O -Iodoxybenzoic Acid (IBX)-Iodine Mediated One-Pot Deacylative Sulfonylation of 1,3-Dicarbonyl Compounds: A Synthesis of β-Carbonyl Sulfones

Article abstract of DOI:10.1055/s-0036-1588900

A combination of o-iodoxybenzoic acid (IBX) and a catalytic amount of iodine is found to promote a facile one-pot deacylative sulfonylation reaction of 1,3-dicarbonyl compounds with sodium sulfinates to yield β-carbonyl sulfones. The present method provides the target products bearing a wide variety of functional groups in one step and in good yields.

Full text of DOI:10.1055/s-0036-1588900

SYNTHESIS
0
0
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9
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8
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1
1
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7
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1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–M
paper
A
P. Katrun et al.
Paper
Synthesis
o-Iodoxybenzoic Acid (IBX)–Iodine Mediated One-Pot Deacylative
Sulfonylation of 1,3-Dicarbonyl Compounds: A Synthesis of β-Car-
bonyl Sulfones
Praewpan Katrun
O
O
O
O
O
Teerawat Songsichan
Darunee Soorukram
Manat Pohmakotr
Vichai Reutrakul
I
2 (cat.), IBX
S
R1
R3
R1
R4
R4SO2Na
+
EtOAc, reflux
R2
R2
Chutima Kuhakarn*
1,3-diketones,
β-keto esters,
β-keto amides
34 examples
(35–89% yields)
R
4 = C6H5, p-CH3C6H4,
p-ClC6H4,
Department of Chemistry and Center of Excellence for
Innovation in Chemistry (PERCH-CIC), Faculty of Science,
Mahidol University, Rama 6 Road, Bangkok 10400,
Thailand
p-H3COC6H4,
p-O2NC6H4, CH3
R3 = CH3, Et,
chutima.kon@mahidol.ac.th
C6H5, m-ClC6H5
Received: 22.07.2016
Accepted after revision: 28.09.2016
Published online: 26.10.2016
(g) reactions of 2-arylacrylic acids with sulfinic acids,20 (h)
reactions of oxime acetates with sodium sulfinates,21 (i) re-
actions of activated alkenes with sulfinic acids, sodium sul-
finates or sulfonyl hydrazides,22 (j) free-radical rearrange-
ment of enol sulfonates,23 (k) reactions of alkyl- and
arylacetylenes with polystyrene-supported areneselenosul-
fonates,24 and (l) reactions of arylboronic acids with arene-
sulfonylacetonitriles.25 Recently, the straightforward syn-
thesis of β-keto sulfones by the reaction of 1,3-dicarbonyl
compounds with sodium sulfinates was also described.26
Gao and co-workers first reported the C-sulfonylation of
1,3-dicarbonyl compounds mediated by I2 to form both β-
dicarbonyl sulfones and β-keto sulfones.26a,b They claimed
that β-keto sulfones were formed through I2-mediated sul-
fonylation followed by Na2SO3-mediated deacylation of β-
dicarbonyl sulfones.26b In the same year, Yuan et al. demon-
strated an efficient and convenient electrochemical synthe-
sis of β-keto sulfones from sulfinates and 1,3-dicarbonyl
compounds by using ammonium iodide as a supporting
electrolyte (Scheme 1).26c From the perspective view of syn-
thetic methodology toward β-keto sulfone synthesis, it is
still desirable to develop alternative methods to access β-
keto sulfones employing fast and convenient experimental
procedures.
Our research group has a long-standing interest in the
synthesis of sulfur-containing molecules mediated by io-
dine and hypervalent iodines.15i,27 In 2012, we reported a
facile two-step synthesis, in one pot, of β-keto sulfones
from alkenes mediated by a combination of o-iodoxybenzo-
ic acid (IBX) and iodine in the presence of sodium arenesul-
finates.15i We report herein a one-pot synthesis of β-car-
bonyl sulfones by deacylative sulfonylation of 1,3-dicarbon-
yl compounds with sodium sulfinates mediated by a
combination of o-iodoxybenzoic acid (IBX) and molecular
iodine (I2). It is worth mentioning here that hypervalent io-
DOI: 10.1055/s-0036-1588900; Art ID: ss-2016-n0517-op
Abstract A combination of o-iodoxybenzoic acid (IBX) and a catalytic
amount of iodine is found to promote a facile one-pot deacylative sulfo-
nylation reaction of 1,3-dicarbonyl compounds with sodium sulfinates
to yield β-carbonyl sulfones. The present method provides the target
products bearing a wide variety of functional groups in one step and in
good yields.
Key words deacylation, sulfonylation, β-keto sulfone, o-iodoxybenzoic
acid, iodine
β-Carbonyl sulfones, particularly β-keto sulfones, are a
class of organosulfur compound that has found different
applications in various fields including polymeric materials,
medicinal chemistry and synthetic organic chemistry.1 β-
Keto sulfones are desirable units and the presence of the
sulfonyl moiety aids in enhancing their biological proper-
ties,2 which include fungicidal,2a antibacterial2d and the in-
hibition of 11β-hydroxysteroid dehydrogenase type 1.2b,c In
view of the synthetic applications, a variety of compounds,
for example, olefins,3 disubstituted alkynes,4 allenes,5 flava-
nones,6 vinyl sulfones,7 amides,8 aromatic amines,9 2,3-di-
hydrofurans,10 naphthols,11 naphthalenes,11 quinolines12
and ketones13 have been prepared via the intermediacy of
β-keto sulfones. The numerous applications of β-keto sul-
fones have driven the development of several synthetic
strategies toward the synthesis of β-keto sulfones includ-
ing: (a) oxidation of β-keto sulfides, β-keto sulfoxides and
β-hydroxy sulfones,14 (b) alkylation of sodium sulfinates
with either α-halo ketones or α-tosyloxy ketones,15 (c) acy-
lation of alkyl sulfones,16 (d) sulfonylation of alkyl ketones
or silyl enol ethers,17 (e) oxysulfonylation of alkenes or
alkynes,18 (f) reactions of diazo sulfones with aldehydes,19
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–M

B
P. Katrun et al.
Paper
Synthesis
O
S(O)R2
O
R1
or
OH
O
O
O
O
O
S
R2SO2Na
X
R1
+
R2
R1
X = Cl, Br, I, OTs
S
+
R1
R2
X
R3
[ref. 14]
[ref. 15]
[ref. 16]
[ref. 18]
O
X
R1
O
O
R1
or
[ref. 22]
R2SO2Y
S
+
+
R1
R1
R2
R2SO2X
R3
X = Cl, Br, NHAc, OAc, OP(O)(OEt)2
Y = H, Na, NHNH2
X = H, Cl, Na, NHNH2
NHAc
HOOC
R1
(H)R3
R2SO2Na
+
R2SO2H
R1
CH3
+
Gao's work 26b
O
(1) I2 (1.5 equiv), K2CO3 (2 equiv)
THF, r.t.
O
O
O
O O
S
+
+
R2SO2Na
R1
R2
R1
CH3
(2) Na2SO3 (4 equiv), H2O, 60 °C
Yuan's work 26c
O
O
O
O
NH4I
R2SO2Na
S
R1
R2
R1
CH3
electrolysis
R3
R3
Scheme 1 The synthetic strategies toward β-keto sulfone synthesis
dines and molecular iodine are widely employed as re-
agents to promote sulfonylation reactions for organosul-
fone synthesis.28
MeOH, acetone, THF and EtOAc (Table 1, entries 2–9).
Among these, EtOAc was found to be the optimum solvent
yielding β-keto sulfone 3aa in 85% yield (Table 1, entry 9).
With the best solvent (EtOAc) in hand, we further attempt-
ed to optimize the molar ratios of 2a, IBX and I2 and the re-
sults are summarized in Table 1 (entries 10–14). While in-
creasing the stoichiometry of 2a (from 3 to 4 equiv) did not
improve the yield of 3aa, lowering the amount of 2a (from 3
to 2 or 1 equiv) significantly decreased the product yields to
60% and 35%, respectively (Table 1, entries 10–12). Further-
more, while molecular iodine can be employed in a lesser
amount (from 0.5 to 0.25 equiv), a further decrease in the
quantity of IBX (from 2 to 1.2 equiv) caused a decrease in
the yield of the desired product from 85% to 68% (Table 1,
entries 13 and 14). No improvement was observed when
the reaction time was extended (from 2 h to 5 h) (Table 1,
entry 15). Finally, the reaction proceeded with poorer effi-
ciency at room temperature (Table 1, entry 16).
To begin with, benzoylacetone (1a) and sodium p-tolue-
nesulfinate (2a) were chosen as the substrates in the model
reactions. On the basis of our previous work,15i a combina-
tion of molecular iodine and o-iodoxybenzoic acid (IBX)
was primarily employed to screen for optimized reaction
conditions. A variety of reaction factors including the sol-
vent, reagent stoichiometry, reaction time, temperature,
oxidizing agent and iodide source were screened. First, var-
ious solvents were examined and the reactions were per-
formed using benzoylacetone (1a) (0.5 mmol), sodium p-
toluenesulfinate (2a) (3 equiv), IBX (2 equiv) and iodine (0.5
equiv) at 80 °C or at reflux temperature for two hours (Ta-
ble 1). Although the reaction did not proceed in water (Ta-
ble 1, entry 1), β-keto sulfone 3aa was obtained in variable
yields (40–85%) when the reactions were carried out in or-
ganic solvents including 1,4-dioxane, DCE, DMF, EtOH,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–M

C
P. Katrun et al.
Paper
Synthesis
Table 1 Optimization of the Reaction Conditionsa
Table 2 Optimization of the Reaction Conditionsa
O
O
O
O
O
O
IBX, I2
oxidant, I2 or I–
+ p-TolSO2Na
p-TolSO2Na
SO2p-Tol
3aa
SO2p-Tol
+
solvent, temp
Ph
CH3
Ph
CH3
Ph
Ph
EtOAc, reflux, 2 h
1a
2a
2a
1a
3aa
2a
Entry
IBX
I2
Solvent
Temp
(°C)
Yield
(%)b
(equiv)
(equiv) (equiv)
Entry
Oxidant
I2 or I– (equiv)
Yield (%)b
1
2
3
3
3
3
3
3
3
3
3
4
2
1
3
3
3
3
2
2
2
2
2
2
2
2
2
2
2
2
1.2
2
2
2
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.25
0.25
0.25
H2O
80
NR
69
49
41
62
40
52
79
85
80
60
35
68
85
83
70
1
2
IBX
I2 (0.25)
I2 (0.25)
I2 (0.25)
I2 (0.25)
I2 (0.25)
I2 (0.25)
KI (0.5)
85
1,4-dioxane
DCE
80
IBA
73
3
80
3
DIB
TBHP
OXONE®
K2S2O8
IBX
32
4
DMF
80
4
49
5
EtOH
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
r.t.
5
25c
26c
71
6
MeOH
acetone
THF
6
7
7
8
8
IBX
NaI (0.5)
Et4NI (0.5)
Bu4NI (0.5)
I2 (0.25)
I2 (0.5)
68
9
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
9
IBX
61
10
11
12
13
14
15c
16d
10
11
12
13
IBX
55
–
10c
20c
23c
–
–
I2 (1.0)
a Reaction conditions: 1a (0.5 mmol), 2a (3 equiv), oxidant (2 equiv), EtOAc
(3 mL), open air, 2 h.
b Yield of isolated product after column chromatography (SiO2).
c Substrate 1a was recovered in the range of 55–65%.
a Reaction conditions: 1a (0.5 mmol), solvent (3 mL), open air, 2 h.
b Yield of isolated product after column chromatography (SiO2); NR = no
reaction.
tions of the procedure were investigated and the results are
summarized in Scheme 2 and Scheme 3. Initially, the reac-
tions of sodium p-toluenesulfinate (2a) with aroylacetone
derivatives bearing electronically different substituents on
the phenyl ring were investigated. Benzoylacetone deriva-
tives containing electron-donating groups on the phenyl
ring including m-CH3, p-t-Bu, m-CH3O, p-CH3O and 3,5-
(CH3O)2 gave the corresponding β-keto sulfones 3ba–fa in
good yields (70–78%). It is evident that the steric and elec-
tronic nature of the chlorine atom at ortho-, meta- and
para-positions of the phenyl ring affected the yields of the
corresponding β-keto sulfones; products 3ga, 3ha and 3ia
were obtained in 51%, 58% and 72% yields, respectively. The
benzoylacetone bearing a strong electron-attracting group
(m-NO2) was also a suitable substrate although it was con-
verted into the corresponding product 3ja in moderate
yield (44%). Compound 1k bearing a furfuryl group also
worked well and could be converted into the desired prod-
uct 3ka under standard reaction conditions in 59% yield.
When 2-methyl-1-phenylbutane-1,3-dione (1l) was used
as a substrate, no desired product 3la was observed and 2-
methyl-1-phenylbutane-1,3-dione (1l) was recovered in
59% yield. Acetylacetone was employed as a representative
substrate for aliphatic 1,3-diketones. Unfortunately, it could
only be transformed into β-keto sulfone 3ma with relatively
low efficiency (38% yield). In addition to the 1,3-diketone
c Reaction time = 5 h.
d Reaction time = 16 h.
Having established the primary reaction conditions (Ta-
ble 1, entry 14), different types of oxidizing agent and io-
dide source were next investigated and the results are listed
in Table 2.
Among the oxidizing agents screened including IBX, o-
iodosobenzoic acid (IBA), (diacetoxyiodo)benzene (DIB),
tert-butyl hydroperoxide (TBHP), OXONE® and K2S2O8, IBX
was the optimum oxidizing agent for the present reaction
(Table 2, entries 1–6). When iodine was replaced with other
iodide sources including KI, NaI, Et4NI and Bu4NI, 3aa was
obtained in lower yields (55–71%) (Table 2, entries 7–10).
When IBX was excluded from the reactions performed by
employing variable molar ratios of I2 (0.25, 0.5 and 1.0
equiv), a significant decrease in the product yield was ob-
served (Table 2, entries 11–13). Based on the results shown
in Tables 1 and 2, the optimum reaction conditions were
chosen as the following: substrate 1 (1 equiv), sodium sulfi-
nate 2 (3 equiv), IBX (2 equiv) and I2 (0.25 equiv) in reflux-
ing EtOAc for two hours (Table 1, entry 14).
With optimized reaction conditions in hand, a series of
1,3-dicarbonyl compounds including 1,3-diketones, β-keto
esters and β-keto amides, sodium sulfinates and the limita-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–M

D
P. Katrun et al.
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Synthesis
O
O
O
SO2p-Tol
IBX, I2
+
R1
R1
CH3
p-TolSO2Na
R2
EtOAc, reflux, 2 h
R2
1
2a
3
O
O
O
SO2p-Tol
SO2p-Tol
SO2p-Tol
t-Bu
CH3
3aa, 85% (71%)a
3ba, 78%
3ca, 70%
O
O
O
SO2p-Tol
SO2p-Tol H3CO
SO2p-Tol
H3CO
OCH3
OCH3
3da, 71%
3ea, 77%
3fa, 75%
O
O
O
SO2p-Tol
SO2p-Tol
SO2p-Tol
Cl
Cl
Cl
3ga, 51%
3ha, 58%
3ia, 72%
O
O
O
SO2p-Tol
SO2p-Tol
SO2p-Tol
CH3
3la, 0%
O
NO2
3ja, 44%
3ka, 59%
O
O
O
SO2p-Tol
SO2p-Tol
SO2p-Tol
H3C
H3CO
BnO
EtO
3na, 56%
3oa, 60%
3ma, 38%
O
O
O
SO2p-Tol
SO2p-Tol
SO2p-Tol
t-BuO
O
3qa, 35%
3pa, 40%
3ra, 85%
O
O
O
SO2p-Tol
SO2p-Tol
SO2p-Tol
PhHN
PhN
Et2N
CH3
3ua, 84%
3sa, 57%
3ta, 80%
O
O
O
H3C
SO2p-Tol
SO2p-Tol
SO2p-Tol
N
N
N
O
3wa, 86%
3xa, 84%
3va, 89%
O
O
O
SO2p-Tol
SO2p-Tol
N
OH
4, 55%
3ya, 78%
Scheme 2 Scope of 1,3-dicarbonyl compounds. Reagents and conditions: 1 (0.5 mmol), 2a (3 equiv), IBX (2 equiv), I2 (0.25 equiv), EtOAc (3 mL), open
air, 2 h. Yields are those of isolated products after column chromatography (SiO2). a 1-Phenylpentane-1,3-dione was employed as the substrate.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–M

E
P. Katrun et al.
Paper
Synthesis
substrates, the present method was also found to be appli-
cable to reactions employing β-keto esters as the substrates.
Thus, methyl, ethyl, tert-butyl, and benzyl 3-oxobutanoates
yielded the corresponding products 3na–qa in low to mod-
erate yields (35–60%). The reaction of 2-acetylbutyrolac-
tone (1r) proceeded readily to yield the corresponding
product 3ra in 85% yield. β-Keto amides, including simple
open-chain secondary and tertiary amides (1s–u), cyclic
tertiary amides (1v and 1w), 3-acetyl-1-methylpyrrolidin-
2-one (1x) and 1-(2-oxopyrrolidin-1-yl)butane-1,3-dione
(1y), provided the corresponding products 3sa–ya in mod-
erate to good yields (57–89%). Interestingly, when 1-phen-
ylpentane-1,3-dione was employed as a substrate under
standard reaction conditions, depropionylation took place
to yield 1-phenyl-2-(p-tosyl)ethanone (3aa) in 71% yield.
Finally, cyclohexane-1,3-dione did not provide the expect-
ed ring-opened product, but yielded 3-hydroxy-2-(p-to-
syl)cyclohex-2-enone (4) in 55% yield.
Next, the reactions of benzoylacetone (1a) with a series
of sodium sulfinates 2 were evaluated and the results are
shown in Scheme 3. Sodium arenesulfinates bearing elec-
tronically different groups on the para-position (p-Cl, p-
CH3O, p-O2N) gave the corresponding products 3ab–3ae in
variable yields (37–73%), the example with a strong elec-
tron-withdrawing group (p-O2N) giving a poor yield (37%).
Under the standard reaction conditions, sodium methane-
sulfinate gave the corresponding product 3af in low yield
(34%). A better yield of 3af (46%) was obtained when the re-
action was carried out over a prolonged reaction time (5 h).
Finally, no formation of the corresponding product 3ag was
observed when sodium trifluoromethanesulfinate was em-
ployed as the sulfone source under the typical reaction con-
ditions.
To further demonstrate the synthetic utility of the pres-
ent methodology, the reactions of 1,3-diarylpropane-1,3-
diones with sodium p-toluenesulfinate (2a) were investi-
gated and the results are summarized in Table 3. Although a
longer reaction time (6 h) followed by stirring with a mix-
ture of saturated Na2S2O3 and NaHCO3 (1:1 v/v) was re-
quired, it was gratifying to observe that the symmetrical
1,3-diarylpropane-1,3-dione, 1,3-diphenylpropane-1,3-di-
one (5a), smoothly underwent debenzoylative sulfonylation
to afford 3aa in 61% yield (Table 3, entry 1). The reactions of
unsymmetrical 1,3-diarylpropane-1,3-diones were also in-
vestigated. 1-(3-Chlorophenyl)-3-(4-methoxyphenyl)pro-
pane-1,3-dione (5b) exclusively yielded 3ea derived from
chemoselective cleavage of the 3-chlorobenzoyl group in
63% yield (Table 3, entry 2). However, 1-(4-methoxyphe-
nyl)-3-phenylpropane-1,3-dione (5c) yielded an insepara-
ble mixture of 3ea and primarily formed sulfonylation ad-
duct 6 (60% yield, 3ea/6 = 1:3) while 1-(4-methoxyphenyl)-
3-(3,4,5-trimethoxyphenyl)propane-1,3-dione (5d) exclu-
sively gave an initially formed sulfonylation adduct 7 in 66%
yield (Table 3, entries 3 and 4).
It is worth emphasizing here that scaling up experi-
ments were also investigated (Scheme 4). The reactions
took place readily and the β-carbonyl sulfones 3aa and 3va
were obtained in somewhat lower efficiency (85% vs 74%
for 3aa; 89% vs 79% for 3va). Pleasingly, product 3na was
isolated in a slightly better yield after a prolonged reaction
time [56% (2 h) vs 68% (3 h)].
At this point, a series of control experiments was car-
ried out in order to obtain some insights regarding the pos-
sible mechanism (Scheme 5). High-resolution mass spec-
trometry (HRMS) was employed as a tool for the detection
and confirmation of some intermediates formed due to
their instability (see the Supporting Information for mass
O
O
O
O
IBX, I2
SO2R
Ph
R
SO2Na
+
Ph
CH3
EtOAc, reflux, 2 h
1a
2
3
O
O
O
O
O
O
O
O
S
S
S
Ph
Ph
Ph
OCH3
Cl
3ab, 70%
3ac, 73%
3ad, 60%
O
O
O
O
O
O
O
O
O
S
S
S
Ph
Ph
CF3
Ph
CH3
NO2
3ae, 37%
3af, 34% (46%, 5 h)
3ag, 0%
Scheme 3 The scope of sodium sulfinates. Reaction conditions: 1a (0.5 mmol), 2 (3 equiv), IBX (2 equiv), I2 (0.25 equiv), EtOAc (3 mL), open air, 2 h.
Yields are those of isolated products after column chromatography (SiO2).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–M

F
P. Katrun et al.
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Synthesis
Table 3 Reactions of 1,3-Diarylpropane-1,3-diones 5 with Sodium p-Toluenesulfinate (2a)a
O
O
O
IBX, I2, EtOAc
reflux, 6 h
SO2p-Tol
R1
R1
R2
p-TolSO2Na
+
then
Na2S2O3, NaHCO3
r.t., 1 h
2a
3
5
Entry
1
Substrate
Productb
O
O
O
SO2p-Tol
5a
3aa, 61%
O
O
O
SO2p-Tol
2
H3CO
H3CO
3ea, 63%
Cl
5b
O
O
SO2p-Tol
O
O
O
SO2p-Tol
H3CO
3
H3CO
3ea
H3CO
5c
6
inseparable mixture
(60%, 3ea/6 = 1:3)
O
O
O
O
H3CO
H3CO
SO2p-Tol
H3CO
4
H3CO
OCH3
OCH3
OCH3
OCH3
5d
7, 66%
a Reaction conditions: 5 (0.5 mmol), 2a (3 equiv), IBX (2 equiv), I2 (0.25 equiv), EtOAc (3 mL), open air, 6 h.
b Yields are those of isolated compounds after column chromatography (SiO2).
spectra). Primarily, when benzoylacetone (1a) was treated
with molecular iodine (0.25 equiv) in EtOAc at 80 °C for two
hours, the α-iodinated adduct 8 was detected by TLC and
HRMS analysis (see the Supporting Information for the
mass spectrum) (Scheme 5, a). Without aqueous work-up,
the solvent was removed followed by chromatographic pu-
rification. The α-iodinated adduct 8 was isolated in 7% yield
and 1a was recovered in 88% yield. Next, the reaction of 1a
with 2a was performed in the absence of IBX under the
standard conditions and the reaction solution was taken for
HRMS analysis after two hours (Scheme 5, b). The mass
spectrum indicated the presence of 8, 3aa and 9 (see the
Supporting Information for the mass spectrum). After sol-
vent removal followed by chromatographic purification,
3aa was isolated in 10% yield (see also Table 2, entry 11),
while compounds 8 and 9 could not be isolated. In the con-
ventional reaction of 1a with 2a, when the reaction solu-
tion was taken for HRMS analysis after 20 minutes, 3aa was
detected as a major component along with o-iodobenzoic
acid, while compound 9 was hardly observed (Scheme 5, c)
(see the Supporting Information for the mass spectrum).
Since sulfonyl iodide was also possibly formed from sodium
sulfinate under the present reaction conditions,27b the reac-
tion of 1a with p-toluenesulfonyl iodide (p-TolSO2I) was
evaluated (Scheme 5, d). It was found that 3aa was detected
in trace amount (TLC analysis) indicating that sulfonyl io-
dide was not an intermediate in this reaction.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–M

G
P. Katrun et al.
Paper
Synthesis
On the basis of optimization of the reaction conditions
(Table 2), the results of the control experiments (Scheme 5)
and the previously reported literature,26 we postulate two
possible reaction mechanisms for the deacylative sulfonyla-
tion of 1,3-dicarbonyl compounds as depicted in Scheme 6.
In the presence of I2, iodination of 1,3-dicarbonyl com-
pound 1 proceeds to form intermediate A followed by nuc-
leophilic attack of sulfinate 2 to give β-dicarbonyl sulfone B.
Subsequently, deacylation takes place following the attack
of the nucleophilic species, possibly as the by-products de-
rived from IBX or sodium sulfinate, to form the intermedi-
ate C, which then eliminates NuCOCH3 followed by protona-
tion to afford the final β-carbonyl sulfone 3 (Route A). Un-
fortunately, we were unable to isolate or determine the
nature of any adducts derived from the deacylation process.
Alternatively, due to the enhanced acidity of the methine
proton of the dicarbonyl sulfone B, it is believed that B′
could exist as a major tautomer which then undergoes io-
dination to produce fully substituted intermediate D (Route
B). The intermediate D is highly susceptible to nucleophilic
attack. Thus, deacylation leads to intermediate E followed
by deiodination to afford the β-carbonyl sulfone 3. Finally,
the iodide ion generated in the reaction could be reoxidized
by IBX or IBA leading to I2 to resume the catalytic cycle.
O
O
O
O
I2 (0.25 equiv)
(a)
Ph
CH3
Ph
CH3
EtOAc, reflux, 2 h
I
8
1a
1a
Found m/z 310.9547 (M+Na)
Calcd m/z 310.9545 (M+Na)
O
O
O
I2 (0.25 equiv)
SO2p-Tol
8
Ph
+
(b)
Ph
CH3
p-TolSO2Na (2a) (3 equiv)
3aa
EtOAc, reflux, 2 h
Found m/z 297.0542 (M+Na)
Calcd m/z 297.0561 (M+Na)
O
O
+
Ph
CH3
SO2p-Tol
9
Found m/z 339.0664 (M+Na)
Calcd m/z 339.0667 (M+Na)
I2 (0.25 equiv)
IBX (2 equiv)
O
O
CO2H
3aa
+
(c)
Ph
CH3
p-TolSO2Na (2a) (3 equiv)
I
1a
EtOAc, reflux, 20 min
Found m/z 270.9134 (M+Na)
Calcd m/z 270.9232 (M+Na)
O
O
O
IBX, I2
p-TolSO2Na
+
9, trace
+
SO2p-Tol
R1
R1
EtOAc, reflux, 2 h
CH3
O
O
1 (10 mmol)
2a
3
p-TolSO2I (3 equiv)
3aa
O
O
(d)
Ph
O
CH3
with or without IBX
EtOAc, reflux, 2 h
SO2p-Tol
SO2p-Tol
SO2p-Tol
trace
1a
N
H3CO
Scheme 5 Control experiments for mechanistic studies
3aa, 74%
3va, 79%
3na, 68% (3 h)
13C NMR spectroscopy, and HRMS data. Reactions were monitored by
thin-layer chromatography on Merck aluminium-backed silica gel 60
F254 TLC sheets, and samples were made visual under UV and with a
solution of KMnO4. Melting points were recorded with a Sanyo
Gallenkamp apparatus. Infrared spectra were recorded on a Bruker
Scheme 4 Gram-scale reactions
In summary, we have described a facile protocol for the
formation of β-carbonyl sulfones through an IBX–I2-medi-
ated deacylative sulfonylation reaction of 1,3-dicarbonyl
compounds with sodium sulfinates. The present procedure
offers experimental simplicity as a one-pot reaction and is
an important alternative to the existing methods for the
synthesis of β-carbonyl sulfones.
1
ALPHA FT-IR spectrophotometer. H NMR and 13C NMR spectra were
recorded on a Bruker Ascend™ spectrometer and the chemical shifts
are reported in ppm using tetramethylsilane (TMS) or residual non-
deuterated solvent peaks as internal standards. High-resolution mass
spectra (HRMS) were recorded on a Bruker micrOTOF spectrometer in
ESI mode.
β-Keto Sulfones 3; General Procedure
1,3-Diketone compounds [1a,m,n,p–s,z, 5a] and solvents were ob-
tained from commercial sources and were used without further puri-
fication. Unless otherwise noted, 1,3-diketone derivatives (1b–l, 5b–
d), β-keto ester 1o and β-keto amides 1t–y were synthesized accord-
ing to literature procedures.29 Purification of the reaction products
was carried out by column chromatography on Merck silica gel 60
(0.063–0.200 mm). After column chromatography, analytically pure
solids were obtained by crystallization from CH2Cl2–hexanes. All iso-
Iodine (31.8 mg, 0.125 mmol) was added to a suspension of 1,3-dicar-
bonyl compound 1 or 5 (0.5 mmol), sodium sulfinate 2 (1.5 mmol)
and o-iodoxybenzoic acid (IBX) (1.0 mmol) in EtOAc (3 mL), and the
reaction mixture was stirred at reflux temperature for 2 h (6 h in the
case of 1,3-diarylpropane-1,3-diones). After cooling to r.t., the reac-
tion mixture was quenched by the addition of sat. aq Na2S2O3 (5 mL)
and sat. aq NaHCO3 (5 mL). Further stirring was followed by ex-
traction with EtOAc (2 × 20 mL). The combined organic extracts were
washed with H2O (20 mL) and brine (20 mL), dried over MgSO4, fil-
1
lated compounds were characterized on the basis of IR, H NMR and
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–M

H
P. Katrun et al.
Paper
Synthesis
O
O
O
S
O
O
O
R1
R2
O
O
3
R1
CH3
R1
CH3
R2SO2Na
1
I
2
+ H
– NuCOCH3
O
A
OH
HI
O
O
O
R1
NuH
CH3
NuH
CH3
R1
R1
CH3
1'
route A
I2
I
SO2R2
SO2R2
B
C
route B
IBX
(or IBA)
IBA
(or BA)
OH
O
O
O
R1
CH3
SO2R2
R1
CH3
SO2R2
I
I2
HI
B'
D
1) NuH
2) – NuCOCH3
+ H
O
O
O
O
O O
S
S
R1
R1
R2
R2
I
I2
HI
3
E
Scheme 6 Possible reaction mechanisms
tered, and concentrated (aspirator). The residue was purified by col-
umn chromatography (EtOAc/hexanes) to afford the corresponding
product.
IR (neat): 1669 (C=O), 1317, 1148 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.73–7.66 (m, 4 H), 7.37–7.26 (m, 4 H),
4.68 (s, 2 H), 2.38 (s, 3 H), 2.33 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 188.2 (C), 145.1 (C), 138.5 (C), 135.7
(C), 135.6 (C), 134.9 (CH), 129.6 (2 × CH), 129.5 (CH), 128.5 (CH),
128.4 (2 × CH), 126.4 (CH), 63.3 (CH2), 21.5 (CH3), 21.1 (CH3).
1-Phenyl-2-(p-tosyl)ethanone (3aa)15i
Prepared from benzoylacetone (1a) (81.1 mg, 0.5 mmol) and p-Tol-
SO2Na (2a) (267.3 mg, 1.50 mmol); yield: 116.5 mg (85%).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C16H16O3SNa: 311.0718;
Prepared from 1,3-diphenylpropane-1,3-dione (5a) (112.1 mg, 0.5
mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol); yield: 83.7 mg
(61%).
White solid; mp 104.5–106.0 °C (Lit.15i 106.1–108.0 °C); Rf = 0.48 (40%
found: 311.0720.
1-[4-(tert-Butyl)phenyl]-2-(p-tosyl)ethanone (3ca)
Prepared from 1-[4-(tert-butyl)phenyl]butane-1,3-dione (1c) (109.1
mg, 0.5 mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
EtOAc in hexanes).
IR (neat): 1676 (C=O), 1318, 1147 (–SO2–) cm–1
.
Yellow solid; yield: 115.5 mg (70%); mp 93.5–95.0 °C; Rf = 0.63 (40%
EtOAc in hexanes).
IR (neat): 1679 (C=O), 1300, 1140 (–SO2–) cm–1
1H NMR (400 MHz, CDCl3): δ = 7.86 (d, J = 8.5 Hz, 2 H), 7.74 (d, J = 8.3
Hz, 2 H), 7.46 (d, J = 8.5 Hz, 2 H), 7.31 (d, J = 8.1 Hz, 2 H), 4.67 (s, 2 H),
2.42 (s, 3 H), 1.31 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 187.6 (C), 158.3 (C), 145.2 (C), 135.8
(C), 133.2 (C), 129.8 (2 × CH), 129.3 (2 × CH), 128.6 (2 × CH), 125.8
(2 × CH), 63.5 (CH2), 35.3 (C), 31.0 (3 × CH3), 21.7 (CH3).
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 8.5 Hz, 2 H), 7.73 (d, J = 8.3
Hz, 2 H), 7.57 (t, J = 7.4 Hz, 1 H), 7.43 (t, J = 7.9 Hz, 2 H), 7.28 (d, J = 8.1
Hz, 2 H), 4.70 (s, 2 H), 2.39 (s, 3 H).
.
1-(m-Tolyl)-2-(p-tosyl)ethanone (3ba)
Prepared from 1-(m-tolyl)butane-1,3-dione (1b) (88.1 mg, 0.5 mmol)
and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
Pale yellow solid; yield: 112.3 mg (78%); mp 91.0–92.5 °C; Rf = 0.54
(40% EtOAc in hexanes).
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P. Katrun et al.
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Synthesis
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H22O3SNa: 353.1187;
IR (neat): 1679 (C=O), 1314, 1146 (–SO2–) cm–1
.
found: 353.1183.
1H NMR (400 MHz, CDCl3): δ = 7.81–7.78 (m, 2 H), 7.71 (d, J = 8.3 Hz, 2
H), 7.54–7.51 (m, 1 H), 7.38 (t, J = 8.2 Hz, 1 H), 7.29 (d, J = 8.0 Hz, 2 H),
4.67 (s, 2 H), 2.41 (s, 3 H).
1-(3-Methoxyphenyl)-2-(p-tosyl)ethanone (3da)22a
Prepared from 1-(3-methoxyphenyl)butane-1,3-dione (1d) (96.1 mg,
0.5 mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
1-(4-Chlorophenyl)-2-(p-tosyl)ethanone (3ia)15i
Colorless solid; yield: 107.9 mg (71%); mp 92.0–93.0 °C; Rf = 0.45 (40%
EtOAc in hexanes).
Prepared from 1-(4-chlorophenyl)butane-1,3-dione (1i) (98.3 mg, 0.5
mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
IR (neat): 1672 (C=O), 1316, 1147 (–SO2–) cm–1
.
Pale yellow solid; yield: 110.9 mg (72%); mp 131.0–132.5 °C (Lit.15i
135.7–136.5 °C); Rf = 0.54 (40% EtOAc in hexanes).
1H NMR (400 MHz, CDCl3): δ = 7.73 (d, J = 8.3 Hz, 2 H), 7.47 (d, J = 7.7
Hz, 1 H), 7.39 (t, J = 1.8 Hz, 1 H), 7.35–7.28 (m, 3 H), 7.11 (dd, J = 8.2,
2.6 Hz, 1 H), 4.69 (s, 2 H), 3.78 (s, 3 H), 2.39 (s, 3 H).
IR (neat): 1677 (C=O), 1313, 1145 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 8.7 Hz, 2 H), 7.70 (d, J = 8.3
Hz, 2 H), 7.39 (d, J = 8.7 Hz, 2 H), 7.29 (d, J = 8.0 Hz, 2 H), 4.67 (s, 2 H),
2.39 (s, 3 H).
1-(4-Methoxyphenyl)-2-(p-tosyl)ethanone (3ea)15i
Prepared from 1-(4-methoxyphenyl)butane-1,3-dione (1e) (96.1 mg,
0.5 mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol); yield: 117.0
mg (77%).
1-(3-Nitrophenyl)-2-(p-tosyl)ethanone (3ja)15i
Prepared from 1-(3-nitrophenyl)butane-1,3-dione (1j) (103.6 mg, 0.5
mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
Pale yellow solid; yield: 70.2 mg (44%); mp 126.0–127.0 °C (Lit.15i
Prepared from 1-(3-chlorophenyl)-3-(4-methoxyphenyl)propane-
1,3-dione (5b) (144.4 mg, 0.5 mmol) and p-TolSO2Na (2a) (267.3 mg,
1.50 mmol); yield: 95.8 mg (63%).
White solid; mp 122.0–123.0 °C (Lit.15i 124.0–124.8 °C); Rf = 0.35 (40%
128.0–128.7 °C); Rf = 0.34 (40% EtOAc in hexanes).
IR (neat): 1685 (C=O), 1146 (–SO2–) cm–1
.
EtOAc in hexanes).
1H NMR (400 MHz, CDCl3): δ = 8.68 (t, J = 1.9 Hz, 1 H), 8.42 (ddd, J =
8.2, 2.2, 1.0 Hz, 1 H), 8.30 (dt, J = 7.6, 1.2 Hz, 1 H), 7.72–7.67 (m, 3 H),
7.32 (d, J = 8.0 Hz, 2 H), 4.77 (s, 2 H), 2.41 (s, 3 H).
IR (neat): 1665 (C=O), 1318, 1149 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.88 (d, J = 8.9 Hz, 2 H), 7.71 (d, J = 8.3
Hz, 2 H), 7.27 (d, J = 8.1 Hz, 2 H), 6.88 (d, J = 8.9 Hz, 2 H), 4.64 (s, 2 H),
3.81 (s, 3 H), 2.38 (s, 3 H).
1-(Furan-2-yl)-2-(p-tosyl)ethanone (3ka)26c
Prepared from 1-(furan-2-yl)butane-1,3-dione (1k) (76.1 mg, 0.5
mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
1-(3,5-Dimethoxyphenyl)-2-(p-tosyl)ethanone (3fa)
Prepared from 1-(3,5-dimethoxyphenyl)butane-1,3-dione (1f) (111.1
mg, 0.5 mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
Yellow solid; yield: 77.9 mg (59%); mp 124.5–125.5 °C; Rf = 0.30 (40%
EtOAc in hexanes).
Colorless solid; yield: 125.3 mg (75%); mp 148.5–149.5 °C; Rf = 0.41
(40% EtOAc in hexanes).
IR (neat): 1645 (C=O), 1313, 1152 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.3 Hz, 2 H), 7.55 (t, J = 1.0
Hz, 1 H), 7.29–7.27 (m, 3 H), 6.52 (dd, J = 3.7, 1.7 Hz, 1 H), 4.53 (s, 2 H),
2.37 (s, 3 H).
IR (neat): 1673 (C=O), 1318, 1147 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.74 (d, J = 8.3 Hz, 2 H), 7.29 (d, J = 8.0
Hz, 2 H), 7.00 (d, J = 2.3 Hz, 2 H), 6.64 (t, J = 2.3 Hz, 1 H), 4.66 (s, 2 H),
3.77 (s, 6 H), 2.40 (s, 3 H).
1-(p-Tosyl)propan-2-one (3ma)26b
13C NMR (100 MHz, CDCl3): δ = 187.8 (C), 160.8 (2 × C), 145.2 (C),
137.5 (C), 135.7 (C), 129.7 (2 × CH), 128.5 (2 × CH), 106.8 (2 × CH),
106.7 (CH), 63.5 (CH2), 55.5 (2 × CH3), 21.6 (CH3).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C17H18O5SNa: 357.0773;
found: 357.0775.
Prepared from acetylacetone (1m) (50.1 mg, 0.5 mmol) and p-TolSO2Na
(2a) (267.3 mg, 1.50 mmol).
Colorless oil; yield: 40.3 mg (38%); Rf = 0.38 (40% EtOAc in hexanes).
IR (neat): 1715 (C=O), 1317, 1146 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.73 (d, J = 8.3 Hz, 2 H), 7.34 (d, J = 8.1
Hz, 2 H), 4.11 (s, 2 H), 2.42 (s, 3 H), 2.37 (s, 3 H).
1-(2-Chlorophenyl)-2-(p-tosyl)ethanone (3ga)15i
Prepared from 1-(2-chlorophenyl)butane-1,3-dione (1g) (98.3 mg,
0.5 mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
Pale yellow solid; yield: 78.5 mg (51%); mp 90.5–92.0 °C (Lit.15i 96.0–
Methyl 2-(p-Tosyl)acetate (3na)26c
Prepared from methyl acetoacetate (1n) (58.1 mg, 0.5 mmol) and p-
TolSO2Na (2a) (267.3 mg, 1.50 mmol).
97.0 °C); Rf = 0.48 (40% EtOAc in hexanes).
Colorless oil; yield: 63.8 mg (56%); Rf = 0.38 (40% EtOAc in hexanes).
IR (neat): 1739 (C=O ester), 1146 (–SO2–) cm–1
1H NMR (400 MHz, CDCl3): δ = 7.77 (d, J = 8.3 Hz, 2 H), 7.33 (d, J = 8.1
Hz, 2 H), 4.07 (s, 2 H), 3.66 (s, 3 H), 2.41 (s, 3 H).
IR (neat): 1695 (C=O), 1307, 1139 (–SO2–) cm–1
.
.
1H NMR (400 MHz, CDCl3): δ = 7.73 (d, J = 8.3 Hz, 2 H), 7.51 (dd, J = 7.6,
1.6 Hz, 1 H), 7.42–7.28 (m, 5 H), 4.49 (s, 2 H), 2.40 (s, 3 H).
1-(3-Chlorophenyl)-2-(p-tosyl)ethanone (3ha)15i
Ethyl 2-(p-Tosyl)acetate (3oa)26c
Prepared from 1-(3-chlorophenyl)butane-1,3-dione (1h) (98.3 mg,
0.5 mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
Pale yellow solid; yield: 89.3 mg (58%); mp 120.0–121.0 °C (Lit.15i
Prepared from ethyl acetoacetate (1o) (65.1 mg, 0.5 mmol) and p-Tol-
SO2Na (2a) (267.3 mg, 1.50 mmol).
Colorless oil; yield: 73.2 mg (60%); Rf = 0.30 (25% EtOAc in hexanes).
123.8–125.5 °C); Rf = 0.50 (40% EtOAc in hexanes).
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P. Katrun et al.
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Synthesis
IR (neat): 1735 (C=O ester), 1323, 1146 (–SO2–) cm–1
.
13C NMR (100 MHz, CDCl3): δ = 161.4 (C), 144.9 (C), 142.6 (C), 136.5
(C), 130.1 (2 × CH), 129.5 (2 × CH), 128.6 (2 × CH), 128.5 (CH), 127.4
(2 × CH), 59.0 (CH2), 37.6 (CH3), 21.6 (CH3).
1H NMR (400 MHz, CDCl3): δ = 7.81 (d, J = 8.3 Hz, 2 H), 7.36 (d, J = 8.4
Hz, 2 H), 4.14 (q, J = 7.1 Hz, 2 H), 4.08 (s, 2 H), 2.45 (s, 3 H), 1.19 (t, J =
7.1 Hz, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H18NO3S: 304.1007; found:
304.1008.
tert-Butyl 2-(p-Tosyl)acetate (3pa)26c
N,N-Diethyl-2-(p-tosyl)acetamide (3ua)26c
Prepared from tert-butyl acetoacetate (1p) (79.1 mg, 0.5 mmol) and
p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
Prepared from N,N-dimethyl-3-oxobutanamide (1u) (64.6 mg, 0.5
mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
White solid; yield: 116.4 mg (84%); mp 84.0–85.0 °C (Lit.26c 87.0–
88.0 °C); Rf = 0.59 (100% EtOAc).
IR (neat): 1641 (C=O amide), 1317, 1148 (–SO2–) cm–1
1H NMR (400 MHz, CDCl3): δ = 7.80 (d, J = 8.3 Hz, 2 H), 7.35 (d, J = 8.2
Hz, 2 H), 4.19 (s, 2 H), 3.48 (q, J = 7.2 Hz, 2 H), 3.34 (q, J = 7.1 Hz, 2 H),
2.44 (s, 3 H), 1.21 (t, J = 7.2 Hz, 3 H), 1.10 (t, J = 7.1 Hz, 3 H).
Colorless oil; yield: 54.0 mg (40%); Rf = 0.56 (40% EtOAc in hexanes).
IR (neat): 1729 (C=O ester), 1324, 1141 (–SO2–) cm–1
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 8.3 Hz, 2 H), 7.34 (d, J = 8.1
Hz, 2 H), 3.98 (s, 2 H), 2.42 (s, 3 H), 1.34 (s, 9 H).
.
.
Benzyl 2-(p-Tosyl)acetate (3qa)30a
Prepared from benzyl acetoacetate (1q) (96.1 mg, 0.5 mmol) and p-
TolSO2Na (2a) (267.3 mg, 1.50 mmol).
1-(Piperidin-1-yl)-2-(p-tosyl)ethan-1-one (3va)30b
Pale yellow oil; yield: 53.2 mg (35%); Rf = 0.50 (40% EtOAc in hexanes).
IR (neat): 1736 (C=O ester), 1324, 1145 (–SO2–) cm–1
1H NMR (400 MHz, CDCl3): δ = 7.73 (d, J = 8.3 Hz, 2 H), 7.36–7.33 (m, 3
H), 7.29–7.25 (m, 4 H), 5.11 (s, 2 H), 4.13 (s, 2 H), 2.43 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 162.3 (C), 145.3 (C), 135.5 (C), 134.4
(C), 129.8 (2 × CH), 128.61 (CH), 128.57 (2 × CH), 128.53 (2 × CH),
128.47 (2 × CH), 67.9 (CH2), 61.0 (CH2), 21.7 (CH3).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C16H16O4SNa: 327.0667;
found: 327.0673.
Prepared from 1-(piperidin-1-yl)butane-1,3-dione (1v) (84.6 mg, 0.5
mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
.
White solid; yield: 127.6 mg (89%); mp 117.0–119.0 °C; Rf = 0.56
(100% EtOAc).
IR (neat): 1639 (C=O amide), 1313, 1143 (–SO2–) cm–1
1H NMR (400 MHz, CDCl3): δ = 7.78 (d, J = 8.3 Hz, 2 H), 7.34 (d, J = 8.0
Hz, 2 H), 4.22 (s, 2 H), 3.55–3.49 (m, 4 H), 2.42 (s, 3 H), 1.70–1.60 (m, 4
H), 1.55–1.50 (m, 2 H).
.
1-Morpholino-2-(p-tosyl)ethan-1-one (3wa)30c
3-(p-Tosyl)dihydrofuran-2(3H)-one (3ra)26c
Prepared from 1-morpholinobutane-1,3-dione (1w) (85.6 mg, 0.5
mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
Prepared from 2-acetylbutyrolactone (1r) (64.1 mg, 0.5 mmol) and p-
TolSO2Na (2a) (267.3 mg, 1.50 mmol).
White solid; yield: 121.8 mg (86%); mp 163.0–164.0 °C; Rf = 0.41
(100% EtOAc).
IR (neat): 1643 (C=O amide), 1308, 1145 (–SO2–) cm–1
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 8.2 Hz, 2 H), 7.36 (d, J = 8.0
Hz, 2 H), 4.21 (s, 2 H), 3.77 (t, J = 4.4 Hz, 2 H), 3.67 (t, J = 4.4 Hz, 2 H),
3.63 (t, J = 4.4 Hz, 2 H), 3.59 (t, J = 4.4 Hz, 2 H), 2.44 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.9 (C), 145.5 (C), 135.6 (C), 129.9
(2 × CH), 128.3 (2 × CH), 66.6 (CH2), 66.5 (CH2), 59.6 (CH2), 47.5 (CH2),
42.6 (CH2), 21.7 (CH3).
White solid; yield: 102.5 mg (85%); mp 76.0–78.0 °C; Rf = 0.23 (40%
EtOAc in hexanes).
IR (neat): 1761 (C=O ester), 1315, 1142 (–SO2–) cm–1
1H NMR (400 MHz, CDCl3): δ = 7.77 (d, J = 8.3 Hz, 2 H), 7.34 (d, J = 8.1
Hz, 2 H), 4.40–4.28 (m, 2 H), 4.04 (dd, J = 10.0, 4.7 Hz, 1 H), 2.91–2.85
(m, 1 H), 2.72–2.64 (m, 1 H), 2.42 (s, 3 H).
.
.
N-Phenyl-2-(p-tosyl)acetamide (3sa)26c
Prepared from 3-oxo-N-phenylbutanamide (1s) (88.6 mg, 0.5 mmol)
and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H18NO4S: 284.0957; found:
284.0959.
White solid; yield: 82.4 mg (57%); mp 164.0–166.0 °C; Rf = 0.33 (40%
EtOAc in hexanes).
IR (neat): 3326 (N–H), 1665 (C=O amide), 1314, 1150 (–SO2–) cm–1
1H NMR (400 MHz, CDCl3): δ = 8.54 (br s, 1 H), 7.78 (d, J = 8.3 Hz, 2 H),
7.48 (d, J = 8.7 Hz, 2 H), 7.35–7.30 (m, 4 H), 7.14 (t, J = 7.4 Hz, 1 H),
4.14 (s, 2 H), 2.42 (s, 3 H).
1-Methyl-3-(p-tosyl)pyrrolidin-2-one (3xa)30d
.
Prepared from 3-acetyl-1-methylpyrrolidin-2-one (1x) (70.6 mg, 0.5
mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
Yellow solid; yield: 105.8 mg (84%); mp 108.0–109.0 °C; Rf = 0.33
(100% EtOAc).
IR (neat): 1687 (C=O lactam), 1301, 1141 (–SO2–) cm–1
.
N-Methyl-N-phenyl-2-(p-tosyl)acetamide (3ta)
1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 8.3 Hz, 2 H), 7.30 (d, J = 8.0
Hz, 2 H), 3.89 (dd, J = 10.0, 4.2 Hz, 1 H), 3.39–3.32 (m, 1 H), 3.25 (td, J =
9.1, 3.4 Hz, 1 H), 2.76 (s, 3 H), 2.70–2.61 (m, 1 H), 2.46–2.35 (m, 1 H),
2.39 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 165.3 (C), 145.0 (C), 134.4 (C), 129.4
(2 × CH), 129.0 (2 × CH), 65.6 (CH), 46.9 (CH2), 29.9 (CH3), 21.5 (CH3),
19.6 (CH2).
Prepared from N-methyl-3-oxo-N-phenylbutanamide (1t) (95.6 mg,
0.5 mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
White solid; yield: 121.2 mg (80%); mp 106.0–108.0 °C; Rf = 0.31 (50%
EtOAc in hexanes).
IR (neat): 1660 (C=O amide), 1301, 1142 (–SO2–) cm–1
1H NMR (400 MHz, CDCl3): δ = 7.77 (d, J = 8.3 Hz, 2 H), 7.44–7.35 (m, 3
H), 7.33 (d, J = 8.3 Hz, 2 H), 7.18 (d, J = 7.3 Hz, 2 H), 3.96 (s, 2 H), 3.24
(s, 3 H), 2.43 (s, 3 H).
.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C12H15NO3SNa: 276.0670;
found: 276.0679.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–M

K
P. Katrun et al.
Paper
Synthesis
1-[2-(p-Tosyl)acetyl]pyrrolidin-2-one (3ya)30e
1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 8.2 Hz, 2 H), 7.78 (d, J = 9.0
Hz, 2 H), 7.59 (t, J = 7.4 Hz, 1 H), 7.45 (t, J = 7.4 Hz, 2 H), 6.96 (d, J = 9.0
Hz, 2 H), 4.70 (s, 2 H), 3.85 (s, 3 H).
Prepared from 1-(2-oxopyrrolidin-1-yl)butane-1,3-dione (1y) (84.6
mg, 0.5 mmol) and p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
Yellow solid; yield: 109.7 mg (78%); mp 78.0–80.0 °C; Rf = 0.19 (50%
EtOAc in hexanes).
2-[(4-Nitrophenyl)sulfonyl]-1-phenylethanone (3ae)
Prepared from benzoylacetone (1a) (81.1 mg, 0.5 mmol) and 4-
O2NC6H4SO2Na (2e) (313.7 mg, 1.50 mmol).
IR (neat): 1737 and 1687 (C=O lactam), 1315, 1136 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.78 (d, J = 8.2 Hz, 2 H), 7.32 (d, J = 8.0
Hz, 2 H), 4.88 (s, 2 H), 3.75 (t, J = 7.2 Hz, 2 H), 2.52 (t, J = 8.0 Hz, 2 H),
2.41 (s, 3 H), 1.97 (quin, J = 7.9 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 175.3 (C), 161.6 (C), 145.0 (C), 136.3
(C), 129.6 (2 × CH), 128.4 (2 × CH), 60.6 (CH2), 45.5 (CH2), 33.0 (CH2),
21.5 (CH3), 16.6 (CH2).
Pale yellow solid; yield: 56.4 mg (37%); mp 168.5–169.5 °C; Rf = 0.45
(40% EtOAc in hexanes).
IR (neat): 1672 (C=O), 1307, 1152 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.38 (d, J = 9.0 Hz, 2 H), 8.11 (d, J = 9.0
Hz, 2 H), 7.92 (d, J = 8.3 Hz, 2 H), 7.65 (t, J = 7.4 Hz, 1 H), 7.50 (t, J = 7.9
Hz, 2 H), 4.80 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 187.6 (C), 151.0 (C), 144.0 (C), 135.3
(C), 134.8 (CH), 130.3 (2 × CH), 129.2 (2 × CH), 129.1 (2 × CH), 124.3
(2 × CH), 62.9 (CH2).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C13H15NO4SNa: 304.0619;
found: 304.0622.
3-Hydroxy-2-(p-tosyl)cyclohex-2-en-1-one (4)
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C14H11NO5SNa: 328.0256;
found: 328.0253.
Prepared from cyclohexane-1,3-dione (1z) (56.1 mg, 0.5 mmol) and
p-TolSO2Na (2a) (267.3 mg, 1.50 mmol).
Yellow solid; yield: 73.2 mg (55%); mp 145.0–147.0 °C; Rf = 0.19 (10%
MeOH in EtOAc).
2-(Methylsulfonyl)-1-phenylethanone (3af)26c
Prepared from benzoylacetone (1a) (81.1 mg, 0.5 mmol) and CH3SO2-
Na (2f) (153.2 mg, 1.50 mmol).
IR (neat): 1668 (C=O), 1114 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 12.46 (br s, 1 H), 7.91 (d, J = 8.4 Hz, 2
H), 7.31 (d, J = 8.0 Hz, 2 H), 2.67 (t, J = 6.0 Hz, 2 H), 2.42 (s, 3 H), 2.35 (t,
J = 6.4 Hz, 2 H), 1.95 (quin, J = 6.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 191.4 (C), 183.5 (C), 144.8 (C), 137.6
(C), 129.3 (2 × CH), 128.4 (2 × CH), 114.0 (C), 37.3 (CH2), 31.1 (CH2),
21.6 (CH3), 19.1 (CH2).
Pale yellow solid; yield: 45.5 mg (46%); mp 98.5–100.0 °C; Rf = 0.29
(40% EtOAc in hexanes).
IR (neat): 1674 (C=O), 1297, 1151 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 8.6 Hz, 2 H), 7.63 (t, J = 7.4
Hz, 1 H), 7.50 (t, J = 7.4 Hz, 2 H), 4.59 (s, 2 H), 3.12 (s, 3 H).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C13H14O4SNa: 289.0510;
found: 289.0511.
1-(4-Methoxyphenyl)-2-(p-tosyl)-3-(3,4,5-trimethoxyphenyl)pro-
pane-1,3-dione (7)
1-Phenyl-2-(phenylsulfonyl)ethanone (3ab)26b
Prepared
from
1-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphe-
nyl)propane-1,3-dione (5d) (172.2 mg, 0.5 mmol) and p-TolSO2Na
(2a) (267.3 mg, 1.50 mmol).
Prepared from benzoylacetone (1a) (81.1 mg, 0.5 mmol) and PhSO2Na
(2b) (246.2 mg, 1.50 mmol).
White solid; yield: 163.5 mg (66%); mp 155.5–157.5 °C; Rf = 0.34 (50%
EtOAc in hexanes).
Pale yellow solid; yield: 91.0 mg (70%); mp 88.0–89.0 °C (Lit.26b 90–
92 °C); Rf = 0.48 (40% EtOAc in hexanes).
IR (neat): 1693, 1655 (C=O), 1322, 1146 (–SO2–) cm–1
.
IR (neat): 1672 (C=O), 1307, 1153 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 8.8 Hz, 2 H), 7.89 (d, J = 8.4
Hz, 2 H), 7.31 (d, J = 8.0 Hz, 2 H), 7.15 (s, 2 H), 7.13 (s, 1 H), 6.93 (d, J =
9.2 Hz, 2 H), 3.87 (s, 3 H), 3.83 (s, 3 H), 3.70 (s, 6 H), 2.40 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.90–7.85 (m, 4 H), 7.63–7.55 (m, 2 H),
7.50 (t, J = 7.6 Hz, 2 H), 7.43 (t, J = 7.7 Hz, 2 H), 4.73 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 185.3 (C), 184.6 (C), 164.4 (C), 152.8
(2 × C), 145.3 (C), 143.2 (C), 134.3 (C), 131.8 (2 × CH), 130.4 (2 × CH),
129.8 (C), 128.9 (2 × CH), 128.1 (C), 114.1 (2 × CH), 106.2 (2 × CH),
77.3 (CH), 60.6 (CH3), 55.8 (2 × CH3), 55.4 (CH3), 21.4 (CH3).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C26H26O8SNa: 521.1246;
found: 521.1240.
2-[(4-Chlorophenyl)sulfonyl]-1-phenylethanone (3ac)22a
Prepared from benzoylacetone (1a) (81.1 mg, 0.5 mmol) and 4-
ClC6H4SO2Na (2c) (297.9 mg, 1.50 mmol).
Yellow solid; yield: 107.3 mg (73%); mp 126.0–128.0 °C (Lit.22a 135–
136 °C); Rf = 0.54 (40% EtOAc in hexanes).
IR (neat): 1686 (C=O), 1305, 1140 (–SO2–) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.89 (d, J = 8.5 Hz, 2 H), 7.80 (d, J = 8.7
Hz, 2 H), 7.60 (t, J = 7.4 Hz, 1 H), 7.49–7.43 (m, 4 H), 4.74 (s, 2 H).
Acknowledgment
2-[(4-Methoxyphenyl)sulfonyl]-1-phenylethanone (3ad)22a
We thank the Thailand Research Fund (BRG5850012 and
IRN58W0005), the Center of Excellence for Innovation in Chemistry
(PERCH-CIC), the Office of the Higher Education Commission, Mahi-
dol University under the National Research Universities Initiative and
PICS6663 ISMA (France/Thailand) for financial support. The Develop-
ment and Promotion of Science and Technology Talents Project
(DPST), the Institute for the Promotion of Teaching Science and Tech-
nology for financial support through student scholarships to P.K. and
T.S. is also gratefully acknowledged.
Prepared from benzoylacetone (1a) (81.1 mg, 0.5 mmol) and 4-
CH3OC6H4SO2Na (2d) (291.3 mg, 1.50 mmol).
Yellow solid; yield: 87.0 mg (60%); mp 99.0–101.0 °C (Lit.22a 93–
94 °C); Rf = 0.35 (40% EtOAc in hexanes).
IR (neat): 1674 (C=O), 1143 (–SO2–) cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–M

L
P. Katrun et al.
Paper
Synthesis
Supporting Information
P.; Techajaroonjit, T.; Hlekhlai, S.; Pohmakotr, M.; Reutrakul, V.;
Jaipetch, T.; Soorukram, D.; Kuhakarn, C. Synthesis 2012, 44,
1693.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588900.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
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