IBX/Imediated reaction of sodium arenesulfinates with alkenes: Facile synthesis of β-keto sulfones

Article abstract of DOI:10.1055/s-0031-1290952

A direct synthesis of -keto sulfones from alkenes is described. A combination of o-iodoxybenzoic acid/iodine (IBX/I was found to mediate the reactions of alkenes with arenesulfinates to yield -keto sulfones in good yields via a one-pot reaction. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290952

PAPER
▌1693
paper
IBX/I2-Mediated Reaction of Sodium Arenesulfinates with Alkenes:
Facile Synthesis of β-Keto Sulfones
β-Keto Sulfone Synthesis
Natthapol Samakkanad,a Praewpan Katrun,a Thanachart Techajaroonjit,a Sornsiri Hlekhlai,a Manat Pohmakotr,a
Vichai Reutrakul,a Thaworn Jaipetch,b Darunee Soorukram,a Chutima Kuhakarn*a
a
Department of Chemistry and Center for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Rama 6 Road,
Bangkok 10400, Thailand
Fax +88(6)3547151; E-mail: chutima.kon@mahidol.ac.th
b
Mahidol University, Kanchanaburi Campus, Saiyok, Kanchanaburi 71150, Thailand
Received: 13.02.2012; Accepted after revision: 19.03.2012
proach to α-iodo ketones from alkenes is potentially
Abstract: A direct synthesis of β-keto sulfones from alkenes is de-
scribed. A combination of o-iodoxybenzoic acid/iodine (IBX/I2)
was found to mediate the reactions of alkenes with arenesulfinates
to yield β-keto sulfones in good yields via a one-pot reaction.
useful and methods for their syntheses are available.19
Our research group has been interested in the synthetic ap-
plications of hypervalent iodine reagents in organic syn-
thesis for many years.20 The recent publications by
Donohoe et al. on the use of the reagent combination o-io-
doxybenzoic acid and iodine for the direct preparation of
heteroaromatic compounds from alkenes,21 prompted us
to report our own findings. We report herein a facile one-
pot synthesis of β-keto sulfones from alkenes mediated by
a combination of o-iodoxybenzoic acid (IBX) and iodine
in the presence of sodium arenesulfinates.
Key words: IBX, iodine, alkenes, β-keto sulfones
β-Keto sulfones are important synthetic units in organic
synthesis due to their chemical reactivity and the versatil-
ity of the sulfone unit.1 Several useful classes of com-
pounds have been prepared via the intermediacy of β-keto
sulfones, for example olefins,2 disubstituted acetylenes,3
allenes,4 vinyl sulfones,5 and ketones.6 In particular, β-
keto sulfones are employed as convenient synthetic inter-
mediates or reagents in the synthesis of natural products
and important classes of compounds.7 In addition, certain
β-keto sulfone containing molecules have been shown to
exhibit important biological activity; for example, fungi-
cidal and antibacterial activity.8 A number of synthetic
routes are available for the synthesis of β-keto sulfones in-
cluding: (a) alkylation of sodium sulfinates with either α-
halo ketones or α-tosyloxy ketones,9 (b) oxidation of β-
keto sulfides, β-keto sulfoxides, and β-hydroxy sul-
fones,10 (c) reaction of sulfonyl chlorides with silyl enol
ethers,11 (d) reaction of diazo sulfones with aldehydes,12
(e) acylation of alkyl sulfones,13 (f) reaction of sulfonyl
chlorides with arylacetylenes,14 (g) free radical rearrange-
ment of enol sulfonates,15 (h) in situ generation of α-tosyl-
oxy ketones followed by alkylation of sodium sulfinates,16
and (i) reaction of alkyl- and arylacetylenes with polysty-
rene-supported areneselenosulfonate.17
Initially in a model reaction to optimize conditions, 4-bro-
mostyrene (1a) was treated with o-iodoxybenzoic acid
(2.0 equiv) and iodine (1.1 equiv) in dimethyl sulfoxide
for 30 minutes followed by addition of sodium p-toluene-
sulfinate (4.0 equiv), and the reaction mixture was stirred
at room temperature for an additional one hour. The cor-
responding β-keto sulfone 2a and iodohydrin 3a22 were
obtained in 58% and 20% yields, respectively, after col-
umn chromatography (Table 1, entry 1). Under the stated
reaction conditions, we also anticipated a competing
Kornblum oxidation of the alkyl iodide by o-iodoxyben-
zoic acid.23 To our delight, it was found that by employing
a mixture acetonitrile–dimethyl sulfoxide (2:1) as the sol-
vent, a substantial increase in the yield of 2a was obtained
leading to β-keto sulfone 2a and iodohydrin 3a in 80%
and 10% yields, respectively (entry 2). A complex mix-
ture was observed when the reaction was conducted in
pure acetonitrile. Among solvent systems screened, the
combination of acetonitrile–dimethyl sulfoxide (2:1) gave
the best results (entry 2 versus entries 3–8). When the re-
action was carried out either at 80 °C or using higher ra-
tios of dimethyl sulfoxide to acetonitrile significantly
lower yields of 2a were obtained (entries 9 and 10). In ad-
dition, no further improvement was observed when the re-
action was carried out either under an inert atmosphere or
in the presence of 4 Å molecular sieves (entries 11 and
12). It is worth mentioning that no reaction took place in
the absence of molecular iodine. Iodohydrin 3a along with
a significant amount of the starting material were ob-
served when the reaction was conducted in the absence of
o-iodoxybenzoic acid. Thus, upon addition of sodium p-
toluenesulfinate, unreacted 4-bromostyrene was convert-
Among a number of methods for β-keto sulfone synthesis,
the reaction of α-halo ketones with sodium arenesulfinates
is a direct and straightforward route. However, the inade-
quacy of the method is due to the low solubility of sodium
arenesulfinates in common organic solvents. Therefore, a
one-pot method involving the in situ generation of α-iodo
ketones from their precursors followed by alkylation of
sodium sulfinates is attractive. α-Iodo ketones can be pre-
pared from ketones by iodination.18 However, an ap-
SYNTHESIS 2012, 44, 1693–1699
Advanced online publication: 27.04.2012
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DOI: 10.1055/s-0031-1290952; Art ID: SS-2012-N0148-OP
© Georg Thieme Verlag Stuttgart · New York

1694
N. Samakkanad et al.
PAPER
Table 2 Optimization of the Hypervalent Iodine Reagenta
ed into the corresponding vinyl sulfone.24 Finally, the re-
action in which sodium p-toluenesulfinate was introduced
at the beginning of the reaction gave the respective vinyl
sulfone as the major product.
O
O
O
S
Ar
p-Tol
2a
hypervalent iodine, I2
r.t., 30 min
MeCN–DMSO (2:1)
+
Table 1 Optimization of the Solvent Systema
OH
Ar
O
O
O
I
then p-TolSO2Na, 1 h
Ar
1a
S
3a
+
O
p-Tol
Ar = 4-BrC6H4
O
Br
S
2a
IBX, I2, 30 min
Ar
p-Tol
+
4a
then p-TolSO2Na, 1 h
OH
Br
solvent, temp
Yieldb (%)
1a
Entry
Hypervalent iodine
I
2a
80
–
3a
10
6
4a
–
Br
3a
1
2
3
4
IBX
Yieldb (%)
Entry
Solvent
DMSO
Temp
NaIO4
59
51
2a
58
80
56
42
64
75
65
3a
PhI(OAc)2
PhI(OCOCF3)2
8
5
c
c
c
1
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
80 °C
r.t.
r.t.
r.t.
20
10
26
30
21
12
15
–
–
–
2
MeCN–DMSO (2:1)
CH2Cl2–DMSO (2:1)
EtOAc–DMSO (2:1)
THF–DMSO (2:1)
a Reaction conditions: 4-bromostyrene (0.5 mmol), hypervalent io-
dine (2.0 equiv), I2 (1.1 equiv), p-TolSO2Na (4.0 equiv).
b Isolated yields after chromatographic purification.
3
c A complex mixture was obtained.
4
5
Next, the halogen source was optimized; an array of halo-
gen sources were screened, including NIS, NBS, NCS,
NaI, KI, Et4NI, NaBr, KBr, and Et4NBr. Molecular iodine
was found to mediate the reaction most effectively. When
iodine was replaced with either N-bromosuccinimide or
N-iodosuccinimide under standard reaction conditions, β-
keto sulfone 2a was obtained in 74% and 44% yields, re-
spectively. No reaction took place when N-chlorosuccin-
imide was employed as the halogen source, while the
remaining metal halides and tetraalkylammonium halides
(NaI, KI, Et4NI, NaBr, KBr, and Et4NBr) led to vinyl sul-
fone 4a exclusively in good to excellent yields (55–94%).
6
DCE–DMSO (2:1)
acetone–DMSO (2:1)
MeOH–DMSO (2:1)
MeCN–DMSO (2:1)
MeCN–DMSO (1:2)
MeCN–DMSO (2:1)d
MeCN–DMSO (2:1)e
7
c
c
8
–
–
9
48
65
82
82
4
10
11
12
18
9
6
a Reaction conditions: 4-bromostyrene (0.5 mmol), IBX (2.0 equiv),
I2 (1.1 equiv), p-TolSO2Na (4.0 equiv).
After identifying the appropriate reagents, we further ex-
amined other essential reaction parameters with respect to
reagent stoichiometry. Lower yields of 2a were observed
when the reactions were carried out with a decrease in the
loading of either o-iodoxybenzoic acid (from 2.0 to 1.5
and 1.0 equiv) or iodine (from 1.1 to 0.5 equiv). Increas-
ing the stoichiometry of o-iodoxybenzoic acid (from 2.0
to 3.0 equiv) or iodine (from 1.1 to 2.0 equiv) lowered the
yield of β-keto sulfone 2a and enhanced the conversion of
1a into iodohydrin 3a. Lowering the stoichiometry of so-
dium p-toluenesulfinate (from 4.0 to 2.0 equiv) led to a
decrease in reaction yield while increasing the amount of
p-toluenesulfinate (from 4.0 to 5.0 equiv) did not cause
significant improvement.
b Isolated yields after chromatographic purification.
c Compounds 2a and 3a were not observed and a complex mixture
was obtained.
d Using anhyd DMSO and under an argon atmosphere.
e Molecular sieves (4 Å) (100 mg) were added.
Having established the most efficient reaction conditions
(Table 1, entry 2), we next investigated the efficiency of
various hypervalent iodine reagents and types of halogen
source. Among the hypervalent iodine reagents screened
(Table 2), including o-iodoxybenzoic acid, sodium peri-
odate, (diacetoxyiodo)benzene, and [bis(trifluoroacet-
oxy)iodo]benzene, o-iodoxybenzoic acid gave optimal
results (entry 1). Sodium periodate and (diacetoxyio-
do)benzene gave vinyl sulfone 4a as the major product
(entries 2 and 3) while [bis(trifluoroacetoxy)iodo]benzene
resulted in complex NMR patterns (entry 4).
On the basis of the optimization results, the optimized re-
action conditions were selected for further exploration of
the generality and functional group compatibility of this
reaction and the results are summarized in Table 3. It was
found that most styrene derivatives underwent the reac-
Synthesis 2012, 44, 1693–1699
© Georg Thieme Verlag Stuttgart · New York

PAPER
β-Keto Sulfone Synthesis
1695
tion to provide the corresponding β-keto sulfones in good readily available starting materials, and is an important al-
yields (Table 3). Even though the reaction proceeded ternative to existing methods for the synthesis of β-keto
more vigorously, sodium benzenesulfinate gave compara- sulfones. The extension of this method with other nucleo-
ble results to those of p-toluenesulfinate. Moderate to low philes is currently being in progress and will be reported
yields were observed for styrenes substituted with elec- in due course.
tron-releasing groups and aliphatic alkenes (entries 12–
14).
All compounds were characterized by 1H and 13C NMR, IR, HRMS,
1
and microelemental analysis. H and 13C NMR spectra were ob-
Table 3 Synthesis of Keto Sulfonesa
tained by using Bruker DPX-300 MHz and Bruker Avance 500
MHz spectrometers in CDCl3 relative to the residual proton reso-
nance in the indicated deuterated solvent or TMS. IR spectroscopy
was carried out on a Perkin Elmer GX FT-IR System spectropho-
tometer, HRMS was carried out on a Bruker micro TOF spectrom-
eter and melting points (uncorrected) were determined on a Sanyo
Gallenkemp Apparatus. The elemental analyses were performed by
a Perkin Elmer Elemental Analyzer 2400 CHN.
IBX, I2, r.t., 30 min
MeCN–DMSO (2:1)
O
O
O
S
R
Ar
R
then ArSO2Na, 1 h
1
2
Yieldb (%)
Entry Substrate
R
Ar
Product
1
1a
1b
1c
1d
1e
1f
4-BrC6H4
Ph
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
2a
2b
2c
2d
2e
2f
80
76
79
68
82
75
Keto Sulfones Derived from Styrene Derivatives; General Pro-
cedure
2
A suspension of alkene (0.5 mmol), IBX (279.9 mg, 1.0 mmol), and
I2 (139.6 mg, 0.55 mmol) was dispersed in a mixture MeCN (2 mL)
and DMSO (1 mL). The reaction was vigorously stirred at r.t. for 30
min. To this mixture, was added sodium arenesulfinate (2.0 mmol)
[in the case of sodium benzenesulfinate, the mixture must be cooled
(ice bath) before its addition]. The resulting mixture was continu-
ously stirred at r.t. for an additional 1 h before it was quenched by
the addition of sat. aq Na2S2O3 soln (5 mL) and sat. aq NaHCO3 soln
(5 mL), and diluted with EtOAc (2 mL). Further stirring was fol-
lowed by extraction with EtOAc (3 × 15 mL). The combined organ-
ic extracts were washed with H2O (15 mL) and brine (15 mL), dried
(MgSO4), filtered, and concentrated (aspirator). The crude product
was purified by column chromatography (silica gel), preparatory
layer chromatography (PLC, silica gel), and crystallization (for sol-
id compounds) (hexane–CH2Cl2).
3
4-ClC6H4
2-ClC6H4
3-ClC6H4
4-FC6H4
3-O2NC6H4
4-MeC6H4
4
5
6
52c
74
74
81
70
35
40
35
76
72
73
7
1g
1h
1i
2g
2h
2i
8
9
4-ClCH2C6H4 p-Tol
10
11
12
13
14
15
16
17
1j
3-HOCC6H4
4-AcOC6H4
4-MeOC6H4
Me(CH2)5
PhO(CH2)3
4-BrC6H4
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
Ph
2j
1k
1l
2k
2l
1-(4-Bromophenyl)-2-tosylethanone (2a)
Following the general procedure using 4-bromostyrene (1a, 91.5
mg, 0.5 mmol). The crude product was purified by column chroma-
tography (silica gel, hexanes–EtOAc–CH2Cl2, 8.5:0.5:1 to 7:2:1) to
give 2a as a white solid; yield: 142.0 mg (80%); mp 143.8–144.3 °C
(Lit.17 144–146 °C); Rf = 0.55 (EtOAc–hexanes, 2:3).
1m
1n
1a
1c
1e
2m
2n
2o
2p
2q
IR (KBr): 1681 (C=O), 1314, 1149 cm–1 (S=O).
1H NMR (300 MHz, CDCl3): δ = 7.83 (d, J = 8.7 Hz, 2 H), 7.76 (d,
J = 8.3 Hz, 2 H), 7.64 (d, J = 8.7 Hz, 2 H), 7.36 (d, J = 8.1 Hz, 2 H),
4.70 (s, 2 H), 2.47 (s, 3 H).
4-ClC6H4
Ph
13C NMR (75 MHz, CDCl3): δ = 187.2, 145.5, 135.5, 134.4, 132.2,
3-ClC6H4
Ph
130.8, 129.89, 129.87, 128.5, 63.7, 21.7.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C15H13O3SBrNa:
376.9646; found: 376.9644.
a Reaction conditions: styrene 1 (0.5 mmol), IBX (2.0 equiv), I2 (1.1
equiv), ArSO2Na (4.0 equiv).
b Isolated yields after chromatographic purification.
c 1g was stirred in IBX/I2 for 45 min before p-TolSO2Na was added.
1-Phenyl-2-tosylethanone (2b)
Following the general procedure using styrene (1b, 52.1 mg, 0.5
mmol). The crude product was purified by column chromatography
(silica gel, hexanes–EtOAc–CH2Cl2, 8.5:0.5:1 to 7:2:1) to give 2b
as a white solid; yield: 104.5 mg (76%); mp 106.1–108.0 °C (Lit.17
105–107 °C); Rf = 0.43 (EtOAc–hexanes, 2:3).
The mechanistic pathway shown in Scheme 1 for ketoio-
dination mediated by a combination of o-iodoxybenzoic
acid/iodine was assumed based on recent work by
Donohoe et al.21b The formation of β-keto sulfones fol-
IR (KBr): 1681 (C=O), 1320, 1150 cm–1 (S=O).
lows nucleophilic attack of the sulfur atom of the sodium 1H NMR (300 MHz, CDCl3): δ = 7.96 (d, J = 7.2 Hz, 2 H), 7.78 (d,
J = 8.3 Hz, 2 H), 7.64 (t, J = 7.3 Hz, 1 H), 7.50 (t, J = 7.4 Hz, 2 H),
arenesulfinate on the phenacyl iodide 5.
7.35 (d, J = 8.2, 2 H), 4.74 (s, 2 H), 2.46 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 188.1, 145.4, 135.8, 134.3, 129.8,
129.3, 128.8, 128.6, 63.6, 21.7.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C15H14O3SNa:
In summary, we have described the direct synthesis of β-
keto sulfones from olefins, including both styrene deriva-
tives and aliphatic alkenes. The present procedure offers
experimental simplicity, mild reaction conditions, and
297.0561; found: 297.0520.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1693–1699

1696
N. Samakkanad et al.
PAPER
O
O
I
OH
O
O
S
O
S
IBX
Me
Me
Me
O
Me
O
O
Me
Me
O
S
Me
S
I
O
O
I
Me
OH
O
C
OH
I
O
I
I2
I
R
R
R
R
I
D
A
B
1
O
S
+ I
Me
Me
O
O
S
Na
O
O
O
Ar
O
O
O
S
I
I
Ar
O
R
O
I
3
O
H
R
5
E
O
I
HO
IBA
Scheme 1 Mechanistic pathway
1-(4-Chlorophenyl)-2-tosylethanone (2c)
1-(3-Chlorophenyl)-2-tosylethanone (2e)
Following the general procedure using 4-chlorostyrene (1c, 69.3
mg, 0.5 mmol). The crude product was purified by column chroma-
tography (silica gel, hexanes–EtOAc–CH2Cl2, 8.5:0.5:1 to 7:2:1) to
give 2c as a white solid; yield: 122.6 mg (79%); mp 135.7–136.5 °C
(Lit.11 134.4–139.9 °C); Rf = 0.55 (EtOAc–hexanes, 2:3).
Following the general procedure using 3-chlorostyrene (1e, 69.3
mg, 0.5 mmol). The crude product was purified by column chroma-
tography (silica gel, hexanes–EtOAc–CH2Cl2, 8.5:0.5:1 to 7:2:1) to
give 2e as a white solid; yield: 126.9 mg (82%); mp 123.8–125.5
°C; Rf = 0.51 (EtOAc–hexanes, 2:3).
IR (KBr): 1681 (C=O), 1315, 1148 cm–1 (S=O).
IR (KBr): 1682 (C=O), 1316, 1149 cm–1 (S=O).
1H NMR (300 MHz, CDCl3): δ = 7.90 (d, J = 8.7 Hz, 2 H), 7.75 (d,
J = 8.3 Hz, 2 H), 7.44 (d, J = 8.6 Hz, 2 H), 7.34 (d, J = 8.1 Hz, 2 H),
4.71 (s, 2 H), 2.44 (s, 3 H).
1H NMR (300 MHz, CDCl3): δ = 7.88–7.85 (m, 2 H), 7.77 (d, J =
8.3 Hz, 2 H), 7.60 (d, J = 8.2 Hz, 1 H), 7.45 (t, J = 8.1 Hz, 1 H), 7.36
(d, J = 8.0 Hz, 2 H), 4.71 (s, 2 H), 2.47 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 187.0, 145.4, 140.9, 135.5, 134.0,
13C NMR (75 MHz, CDCl3): δ = 187.0, 145.6, 137.2, 135.5, 135.2,
130.7, 129.8, 129.1, 128.4, 63.5, 21.6.
134.2, 130.1, 129.9, 129.1, 128.5, 127.5, 63.7, 21.7.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C15H13O3SClNa:
HRMS (ESI-TOF): m/z [M + Na+] calcd for C15H13O3SClNa:
331.0172; found: 331.0127.
331.0172; found: 331.0151.
1-(2-Chlorophenyl)-2-tosylethanone (2d)
1-(4-Fluorophenyl)-2-tosylethanone (2f)
Following the general procedure using 2-chlorostyrene (1d, 69.3
mg, 0.5 mmol). The crude product was purified by column chroma-
tography (silica gel, hexanes–EtOAc–CH2Cl2, 8.5:0.5:1 to 7:2:1) to
give 2d as a white solid; yield: 105.2 mg (68%); mp 96.0–97.0 °C;
Rf = 0.47 (EtOAc–hexanes, 2:3).
Following the general procedure using 4-fluorostyrene (1f, 61.1 mg,
0.5 mmol). The crude product was purified by column chromatog-
raphy (silica gel, hexanes–EtOAc–CH2Cl2, 8.5:0.5:1 to 7:2:1) to
give 2f as a white solid; yield: 109.6 mg (75%); mp 133.9–135.0 °C
(Lit.11 134.0–134.4 °C); Rf = 0.48 (EtOAc–hexanes, 2:3).
IR (KBr): 1698 (C=O), 1310, 1142 cm–1 (S=O).
IR (KBr): 1677 (C=O), 1312, 1148 cm–1 (S=O).
1H NMR (500 MHz, CDCl3): δ = 7.78 (d, J = 8.3 Hz, 2 H), 7.57 (dd,
J = 7.7, 1.6 Hz, 1 H), 7.45 (td, J = 7.4, 1.8 Hz, 1 H), 7.39 (dd, J =
8.1, 1.3 Hz, 1 H), 7.38–7.34 (m, 3 H), 4.84 (s, 2 H), 2.46 (s, 3 H).
1H NMR (300 MHz, CDCl3): δ = 8.00 (dd, J = 8.9, 5.3 Hz, 2 H),
7.75 (d, J = 8.2 Hz, 2 H), 7.34 (d, J = 8.0 Hz, 2 H), 7.16 (t, J = 8.5
Hz, 2 H), 4.69 (s, 2 H), 2.45 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 190.2, 145.3, 137.3, 135.9, 133.0,
131.5, 130.6, 130.5, 129.8, 128.5, 127.1, 66.4, 21.6.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C15H13O3SClNa:
13C NMR (75 MHz, CDCl3): δ = 186.6, 166.5 (d, JCF = 256.3 Hz),
145.5, 135.7, 132.30 (d, JCF = 9.6 Hz), 132.29 (d, JCF = 3.2 Hz),
129.9, 128.6, 116.1 (d, JCF = 22.0 Hz), 63.8, 21.7.
331.0172; found: 331.0150.
Synthesis 2012, 44, 1693–1699
© Georg Thieme Verlag Stuttgart · New York

PAPER
β-Keto Sulfone Synthesis
4-(2-Tosylacetyl)phenyl Acetate (2k)
1697
HRMS (ESI-TOF): m/z [M + Na+] calcd for C15H13O3SFNa:
Following the general procedure using 4-acetoxystyrene (1k, 81.1
mg, 0.5 mmol). The crude product was purified by column chroma-
tography (silica gel, hexanes–EtOAc–CH2Cl2, 8:1:1 to 6:3:1) to
give 2k as a white solid; yield: 116.7 mg (70%); mp 130.2–131.9
°C; Rf = 0.33 (EtOAc–hexanes, 2:3).
315.0467; found: 315.0449.
1-(3-Nitrophenyl)-2-tosylethanone (2g)
Following the general procedure using 3-nitrostyrene (1g, 74.6 mg,
0.5 mmol). The crude product was purified by column chromatog-
raphy (silica gel, hexanes–EtOAc–CH2Cl2, 8:1:1 to 6:3:1) to give
2g as a pale yellow solid; yield: 83.2 mg (52%); mp 128.0–128.7 °C
(Lit.16a 126–128 °C); Rf = 0.26 (EtOAc–hexanes, 2:3).
IR (KBr): 1755, 1669 (C=O), 1316, 1160 cm–1 (S=O).
1H NMR (300 MHz, CDCl3): δ = 7.98 (d, J = 8.7 Hz, 2 H), 7.76 (d,
J = 8.3 Hz, 2 H), 7.34 (d, J = 8.1 Hz, 2 H), 7.21 (d, J = 8.7 Hz, 2 H),
4.71 (s, 2 H), 2.44 (s, 3 H), 2.33 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 186.9, 168.5, 155.2, 145.4, 135.6,
133.2, 131.0, 129.8, 128.5, 122.0, 63.5, 21.6, 21.1.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C17H16O5SNa:
355.0616; found: 355.0590.
IR (KBr): 1687 (C=O), 1314, 1149 cm–1 (S=O).
1H NMR (300 MHz, CDCl3): δ = 8.69 (s, 1 H), 8.43 (d, J = 7.7 Hz,
1 H), 8.31 (d, J = 7.8 Hz, 1 H), 7.74–7.67 (m, 3 H), 7.33 (d, J = 8.2
Hz, 2 H), 4.79 (s, 2 H), 2.43 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 186.4, 148.3, 145.8, 136.8, 135.3,
134.8, 130.1, 130.0, 128.4, 128.2, 124.0, 63.7, 21.6.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C15H13O5NSNa:
342.0412; found: 342.0400.
1-(4-Methoxyphenyl)-2-tosylethanone (2l)
Following the general procedure using 4-methoxystyrene (1l, 67.1
mg, 0.5 mmol). The crude product was purified by column chroma-
tography (silica gel, hexanes–EtOAc–CH2Cl2, 8:1:1 to 6:3:1) to
give 2l as a white solid; yield: 53.4 mg (35%); mp 124.0–124.8 °C
(Lit.11 124.0–124.4 °C); Rf = 0.30 (EtOAc–hexanes, 2:3).
1-(p-Tolyl)-2-tosylethanone (2h)
Following the general procedure using 4-methylstyrene (1h, 59.1
mg, 0.5 mmol). The crude product was purified by column chroma-
tography (silica gel, hexanes–EtOAc–CH2Cl2, 8.5:0.5:1 to 7:2:1) to
give 2h as a white solid; yield: 106.7 mg (74%); mp 112.4–113.1 °C
(Lit.11 112.1–112.4 °C); Rf = 0.32 (EtOAc–hexanes, 2:3).
IR (KBr): 1676 (C=O), 1315, 1141 cm–1 (S=O).
1H NMR (300 MHz, CDCl3): δ = 7.92 (d, J = 9.0 Hz, 2 H), 7.74 (d,
J = 8.3 Hz, 2 H), 7.31 (d, J = 8.0 Hz, 2 H), 6.93 (d, J = 9.0 Hz, 2 H),
4.66 (s, 2 H), 3.87 (s, 3 H), 2.42 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 186.3, 164.5, 145.2, 135.8, 131.8,
129.7, 128.8, 128.5, 114.0, 63.5, 55.6, 21.6.
HRMS (ESI-TOF): m/z [M + H+] calcd for C16H17O4S: 305.0848;
found: 305.0843.
IR (KBr): 1679 (C=O), 1320, 1150 cm–1 (S=O).
1H NMR (500 MHz, CDCl3): δ = 7.85 (d, J = 8.3 Hz, 2 H), 7.77 (d,
J = 8.3 Hz, 2 H), 7.34 (d, J = 8.1 Hz, 2 H), 7.28 (d, J = 8.3 Hz, 2 H),
4.71 (s, 2 H), 2.44 (s, 3 H), 2.43 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 187.6, 145.4, 145.1, 136.0, 133.4,
129.7, 129.42, 129.39, 128.5, 63.5, 21.63, 21.55.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C16H16O3SNa:
311.0718; found: 311.0709.
1-Tosyloctan-2-one (2m)
Following the general procedure using oct-1-ene (1m, 56.1 mg, 0.5
mmol). The crude product was purified by PLC (silica gel, EtOAc–
hexanes, 1.5:8.5) to give 2m as a pale yellow liquid; yield: 56.5 mg
(40%); Rf = 0.53 (EtOAc–hexanes, 2:3).
1-[4-(Chloromethyl)phenyl]-2-tosylethanone (2i)
Following the general procedure using 4-vinylbenzyl chloride (1i,
76.3 mg, 0.5 mmol). The crude product was purified by column
chromatography (silica gel, hexanes–EtOAc–CH2Cl2, 8.5:0.5:1 to
7:2:1) to give 2i as a white solid; yield: 119.5 mg (74%); mp 126.1–
126.4 °C; Rf = 0.34 (EtOAc–hexanes, 2:3).
IR (KBr): 1720 (C=O), 1323, 1154 cm–1 (S=O).
1H NMR (400 MHz, CDCl3): δ = 7.74 (d, J = 8.3 Hz, 2 H), 7.35 (d,
J = 8.1 Hz, 2 H), 4.12 (s, 2 H), 2.68 (t, J = 7.3 Hz, 2 H), 2.44 (s, 3
H), 1.55–1.51 (m, 2 H), 1.30–1.24 (m, 6 H), 0.86 (t, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 198.7, 145.6, 136.0, 130.2, 128.5,
67.2, 44.7, 31.7, 29.9, 28.7, 23.3, 22.7, 21.9, 14.2.
IR (KBr): 1689 (C=O), 1331, 1136 cm–1 (S=O).
1H NMR (300 MHz, CDCl3): δ = 7.96 (d, J = 8.3 Hz, 2 H), 7.77 (d,
J = 8.3 Hz, 2 H), 7.52 (d, J = 8.3 Hz, 2 H), 7.35 (d, J = 8.2 Hz, 2 H),
4.73 (s, 2 H), 4.63 (s, 2 H), 2.47 (s, 3 H).
HRMS (ESI-TOF): m/z [M + Na+] calcd for C15H22O3SNa:
305.1187; found: 305.1182.
13C NMR (75 MHz, CDCl3): δ = 187.5, 145.5, 143.7, 135.6, 135.5,
129.85, 129.78, 128.8, 128.5, 63.7, 45.0, 21.7.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C16H15O3SClNa:
345.0328; found: 345.0320.
5-Phenoxy-1-tosylpentan-2-one (2n)
Following the general procedure using 5-phenoxypent-1-ene (1n,
81.1 mg, 0.5 mmol). The crude product was purified by PLC (silica
gel, EtOAc–hexanes, 1.5:8.5) to give 2n as a white solid; yield: 58.2
mg (35%); mp 82.8–85.0 °C; Rf = 0.40 (EtOAc–hexanes, 2:3).
3-(2-Tosylacetyl)benzaldehyde (2j)
Following the general procedure using 3-vinylbenzaldehyde (1j,
66.1 mg, 0.5 mmol). The crude product was purified by column
chromatography (silica gel, hexanes–EtOAc–CH2Cl2, 8:1:1 to
6:3:1) to give 2j as a white solid; yield: 122.5 mg (81%); mp 97.3–
97.9 °C; Rf = 0.39 (EtOAc–hexanes, 2:3).
IR (KBr): 1720 (C=O), 1315, 1147 cm–1 (S=O).
1H NMR (300 MHz, CDCl3): δ = 7.74 (d, J = 8.4 Hz, 2 H), 7.33–
7.24 (m, 4 H), 6.94 (t, J = 7.4 Hz, 1 H), 6.84 (d, J = 8.7 Hz, 2 H),
4.17 (s, 2 H), 3.94 (t, J = 6.0 Hz, 2 H), 2.94 (t, J = 6.9 Hz, 2 H), 2.43
(s, 3 H), 2.06 (quint, J = 6.8 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 197.9, 158.6, 145.5, 135.6, 130.0,
129.5, 128.3, 120.8, 114.4, 67.2, 66.1, 40.7, 23.1, 21.7.
IR (KBr): 1702, 1678 (C=O), 1314, 1144 cm–1 (S=O).
1H NMR (300 MHz, CDCl3): δ = 10.04 (s, 1 H), 8.38 (s, 1 H), 8.22
(d, J = 7.8 Hz, 1 H), 8.11 (d, J = 7.6 Hz, 1 H), 7.75 (d, J = 8.2 Hz, 2
H), 7.66 (t, J = 7.7 Hz, 1 H), 7.32 (d, J = 8.1 Hz, 2 H), 4.83 (s, 2 H),
2.42 (s, 3 H).
Anal. Calcd for C18H20O4S: C, 65.04; H, 6.06; found: C, 64.74; H,
6.07.
13C NMR (75 MHz, CDCl3): δ = 190.9, 187.3, 145.5, 136.5, 136.3,
135.5, 134.5, 134.1, 130.5, 129.8, 129.6, 128.4, 63.5, 21.5.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C16H14O4SNa:
325.0510; found: 325.0478.
1-(4-Bromophenyl)-2-(phenylsulfonyl)ethanone (2o)
Following the general procedure using 4-bromostyrene (1a, 91.5
mg, 0.5 mmol). The crude product was purified by column chroma-
tography (silica gel, hexanes–EtOAc–CH2Cl2, 8.5:0.5:1 to 7:2:1) to
© Georg Thieme Verlag Stuttgart · New York
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N. Samakkanad et al.
PAPER
(5) Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron:
give 2o as a white solid; yield: 129.1 mg (76%); mp 135.5–136.8 °C
(Lit.17 134–136 °C); Rf = 0.50 (EtOAc–hexanes, 2:3).
Asymmetry 1998, 9, 2311.
(6) (a) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1964,
86, 1639. (b) Trost, B. M.; Arndt, H. C.; Strege, P. E.;
Verhoeven, T. R. Tetrahedron Lett. 1976, 17, 3477.
(c) Kurth, M. J.; O’Brien, M. J. J. Org. Chem. 1985, 50,
3846. (d) Fuju, M.; Nakamura, K.; Mekata, H.; Oka, S.;
Ohno, A. Bull. Chem. Soc. Jpn. 1988, 61, 495. (e) Guo, H.;
Ye, S.; Wang, J.; Zhang, Y. J. Chem. Res., Synop. 1997, 114.
(f) Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron
1998, 54, 9791. (g) Guo, H.; Zhang, Y. Synth. Commun.
2000, 30, 2564.
IR (KBr): 1678 (C=O), 1313, 1150 cm–1 (S=O).
1H NMR (300 MHz, CDCl3): δ = 7.88 (d, J = 7.4 Hz, 2 H), 7.81 (d,
J = 8.6 Hz, 2 H), 7.71–7.61 (m, 3 H), 7.56 (t, J = 7.4 Hz, 2 H), 4.70
(s, 2 H).
13C NMR (75 MHz, CDCl3): δ = 187.0, 138.5, 134.41, 134.36,
132.2, 130.8, 130.0, 129.3, 128.5, 63.5.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C14H11O3SBrNa:
362.9490; found: 362.9459.
(7) (a) Yang, H.; Carter, R. G.; Zakharov, L. N. J. Am. Chem.
Soc. 2008, 130, 9238. (b) Alemán, J.; Marcos, V.; Marzo, L.;
Ruano, J. L. G. Eur. J. Org. Chem. 2010, 4482.
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Laget, M.; Carle, A. O.; Gellis, A.; Vanelle, P. Eur. J. Med.
Chem. 2007, 42, 880.
1-(4-Chlorophenyl)-2-(phenylsulfonyl)ethanone (2p)
Following the general procedure using 4-chlorostyrene (1c, 69.3
mg, 0.5 mmol). The crude product was purified by column chroma-
tography (silica gel, hexanes–EtOAc–CH2Cl2, 8.5:0.5:1 to 7:2:1) to
give 2p as a white solid; yield: 106.5 mg (72%); mp 133.0–133.8
°C; Rf = 0.52 (EtOAc–hexanes, 2:3).
IR (KBr): 1691 (C=O), 1331, 1141 cm–1 (S=O).
(9) (a) Vennstra, G. E.; Zwaneburg, B. Synthesis 1975, 519.
(b) Wildeman, J.; van Leusen, A. M. Synthesis 1979, 733.
(c) Xie, Y.-Y.; Chen, Z.-C. Synth. Commun. 2001, 31, 3145.
(d) Suryakiran, N.; Prabhakar, P.; Rajesh, K.; Suresh, V.;
Venkateswarlu, Y. J. Mol. Catal. A: Chem. 2007, 207, 201.
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5368.
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1287. (b) Fan, A.-L.; Cao, S.; Zhang, Z. J. Heterocycl.
Chem. 1997, 34, 1657. (c) Zweifel, T.; Nielsen, M.;
Overgaard, J.; Jacobsen, C. B.; Jørgensen, K. A. Eur. J. Org.
Chem. 2011, 47.
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Perkin Trans. 1 1997, 783.
(12) Holmquist, C. R.; Roskamp, E. J. Tetrahedron Lett. 1992,
33, 1131.
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5063. (b) House, H. O.; Larson, J. R. J. Org. Chem. 1968,
33, 61. (c) Truce, W. E.; Bannister, W. M.; Knospe, R. H.
J. Org. Chem. 1962, 27, 2821. (d) Thomsen, M. W.;
Handwerker, B. M.; Katz, S. A.; Belser, R. B. J. Org. Chem.
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54, 5620. (f) Katritzky, A. R.; Abdel-Fattah, A. A.; Wang,
M. Y. J. Org. Chem. 2003, 68, 1443.
1H NMR (300 MHz, CDCl3): δ = 7.90–7.86 (m, 4 H), 7.67 (t, J = 7.4
Hz, 1 H), 7.55 (t, J = 7.9 Hz, 2 H), 7.45 (d, J = 8.1 Hz, 2 H), 4.71 (s,
2 H).
13C NMR (75 MHz, CDCl3): δ = 186.8, 141.1, 138.5, 134.3, 134.0,
130.7, 129.25, 129.19, 128.5, 63.5.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C14H11O3SClNa:
317.0015; found: 317.0012.
1-(3-Chlorophenyl)-2-(phenylsulfonyl)ethanone (2q)
Following the general procedure using 3-chlorostyrene (1e, 69.3
mg, 0.5 mmol). The crude product was purified by column chroma-
tography (silica gel, hexanes–EtOAc–CH2Cl2, 8.5:0.5:1 to 7:2:1) to
give 2q as a white solid; yield: 108.2 mg (73%); mp 105.2–107.0
°C; Rf = 0.46 (EtOAc–hexanes, 2:3).
IR (KBr): 1677 (C=O), 1311, 1160 cm–1 (S=O).
1H NMR (300 MHz, CDCl3): δ = 7.89–7.82 (m, 4 H), 7.68 (t, J = 7.7
Hz, 1 H), 7.58–7.53 (m, 3 H), 7.43 (t, J = 7.9 Hz, 1 H), 4.71 (s, 2 H).
13C NMR (75 MHz, CDCl3): δ = 186.9, 138.5, 137.1, 135.2, 134.4,
134.2, 130.1, 129.3, 129.1, 128.5, 127.5, 63.5.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C14H11O3SClNa:
317.0015; found: 316.9991.
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46, 513.
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Kamata, S. J. Am. Chem. Soc. 1970, 92, 3203.
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(b) Kumar, D.; Sundaree, S.; Rao, V. S.; Varma, R. S.
Tetrahedron Lett. 2006, 47, 4197.
(17) Qian, H.; Huang, X. Synthesis 2006, 1934.
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3493. (b) Rubottom, G. M.; Mott, R. C. J. Org. Chem. 1979,
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J. Org. Chem. 1987, 52, 3919. (e) Sket, B.; Zupet, P.; Zupan,
M.; Dolenc, D. Bull. Chem. Soc. Jpn. 1989, 62, 3406.
(f) Okamoto, T.; Kakinami, T.; Nishimura, T.; Hermawan,
I.; Kajigaeshi, S. Bull. Chem. Soc. Jpn. 1992, 65, 1731.
(g) Olah, G. A.; Wang, Q.; Sandford, G.; Surya, Prakash. G.
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Zupan, M. Chem. Commun. 2002, 488. (i) Jereb, M.;
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Acknowledgment
We thank the Thailand Research Fund (TRF-DBG54), the Center
for Innovation in Chemistry (PERCH-CIC), the Office of the High-
er Education Commission, and the Mahidol University under the
National Research Universities Initiative for financial support. We
also thank Chulabhorn Research Institute and National Center for
Genetic Engineering and Biotechnology for HRMS analysis.
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