Iron(III)-catalyzed aerobic oxidation and cleavage/formation of a C-S bond

Article abstract of DOI:10.1002/ejoc.201402377

A new iron(III)-catalyzed synthesis of β-oxo sulfones is described that employs vinylarenes and readily available dimethyl sulfoxide (DMSO) with hydrazine and oxygen as the oxidant. The reaction tolerates various functional group substituents on the vinylarene substrates to afford β-oxo sulfones in moderate to good yields. The cleavage and formation of the C-S bond are the key steps of this transformation.

Full text of DOI:10.1002/ejoc.201402377

FULL PAPER
DOI: 10.1002/ejoc.201402377
Iron(III)-Catalyzed Aerobic Oxidation and Cleavage/Formation of a C–S Bond
Xiaokang Shi,[a][‡] Xiaoyu Ren,[a][‡] Zhiyong Ren,[a] Jian Li,[a] Yuling Wang,[a]
Sizhuo Yang,[a] Jixiang Gu,[a] Qiang Gao,[b] and Guosheng Huang*[a]
Keywords: Synthetic methods / Sulfur / Iron / Substituent effects / Cleavage reactions / Reaction mechanisms
A new iron(III)-catalyzed synthesis of β-oxo sulfones is de-
scribed that employs vinylarenes and readily available di-
methyl sulfoxide (DMSO) with hydrazine and oxygen as the
oxidant. The reaction tolerates various functional group sub-
stituents on the vinylarene substrates to afford β-oxo sulfones
in moderate to good yields. The cleavage and formation of
the C–S bond are the key steps of this transformation.
precursors in the preparation of ketones, chalcones,[15]
allenes, acetylenes, vinyl sulfones,[16] and polyfunctionlized
4H-pyrans.[17] Additionally, β-oxo sulfones play an impor-
tant role in the synthesis of optically active β-hydroxy
sulfones and α-halomethyl sulfones.[18,19] Generally, β-oxo
sulfones can be prepared by either a Claisen condensa-
tion,[20] the reaction of an α-halo ketone with a sodium alk-
ane-/arenesulfinate,[21] or an acid-catalyzed reaction be-
tween sulfonyl chlorides and arylacetylenes.[22] Although
several methods have been explored, tremendous limitations
remain in the syntheses of β-oxo sulfones, such as long reac-
tion times, unavailability of starting materials, harsh reac-
tion conditions, and low yields. Therefore, a direct, mild,
and efficient process to access β-oxo sulfones is highly de-
sired. Recently, we discovered a significant method to ob-
tain β-oxo sulfones that employs an iron-catalyzed reaction
of vinylarenes and commercially available DMSO as the
sulfur source. Moreover, various β-oxo sulfones could be
produced in moderate to good yields by using this strategy.
Herein, we wish to report our preliminary results on this
topic.
Introduction
The development of methods for the direct conversion of
C–C bonds into C–S bonds remains a critical challenge in
organic chemistry.[1,2] The cleavage and formation of a C–S
bond through a transition-metal-catalyzed approach is a
very attractive and fascinating branch of synthetic chemis-
try with few reports until now.[3] In 2006, Yu described the
copper(II)-catalyzed thioetherification of 2-phenylpyridine
by using PhSH and MeSSMe under oxygen.[4] In addition,
Qing reported a copper(II)-mediated methylthiolation of
aryl C–H bonds by using dimethyl sulfoxide (DMSO).[5]
Furthermore, Yuan disclosed the synthesis of aryl methyl
sulfones from aryl halides and DMSO through a copper-
catalyzed aerobic oxidation.[6] Recently, a variety of meth-
ods have been developed that employ sulfonyl hydrazides,[7]
sulfinic acids,[8] sulfonyl chlorides, and sulfonyl bromides[9]
as substrates for the formation of the C–S bond. These ap-
proaches proceed through a radical addition that is cata-
lyzed by iron, copper, or iodine or in the absence of a cata-
lyst. In spite of these advances, there still remain great chal-
lenges in the formation of a C–S bond by using DMSO as
the substrate because of the difficulties in the cleavage of a
C–S bond.
Results and Discussion
Compounds that contain a sulfone group have been
widely used for a variety of reactions such as C–C bond
Initially, we investigated the possibility of a cross-cou-
pling reaction between styrene and DMSO, which was also
the solvent, along with benzohydrazide as an additive. To
our surprise, the preparation of a β-oxo sulfone was suc-
cessful. The desired 2-(methylsulfonyl)-1-phenylethanone
(2a) was obtained from the reaction of styrene (1a,
0.2 mmol) and DMSO (1.0 mL) in the presence of FeCl2
and benzohydrazide (1 mmol) at 20 °C in air for 36 h (see
Table 1, Entry 1). Among the examined catalysts, FeCl3
demonstrated the highest activity (see Table 1, Entries 2–
4). No product, however, was observed in the absence of
benzohydrazide, which suggests that it served an important
role in this reaction (see Table 1, Entry 5). In addition, re-
formations,[10] eliminations,[11] and rearrangements[12]
.
Among the derivatives of sulfones, β-oxo sulfones cannot
only act as a versatile intermediates in Michael additions
and Knoevenagel reactions[13,14] but also work as valuable
[a] State Key Laboratory of Applied Organic Chemistry, Lanzhou
University,
Lanzhou 730000, P. R. China
E-mail: hgs@lzu.edu.cn
http://chem.lzu.edu.cn/ArticleShow.asp?ArtID=1219
[b] Xi’an Meihao Plastic and Cosmetic Hospital,
Xi’an 710000, P. R. China
[‡] These authors contributed equally to this work
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402377.
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G. Huang et al.
FULL PAPER
Table 1. Optimization of reaction conditions.[a]
Entry
Catalyst
Additive
Oxidant
T
[°C]
t
[h]
Yield
[%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20[d]
21[e]
22[f]
23[g]
FeCl2
Ni(dppe)Cl2
PdCl2
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
benzohydrazide
benzohydrazide
benzohydrazide
air
air
air
air
air
air
air
DDQ
O2
H2O2
TBHP
O2
O2
O2
O2
O2
O2
O2
O2
O2
20
20
20
20
20
20
20
20
20
20
20
0
10
30
40
60
80
40
40
40
40
40
40
36
36
36
36
36
36
36
36
36
36
36
36
36
36
36
36
36
24
48
36
36
36
36
18
Ͻ5
22
45
n.r.[c]
42
58
66
68
33
23
15
20
65
72
52
39
53
68
26
52
40
35
[b]
benzohydrazide
none
hydrazine dihydrochloride
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
hydrazine hydrate
O2
O2
O2
[a] Reagents and conditions: styrene (0.2 mmol), DMSO (1.0 mL), catalyst (10 mol-%), additive (1.0 mmol), and oxidant (0.2 mmol).
[b] dppe = 1,2-bis(diphenylphosphino)ethane. [c] n.r. = no reaction. [d] Additive (0.4 mmol). [e] DMSO (0.6 mmol), 1,4-dioxane as solvent.
[f] DMSO (0.6 mmol), xylene as solvent. [g] DMSO (0.6 mmol), toluene as solvent.
placing benzohydrazide with hydrazine dihydrochloride or tions of vinylarenes with substituents at the ortho, meta, and
hydrazine hydrate improved the yields of the desired prod- para positions proceeded smoothly, but those with groups
uct; however, hydrazine hydrate showed the best activity at the para position gave higher yields. Of the para-substi-
(see Table 1, Entries 6 and 7). Notably, the addition of 2,3- tuted vinylarenes, those with the electron-donating meth-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) increased oxy, tert-butyl, and methyl groups promoted the reaction
the yield from 58 to 66% (see Table 1, Entry 8), but by and led to the formation of the products (i.e., 2b, 2c, and
using O2 as the oxidant, we obtained the β-oxo sulfone in 2d, respectively) in higher yields than those obtained from
a higher yield (see Table 1, Entry 9). The yields did decrease the halogenated vinylarenes (to give 2e, 2f, and 2g). The
when hydrogen peroxide or tert-butyl hydroperoxide reaction was enhanced by the para-substituted methoxy
(TBHP) were used as the oxidant (see Table 1, Entries 10 group to give 2b in the highest yield of 82%. On the other
and 11). In addition, the screening of various reaction tem- hand, the vinylarene with a para-substituted nitro group ex-
peratures showed it to be a crucial factor, as the yield of 2a hibited very low activity, and none of the desired product
decreased when the reaction was conducted at a higher and 2h was obtained. Similarly, electron-rich analogues with a
lower temperature than 40 °C. These results suggest that meta or ortho substituent also afforded products (i.e., 2i and
40 °C was favorable for the formation of the target product, 2l) in higher yields than those obtained from electron-de-
and the desired β-oxo sulfone was finally obtained in 72% ficient substrates (to give 2j, 2k, and 2m). Moreover, sub-
yield (see Table 1, Entries 12–17). Furthermore, when the strates with two or three electron-donating substituents on
reaction time was changed to either 24 or 48 h, the yield the aromatic ring afforded better yields of product (i.e., 2n
decreased (see Table 1, Entries 18 and 19). Taking all of and 2o). With the electron-deficient trifluoromethyl group
these results into account, the conditions listed in Table 1, at the meta position, the yield of the β-oxo sulfone (i.e.,
Entry 15 were chosen as the optimal reaction conditions.
2p) decreased. It is noteworthy that the bulky substrates 5-
With these optimized conditions in hand, we examined vinylbenzo[d][1,3]dioxole and 1-vinylnaphthalene also ef-
the reactions of various vinylarenes. As shown in Table 2, a ficiently underwent the reaction with DMSO to give the
wide range of substrates, which include those with electron- product (i.e., 2q and 2r) in 71 and 59% yield, respectively.
donating and -withdrawing substituents, exhibited reactiv- In addition, when styrene was replaced with 2-vinylpyr-
ity; however, those substrates with electron-rich substituents idine, the transformation did not proceed (to give 2s),
provided better yields of the product. In addition, the reac- which, suggests that heterocyclic compounds were not reac-
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FeIII-Catalyzed Aerobic Oxidation and Cleavage/Formation of a C–S Bond
tive under these conditions. Furthermore, 1,2,3,4,5-penta- First, the reaction of styrene with deuterated DMSO under
fluoro-6-vinylbenzene and sodium 4-vinylbenzenesulfonate the standard reaction conditions generated deuterium-
1
failed to furnish the desired products (i.e., 2t and 2u, respec- labeled product 3a in 70% yield. The H spectrum for this
tively) because of their strong electron-withdrawing substit- product displayed no signals in the range of δ = 2.0–
uents. These results demonstrate that the electronic proper- 4.0 ppm, but there was a single resonance at δ = 4.61 ppm.
ties of the substituents on the aromatic ring had consider- This result demonstrates that the methylene hydrogen atoms
able influence on the formation of the target products. To of the β-oxo sulfone came from styrene instead of DMSO.
explore the applicability of this significant method further, Therefore, both the C–S bond cleavage of DMSO and the
we then examined the scope of the sulfoxides. The reaction C–S bond formation to give the β-oxo sulfone took place
of styrene with diethyl sulfoxide afforded the corresponding during the reaction. Second, the reaction of styrene and
product 2v in 66% yield.
DMSO under 18O2 and using the standard conditions af-
forded the 18O-labeled product in 65% yield. This result
illustrates that O2 took part in this reaction, and the oxygen
atom in the product came from O2.
Table 2. Synthesis of 2-(methylsulfonyl)-1-phenylethanones from
substituted styrenes and sulfoxides.[a]
Scheme 1. Isotope labeling experiment.
To obtain some insight into the reaction mechanism, we
performed a kinetic isotope effect study under the reaction
conditions to reveal that the intermolecular kinetic isotope
effect (kH/kD) is 1.25 (see Scheme 2).
Scheme 2. Kinetic isotope effect study.
A radical pathway was supposedly involved in this trans-
formation, and a radical trapping experiment further sup-
ported this assumption (see Scheme 3). This reaction was
greatly inhibited in the presence of TEMPO (2,2,6,6-tet-
ramethyl-1-piperidinyloxy), a well-known radical scavenger,
and this result suggests that the reaction presumably pro-
ceeded through a radical pathway (see radical trapping ex-
periment in the Supporting Information).
[a] Reagents and conditions: styrene (0.2 mmol), DMSO (1.0 mL),
FeCl3 (10 mol-%), and hydrazine hydrate (1.0 mmol) under O2 at
40 °C for 36 h.
Scheme 3. Radical trapping experiment.
To gain insight into the reaction mechanism, we designed
On the basis of the aforementioned results and previous
some experiments (see Scheme 1). The first isotope labeling reports, a plausible mechanism is proposed for the forma-
experiment was conducted to elucidate the origin of the tion of the β-oxo sulfone (see Scheme 4). The reaction may
methylene hydrogen atoms of the β-oxo sulfone, and the be initiated by DMSO and a high-valent iron complex that
second was carried out to verify the source of oxygen atoms. is generated from hydrazine hydrate and FeCl3 to give A
Eur. J. Org. Chem. 2014, 5083–5088
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G. Huang et al.
FULL PAPER
Scheme 4. Plausible mechanistic pathway.
vent and TMS as the internal standard. IR spectra were recorded
with an FTIR spectrometer, and only the major peaks are reported
in cm–1. All new compounds were further characterized by HRMS,
through an oxidative cleavage under O2, in which the
methyl group of DMSO is eliminated.[23] In this procedure,
hydrazine hydrate acts as a ligand. Methanesulfinic acid (A)
then undergoes a reaction with hydrazine to release the free
sulfinyl anion B, which could be further oxidized by oxygen
through a single-electron transfer (SET) to induce the for-
mation of oxygen-centered radical C and its resonance
structure sulfonyl radical D.[24] Moreover, the addition of
radical D to styrene (1a) affords carbon-centered radical E,
which is trapped by O2 under diffusion control to give the
corresponding peroxyl radical F, and a hydrogen atom from
hydrazine is abstracted. The obtained hydroperoxyl com-
pound is then dehydrated to give the product ketone.
To rationalize this possible mechanism, we carried out
an additional experiment with methanesulfinic acid and
styrene as substrates under the optimized conditions and
obtained β-oxo sulfone. As a result, we assume that meth-
anesulfinic acid is an intermediate in this transformation.
Nevertheless, the applications of the reaction are wider with
sulfoxide than sulfinic acid, and because of this, the sulfox-
ide is employed in the C–S bond cleavage, a process that is
not easy to achieve.
1
and copies of their H and 13C NMR spectra are provided in the
Supporting Information. Commercially available reagents and sol-
vents were used without further purification. CCDC-960134 (for
2a) contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_
request/cif.
Typical Procedure for the Preparation of 2-(Methylsulfonyl)-1-phen-
ylethanone (2a): A test tube was charged with styrene (1a,
0.2 mmol), FeCl3 (0.04 mmol), and DMSO (1 mL). Then, hydraz-
ine hydrate (1.0 mmol) was added, and the resulting mixture was
stirred at 40 °C for 36 h under O2. After cooling to room tempera-
ture, the mixture was diluted with ethyl acetate (10 mL), and the
resulting solution was washed with brine (5 mL) and dried with
anhydrous Na2SO4. After the solvent had been evaporated in
vacuo, the residue was purified by column chromatography (petro-
leum ether/EtOAc) to afford pure 2a (see Figure 1).
Conclusions
We have developed the first general method for the for-
mation of β-oxo sulfones that proceeds through a C–S bond
cleavage and formation. The procedure tolerates a wide
range of functional groups and employs an inexpensive and
nontoxic iron catalyst. The new synthetic approach pro-
ceeds without additional initiators and forms a new C–S
bond by using DMSO as the substrate. These factors make
this transformation sustainable and flexible. Further studies
to clearly understand the reaction mechanism and the syn-
thetic applications are ongoing by our group.
Figure 1. X-ray crystal structure of 2a.
Characterization Data of Compounds 2:
2-(Methylsulfonyl)-1-phenylethanone (2a): Yellow solid (29 mg,
1
72%); m.p. 86–90 °C. H NMR (400 MHz, CDCl3): δ = 8.00 (dd,
J = 8.8 Hz, J = 1.2 Hz, 2 H), 7.68–7.64 (m, 1 H), 7.55–7.51 (m, 2
Experimental Section
H), 4.62 (s, 2 H), 3.16 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
General Methods: Column chromatography was carried out on sil-
ica gel. The 1H NMR spectroscopic data were recorded at
400 MHz, and CDCl3 was used as the solvent. The 13C NMR spec-
troscopic data were recorded at 100 MHz with CDCl3 as the sol-
δ = 189.2, 135.6, 134.7, 129.2, 129.0, 61.2, 41.8 ppm. IR (neat): ν
˜
= 3333, 3023, 2998, 2949, 2929, 1675, 1616, 1597, 1301, 1219, 1152,
1118, 1006, 964, 907, 734, 689, 583, 495, 455 cm–1. HRMS (ESI):
calcd. for C9H11O3S [M + H]+ 199.0429; found 199.0431.
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FeIII-Catalyzed Aerobic Oxidation and Cleavage/Formation of a C–S Bond
1-(4-Methoxyphenyl)-2-(methylsulfonyl)ethanone (2b): Yellow solid
8.14 (s, 1 H), 7.93 (d, J = 7.6 Hz, 1 H), 7.79 (d, J = 8.0 Hz, 1 H),
1
(37 mg, 82%); m.p. 132–138 °C. H NMR (400 MHz, CDCl3): δ = 7.42 (t, J = 8.0 Hz, 1 H), 4.58 (s, 2 H), 3.16 (s, 3 H) ppm. 13C
7.98 (d, J = 8.8 Hz, 2 H), 6.98 (d, J = 8.8 Hz, 2 H), 4.55 (s, 2 H),
3.89 (s, 3 H), 3.13 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 187.3, 164.8, 131.8, 128.7, 114.3, 61.2, 55.6, 41.7 ppm. IR (neat):
NMR (100 MHz, CDCl3): δ = 188.1, 137.5, 132.0, 130.6, 128.8,
127.9, 123.4, 61.2, 41.8 ppm. IR (neat): ν = 3287, 2957, 2927, 2852,
˜
1725, 1567, 1422, 1318, 1209, 1127, 1074, 967, 909, 733, 648,
447 cm–1. HRMS (ESI): calcd. for C9H10BrO3S [M + H]+ 276.9534;
found 276.9536.
ν = 3350, 3051, 3017, 2973, 2923, 1603, 1572, 1513, 1450, 1422,
˜
1300, 1263, 1176, 1128, 1028, 976, 911, 830, 797, 766, 735,
500 cm–1. HRMS (ESI): calcd. for C10H13O4S [M + H]+ 229.0535;
found 229.0538.
1-(3-Chlorophenyl)-2-(methylsulfonyl)ethanone (2k): Yellow solid
(26 mg, 56%); m.p. 88–97 °C. 1H NMR (400 MHz, CDCl3): δ =
7.98 (s, 1 H), 7.88 (d, J = 8.0 Hz, 1 H), 7.62 (d, J = 9.2 Hz, 1 H),
1-[4-(tert-Butyl)phenyl]-2-(methylsulfonyl)ethanone (2c): Yellow li-
1
quid (41 mg, 80%). H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 7.45 (t, J = 8.0 Hz, 1 H), 4.56 (s, 2 H), 3.14 (s, 3 H) ppm. 13C
8.4 Hz, 2 H), 7.53 (d, J = 8.4 Hz, 2 H), 4.58 (s, 2 H), 3.15 (s, 3 H),
NMR (100 MHz, CDCl3): δ = 186.9, 135.2, 134.5, 130.2, 129.4,
1.35 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 188.7, 158.9, 127.4, 126.9, 62.2, 41.8 ppm. IR (neat): ν = 3281, 2953, 2926, 2851,
˜
133.1, 129.3, 126.1, 61.3, 41.8, 35.2, 30.9 ppm. IR (neat): ν = 3615,
1724, 1561, 1421, 1308, 1200, 1124, 1070, 966, 901, 734, 640,
441 cm–1. HRMS (ESI): calcd. for C9H10ClO3S [M + H]+ 233.0039;
found 233.0040.
˜
3335, 2963, 2909, 1677, 1604, 1464, 1410, 1365, 1314, 1219, 1130,
1105, 969, 900, 853, 802, 734, 540, 514, 484, 458 cm–1. HRMS
(ESI): calcd. for C13H19O3S [M + H]+ 255.1055; found 255.1058.
2-(Methylsulfonyl)-1-(o-tolyl)ethanone (2l): Yellow solid (30 mg,
1
2-(Methylsulfonyl)-1-(p-tolyl)ethanone (2d): Yellow solid (31 mg,
71%); m.p. 92–98 °C. H NMR (400 MHz, CDCl3): δ = 8.07 (d, J
1
73%); m.p. 110–114 °C. H NMR (400 MHz, CDCl3): δ = 7.90 (d,
= 8.0 Hz, 1 H), 7.47–7.43 (m, 1 H), 7.29–7.24 (m, 2 H), 4.55 (s, 2
J = 8.0 Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H), 4.59 (s, 2 H), 3.15 (s, H), 3.05 (s, 3 H), 2.67 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
3 H), 2.44 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 188.7,
δ = 191.5, 141.4, 132.9, 131.9, 131.6, 128.4, 125.9, 62.1, 42.1,
146.0, 133.1, 129.7, 129.4, 61.1, 41.7, 21.8 ppm. IR (neat): ν = 3042,
22.1 ppm. IR (neat): ν = 3277, 2942, 2917, 2852, 1724, 1563, 1432,
˜
˜
3018, 2960, 2932, 2915, 1687, 1604, 1298, 1206, 1220, 1189, 1175,
1126, 979, 901, 814, 733, 522, 462 cm–1. HRMS (ESI): calcd. for
C10H13O3S [M + H]+ 213.0585; found 213.0589.
1328, 1219, 1107, 1034, 957, 905, 731, 644, 443 cm–1. HRMS (ESI):
calcd. for C10H13O3S [M + H]+ 213.0585; found 213.0588.
1-(2-Chlorophenyl)-2-(methylsulfonyl)ethanone (2m): Yellow liquid
(28 mg, 61%). 1H NMR (400 MHz, CDCl3): δ = 7.67 (dd, J =
7.6 Hz, J = 1.2 Hz, 1 H), 7.50–7.46 (m, 2 H), 7.43–7.39 (m, 1 H),
1-(4-Fluorophenyl)-2-(methylsulfonyl)ethanone (2e): Yellow solid
1
(25 mg, 58%); m.p. 92–100 °C. H NMR (400 MHz, CDCl3): δ =
8.07–8.04 (m, 2 H), 7.23–7.18 (m, 2 H), 4.59 (s, 2 H), 3.15 (s, 3 H) 4.67 (s, 2 H), 3.19 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
ppm. 13C NMR (100 MHz, CDCl3): δ = 187.6, 167.9, 165.4, 132.2,
= 191.5, 137.2, 133.6, 130.8, 130.5, 128.9, 127.4, 64.4, 42.2 ppm.
132.13, 132.05, 132.0, 116.5, 116.4, 116.3, 116.2, 61.3, 41.7 ppm.
IR (neat): ν = 2956, 2928, 2872, 2854, 1726, 1589, 1434, 1320, 1127,
˜
IR (neat): ν = 3325, 3112, 3073, 3018, 2958, 2931, 1671, 1595, 1508,
1072, 967, 910, 733, 649, 496, 458 cm–1. HRMS (ESI): calcd. for
C9H10ClO3S [M + H]+ 233.0039; found 233.0042.
˜
1420, 1311, 1235, 1167, 1134, 969, 910, 860, 797, 733, 568, 512,
488, 405 cm–1. HRMS (ESI): calcd. for C9H10FO3S [M + H]+
217.0335; found 217.0340.
2-(Methylsulfonyl)-1-(2,4,5-trimethoxyphenyl)ethanone (2n): Yellow
solid (48 mg, 84%); m.p. 122–134 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.32 (s, 1 H), 6.49 (s, 1 H), 4.64 (s, 2 H), 3.98 (s, 3 H),
3.93 (s, 3 H), 3.88 (s, 3 H), 3.17 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 187.9, 158.6, 155.7, 143.5, 117.3, 108.9, 95.9, 62.6,
1-(4-Bromophenyl)-2-(methylsulfonyl)ethanone (2f): Yellow solid
1
(35 mg, 63%); m.p. 134–139 °C. H NMR (400 MHz, CDCl3): δ =
7.87 (d, J = 8.4 Hz, 2 H), 7.68 (d, J = 8.4 Hz, 2 H), 4.56 (s, 2 H),
3.14 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 188.3, 134.4, 56.2, 56.15, 56.12, 31.1 ppm. IR (neat): ν = 3335, 3036, 2962, 1678,
˜
132.4, 130.7, 130.4, 61.4, 41.7 ppm. IR (neat): ν = 3331, 2955, 2921,
1590, 1508, 1480, 1421, 1342, 1280, 1220, 1165, 1122, 1092, 1024,
1016, 988, 900, 836, 764, 620, 521, 470 cm–1. HRMS (ESI): calcd.
for C12H17O6S [M + H]+ 289.0746; found 289.0749.
˜
2852, 1672, 1581, 1459, 1400, 1293, 1213, 1160, 1108, 1067, 1024,
997, 966, 894, 796, 714, 581, 502, 462 cm–1. HRMS (ESI): calcd.
for C9H10BrO3S [M + H]+ 276.9534; found 276.9538.
1-(2,5-Dimethylphenyl)-2-(methylsulfonyl)ethanone (2o): Yellow so-
1
1-(4-Chlorophenyl)-2-(methylsulfonyl)ethanone (2g): Yellow solid
lid (34 mg, 76%); m.p. 100–104 °C. H NMR (400 MHz, CDCl3):
1
(31 mg, 66%); m.p. 122–128 °C. H NMR (400 MHz, CDCl3): δ =
δ = 7.57 (s, 1 H), 7.28 (d, J = 10.4 Hz, 1 H), 7.19 (d, J = 7.6 Hz, 1
7.83 (d, J = 8.4 Hz, 2 H), 7.52 (d, J = 8.4 Hz, 2 H), 4.49 (s, 2 H),
H), 4.56 (s, 2 H), 3.18 (s, 3 H), 2.50 (s, 3 H), 2.39 (s, 3 H) ppm.
3.15 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 190.9, 131.6, 13C NMR (100 MHz, CDCl3): δ = 191.7, 136.9, 135.8, 135.5, 133.9,
130.9, 129.5, 129.4, 61.3, 41.7 ppm. IR (neat): ν = 3327, 3014, 2955,
132.4, 130.7, 63.2, 42.0, 21.2, 20.9 ppm. IR (neat): ν = 3349, 3038,
˜
˜
2924, 2853, 1676, 1596, 1448, 1418, 1306, 1215, 1123, 1117, 1109,
966, 909, 821, 734, 687, 651, 585, 512, 456 cm–1. HRMS (ESI):
calcd. for C9H10ClO3S [M + H]+ 233.0039; found 233.0044.
3013, 2962, 2949, 2926, 1684, 1496, 1306, 1230, 1153, 1137, 1112,
1017, 982, 967, 807, 499, 445 cm–1. HRMS (ESI): calcd. for
C11H15O3S [M + H]+ 227.0742; found 227.0739.
2-(Methylsulfonyl)-1-(m-tolyl)ethanone (2i): Yellow solid (28 mg,
2-(Methylsulfonyl)-1-[3-(trifluoromethyl)phenyl]ethanone (2p): Yel-
65%); m.p. 112–116 °C. 1H NMR (400 MHz, CDCl3): δ = 7.93– low solid (32 mg, 60%); m.p. 88–92 °C. 1H NMR (400 MHz,
7.91 (m, 2 H), 7.40 (d, J = 7.6 Hz, 1 H), 7.34 (t, J = 8.0 Hz, 1 H), CDCl3): δ = 8.27 (s, 1 H), 8.21 (d, J = 8.0 Hz, 1 H), 7.93 (d, J =
4.55 (s, 2 H), 3.14 (s, 3 H), 2.40 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 182.8, 138.3, 134.6, 130.7, 129.3, 128.3, 127.4, 61.2,
7.6 Hz, 1 H), 7.71 (t, J = 8.0 Hz, 1 H), 4.64 (s, 2 H), 3.17 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 188.2, 136.0, 132.5, 131.0,
41.8, 21.2 ppm. IR (neat): ν = 3327, 3014, 2958, 2921, 2851, 1687,
129.8, 126.0, 125.9, 61.3, 41.8 ppm. IR (neat): ν = 3632, 3548, 3348,
˜
˜
1596, 1451, 1421, 1311, 1208, 1128, 1106, 1101, 964, 901, 820, 734,
687, 651, 583, 511, 452 cm–1. HRMS (ESI): calcd. for C10H13ClO3S
[M + H]+ 213.0585; found 213.0588.
3013, 2963, 2928, 2865, 1684, 1568, 1496, 1451, 1408, 1306, 1229,
1115, 1015, 967, 908, 808, 733, 649, 604, 498, 465, 447 cm–1. HRMS
(ESI): calcd. for C10H10F3O3S [M + H]+ 267.0303; found 267.0300.
1-(3-Bromophenyl)-2-(methylsulfonyl)ethanone (2j): Yellow solid
(29 mg, 53%); m.p. 91–96 °C. 1H NMR (400 MHz, CDCl3): δ =
1-(Benzo[d][1,3]dioxol-5-yl)-2-(methylsulfonyl)ethanone (2q): Yellow
solid (34 mg, 71%); m.p. 128–132 °C. 1H NMR (400 MHz,
Eur. J. Org. Chem. 2014, 5083–5088
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5087

G. Huang et al.
FULL PAPER
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CDCl3): δ = 7.41–7.39 (m, 1 H), 7.32 (s, 1 H), 6.92 (d, J = 8.0 Hz,
1 H), 6.06 (s, 2 H), 4.59 (s, 2 H), 3.18 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 190.2, 153.0, 148.6, 131.8, 128.5, 108.3,
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106.8, 102.0, 59.9, 42.6 ppm. IR (neat): ν = 3068, 3013, 2852, 2972,
˜
2848, 1670, 1664, 1598, 1511, 1495, 1423, 1323, 1267, 1113, 1030,
925, 882, 810, 745, 721, 613, 554, 468 cm–1. HRMS (ESI): calcd.
for C10H11O5S [M + H]+ 243.0327; found 243.0331.
2-(Methylsulfonyl)-1-(naphthalen-1-yl)ethanone (2r): Yellow solid
(29 mg, 59%); m.p. 86–90 °C. 1H NMR (400 MHz, CDCl3): δ =
8.76 (d, J = 8.4 Hz, 1 H), 8.11–8.08 (m, 2 H), 7.92 (d, J = 8.0 Hz,
1 H), 7.69–7.65 (m, 1 H), 7.61–7.56 (m, 2 H), 4.72 (s, 2 H), 3.24 (s,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 191.6, 131.1, 130.1,
130.9, 129.0, 128.9, 128.8, 128.7, 127.0, 125.4, 124.4, 64.0,
42.1 ppm. IR (neat): ν = 3332, 3059, 2955, 2927, 2871, 2852, 1676,
˜
1596, 1576, 1507, 1435, 1381, 1289, 1131, 1076, 948, 909, 795, 770,
733, 649, 582, 562, 504, 436 cm–1. HRMS (ESI): calcd. for
C13H13O3S [M + H]+ 249.0585; found 249.0588.
2-(Ethylsulfonyl)-1-phenylethanone (2v): Yellow solid (28 mg, 66%);
m.p. 92–98 °C. 1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J =
7.2 Hz, 2 H), 7.62 (t, J = 7.6 Hz, 1 H), 7.51–7.47 (m, 2 H), 4.59 (s,
2 H), 3.10 (q, J = 14.8 Hz, J = 7.6 Hz, 2 H), 1.35 (t, J = 7.6 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 189.2, 135.5, 134.7,
129.2, 129.0, 61.2, 48.8, 11.8 ppm. IR (neat): ν = 3330, 3049, 2995,
˜
2947, 2929, 1727, 1676, 1596, 1311, 1225, 1161, 1016, 968, 909,
733, 694, 582, 504, 436 cm–1. HRMS (ESI): calcd. for C10H13O3S
[M + H]+ 213.0585; found 213.0587.
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A. R. Touati, T. Homri, B. B. Hassine, Tetrahedron: Asymmetry
1999, 10, 1369.
Deuterated 2-(Methylsulfonyl)-1-phenylethanone (3a): Yellow solid
(25 mg, 62%). 1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J =
7.2 Hz, 2 H), 7.67–7.65 (m, 1 H), 7.56–7.52 (m, 2 H), 4.61 (s, 2 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 189.2, 135.5, 134.7, 129.2,
129.0, 61.2, 42.1 ppm.
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of the products.
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Acknowledgments
We are grateful for financial support by the State Key Laboratory
of Applied Organic Chemistry.
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Received: April 8, 2014
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Published Online: June 26, 2014
5088
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5083–5088