Base-Mediated synthesis of 1-aryl-4-(phenylsulfonyl)butan-1-ones from 1,2-bis(phenylsulfonyl)ethane and ketones

Article abstract of DOI:10.1055/s-0033-1338557

A new, simple, base-mediated addition reaction of 1,2-bis(phenylsulfonyl) ethane to ketones has been developed for the synthesis of 1-aryl-4- (phenylsulfonyl)butan-1-ones. This method represents the first example of preparing sulfones using 1,2-bis(phenylsulfonyl)ethane as the sulfone resource.

Full text of DOI:10.1055/s-0033-1338557

PAPER
▌203
paper
Base-Mediated Synthesis of 1-Aryl-4-(phenylsulfonyl)butan-1-ones from
1,2-Bis(phenylsulfonyl)ethane and Ketones
Synthesis of 1-Aryl-4-(phenylsulfonyl)butan-1-ones
Ye-Xiang Xie, Ren-Jie Song,* Yu Liu, Zhi-Qiang Wang, Jian-Nan Xiang,* Jin-Heng Li*
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University,
Changsha 410082, P. R. of China
Fax +86(731)88713642; E-mail: jhli@hnu.edu.cn; E-mail: srj0731@hnu.edu.cn; E-mail: jnxiang@hnu.edu.cn
Received: 20.08.2013; Accepted after revision: 23.10.2013
not been reported. Herein, we wish to report a new ap-
proach to sulfones via base-mediated addition of 1,2-
bis(phenylsulfonyl)ethane with ketones; this simple and
selective approach expands the scope to common ketones
and involves the use of the commercial available 1,2-
bis(phenylsulfonyl)ethane instead of vinyl sulfones
for the preparation of new functionalized sulfones
[Scheme 1 (b)].8
Abstract: A new, simple, base-mediated addition reaction of 1,2-
bis(phenylsulfonyl)ethane to ketones has been developed for the
synthesis of 1-aryl-4-(phenylsulfonyl)butan-1-ones. This method
represents the first example of preparing sulfones using 1,2-bis(phe-
nylsulfonyl)ethane as the sulfone resource.
Key words: base, addition, 1,2-bis(phenylsulfonyl)ethane, ketones,
sulfones
The reaction between 1,2-bis(phenylsulfonyl)ethane (1a)
and 2-phenoxy-1-phenylethanone (2a) was initially inves-
tigated to optimize the reaction conditions, and the results
are summarized in Table 1. To our delight, treatment of
substrate 1a with ketone 2a and potassium tert-butoxide
successfully afforded the desired product 3 in 65% yield
(entry 1). Screening revealed that the amount of potassi-
um tert-butoxide affected the reaction, and the reaction
using two equivalents of potassium tert-butoxide gave the
best results (entries 1–4): while moderate yields of 3 were
obtained using two or three equivalents of potassium tert-
butoxide, the yield was lowered to 37% using one equiv-
alent of potassium tert-butoxide and to 12% yield using
0.2 equivalents of potassium tert-butoxide. Among the re-
action temperatures examined, the viable temperature was
120 °C (entry 1 vs. 5 and 6). A series of bases, such as ce-
sium carbonate, potassium carbonate, cesium fluoride,
Sulfones are important units found in organic materials,
bioactive molecules, and pharmaceuticals (Figure 1),1
they also serve widely as valuable intermediates in syn-
thetic chemistry.1–3 As a result, considerable effort has
been paid to the development of new and efficient meth-
ods for sulfone synthesis. Generally, conjugate addition of
carbon nucleophiles to vinyl sulfones is one of the most
important accesses to various sulfones by a carbon–car-
bon bond-forming process.4–7 In this context, the Brønsted
base-catalyzed Michael addition of α-carbon nucleophiles
in carbonyl compounds with vinyl sulfones is particularly
popular [Scheme 1 (a)].6,7 Despite impressive progress in
this field, the methods are limited to aldehydes, imines,
and other activated α-C–H bond-containing reagents (of-
ten 1,3-dicarbonyl compounds); moreover, examples of
using common ketones as the carbon nucleophiles have
O
O
OH
HO2C
O
H
O
O
ABz
O
O
S
S
ABz
S
Me
R
tBu
O
N
HN
H2N
S
O
NH
NHAc
O
CO2K
O
OH
1 (penem sulfoxide)
2
3 (oligonucleotide analogue)
Cl
O
O
O
S
Ph
Me
N
O
S
O
O
S
O
N
R1
R2
H2N
NH2
4 (chalcone-based sulfones)
5 (dapsone)
6 (etoricoxib)
Figure 1 Examples of important sulfones
SYNTHESIS 2014, 46, 0203–0211
Advanced online publication: 14.11.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338557; Art ID: SS-2013-H0578-OP
© Georg Thieme Verlag Stuttgart · New York

204
Y.-X. Xie et al.
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(a) reported work (refs. 6 and 7)
R1
Y
R2
Y
R2
EWG
Brønsted base
+
EWG
SO2Ph
H
SO2Ph
H
R1
EWG = aldehyde, imine, ketone (R2 = EWG), ester (R2 = EWG)
Y = H, SO2Ph
(b) this work
O
O
Ph
O
R2
S
R2
KOtBu
O
SO2Ph
+
R3
O
R3
toluene, 120 °C
S
R1
R1
O
Ph
2
1a
Scheme 1 Synthesis of sulfones
Table 1 Screening Optimal Conditionsa
and lithium hexamethyldisilazanide, were also evaluated,
and they were all less effective than potassium tert-butox-
ide (entry 1 vs. 6–10). Notably, the effect of the solvent
played an important role in the reaction (entry 1 vs. 11–
13): a series of solvents, including acetonitrile, 1,2-dichlo-
roethane, and N,N-dimethylformamide, were examined,
and they were less effective.
O
O
SO2Ph
base
OPh
SO2Ph
+
Ph
Ph
PhO2S
OPh
3
1a
2a
Entry
Base (equiv)
Solvent
T ( °C) Isolated yield (%)
With the optimal conditions in hand, we next set out to ex-
plore the scope of the ketone 2 with respect to 1,2-bis(phe-
nylsulfonyl)ethane (1a) (Table 2). Initially, a variety of 1-
aryl-2-aryloxyethanones 2b–n were investigated, and
they were compatible with the optimal conditions (entries
1–13). The results demonstrated that substituents, such as
methyl, methoxy, chloro, or iodo groups, on the aromatic
ring of the aryloxy moiety were well tolerated (entries 1–
6). For example, substrate 2f with a chloro group reacted
with 1,2-bis(phenylsulfonyl)ethane (1a) smoothly, pro-
viding the target product 8 in 67% yield (entry 5). To our
delight, 2-(naphthalen-1-yloxy)-1-phenylethanone (2h)
reacted with 1a to give 10 in 64% yield (entry 7). Exten-
sive screening revealed that substituents, either electron-
donating or electron-withdrawing groups, on the aromatic
ring of the arylethanone moiety were also tolerated (en-
tries 8–12). Using substrate 2l bearing a bulky 2-methoxy
group in the presence of 1a and potassium tert-butoxide,
for instance, gave a good yield of product 14 (entry 11).
Interestingly, 2-phenoxy-1-phenylpropan-1-one (2n) was
also viable in the reaction (entry 13). Notably, two other
acetophenones 2o and 2p, with a CO2Et or CN group at
the α-position, reacted successfully with 1a and potassium
tert-butoxide, furnishing the corresponding products 17
and 18 in 73% and 27% yields, respectively (entries 14
and 15). We were happy to find that reaction of acetophe-
none (2q), a common ketone, with 1a was successful un-
der the optimal conditions (entry 16). It is noteworthy that
1
KOt-Bu (2.0)
KOt-Bu (3.0)
KOt-Bu (1.0)
KOt-Bu (0.2)
KOt-Bu (2.0)
KOt-Bu (2.0)
Cs2CO3 (2.0)
K2CO3 (2.0)
CsF (2.0)
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
120
120
120
120
100
80
65
63
37
12
46
29
61
52
24
59
48
22
trace
2
3
4
5
6
7
120
120
120
120
120
120
120
8
9
10
11
12
13
LiHMDS (2.0) toluene
KOt-Bu (2.0)
KOt-Bu (2.0)
KOt-Bu (2.0)
MeCN
DCE
DMF
a Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), solvent (2 mL),
36 h.
scope of this current protocol can be expanded to benzo-
furan-3(2H)-one (2r), a heterocyclic compounds, which
makes the application of this methodology more attractive
in organic synthesis (entry 17).
Synthesis 2014, 46, 203–211
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Synthesis of 1-Aryl-4-(phenylsulfonyl)butan-1-ones
205
Table 2 Addition of 1,2-Bis(phenylsulfonyl)ethane (1a) to Ketones 2a
O
O
Ph
O
O
R2
S
R2
KOtBu
SO2Ph
+
R3
O
R3
toluene, 120 °C
S
R1
R1
O
Ph
1a
2
Entry
Substrate 2
Product
Isolated yield (%)
PhO2S
O
O
1
45
O
O
2b
4
PhO2S
O
O
2
3
4
5
6
7
56
O
O
2c
5
PhO2S
OMe
O
O
59
O
OMe
O
2d
6
PhO2S
O
O
O
OMe
54
67
67
64
O
OMe
2e
7
PhO2S
Cl
O
O
O
Cl
O
2f
8
PhO2S
I
O
O
O
O
I
2g
9
PhO2S
O
O
O
O
2h
10
© Georg Thieme Verlag Stuttgart · New York
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Table 2 Addition of 1,2-Bis(phenylsulfonyl)ethane (1a) to Ketones 2a (continued)
O
O
Ph
O
O
R2
S
R2
KOtBu
SO2Ph
+
R3
O
R3
toluene, 120 °C
S
R1
R1
O
Ph
1a
2
Entry
Substrate 2
Product
Isolated yield (%)
PhO2S
O
O
8
74
O
O
2i
11
PhO2S
O
O
O
9
71
69
89
76
O
2j
12
PhO2S
MeO
O
O
O
10
11
12
O
MeO
2k
13
PhO2S
O
O
OMe
O
OMe
O
2l
14
PhO2S
O
O
O
O
F
F
2m
15
PhO2S
O
O
13
14
81
73
O
O
2n
2o
16
O
CO2Et
CO2Et
SO2Ph
O
17
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Synthesis of 1-Aryl-4-(phenylsulfonyl)butan-1-ones
207
Table 2 Addition of 1,2-Bis(phenylsulfonyl)ethane (1a) to Ketones 2a (continued)
O
O
Ph
O
O
R2
S
R2
KOtBu
SO2Ph
+
R3
O
R3
toluene, 120 °C
S
R1
R1
O
Ph
1a
2
Entry
15
Substrate 2
Product
Isolated yield (%)
O
CN
CN
27
SO2Ph
O
2p
18
SO2Ph
O
16
46
46
SO2Ph
SO2Ph
O
2q
19
20
O
O
17
O
SO2Ph
O
2r
a Reaction conditions: 1a (0.2 mmol), 2 (0.3 mmol), KOt-Bu (2.0 equiv), toluene (2 mL), 120 °C, 36 h.
With 2-(2-iodophenoxy)-1-phenyl-4-(phenylsulfonyl)bu- lowed by intramolecular cyclization of compound 21 in
tan-1-one (9) in hand, we turned our attention to the appli- the presence of iron(III) chloride9 resulted in naphthalen-
cation of this product in the synthesis of naphthalene 1-ol 22 in 36% yield.
derivatives (Scheme 2). Treatment of 9 with phenylacety-
lene, PdCl2(MeCN)2, and copper(I) iodide afforded the
corresponding Sonogashira product 21 in 89% yield, fol-
A possible mechanism for the reaction of 1a with ketones
2 is presented in Scheme 3.7,8 In the presence of a base, an-
ion intermediate A can be readily obtained from a ketone.
Ph
Ph
Ph
I
PdCl2(MeCN)2
CuI
FeCl3 (20 mol%)
KOAc, 4 A MS
Ph
O
Ph
OH
O
Et3N, THF, r.t.
89%
MeCN
120 °C, 24 h
O
O
OH
SO2Ph
SO2Ph
36%
SO2Ph
9
21
22
Scheme 2 Application of product 9
SO2Ph
PhO2S
SO2Ph
1a
– PhSO2
SO2Ph
O
+
O
O
KOtBu
– H
C
SO2Ph
B
OPh
Ph
OPh
Ph
Ph
OPh
2a
A
3
Scheme 3 Possible mechanism
© Georg Thieme Verlag Stuttgart · New York
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13C NMR (125 MHz, CDCl3): δ = 197.3, 154.9, 138.8, 134.2, 133.9
(2 C), 131.4, 130.1, 129.4, 129.0, 128.8, 127.9, 115.1, 77.7, 52.0,
26.0, 20.4.
LRMS (EI, 70 eV): m/z (%) = 396 (1), 394 (M+, 5), 289 (14), 147
(100).
HRMS (ESI): m/z [M + Na]+ calcd for C23H22O4SNa: 417.1131;
found: 417.1115.
Intermediate A then undergoes addition to sulfone cation
B and vinyl sulfone C, generated in situ from 1,2-bis(phe-
nylsulfonyl)ethane (1a) with the aid of a base, to afford
the desired product 3. Notably, vinyl sulfone C was ob-
served by in situ GC-MS analysis of the reaction between
1,2-bis(phenylsulfonyl)ethane (1a) and 2-phenoxy-1-
phenylethanone (2a).
1-Phenyl-4-(phenylsulfonyl)-2-(o-tolyloxy)butan-1-one (5)
In summary, we have illustrated the first example of the
preparation of sulfones using 1,2-bis(phenylsulfonyl)eth-
ane as the sulfone source. In presence of potassium tert-
butoxide, a variety of ketones were treated with 1,2-
bis(phenylsulfonyl)ethane to afford the corresponding 1-
aryl-4-(phenylsulfonyl)butan-1-one in moderate to good
yields. Notably, this method is simple and general with a
wide range of compatible ketones, which opens a new
route for the synthesis of important sulfones.
Colorless oil; yield: 44.1 mg (56%).
IR (KBr): 1716, 1652, 1558 cm–1.
1H NMR (500 MHz, CDCl3): δ = 8.03 (d, J = 7.5 Hz, 2 H), 7.90 (d,
J = 7.0 Hz, 2 H), 7.65–7.61 (m, 2 H), 7.60–7.53 (m, 2 H), 7.48 (t,
J = 7.5 Hz, 2 H), 7.12–7.02 (m, 1 H), 6.99 (t, J = 7.5 Hz, 1 H), 6.84
(t, J = 7.5 Hz, 1 H), 6.55 (d, J = 7.0 Hz, 1 H), 5.61–5.58 (m, 1 H),
3.48–3.36 (m, 2 H), 2.54–2.51 (m, 1 H), 2.46–2.42 (m, 1 H), 2.22
(s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 197.0, 154.8, 138.6, 134.0, 133.8,
131.0, 129.3, 128.9, 128.5, 127.8, 126.8, 126.7, 121.4, 111.4, 77.2,
51.9, 26.0, 16.3.
LRMS (EI, 70 eV): m/z (%) = 396 (1), 394 (M+, 8), 289 (13), 147
(100).
HRMS (ESI): m/z [M + Na]+ calcd for C23H22O4SNa: 417.1131;
found: 417.1118.
NMR spectroscopy was performed on a Bruker Avance spectrome-
ter operating at 500 MHz (1H NMR) and 125 MHz (13C NMR) or
400 MHz (1H NMR) and 100 MHz (13C NMR). Mass spectrometric
analysis was performed on GC-MS analysis (Shimadzu GCMS-
QP2010) and ESI-Q-TOF (Bruker MicroQTOF-II. Meltingn points
are uncorrected.
2-(4-Methoxyphenoxy)-1-phenyl-4-(phenylsulfonyl)butan-1-
1-Aryl-4-(phenylsulfonyl)butan-1-ones 3–20; General Proce-
dure
one (6)
Red oil; yield: 48.4 mg (59%).
IR (KBr): 1688, 1508, 1461 cm–1.
To a Schlenk tube were added 1,2-bis(phenylsulfonyl)ethane (1a,
0.2 mmol), ketone 2 (0.3 mmol), KOt-Bu (2.0 equiv), and toluene
(2 mL). Then the tube was stirred at 120 °C (oil bath temperature)
in air for the indicated time until complete consumption of starting
material (TLC and GC-MS monitoring). When the reaction was
complete, the mixture was diluted with Et2O (5 mL), and washed
with brine (3 × 1 mL). The aqueous phase was re-extracted with
Et2O (3 × 2 mL). The combined organic extracts were dried
(Na2SO4) and concentrated in vacuo, and the resulting residue was
purified by column chromatography (silica gel, n-hexane–EtOAc,
10:1) to afford the product.
1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 8.0 Hz, 2 H), 7.90 (d,
J = 8.0 Hz, 2 H), 7.64–7.61 (m, 2 H), 7.55 (t, J = 7.6 Hz, 2 H), 7.49
(t, J = 7.6 Hz, 2 H), 6.79–6.73 (m, 4 H), 5.55–5.52 (m, 1 H), 3.71 (s,
3 H), 3.50–3.34 (m, 2 H), 2.54–2.45 (m, 1 H), 2.40–2.31 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 197.3, 154.6, 151.1, 138.8, 134.1,
133.9, 129.4, 128.9, 128.7, 127.9, 116.5, 114.7, 78.3, 55.5, 51.9,
26.0.
LRMS (EI, 70 eV): m/z (%) = 412 (1), 410 (M+, 14), 287 (64), 163
(100).
2-Phenoxy-1-phenyl-4-(phenylsulfonyl)butan-1-one (3)
HRMS (ESI): m/z [M + Na]+ calcd for C23H22O5SNa: 433.1080;
found: 433.1063.
Colorless oil; yield: 49.4 mg (65%).
IR (KBr): 1698, 1653, 1558 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 8.0 Hz, 2 H), 7.90 (d,
J = 7.6 Hz, 2 H), 7.65–7.61 (m, 2 H), 7.57–7.48 (m, 4 H), 7.22 (t,
J = 8.0 Hz, 2 H), 6.95 (t, J = 7.6 Hz, 1 H), 6.81 (d, J = 8.0 Hz, 2 H),
5.63–5.60 (m, 1 H), 3.49–3.34 (m, 2 H), 2.58–2.49 (m, 1 H), 2.44–
2.35 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 197.0, 157.0, 138.8, 134.2, 133.9,
133.8, 129.7, 129.4, 129.0, 128.7, 127.9, 122.0, 115.2, 77.4, 52.0,
26.0.
2-(3-Methoxyphenoxy)-1-phenyl-4-(phenylsulfonyl)butan-1-
one (7)
Red oil; yield: 44.3 mg (54%).
IR (KBr): 1683, 1596 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 7.6 Hz, 2 H), 7.90 (d,
J = 7.6 Hz, 2 H), 7.64–7.61 (m, 2 H), 7.56–7.47 (m, 4 H), 7.09 (t,
J = 8.0 Hz, 1 H), 6.50 (d, J = 8.4 Hz, 1 H), 6.41 (s, 1 H), 6.37 (t,
J = 8.4 Hz, 1 H), 5.64–5.61 (m, 1 H), 3.72 (s, 3 H), 3.45–3.37 (m, 2
H), 2.56–2.48 (m, 1 H), 2.42–2.33 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 196.8, 160.8, 158.1, 138.8, 134.2,
133.9, 133.8, 130.1, 129.4, 129.0, 128.7, 127.9, 107.6, 106.8, 101.7,
55.2, 51.9, 25.9.
LRMS (EI, 70 eV): m/z (%) = 380 (M+, 3), 275 (27), 133 (100).
HRMS (ESI): m/z [M + Na]+ calcd for C22H20O4SNa: 403.0975;
found: 403.0968.
LRMS (EI, 70 eV): m/z (%) = 412 (1), 410 (M+, 14), 287 (64), 163
(100).
HRMS (ESI): m/z [M + Na]+ calcd for C23H22O5SNa: 433.1086;
found: 433.1063.
1-Phenyl-4-(phenylsulfonyl)-2-(p-tolyloxy)butan-1-one (4)
Colorless oil; yield: 35.5 mg (45%).
IR (KBr): 1687, 1643, 1507 cm–1.
1H NMR (500 MHz, CDCl3): δ = 8.05 (d, J = 7.5 Hz, 2 H), 7.90 (d,
J = 7.0 Hz, 2 H), 7.66–7.60 (m, 2 H), 7.55 (t, J = 8.0 Hz, 2 H), 7.50–
7.47 (m, 2 H), 7.00 (d, J = 8.0 Hz, 2 H), 6.72–6.70 (m, 2 H), 5.57–
5.55 (m, 1 H), 3.44–3.36 (m, 2 H), 2.52–2.49 (m, 1 H), 2.40–2.35
(m, 1 H), 2.23 (s, 3 H).
2-(4-Chlorophenoxy)-1-phenyl-4-(phenylsulfonyl)butan-1-one
(8)
Yellow oil; yield: 55.5 mg (67%).
IR (KBr): 1680, 1491 cm–1.
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Synthesis of 1-Aryl-4-(phenylsulfonyl)butan-1-ones
209
1H NMR (500 MHz, CDCl3): δ = 8.04 (d, J = 7.0 Hz, 2 H), 7.91–
7.89 (m, 2 H), 7.66–7.62 (m, 2 H), 7.56–7.49 (m, 4 H), 7.17–7.15
(m, 2 H), 6.75–6.74 (m, 2 H), 5.65–5.63 (m, 1 H), 3.47–3.43 (m, 1
H), 3.37–3.31 (m, 1 H), 2.55–2.53 (m, 1 H), 2.40–2.35 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 196.5, 155.5, 138.7, 134.3, 133.9,
133.5, 129.4, 129.3, 129.0, 128.6, 127.8, 126.8, 116.4, 77.5, 51.7,
25.9.
2-Phenoxy-4-(phenylsulfonyl)-1-p-tolylbutan-1-one (12)
Colorless oil; yield: 55.9 mg (71%).
IR (KBr): 1683, 1558, 1457 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.4 Hz, 2 H), 7.89 (d,
J = 7.6 Hz, 2 H), 7.64 (t, J = 7.6 Hz, 1 H), 7.54 (t, J = 7.6 Hz, 2 H),
7.28 (d, J = 8.0 Hz, 2 H), 7.22–7.19 (m, 2 H), 6.92 (t, J = 7.2 Hz, 1
H), 6.80 (d, J = 8.0 Hz, 2 H), 5.60–5.57 (m, 1 H), 3.49–3.33 (m, 2
H), 2.55–2.47 (m, 1 H), 2.41 (s, 3 H), 2.39–2.33 (m, 1 H).
LRMS (EI, 70 eV): m/z (%) = 416 (1), 414 (M+, 3), 275 (26), 133
13C NMR (100 MHz, CDCl3): δ = 196.5, 157.0, 145.3, 138.8, 133.8,
131.3, 129.7, 129.6, 129.4, 128.8, 127.9, 121.8, 115.1, 77.2, 52.0,
26.1, 21.7.
(100).
HRMS (ESI): m/z [M + Na]+ calcd for C22H19ClO4SNa: 437.0590;
found: 437.0578.
LRMS (EI, 70 eV): m/z (%) = 394 (M+, 5), 275 (32), 133 (100).
HRMS (ESI): m/z [M + Na]+ calcd for C23H22O4SNa: 417.1131;
2-(2-Iodophenoxy)-1-phenyl-4-(phenylsulfonyl)butan-1-one (9)
Yellow oil; yield: 67.8 mg (67%).
found: 417.1118.
IR (KBr): 1696, 1580, 1470 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.07 (d, J = 7.6 Hz, 2 H), 7.93 (d,
J = 8.0 Hz, 2 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.65–7.60 (m, 2 H),
7.55–7.49 (m, 4 H), 7.13 (t, J = 8.0 Hz, 1 H), 6.69 (t, J = 7.6 Hz, 1
H), 6.47 (d, J = 8.0 Hz, 1 H), 5.58–5.55 (m, 1 H), 3.68–3.61 (m, 1
H), 3.51–3.44 (m, 1 H), 2.63–2.55 (m, 1 H), 2.52–2.42 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 196.3, 155.4, 139.7, 138.9, 134.4,
133.9, 133.5, 129.4, 129.1, 128.8, 127.9, 123.6, 112.6, 86.5, 78.7,
52.0, 26.4.
1-(4-Methoxyphenyl)-2-phenoxy-4-(phenylsulfonyl)butan-1-
one (13)
Red oil; yield: 56.6 mg (69%).
IR (KBr): 1683, 1598, 1492 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 8.4 Hz, 2 H), 7.90 (d,
J = 8.0 Hz, 2 H), 7.64 (t, J = 7.5 Hz, 1 H), 7.54 (t, J = 7.5 Hz, 2 H),
7.22–7.19 (m, 2 H), 6.96–6.91 (m, 3 H), 6.80 (d, J = 8.4 Hz, 2 H),
5.54–5.51 (m, 1 H), 3.87 (s, 3 H), 3.46–3.36 (m, 2 H), 2.55–2.47 (m,
1 H), 2.44–2.35 (m, 1 H).
LRMS (EI, 70 eV): m/z (%) = 506 (M+, 7), 401 (32), 259 (84), 105
13C NMR (100 MHz, CDCl3): δ = 195.4, 164.3, 157.0, 138.8, 133.9,
131.2, 129.6, 129.4, 127.9, 126.7, 121.8, 115.1, 114.2, 77.4, 55.5,
52.1, 26.3.
LRMS (EI, 70 eV): m/z (%) = 410 (M+, 7), 275 (22), 135 (100).
HRMS (ESI): m/z [M + Na]+ calcd for C23H22O5SNa: 433.1080;
(100).
HRMS (ESI): m/z [M + Na]+ calcd for C22H19IO4SNa: 528.9941;
found: 528.9927.
2-(Naphthalen-1-yloxy)-1-phenyl-4-(phenylsulfonyl)butan-1-
one (10)
Yellow solid; yield: 55.0 mg (64%); mp 142.4–143.2 °C.
found: 433.1062.
IR (KBr): 1696, 1596, 1578 cm–1.
1-(2-Methoxyphenyl)-2-phenoxy-4-(phenylsulfonyl)butan-1-
one (14)
1H NMR (500 MHz, CDCl3): δ = 8.21 (d, J = 7.5 Hz, 1 H), 8.08 (d,
J = 7.0 Hz, 2 H), 7.90–7.88 (m, 2 H), 7.78–7.76 (m, 1 H), 7.61–7.57
(m, 2 H), 7.51–7.40 (m, 7 H), 7.21 (t, J = 8.0 Hz, 1 H), 6.59 (d,
J = 8.0 Hz, 1 H), 5.77–5.74 (m, 1 H), 3.54–3.43 (m, 2 H), 2.65–2.56
(m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 197.8, 152.6, 138.8, 134.6, 134.2,
133.9, 129.4, 129.0, 128.7, 127.9, 127.5, 126.6, 125.6, 125.4 (2 C),
121.7, 121.6, 105.7, 77.7, 52.1, 26.1.
LRMS (EI, 70 eV): m/z (%) = 432 (2), 430 (M+, 15), 287 (88), 183
(76), 195 (100).
HRMS (ESI): m/z [M + Na]+ calcd for C26H22O4SNa: 453.1131;
found: 453.1126.
Red solid; yield: 73.0 mg (89%); mp 110.1–111.2 °C.
IR (KBr): 1683, 1598, 1492 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.87 (d, J = 7.6 Hz, 2 H), 7.75 (d,
J = 7.6 Hz, 1 H), 7.64 (t, J = 7.6 Hz, 1 H), 7.56–7.52 (m, 3 H), 7.21
(t, J = 7.6 Hz, 2 H), 7.06–7.00 (m, 2 H), 6.92 (t, J = 7.2 Hz, 1 H),
6.78 (t, J = 8.0 Hz, 2 H), 5.80–5.77 (m, 1 H), 3.91 (s, 3 H), 3.40–
3.34 (m, 2 H), 2.57–2.53 (m, 1 H), 2.23–2.14 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 198.0, 158.6, 157.5, 138.9, 134.9,
133.8, 131.4, 129.5, 129.3, 127.9, 125.0, 121.5, 121.3, 115.2, 111.6,
79.7, 55.7, 52.5, 25.0.
LRMS (EI, 70 eV): m/z (%) = 410 (M+, 7), 275 (22), 135 (100).
HRMS (ESI): m/z [M + Na]+ calcd for C23H22O5SNa: 433.1080;
found: 433.1064.
1-(Naphthalen-1-yl)-2-phenoxy-4-(phenylsulfonyl)butan-1-one
(11)
Yellow solid; yield: 63.6 mg (74%); mp 75.4–76.2 °C.
1-(4-Fluorophenyl)-2-phenoxy-4-(phenylsulfonyl)butan-1-one
IR (KBr): 1684, 1653, 1559 cm–1.
(15)
1H NMR (500 MHz, CDCl3): δ = 8.69 (s, 1 H), 8.06 (d, J = 2.0 Hz,
1 H), 8.00 (d, J = 2.0 Hz, 1 H), 7.91–7.87 (m, 4 H), 7.64–7.60 (m, 3
H), 7.53–7.51 (m, 2 H), 7.21–7.19 (m, 2 H), 6.93 (t, J = 7.6 Hz, 1
H), 6.85 (d, J = 8.0 Hz, 2 H), 5.80–5.77 (m, 1 H), 3.55–3.38 (m, 2
H), 2.65–2.42 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 197.0, 157.0, 138.8, 136.0, 133.9,
132.4, 131.0, 130.9, 129.9, 129.7, 129.4, 129.2, 128.9, 127.9, 127.9,
127.8, 127.1, 123.9, 122.0, 115.2, 77.5, 52.0, 26.4.
LRMS (EI, 70 eV): m/z (%) = 432 (1), 430 (M+, 7), 275 (32), 133
(100).
HRMS (ESI): m/z [M + Na]+ calcd for C26H22O4SNa: 453.1131;
found: 453.1119.
Red solid; yield: 60.5 mg (76%); mp 92.9–93.8 °C.
IR (KBr): 1716, 1683, 1558 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.13–8.09 (m, 2 H), 7.90 (d,
J = 8.0 Hz, 2 H), 7.65 (t, J = 7.0 Hz, 1 H), 7.56 (t, J = 7.5 Hz, 2 H),
7.21 (t, J = 8.0 Hz, 2 H), 7.14 (t, J = 7.6 Hz, 2 H), 6.94 (t, J = 7.2
Hz, 1 H), 6.81 (d, J = 8.4 Hz, 2 H), 5.57–5.54 (m, 1 H), 3.48–3.35
(m, 2 H), 2.55–2.35 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 195.6, 167.5, 164.9, 156.8, 138.7,
133.9, 131.6 (2 C), 129.7, 129.4, 127.8, 122.0, 116.3, 116.0, 115.0.
77.6, 51.9, 25.9.
LRMS (EI, 70 eV): m/z (%) = 398 (M+, 2), 275 (18), 133 (100).
HRMS (ESI): m/z [M + Na]+ calcd for C22H19FO4SNa: 421.0880;
found: 421.0866.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 203–211

210
Y.-X. Xie et al.
PAPER
2-Methyl-2-phenoxy-1-phenyl-4-(phenylsulfonyl)butan-1-one
HRMS (ESI): m/z [M + Na]+ calcd for C24H24O5S2Na: 479.0963;
found: 479.0952.
(16)
Colorless oil; yield: 63.8 mg (81%).
2,2-Bis[2-(phenylsulfonyl)ethyl]benzofuran-3(2H)-one (20)
IR (KBr): 1683, 1558, 1457 cm–1.
Yellow solid; yield: 21.6 mg (46%); mp 115.1–116.2 °C.
1H NMR (500 MHz, CDCl3): δ = 8.18 (d, J = 7.0 Hz, 2 H), 7.80 (d,
J = 7.5 Hz, 2 H), 7.61 (t, J = 7.5 Hz, 1 H), 7.51–7.47 (m, 3 H), 7.35
(t, J = 7.5 Hz, 2 H), 7.08 (t, J = 7.5 Hz, 2 H), 6.89 (t, J = 7.5 Hz, 1
H), 6.60 (d, J = 7.5 Hz, 2 H), 3.34–3.22 (m, 2 H), 2.64–2.58 (m, 1
H), 2.35–2.29 (m, 1 H), 1.56 (s, 3 H).
IR (KBr): 1728, 1688 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.84 (d, J = 7.0 Hz, 4 H), 7.69–
7.65 (m, 3 H), 7.60–7.56 (m, 5 H), 7.13–7.08 (m, 2 H), 3.07–3.01
(m, 2 H), 2.91–2.85 (m, 2 H), 2.26–2.14 (m, 4 H).
13C NMR (125 MHz, CDCl3): δ = 200.5, 171.3, 139.3, 138.3, 134.1,
129.5, 128.0, 124.7, 123.0, 120.1, 113.6, 87.7, 50.1, 28.5.
LRMS (EI, 70 eV): m/z (%) = 470 (M+, 1), 133 (100).
HRMS (ESI): m/z [M + Na]+ calcd for C24H22O6S2Na: 493.0756;
13C NMR (125 MHz, CDCl3): δ = 201.1, 154.2, 138.3, 133.9, 133.7,
133.4, 129.8, 129.5, 129.3, 128.5, 127.9, 122.5, 118.3, 85.1, 50.9,
30.8, 22.7.
LRMS (EI, 70 eV): m/z (%) = 394 (M+, 4), 380 (23), 275 (32), 133
(100).
HRMS (ESI): m/z [M + Na]+ calcd for C23H22O4SNa: 417.1137;
found: 417.1130.
found: 493.0743.
1-Phenyl-2-[2-(2-phenylethynyl)phenoxy]-4-(phenylsulfo-
nyl)butan-1-one (21)
Brown oil; yield: 85.4 mg (89%).
Ethyl 2-Benzoyl-4-(phenylsulfonyl)butanoate (17)
Colorless oil; yield: 52.6 mg (73%).
IR (KBr): 1733, 1683, 1457 cm–1.
1H NMR (500 MHz, CDCl3): δ = 8.00–7.98 (m, 2 H), 7.93–7.90 (m,
2 H), 7.68–7.65 (m, 1 H), 7.63–7.56 (m, 3 H), 7.51–7.48 (m, 2 H),
4.67 (d, J = 7.0 Hz, 1 H), 4.14–4.10 (m, 2 H), 3.28–3.19 (m, 2 H),
2.45–2.37 (m, 2 H), 1.14 (t, J = 7.0 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 194.1, 168.8, 138.7, 135.6, 133.9
(2 C), 133.7 (2 C), 129.4, 129.3, 128.8, 128.7, 128.4, 128.0 (2 C),
61.8, 53.4, 51.5, 21.9, 13.8.
1H NMR (500 MHz, CDCl3): δ = 8.07–8.09 (m, 2 H), 7.76–7.78 (m,
2 H), 7.57–7.60 (m, 1 H), 7.42–7.55 (m, 6 H), 7.33–7.39 (m, 5 H),
7.11 (t, J = 7.5 Hz, 1 H), 6.92 (t, J = 7.5 Hz, 1 H), 6.60 (d, J = 8.5
Hz, 1 H), 5.61–5.63 (m, 1 H), 3.58–3.64 (m, 1 H), 3.45–3.51 (m, 1
H), 2.57–2.63 (m, 1 H), 2.44–2.51 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 196.5, 171.0, 157.3, 138.7, 134.2,
133.6, 133.6, 133.4, 131.4, 129.5, 129.2, 128.9, 128.7, 128.3, 128.2,
127.7, 123.2, 121.9, 113.6, 113.5, 93.9, 85.3, 78.6, 60.2, 51.8, 26.2,
20.9, 14.1.
HRMS (ESI): m/z [M + Na]+ calcd for C30H24O4SNa: 503.1293;
found: 503.1280.
LRMS (EI, 70 eV): m/z (%) = 360 (M+, 1), 315 (2), 219 (30), 105
(100).
HRMS (ESI): m/z [M + Na]+ calcd for C19H20O5SNa: 383.0924;
found: 383.0909.
3-(2-Hydroxyphenyl)-4-phenyl-2-[2-(phenylsulfonyl)eth-
yl]naphthalen-1-ol (22)
Yellow solid; yield: 30.8 mg (36%); mp >240 °C.
IR (KBr): 3459, 3422, 2920, 2851 cm–1.
1-Benzoyl-4-(phenylsulfonyl)butanenitrile (18)
Colorless oil; yield: 16.9 mg (27%).
1H NMR (500 MHz, CDCl3): δ = 9.45 (s, 1 H), 9.22 (s, 1 H), 8.27
(d, J = 8.5 Hz, 1 H), 7.65–7.69 (m, 3 H), 7.55–7.58 (m, 2 H), 7.45–
7.46 (m, 1 H), 7.31–7.33 (m, 1 H), 7.20–7.24 (m, 2 H), 7.08–7.13
(m, 3 H), 7.02–7.03 (m, 1 H), 6.83–6.85 (m, 1 H), 6.63–6.64 (m, 1
H), 6.55–6.57 (m, 1 H), 6.43–6.36 (m, 1 H), 3.38–3.44 (m, 1 H),
3.20–3.27 (m, 1 H), 2.68–2.78 (m, 2 H).
IR (KBr): 1699, 1653, 1558 cm–1.
1H NMR (500 MHz, CDCl3): δ = 8.01 (d, J = 1.5 Hz, 2 H), 7.94 (d,
J = 7.0 Hz, 2 H), 7.73–7.68 (m, 2 H), 7.61 (t, J = 7.5 Hz, 2 H), 7.56
(t, J = 8.0 Hz, 2 H), 4.89–4.87 (m, 1 H), 3.41–3.29 (m, 2 H), 2.63–
2.56 (m, 1 H), 2.46–2.38 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 154.4, 149.6, 139.8, 138.6, 137.3,
133.9, 132.4, 131.8, 131.7, 131.4, 131.2, 131.1, 129.9, 129.7, 129.1,
129.0, 128.5, 127.9, 127.6, 127.4, 126.7, 126.6, 126.3, 126.0, 125.0,
124.9, 122.0, 119.5, 118.5, 115.1, 54.1, 31.0, 22.4.
13C NMR (125 MHz, CDCl3): δ = 189.2, 138.5, 138.0, 135.0, 134.6,
134.3, 133.5, 129.7, 129.6, 129.3, 129.2, 129.0, 128.1, 128.0, 116.2,
52.6, 49.5, 37.4, 22.4.
LRMS (EI, 70 eV): m/z (%) = 313 (M+, 5), 285 (5), 208 (5), 105
(100).
LRMS (EI, 70 eV): m/z (%) = 480 (M+, 1), 298 (31), 168 (100).
HRMS (ESI): m/z [M + Na]+ calcd for C30H24O4SNa: 503.1293;
found: 503.1274.
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NO3SNa: 336.0665;
found: 336.0663.
1-Phenyl-4-(phenylsulfonyl)-2-[2-(phenylsulfonyl)ethyl]butan-
1-one (19)
Yellow solid; yield: 21.0 mg (46%); mp 78.1–79.2 °C.
Acknowledgment
We thank the Natural Science Foundation of China (No. 21172060),
Specialized Research Fund for the Doctoral Program of Higher
Education (No. 20120161110041), and Hunan Provincial Natural
Science Foundation of China (No. 13JJ2018) for financial support.
Dr. R.-J. Song also thanks the China Postdoctoral Science Founda-
tion (No. 2012M511716) and Hunan Province Science and Techno-
logy Project (No. 2013RS4026)
IR (KBr): 1732, 1685, 1655 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.89 (d, J = 7.6 Hz, 2 H), 7.83 (d,
J = 7.6 Hz, 4 H), 7.64 (t, J = 7.6 Hz, 2 H), 7.59–7.51 (m, 5 H), 7.46
(t, J = 7.2 Hz, 2 H), 3.96–3.92 (m, 1 H), 3.10–2.97 (m, 4 H), 2.22–
2.13 (m, 2 H), 1.98–1.89 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 201.0, 138.6, 135.7, 133.9, 133.8,
129.3, 128.9, 128.3, 127.8, 53.0, 42.1, 24.2.
LRMS (EI, 70 eV): m/z (%) = 456 (M+, 1), 315 (6), 172 (4), 105
(100).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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Synthesis 2014, 46, 203–211
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 1-Aryl-4-(phenylsulfonyl)butan-1-ones
211
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 203–211