.4 Hz, 2H); 13C NMR (CDCl3): d=25.7, 26.0,
26.0, 27.3, 33.3, 33.6, 44.8, 70.2, 128.9, 129.1, 129.2, 129.7,
134.2, 134.6, 136.3, 137.3, 191.7; IR: n=3066, 2924, 2853,
1673, 1586, 1448, 1417, 1343, 1311, 1269, 1236, 1190, 1130,
1083, 1023, 999, 961, 912, 844, 775, 748, 685, 632, 552,
521 cmÀ1
;
HR-MS (ESI): m/z=435.0694, calcd. for
C22H20NaO4S2 [M+Na]+: 435.0701.
1-Phenyl-2-(phenylsulfonyl)-3-(o-tolylthio)propan-1-one
1
(9o): pale pink solid; mp 97–998C; H NMR (CDCl3): d=
2.10 (s, 3H), 3.44 (dd, Ja =11.6 Hz, Jb =13.2 Hz, 1H), 3.63
(dd, Ja =2.4 Hz, Jb =13.2 Hz, 1H), 5.19 (dd, Ja =2.4 Hz, Jb =
11.6 Hz, 1H), 7.07–7.18 (m, 4H), 7.38 (t, J=8 Hz, 2H), 7.50
(t, J=8 Hz, 2H), 7.56 (t, J=7.2 Hz, 1H), 7.64 (t, J=7.6 Hz,
1H), 7.70–7.75 (m, 4H); 13C NMR (CDCl3): d=20.3, 30.5,
68.5, 126.9, 127.6, 128.7, 129.0, 129.2, 129.7, 130.3, 130.8,
132.2, 134.2, 134.6, 136.2, 137.0, 139.6, 191.1; IR: n=3058,
2975, 1682, 1588, 1448, 1337, 1317, 1295, 1265, 1228, 1143,
1079, 952, 926, 759, 737, 683, 665, 642, 557, 534 cmÀ1; HR-
MS (ESI): m/z=419.0748, calcd. for C22H20NaNaO3S2 [M+
Na]+: 419.0752.
523 cmÀ1
;
HR-MS (ESI): m/z=411.1055, calcd. for
C21H24NaO3S2 [M+Na]+: 411.1065.
3-[(Furan-2-ylmethyl)thio]-1-phenyl-2-(phenylsulfonyl)-
1
propan-1-one (9t): black liquid; H NMR (CDCl3): d=3.15
3-[(2,4-Dimethylphenyl)thio]-1-phenyl-2-(phenylsulfonyl)-
1
(dd, Ja =3.6 Hz, Jb =13.6 Hz, 1H), 3.25 (dd, Ja =11.6 Hz, Jb =
13.6 Hz, 1H),3.65 (dd, Ja =14.8 Hz, Jb =18.0 Hz, 2H), 5.10
(dd, Ja =3.2 Hz, Jb =11.2 Hz, 1H), 6.16 (d, J=3.2 Hz, 1H),
6.33 (dd, Ja =2.0 Hz, Jb =3.2 Hz, 1H), 7.33 (d, J=1.2 Hz,
1H), 7.43 (t, J=8.0 Hz, 2H), 7.49 (t, J=8.0 Hz, 2H), 7.58 (t,
J=7.2 Hz, 1H), 7.63 (t, J=7.2 Hz, 1H), 7.72 (dd, Ja =
1.2 Hz, Jb =8.4 Hz, 2H), 7.84 (dd, Ja =1.2 Hz, Jb =8.4 Hz,
2H); 13C NMR (CDCl3): d=29.2, 29.4, 69.4, 108.4, 110.8,
128.7, 129.1, 129.2, 129.7, 134.2, 134.5, 136.3, 137.1, 142.6,
150.7, 191.5; IR: n=3065, 2930, 1681, 1593, 1052, 1448, 1412,
1325, 1311, 1275, 1232, 1185, 1150, 1083, 1012, 963, 938, 845,
propan-1-one (9p): yellow liquid; H NMR (CDCl3): d=2.09
(s, 3H), 2.26 (s, 3H), 3.39 (dd, Ja =11.2 Hz, Jb =13.2 Hz,
1H), 3.55 (dd, Ja =2.4 Hz, Jb =13.2 Hz, 1H), 5.16 (dd, Ja =
2.4 Hz, Jb =11.2 Hz, 1H), 6.85 (d, J=7.6 Hz, 1H), 6.92 (s,
1H), 7.04 (d, J=7.6 Hz, 1H), 7.39 (t, J=8.0 Hz, 2H), 7.49
(t, J=8.0 Hz, 2H), 7.56 (tt, Ja =1.2 Hz, Jb =7.6 Hz, 1H), 7.63
(tt, Ja =1.2 Hz, Jb =7.6 Hz, 1H), 7.72 (dd, Ja =1.2 Hz, Jb =
8.4 Hz, 2H), 7.75 (dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H);
13C NMR (CDCl3): d=20.2, 21.0, 31.1, 68.6, 127.5, 128.2,
128.6, 129.0, 129.1, 129.6, 131.7, 131.8, 134.1, 134.6, 136.2,
136.9, 138.0, 140.1, 191.1; IR: n=3061, 2920, 2862, 1723,
698
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 688 – 700

Multicomponent Reactions of b-Ketosulfones and Formaldehyde in a Bio-Based Binary Mixture
741, 687, 555, 531 cmÀ1; HR-MS (ESI): m/z=409.0530,
calcd. for C20H18NaO4S2 [M+Na]+: 409.0544.
MS (ESI): m/z=416.1283, calcd. for C23H23NNaO3S [M+
Na]+: 416.1296.
3-(2,4-Dihydroxyphenyl)-1-phenyl-2-(phenylsulfonyl)pro-
pan-1-one (11e): pale brown liquid; 1H NMR (DMSO-d6):
d=3.00 (dd, Ja =10.8 Hz, Jb =13.2 Hz, 1H), 3.10 (dd, Ja =
3.6 Hz, Jb =13.2 Hz, 1H), 5.73 (dd, Ja =3.6 Hz, Jb =10.8 Hz,
1H), 5.88 (dd, Ja =2.4 Hz, Jb =8.0 Hz, 1H), 6.08 (d, J=
2.0 Hz, 1H), 6.52 (d, J=8.4 Hz, 1H), 7.38 (t, J=8.0 Hz,
2H), 7.51–7.60 (m, 3H), 7.66–7.73 (m, 3H), 7.79 (d, J=
7.6 Hz, 2H), 8.90 (s, 1H), 9.42 (s, 1H); 13C NMR (DMSO-
d6): d=29.0, 67.7, 102.8, 106.6, 112.4, 128.8, 129.2, 129.5,
129.8, 131.4, 134.4, 134.9, 137.4, 137.6, 156.4, 157.8, 192.6;
IR: n=3178, 3067, 2961, 1680, 1609, 1521, 1452, 1385, 1306,
1241, 1149, 1104, 1082, 1045, 1024, 1000, 746, 688 cmÀ1; HR-
MS (ESI): m/z=405.0765, calcd. for C21H18NaO5S [M+
Na]+: 405.0773.
1-Phenyl-2-(phenylsulfonyl)-3-(1H-pyrrol-2-yl)propan-1-
one (11f): black solid; mp 116–1188C; 1H NMR (CDCl3):
d=3.42 (dd, Ja =10.4 Hz, Jb =14.8 Hz, 1H), 3.50 (dd, Ja =
4.0 Hz, Jb =14.8 Hz, 1H), 5.34 (dd, Ja =4.0 Hz, Jb =10.0 Hz,
1H), 5.84–5.89 (m, 1H), 5.97 (dd, Ja =2.8 Hz, Jb =6.0 Hz,
1H), 6.53–6.57 (m, 1H), 7.38 (t, J=7.6 Hz, 2H), 7.51 (q, J=
7.6 Hz, 3H), 7.63 (tt, Ja =1.2 Hz, Jb =7.6 Hz, 1H), 7.77 (dd,
Ja =1.2 Hz, Jb =6.4 Hz, 2H), 7.79 (dd, Ja =1.2 Hz, Jb =
6.4 Hz, 2H); 13C NMR (CDCl3): d=26.2, 70.7, 107.5, 108.5,
117.9, 125.6, 128.8, 129.1, 129.2, 129.8, 134.2, 134.5, 136.4,
136.8, 193.0; IR: n=3375, 3066, 2911, 1722, 1657, 1584, 1477,
1446, 1424, 1344, 1310, 1282, 1247, 1184, 1149, 1121, 1082,
1024, 998, 974, 951, 932, 882, 850, 792, 775, 750, 722, 686,
639, 592, 544 cmÀ1; HR-MS (ESI): m/z=362.0819, calcd. for
C19H17NNaO3S [M+Na]+: 362.0827.
3-(2-Hydroxynaphthalen-1-yl)-1-phenyl-2-(phenylsulfon-
yl)propan-1-one (11a): pale yellow solid; mp 194–1968C;
1H NMR (DMSO-d6): d=3.57 (dd, Ja =2.4 Hz, Jb =13.2 Hz,
1H), 3.84 (dd, Ja =10.8 Hz, Jb =13.2 Hz, 1H), 5.81 (dd, Ja =
2.4 Hz, Jb =10.4 Hz, 1H), 7.01 (d, J=8.8 Hz, 1H), 7.23 (t,
J=7.6 Hz, 1H), 7.30 (t, J=7.6 Hz, 2H), 7.40 (t, J=7.6 Hz,
1H), 7.49 (t, J=7.2 Hz, 1H), 7.56 (t, J=7.6 Hz, 3H), 7.64–
7.74 (m , 4H), 7.79 (t, J=7.2 Hz, 1H), 7.99 (d, J=7.6 Hz,
2H), 9.97 (s, 1H); 13C NMR (DMSO-d6): d=24.0, 67.1,
112.8, 117.4, 122.0, 122.4, 126.5, 128.0, 128.4, 128.6, 128.8,
129.2, 129.4, 132.5, 133.8, 134.5, 136.9, 137.4, 153.2, 192.2;
IR: n=3378, 3066, 2931, 1661, 1584, 1513, 1444, 1404, 1355,
1330, 1304, 1268, 1213, 1186, 1131, 1079, 1043, 1004, 984,
950, 810, 741 cmÀ1; HR-MS (ESI): m/z=439.0976, calcd. for
C25H20NaO4S [M+Na]+: 439.0980.
1,5-Dimethyl-4-[3-oxo-3-phenyl-2-(phenylsulfonyl)prop-
yl]-2-phenyl-1H-pyrazol-3(2H)-one (11b): yellow liquid;
1H NMR (CDCl3): d=2.17 (s, 3H), 2.88 (s, 3H), 3.11–3.21
(m, 2H), 6.09 (dd, Ja =6.4 Hz, Jb =8.0 Hz, 1H), 7.16 (dd, Ja =
1.2 Hz, Jb =8.4 Hz, 2H), 7.25 (tt, Ja =1.2 Hz, Jb =7.6 Hz,
1H), 7.3 (t, J=7.6 Hz, 2H), 7.38 (td, Ja =1.6 Hz, Jb =7.6 Hz,
2H), 7.43 (td, Ja =1.6 Hz, Jb =7.6 Hz, 2H), 7.48 (tt, Ja =
1.2 Hz, Jb =7.6 Hz, 1H), 7.54 (tt, Ja =1.2 Hz, Jb =7.2 Hz,
1H), 7.83 (dd, Ja =1.2 Hz, Jb =7.2 Hz, 2H), 7.84 (dd, Ja =
1.2 Hz, Jb =7.2 Hz, 2H); 13C NMR (CDCl3): d=10.9, 22.2,
35.6, 65.7, 103.5, 124.1, 126.8, 128.7, 128.9, 128.9, 129.1,
129.2, 133.8, 134.0, 134.7, 137.2, 138.3, 153.8, 165.4, 193.0;
IR: n=3064, 2929, 1723, 1674, 1660, 1594, 1493, 1449, 1413,
1368, 1312, 1289, 1253, 1148, 1084, 1026, 1000, 968, 932, 865,
824, 754, 725, 690, 551, 536 cmÀ1; HR-MS (ESI) m/z=
483.1335, calcd. for C26H24N2NaO4S [M+Na]+: 483.1354.
1-Phenyl-3-(2-phenyl-1H-indol-3-yl)-2-(phenylsulfonyl)-
propan-1-one (11c): pale green solid; mp 158–1608C;
1H NMR (CDCl3): d=3.74–3.83 (m, 2H), 5.40 (dd, Ja =
6.4 Hz, Jb =8.0 Hz, 1H), 7.05–7.16 (m, 4H), 7.20 (dd, Ja =
1.2 Hz, Jb =7.6 Hz, 1H), 7.33 (s, 2H), 7.34 (d, J=2.8 Hz,
3H), 7.36–7.41 (m, 3H), 7.45 (t, J=8.0 Hz, 2H), 7.52 (dd,
Ja =1.2 Hz, Jb =8.4 Hz, 1H), 7.59 (tt, Ja =1.2 Hz, Jb =7.2 Hz,
1H), 7.76 (dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H), 8.09 (s, 1H);
13C NMR (CDCl3): d=23.6, 69.0, 106.6, 110.9, 118.9, 120.2,
122.6, 127.9, 128.2, 128.4, 128.4, 128.5, 129.0, 129.1, 129.6,
132.4, 133.5, 134.2, 135.4, 135.7, 137.1, 137.1, 192.6; IR: n=
3377, 3057, 3024, 2941, 1680, 1589, 1488, 1446, 1368, 1323,
1295, 1244, 1230, 1181, 1143, 1079, 1023, 999, 972, 937, 905,
842, 815, 775, 759, 744, 730, 686, 589, 538, 531 cmÀ1; HR-MS
(ESI): m/z=488.1288, calcd. for C29H23NNaO3S [M+Na]+:
488.1296.
Acknowledgements
The authors thank for National Natural Science Fundation of
China for the financial support (20903042 and 21173089).
The authors are also grateful for Ms. Ping Liang and all the
other staff members in the Analytical and Testing Center of
HUST, for their supportive and constant contributions to our
works. The Program for new Century Excellent Talents in the
University of China (NCEJ-10-0383) and Chutian Scholar
Program of the Hubei provincial government are also ac-
knowledged.
References
3-(4-(Dimethylamino)phenyl)-1-phenyl-2-(phenylsulfon-
yl)propan-1-one (11d): yellow liquid; H NMR (CDCl3): d=
[1] a) B. Schꢃffner, F. Schꢃffner, S. P. Verevkin, A. Bçrner,
Chem. Rev. 2010, 110, 4554–4581; b) B. Schaffner, F.
Schaffner, S. P. Verevkin, A. Borner, Chem. Rev. 2010,
110, 4554–4581; c) C. Estevez, Sustainable solutions -
green solvents for chemistry, in: Sustainable Solutions
for Modern Economies, RSC Green Chemistry Series,
Vol. 4, Royal Society of Chemistry, 2009, pp 407–424.
[2] a) J. H. Clark, S. J. Tavener, Org. Process Res. Dev.
2007, 11, 149–155; b) F. M. Kerton, Alternative Solvents
for Green Chemistry, RSC Green Chemistry Series,
(Series Ed.: J. Clark), Royal Society of Chemistry,
2009; c) W. Leitner, Green Chem. 2007, 9, 923; d) W.
Leitner, Green Chem. 2009, 11, 603; e) N. Isambert,
1
2.82 (s, 6H), 3.27 (dd, Ja =11.6 Hz, Jb =13.2 Hz, 1H), 3.38
(dd, Ja =3.2 Hz, Jb =13.2 Hz, 1H), 5.29 (dd, Ja =3.2 Hz, Jb =
11.2 Hz, 1H), 6.51 (dd, Ja =2.8 Hz, Jb =11.6 Hz, 2H), 6.93
(dd, Ja =2.8 Hz, Jb =11.6 Hz, 2H), 7.34 (t, J=7.6 Hz, 2H),
7.45–7.55 (m, 3H), 7.64 (tt, Ja =1.2 Hz, Jb =7.6 Hz, 1H), 7.72
(dd, Ja =1.2 Hz, Jb =8.4 Hz, 2H), 7.81 (dd, Ja =1.2 Hz, Jb =
8.4 Hz, 2H); 13C NMR (CDCl3): d=33.2, 40.6, 71.8, 112.9,
123.4, 128.7, 128.9, 129.0, 129.7, 129.9, 133.8, 134.4, 136.7,
137.5, 149.7, 192.7; IR: n=3065, 2927, 2805, 1817, 1724,
1681, 1613, 1524, 1480, 1447, 1312, 1240, 1189, 1149, 1082,
1000, 974, 944, 865, 813, 753, 727, 688, 568, 532 cmÀ1; HR-
Adv. Synth. Catal. 2012, 354, 688 – 700
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
699

Jie Yang et al.
FULL PAPERS
M. M. Sanchez Duque, J.-C. PLaquevent, Y. Gꢄnisson,
J. Rodriguez, T. Constantieux, Chem. Soc. Rev. 2011,
40, 1347–1357.
Aburel, N. Halland, K. A. Jorgensen, Adv. Synth. Catal.
2004, 346, 1077–1080; e) K. Manabe, S. Kobayashi,
Org. Lett. 2003, 5, 3241–3244; f) S. Kiren, A. Padwa, J.
Org. Chem. 2009, 74, 7781–7789; g) H. Loghmani-
Khouzani, M. R. Poorheravi, M. M. M. Sadeghi, L.
Caggiano, R. F. W. Jackson, Tetrahedron 2008, 64,
7419–7425.
[3] a) R. A. Sheldon, Green Chem. 2005, 7, 267–278; b) C.-
J. Li, L. Chen, Chem. Soc. Rev. 2006, 35, 68–82; c) S.
Kobayashi, Pure Appl. Chem. 2007, 79, 235–245;
d) N. V. Plechkova, K. R. Seddon, Chem. Soc. Rev.
2008, 37, 123–150; e) Y. Gu, G. Li, Adv. Synth. Catal.
2009, 351, 817–847.
[9] A. Weichert, H. M. R. Hoffmann, J. Org. Chem. 1991,
56, 4098–4112.
[4] a) S. Aparicio, R. Alcalde, Green Chem. 2009, 11, 65–
78; b) S. Aparicio, R. Alcalde, J. Phys. Chem. B 2009,
113, 14257–14269; c) M. Delample, N. Villandier, J. P.
Douliez, S. Camy, J. S. Condoret, Y. Pouilloux, J. Bar-
rault, F. Jꢄrꢅme, Green Chem. 2010, 12, 804–808; d) S.
Salehpour, M. A. Dube, Green Chem. 2008, 10, 321–
326; e) P. S. Kulkarni, C. Brazinha, C. A. M. Afonso,
J. G. Crespo, Green Chem. 2010, 12, 1990–1994; f) Y.
Simeꢆ, J. V. Sinisterra, A. R. Alcꢇntara, Green Chem.
2009, 11, 855–862; g) S. Shanmuganathan, D. Natalia,
A. van den Wittenboer, C. Kohlmann, L. Greiner, P. D.
de Marꢈa, Green Chem. 2010, 12, 2240–2245; h) F. He,
P. Li, Y. Gu, G. Li, Green Chem. 2009, 11, 1768–1773;
i) M. Li, C. Chen, F. He, Y. Gu, Adv. Synth. Catal.
2010, 352, 519–530; j) J. I. Garcꢈa, H. Garcꢈa-Marꢈn,
J. A. Mayoral, P. Pꢄrez, Green Chem. 2010, 12, 426–
434.
[5] a) Y. Gu, F. Jerome, Green Chem. 2010, 12, 1127–1138;
b) A. E. Dꢈaz-ꢉlvarez, J. Francos, B. Lastra-Barreira, P.
Crochet, V. Cadierno, Chem. Commun. 2011, 47, 6208–
6227.
[6] a) A. P. Abbott, R. C. Harris, K. S. Ryder, C. D’Agosti-
no, L. F. Gladden, M. D. Mantle, Green Chem. 2011,
13, 82–90; b) F. Ilgen, B. Kçnig, Green Chem. 2009, 11,
848–854; c) G. Imperato, R. Vasold, B. Kçnig, Adv.
Synth. Catal. 2006, 348, 2243–2247.
[10] I. M. Bazavova, V. M. Neplyuev, Zhur. Org. Khim.
1983, 19, 1237–1242.
[11] a) M. Sun, S. M. Ramsh, S. Y. Solovꢄva, V. I. Zakharov,
Russ. J. Gen. Chem. 2010, 80, 507–510; b) S. H. Pines,
A. W. Douglas, J. Org. Chem. 1977, 42, 2786–2787; c) S.
Kobayashi, Chem. Lett. 1991, 12, 2187–2190; d) M. H.
Palmer, P. S. McIntyre, Tetrahedron Lett. 1968, 2147–
2150; e) M. Avramoff, Y. Sprinzak, J. Org. Chem. 1961,
26, 1284–1286.
[12] G. Frapper, C. Bachmann, Y. Gu, R. Coval De Sousa,
F. Jerome, Phys. Chem. Chem. Phys. 2011, 13, 628–636.
[13] a) Y. Gu, R. De Sousa, G. Frapper, C. Bachmann, J.
Barrault, F. Jꢄrꢅme, Green Chem. 2009, 11, 1968–1972;
b) J. N. Tan, H. Li, Y. Gu, Green Chem. 2010, 12, 1772–
1782; c) Y. Gu, J. Barrault, F. Jerome, Adv. Synth.
Catal. 2009, 351, 3269–3278.
[14] M. Pohmakotr, S. Khosavanna, Tetrahedron 1993, 49,
6483–6488.
[15] a) M. Li, C. Tang, J. Yang, Y. Gu, Chem. Commun.
2011, 47, 4529–4531; b) M. Li, H. Li, Y. Gu, Org. Lett.
2011, 13, 1064–1067; c) M. Li, J. Yang, Y. Gu, Adv.
Synth. Catal. 2011, 353, 1551–1564.
[16] M. Yamauchi, S. Katayama, T. Watanabe, Synthesis
1982, 935–937.
[17] a) N. Suryakiran, P. Prabhakar, K. Rajesh, V. Suresh, Y.
Venkateswarlu, J. Mol. Catal. A: Chem. 2007, 270, 201–
204; b) N. Suryakiran, T. S. Reddy, K. Ashalatha, M.
Lakshman, Y. Venkateswarlu, Tetrahedron Lett. 2006,
47, 3853–3856; c) D. Villemin, A. A. Ben, Synth.
Commun. 1990, 20, 925–932.
[7] B. Zhou, J. Yang, H. Li, Y. Gu, Green Chem. 2011, 13,
2204–2211.
[8] a) Y. Kuninobu, H. Matsuzaki, M. Nishi, K. Takai, Org.
Lett. 2011, 13, 2959–2961; b) O. Garcia Mancheno, P.
Tangen, R. Rohlmann, R. Froehlich, J. Aleman, Chem.
Eur. J. 2011, 17, 984–992; c) X. Huang, J. Xue, J. Org.
Chem. 2007, 72, 3965–3968; d) J. Pulkkinen, P. S.
[18] D. Kumar, S. Sundaree, V. S. Rao, R. S. Varma, Tetrahe-
dron Lett. 2006, 47, 4197–4199.
700
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 688 – 700