A regioselective catalyst- and additive-free synthesis of β-keto sulfones from aryl acetylenes and sodium arenesulfinates

Article abstract of DOI:10.1055/s-0031-1290318

A facile and regioselective procedure for the preparation of β-keto sulfones has been developed through a simple reaction of aryl acetylenes and sodium arenesulfinates in nitroethane as a solvent at 50°C. The procedure is catalyst- and additive-free and shows a wide range of functional-group tolerance. In this system the formation of new C-O and C-S bonds occurs in a one-pot procedure. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290318

LETTER
413
A Regioselective Catalyst- and Additive-Free Synthesis of b-Keto Sulfones
from Aryl Acetylenes and Sodium Arenesulfinates
Regioselective
C
o
a
ndA
j
dditiv
j
e-Free
aSynthesis of
b
-K
e
S
toSulfones reedhar,* Vikas S. Rawat
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology (Council of Scientific and Industrial Research),
Hyderabad 500007, India
Fax +91(40)27160921; E-mail: sreedharb@iict.res.in
Received 18 July 2011
ous THF.21 However, the presence of acid and use of sul-
fonyl chloride leads to a system of poor functional-group
tolerance. To obviate the use of acid and sulfonyl chloride
it appeared to be beneficial to obtain b-keto sulfones di-
Abstract: A facile and regioselective procedure for the preparation
of b-keto sulfones has been developed through a simple reaction of
aryl acetylenes and sodium arenesulfinates in nitroethane as a sol-
vent at 50 °C. The procedure is catalyst- and additive-free and
shows a wide range of functional-group tolerance. In this system the rectly from alkynes and sodium arenesulfinates, as use of
formation of new C–O and C–S bonds occurs in a one-pot proce-
sodium arenesulfinates can provide weakly basic reaction
dure.
conditions, and hence be suitable for the preparation of b-
keto sulfones containing amine and other acid-sensitive
moieties.
Key words: b-keto sulfone, aryl acetylene, sodium arene sulfi-
nates, vinyl nitronic ester, sulfone, sulfinates salt
Herein we report an efficient one-pot catalyst- and addi-
tive-free procedure for the synthesis of b-keto sulfones via
the reaction of sodium arenesulfinates with aryl acety-
lenes (Scheme 1). To the best of our knowledge, this has
not been reported so far. In this system the formation of
new C–O and C–S bonds occurs with the regioselective
addition of the sulfonyl moiety at the terminal carbon of
the acetylene. In addition reaction conditions are mild,
and the procedure is insensitive to moisture.
Catalyst- and/or additive-free protocols can provide eco-
nomical and environmental benign routes for the synthe-
sis of key organic intermediates.1 Sulfones are versatile
intermediates for organic transformations involving car-
bon–carbon bond formations such as the Julia olefina-
tion.2 Amongst the different derivatives of sulfones,
b-keto sulfones are increasingly drawing interest due to
their synthetic utility as precursors in Michael3 and
Knoevenagel reactions,4 in the synthesis of disubstituted
acetylenes,5 allenes,6 vinyl sulfones,7 polyfunctionalized
4H-pyrans,3,8 ketones,9 epoxy sulfones,10 and optically ac-
tive b-hydroxysulfones.11 In addition, some of these de-
rivatives also show fungicidal activity.12
O
N
O–
O
O
S
O
O
R2
R1
H
+
R2
S
⋅nH2O
Na+
R1
O–
50 °C
Scheme 1 Synthesis of b-keto sulfones with aryl acetylenes and so-
dium arenesulfinates
General protocols for the synthesis of b-keto sulfones in-
clude oxidation of b-keto sulfides or b-hydroxy sul-
fones,13 alkylation of metallic arenesulfinates,14 acylation
of a-sulfonyl carbanions,15 ruthenium(II) complex cata-
lyzed reaction of sulfonyl chlorides with silyl enol
ethers,16 SnCl2-catalyzed reaction of diazo sulfones with
aldehydes,17 free-radical rearrangement of enol sul-
fonates,18 AIBN-catalyzed reaction of polystyrene-
supported arene seleno sulfonates19 with aryl acetylenes
and from ketones using sodium arenesulfinates with the
PhI(OH)OTs/TBAB system.20 However, most of these
methods have one or more drawbacks in terms of func-
tional-group tolerance, presence of side reactions, and
need for strict reaction conditions or complicated proce-
dures.
We have recently developed the highly efficient methods
for b-sulfonation of a,b-enones and direct sulfonylation of
alcohols using sodium arene sulfinates as sulfonylating
agents employing FeCl3/TMSCl as catalyst.22 In continu-
ation of this work, we investigated the preparation of b-
keto sulfones directly from sodium arenesulfinates and
aryl acetylenes. Initially, we examined the reaction be-
tween phenylacetylene and sodium benzenesulfinate as a
model system using various solvents at different tempera-
tures to obtain the desired product 1-phenyl-2-(phenylsul-
fonyl)ethanone (1a, Table 1).
The best conditions were found using nitroethane as sol-
vent at 50 °C, with 1.0 equivalent of phenylacetylene and
1.5 equivalents of sodium benzenesulfinate resulting in
52% isolated yield of the desired product (Table 1, entry
3). Reactions with other solvents such as water and ni-
tromethane (Table 1, entries 1 and 2) provided compara-
tively lower yields of 1a. However, with DMF, DMSO,
CH2Cl2, toluene, THF, MeOH, and PEG 400 no product
was formed (Table 1, entries 4–10). To study the influ-
Recently, Xi et al. reported an attractive method for the
preparation of b-keto sulfones by acid-catalyzed reaction
of sulfonyl chloride with aryl acetylenes at 50 °C in aque-
SYNLETT 2012, 23, 413–417
x
x.
x
x.
2
0
1
2
Advanced online publication: 25.1.2012
DOI: 10.1055/s-0031-1290318; Art ID: D22711ST
© Georg Thieme Verlag Stuttgart · New York

414
B. Sreedhar, V S. Rawat
LETTER
vents at different temperatures, was moderate, attempts at
further optimization were carried out. Unfortunately, add-
ing various catalysts and/or additives such as iron(III)
chloride, ceric ammonium nitrate, PhI(OAc)2, and cat.
H2SO4 led to no further enhancement in yield of 1a.
Table 1 Optimization of Reaction Conditions with Phenylacetylene
and Sodium Benzenesulfinatea
Entry
1
Solvent
H2O
Temp (°C) Time (h)
Yield (%)b
50
50
50
50
50
50
50
50
50
50
25
40
60
70
80
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
18
25
52
0
To explore the scope and the limitations of this reaction,
various structurally diverse aryl acetylenes and sodium
arenesulfinates were examined under the optimized reac-
tion conditions (Table 1, entry 3), and the results are
shown in Table 2.
2
MeNO2
EtNO2
DMF
3
4
5
DMSO
CH2Cl2
toluene
THF
0
The results in Table 2 demonstrate that the reaction pro-
ceeds smoothly using various aryl acetylenes and sodium
arenesulfinates to afford b-keto sulfones in moderate to
good yields. It was found that electron-donating groups,
such as methyl (2b and 2c, Table 2, entries 3–5) and meth-
oxy (2e, Table 2, entries 8 and 9), on the aryl acetylene re-
sulted in the desired product being obtained in good yield.
However, in the case of electron-poor aryl acetylenes such
as 2d (Table 2, entries 6 and 7) low yields were observed.
Sodium p-toluenesulfinate (3b), with an electron-donat-
ing methyl substituent on the aryl ring provides better
yields of b-keto sulfones compared to sodium benzene-
sulfinate (3a), indicating that the addition of the arylsulfo-
nyl moiety to the terminal carbon of the acetylene is
nucleophilic in nature. It is noteworthy that an aryl acety-
lene with a halide substituent 2d (Table 2, entries 6 and 7)
was well tolerated using this protocol; hence giving poten-
tial for further functionalization of the aryl ring.
6
0
7
0
8
0
9
MeOH
PEG 400
EtNO2
EtNO2
EtNO2
EtNO2
EtNO2
0
10
11
12
13
14
15
0
35
42
38
22
0
a Reaction conditions: phenylacetylene (1.0 mmol), sodium benzene-
sulfinate (1.5 mmol), and solvent (5 mL).
b Yield of isolated products.
The C–H acidity of nitroalkanes and their prototropy to
give nitronic acids is well known.23 Moreover, the electro-
philic addition of C–H acids such as nitroalkanes to acet-
ylenic systems, vinyl nitronic ester intermediates, and
their subsequent rearrangement to a-substituted ketones
are also well established.24,25 Based on these observations,
a plausible mechanism is shown in Scheme 2. Protonation
of the terminal carbon of the acetylene will generate a vi-
nyl cationic species I which can react with nitroethane
leading to the formation of vinyl nitronic ester II.25 The
intermediacy of II was supported by mass spectrometric
analysis of the reaction mixture after six hours, showing a
ence of temperature on the reaction, experiments were
carried out with the model substrates in nitroethane in the
range 25–80 °C. As can be seen (Table 1, entries 11–15),
conversion was highly sensitive to temperature change,
being highest at 50 °C. Furthermore, an excellent regio-
selective addition of the sulfonyl group at the terminal
carbon of acetylene was observed resulting in 1a as the
exclusive product of the reaction.
As the yield of 1a, obtained under the optimized reaction
conditions (Table 1, entry 3) after screening various sol-
O–
N+
O–
N+
slow
slow
fast
fast
H3O+
H O
+
2
NO2
+
+
H2O
O–
HO
O
O
+
+
+
N
S
O
H3O+
H+
EtNO2
– H+
N
O
H
O
O
ref. 25
II
O
S
I
III
O– Na+
OH
O
O
O
S
S
O
O
IV
Scheme 2 A plausible mechanism for the synthesis of b-keto sulfone
Synlett 2012, 23, 413–417
© Thieme Stuttgart · New York

LETTER
Regioselective Catalyst- and Additive-Free Synthesis of b-Keto Sulfones
415
peak at m/z = 333 [M + 1]+. Nucleophilic addition of sul- affording moderate to good yields of the desired products.
fonyl anion on II generates an intermediate III which on The addition of the sulfonyl group occurs exclusively at
nitrosoethane elimination and protonation forms enol IV the terminal carbon of the acetylenes. The notable advan-
which subsequently tautomerizes to the more stable keto tages of this methodology over the existing procedures are
form.
simplicity of operation, mild conditions, inexpensive re-
agents, and high functional-group tolerance.
In conclusion, we have developed a new catalyst- and ad-
ditive-free protocol for the synthesis of b-keto sulfones
using various aryl acetylenes and sodium arenesulfinates
Table 2 Reaction of Sodium Arenesulfinates with Aryl Acetylenes in Nitroethane at 50 °Ca
Entry Aryl acetylene
Sodium arene sulfinate
Product
Time (h) Yield (%)b
O
O
O
O
S
S
•nH2O
Na+
1
48
48
48
48
52
57
51
50
O–
O
2a
3a
1a
1b
1c
1d
O–
O
O
S
•nH2O
Na+
S
2
3
4
2a
O
3b
3a
O
O
S
O
2b
2b
O
O
S
3b
3b
O
O
O
S
5
6
48
48
57
39
O
2c
1e
Cl
Cl
O
O
S
3a
O
2d
2d
1f
Cl
O
O
S
7
8
3b
3a
48
48
41
49
O
1g
O
O
S
MeO
MeO
O
2e
1h
© Thieme Stuttgart · New York
Synlett 2012, 23, 413–417

416
B. Sreedhar, V S. Rawat
LETTER
Table 2 Reaction of Sodium Arenesulfinates with Aryl Acetylenes in Nitroethane at 50 °Ca (continued)
Entry Aryl acetylene
Sodium arene sulfinate
Product
Time (h) Yield (%)b
O
O
S
MeO
9
2e
3b
48
48
51
46
O
1i
O
O
S
10
3a
3b
O
MeO
MeO
2f
1j
O
O
S
11
2f
48
49
O
MeO
1k
a Reaction conditions: aryl acetylene (1.0 mmol), sodium arene sulfinate (1.5 mmol), and EtNO2 (5 mL) at 50 °C.
b Yield of isolated products.
Typical Experimental Procedure
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A mixture of aryl acetylene (1 mmol) and sodium arene sulfinate
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V.S.R. thanks University Grant Commission (UGC), New Delhi for
the award of Senior Research Fellowship (SRF).
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Regioselective Catalyst- and Additive-Free Synthesis of b-Keto Sulfones
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