Stereoselective synthesis of (E)-alkenyl sulfones from alkenes or alkynes via copper-catalyzed oxidation of sodium sulfinates

Article abstract of DOI:10.1055/s-0030-1260544

Alkenyl sulfones can be stereoselectively synthesized from alkenes or alkynes using sodium sulfinates. The reaction can be performed by a copper-catalyzed oxidation of sodium sulfinates in air. The reaction of alkenes gives (E)-alkenyl sulfones via anti addition of sulfonyl cation and elimination process. Furthermore, the employment of alkynes produces (E) β- haloalkenyl sulfones in the presence of potassium halides. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0030-1260544

1308
LETTER
Stereoselective Synthesis of (E)-Alkenyl Sulfones from Alkenes or Alkynes via
Copper-Catalyzed Oxidation of Sodium Sulfinates
Stereoselective
Sy
o
nthesis of
(
E
)
-Alkenyl Sul
u
fones kazu Taniguchi*
Department of Chemistry, Fukushima Medical University, Fukushima 960-1295, Japan
Fax +81(24)5471369; E-mail: taniguti@fmu.ac.jp
Received 27 January 2011
Table 1 Investigation of Suitable Conditions for the Synthesis of
Alkenyl Sulfones in Aira
Abstract: Alkenyl sulfones can be stereoselectively synthesized
from alkenes or alkynes using sodium sulfinates. The reaction can
be performed by a copper-catalyzed oxidation of sodium sulfinates
in air. The reaction of alkenes gives (E)-alkenyl sulfones via anti ad-
dition of sulfonyl cation and elimination process. Furthermore, the
employment of alkynes produces (E)-b-haloalkenyl sulfones in the
presence of potassium halides.
SO2C6H4Me-4
Ph
3ab
+
4-MeC6H4SO2Na (2b),
OH
O
cat. [Cu]-bpy
SO2C6H4Me-4
Ph
Ph
Ph
additive, solvent, air,
100 °C
Key words: alkenyl sulfone, copper catalyst, sodium sulfinate,
alkene, alkyne
1a
4
+
SO2C6H4Me-4
5
Transition-metal-catalyzed carbon–sulfur bond forma-
tions are important methodologies for preparations of var-
ious organosulfur derivatives.1 The compounds obtained
herein have been widely utilized in organic synthesis.2 In
particular, alkenyl sulfones are employed as convenient
synthetic intermediates or reagents.3
Entry CuX
Additive Condition
Ratio of
3ab
3ab/4/5b (%)c
1
2
CuI
none
none
none
none
KI
DMFd
–
0
0
CuI
DMSOd
AcOHd
–
To prepare sulfones, numerous procedures have been de-
veloped so far.1,4 For instance, methods by Horner–
Emmons reaction, aldol condensation, and oxidation of
vinyl sulfides are well-known.
3
CuI
67:33:0
50:8:42
86:7:7
14
35
82
4
CuI
AcOH, DMSOe
AcOH, DMSOe
5
CuI
On the contrary, utilizations of sulfinic acid salts as sulfo-
nylation reagents5 are restricted to Michael addition6 or a
transition-metal-catalyzed coupling with alkenyl halides.7
6
CuI
n-Bu4NI AcOH, DMSOe
74:15:11 30
7
CuI
KBr
none
KI
AcOH, DMSOe
AcOH, DMSOe
AcOH, DMSOe
AcOH, DMSOe
AcOH, DMSOe
AcOH, DMSOe
AcOH, DMSOe
AcOH, DMSOe
AcOH, DMSOe
AcOH, DMSOe
80:12:8
0:67:33
77:23:0
80:16:4
83:17:0
84: 8:8
84:16:0
59:35:6
71:29:0
53:26:21
55
0
Furthermore, catalytic syntheses of alkenyl sulfones from
nonactivated alkenes or alkynes have not been reported to
date.
8
None
CuCl
CuBr
CuCl2
CuBr2
9
31
37
29
80
81
39
48
5
10
11
12
13
14f
15g
16h
KI
oxidation
cat. [Cu]
R
ArO2S
•
ArSO2Na
ArSO2
R
KI
+
or ArSO2
KI
Scheme 1 Strategy of the catalytic alkenyl sulfone synthesis using
sulfinic acid salts
Cu(OAc)2 KI
CuI
CuI
CuI
KI
In order to carry out sulfonylations of normal alkenes us-
ing sulfinic acid salts, a generation of sulfonyl radical or
cation by oxidation is required at first step (Scheme 1).
KI
none
In usual method, stoichiometric oxidants such as CAN are
well utilized.8 Regrettably, the catalytic reaction could not
be currently achieved. Although, the use of commercially
available sulfonyl chlorides can produce alkenyl sulfones
from alkenes,9 it is not the convenient and the effective
a The mixture of 1a (0.3 mmol), 4-MeC6H4SO2Na (2b, 0.33 mmol),
additive (0.15 mmol) and CuI–bpy (1:1, 0.024 mmol) was treated in
DMSO or/and AcOH.
b The ratio was determined by 1H NMR.
c Isolated yields after silica gel chromatography.
d 0.3 mL of solvent was used.
e AcOH (0.15 mL) and DMSO (0.15 mL) were used.
f TMEDA was used instead of bpy.
SYNLETT 2011, No. 9, pp 1308–1312
x
x.
x
x.
2
0
1
1
g 2,2¢-Bis(2-oxazoline) was used instead of bpy.
h No bpy was employed.
Advanced online publication: 20.04.2011
DOI: 10.1055/s-0030-1260544; Art ID: U00911ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Stereoselective Synthesis of (E)-Alkenyl Sulfones
1309
method. The reaction is necessary for two steps including tries 6 and 7). The reaction in the absence of a copper
addition and elimination process, and only limited sub- catalyst and KI could not produce 3ab (Table 1, entry 8).
strates are available.
Then, the employment of CuBr2 and Cu(OAc)2 were also
available, and the reactions afforded satisfied results
(Table 1, entries 12 and 13). On the contrary, other copper
salts (CuCl, CuBr, and CuCl2) could not promote the
reaction (Table 1, entries 9–11). The reactions using other
ligands [TMEDA and 2,2¢-Bis(2-oxazoline)] were also
lower yields (Table 1, entries 14 and 15).
As an approach to explore one-step reaction in one pot, a
copper-catalyzed reaction in air was investigated,10 and it
was found that (E)-alkenyl sulfones can be stereoselec-
tively synthesized from sodium sulfinates with alkenes or
alkynes.
The methodology is described in this paper.
On the basis of the developed procedure, numerous alke-
nyl sulfoxides were prepared (Table 2).11,12 The reaction
of terminal alkenes 1 with sodium sulfinates afforded the
corresponding alkenyl sulfones 3 in 60–94% yields
(Table 2, entries 1–11). Similarly, the use of allyl trimeth-
ylsilane produced allyl sulfone 3gb in 43% yield (Table 2,
entry 11).
Initially, a reaction of alkenes with sodium sulfinates was
investigated. When a mixture of styrene 1a (0.3 mmol)
and 4-MeC6H4SO2Na (2b, 0.3 mmol) in DMF or DMSO
was treated by CuI–bpy (1:1, 8 mol%) catalyst, the ex-
pected alkenyl sulfone 3ab was not detected at all
(Table 1, entries 1 and 2). However, the reaction using
acetic acid as a solvent afforded 3ab in 14% yield
(Table 1, entry 3). When a mixture of acetic acid and
DMSO used as the solvent, the production of 3ab in-
creased to 35% yield (Table 1, entry 4).
Not only terminal alkenes but also internal alkenes were
available in this procedure (Table 2, entries 12–15). Reac-
tions of (E)- or (Z)-b-methylstyrenes afforded same (E)-
alkenyl sulfone 3hb without formations of other stereo-
isomers (Table 2, entries 12 and 13).
Fortunately, the addition of KI (0.15 mmol) facilitated the
reaction, and 3ab was obtained in 82% yield with a trace
of hydroxysulfone 4 and a trace of b-ketosulfone 5 as
byproducts (Table 1, entry 5). The stereochemistry of 3ab
was E.7c The addition of n-Bu4NI or KBr reduced the pro-
duction to 30% or 55% yield, respectively (Table 1, en-
Unfortunately, the reaction of stilbene or cyclohexene
barely proceeded (Table 2, entries 16 and 17).
Table 2 Copper-Catalyzed Synthesis of Alkenyl Sulfones from Alkenesa
R3SO2Na (2),
CuI-bpy (8 mol%),
KI (50 mol%)
SO2R3
R2
R1
R1
AcOH, DMSO, air,
100 °C
R2
1
3
Entry
1
1
3
Time (h)
18
Yield of 3 (%)b
SO2Ph
94
Ph
Ph
3aa
SO2C6H4Me-4
SO2C6H4OMe-4
SO2C6H4Cl-4
SO2Me
2
3
4
5
18
18
18
18
82
80
80
74
Ph
3ab
Ph
3ac
Ph
3ad
Ph
3ad
SO2C6H4Me-4
6
7
18
18
71
85
4-MeC6H4
4-MeC6H4
4-ClC6H4
3bb
SO2C6H4Me-4
4-ClC6H4
3cb
SO2C6H4Me-4
8
18
66
3db
Synlett 2011, No. 9, 1308–1312 © Thieme Stuttgart · New York

1310
N. Taniguchi
LETTER
Table 2 Copper-Catalyzed Synthesis of Alkenyl Sulfones from Alkenesa (continued)
R3SO2Na (2),
CuI-bpy (8 mol%),
KI (50 mol%)
SO2R3
R2
R1
R1
AcOH, DMSO, air,
100 °C
R2
1
3
Entry
9
1
3
Time (h)
24
Yield of 3 (%)b
SO2C6H4Me-4
60
73
43
n-C6H13
n-C6H13
3eb
Ph
SO2C6H4Me-4
10
11
24
18
Ph
3fb
TMS
SO2C6H4Me-4
3gb
SO2C6H4Me-4
SO2C6H4Me-4
SO2C6H4Me-4
Ph
12
13
18
18
53
61
Ph
Ph
3hb
Ph
3hb
Ph
14
42
70c
Ph
OH
OH
3ib
SO2C6H4Me-4
15
16
17
72
18
18
68
3jb
SO2C6H4Me-4
Ph
trace
trace
Ph
Ph
Ph
SO2C6H4Me-4
3kb
3lb
a Conditions: The mixture of alkene 1 (0.3 mmol), R3SO2Na 2 (0.33 mmol), KI (0.15 mmol), and CuI–bpy (1:1, 0.024 mmol) in DMSO (0.15
mL) and AcOH (0.15 mL) was stirred at 100 °C.
b Isolated yields after silica gel chromatograpy.
c Acetate was also obtained in 5% yield.
Attention was then focused on the sulfonylation of styrene 1a with 4-MeC6H4SO2Na (2b) was treated under
alkynes. As shown in Table 3, the reaction was performed nitrogen atmosphere, the corresponding alkenyl sulfone
by CuI–bpy (1:1, 8 mol%) in acetic acid, and various 3ab was obtained in 27% yield (Scheme 2). Similarly, in
alkynes 6 were examined.12,13 The procedure could stere-
oselectively give the corresponding (E)-b-haloalkenyl
4-MeC6H4SO2Na (2b),
CuI-bpy (8 mol%),
sulfones 7 from terminal or internal alkynes 6 (Table 3,
KI (50 mol%)
SO2C6H4Me-4
entries 1–6). The sulfonylation proceeded anti-selective-
ly.
Ph
Ph
AcOH, DMSO, 100 °C,
under N2, 18 h
1a
3ab: 27%
Strangely, the reaction using 4-octyne afforded (E)-4-bro-
mo-5-(4-tolylthio)-4-octene in 32% yield, and the forma-
tion of the expected alkenyl sulfone 7db was only 5%
yield (Table 3, entry 7). On the other hand, diphenyl acet-
ylene was lower reactivity (Table 3, entry 8).
Br
4-MeC6H4SO2Na (2b),
KBr, CuI-bpy (8 mol%)
Ph
Ph
AcOH, 100 °C,
under N2, 18 h
6c
SO2C6H4Me-4
7cb: 20%
To investigate reaction mechanisms, sulfonylations in the
absence of oxygen were carried out. When a mixture of
Scheme 2 Sulfonylation of alkene or alkyne in the absence of oxy-
gen
Synlett 2011, No. 9, 1308–1312 © Thieme Stuttgart · New York

LETTER
Stereoselective Synthesis of (E)-Alkenyl Sulfones
1311
ed (E)-alkenyl sulfones via anti additions to alkenes and
eliminations of HI or (E)-b-haloalkenyl sulfones via anti
additions to alkynes.
Table 3 Copper-Catalyzed Synthesis of Alkenyl Sulfones from
Alkynesa
R3SO2Na, KX
X
cat. CuI-bpy (8 mol%)
R2
R2
R1
R1
H+
+
1/4O2
1/2H2O
AcOH, air, 100 °C
I–
oxi.
6
SO2R3
7
by CuII or O2
CuIILn
CuILn
R1
Entry 6
7
Time Yield of 7
H
•
(h) (%)b
I
•
I
ArO2S
ArSO2
ArSO2Na
R1
H
R2
oxi. by CuII
R2
Br
+
1
18 63
18 52
18 74
18 51
18 30
ArSO2
R1
– HI
R2
Ph
Ph
SO2Ph
R2
7aa
Br
KX
R1
X
R1
2
3
4
5
ArO2S
Ph
SO2C6H4Me-4
7ab
Br
R2
ArO2S
Scheme 3 A plausible reaction mechanism
Ph
SO2Me
7ae
I
In conclusion, preparation of alkenyl sulfoxides was con-
veniently achieved via a copper-catalyzed oxidation of
sulfinic acid sodium salts in air. The reaction using al-
kenes afforded (E)-alkenyl sulfones. Furthermore, the
employment of alkynes gave (E)-b-haloalkenyl sulfones.
Ph
SO2Me
7ae-I
Br
n-C6H13
n-C6H13
SO2C6H4Me-4
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
7bb
Br
6
7
8
18 71
Ph
References and Notes
Ph
SO2C6H4Me-4
7cb
Br
(1) Selected reviews: (a) Ley, S. V.; Thomas, A. W. Angew.
Chem. Int. Ed. 2003, 42, 5400. (b) Kondo, T.; Mitsudo, T.
Chem. Rev. 2000, 100, 3205. (c) Comprehensive Organic
Synthesis, Vol. 4; Trost, B. M.; Fleming, I., Eds.; Pergamon
Press: New York, 1991. (d) Krief, A. In Comprehensive
Organometallic Chemistry II, Vol. 11; Abel, E. W.; Stone,
F. G. A.; Wilkinson, G., Eds.; Pergamon Press: New York,
1995, Chap. 13. (e) Metal-Catalyzed Cross-Coupling
Reactions; Meijere, A.; Diederich, F., Eds.; Wiley-VCH:
Weinheim, 2004.
n-Pr
18 5c
n-Pr
Ph
n-Pr
n-Pr
SO2C6H4Me-4
7db
Br
Ph
18 trace
Ph
Ph
SO2C6H4Me-4
7eb
(2) (a) Metzner, P.; Thuillier, A. Sulfur Reagents in Organic
Synthesis; Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W.,
Eds.; Academic Press: San Diego, 1994.
a Conditions: The mixture of 6 (0.3 mmol), R3SO2Na 2 (0.33 mmol),
KX (0.33 mmol), and CuI–bpy (1:1, 0.024 mmol) in AcOH (0.3 mL)
was stirred at 100 °C.
(b) Comprehensive Organic Synthesis, Vol. 6; Trost, B. M.;
Fleming, I., Eds.; Pergamon Press: New York, 1991.
(3) (a) Mauleón, P.; Alonso, I.; Rivero, M. R.; Carretero, J. C.
J. Org. Chem. 2007, 72, 9924. (b) Enders, D.; Müller, S. F.;
Raabe, G.; Runsink, J. Eur. J. Org. Chem. 2000, 879.
(4) (a) Guan, Z.-H.; Zuo, W.; Zhoo, L.-B.; Ren, Z.-H.; Liang,
Y.-M. Synthesis 2007, 1465. (b) Kamigata, N.; Sawada, H.;
Kobayashi, M. J. Org. Chem. 1983, 48, 3793. (c) Gancarz,
R. A.; Kice, J. L. J. Org. Chem. 1981, 46, 4899.
b Isolated yields after silica gel chromatograpy.
c (E)-4-Bromo-5-(4-tolylthio)-4-octene was also obtained in 32%
yield.
the reaction using 1-phenyl-1-propyne (6c), the yield of
(E)-b-bromoalkenyl sulfone 7cb was 20% (Scheme 2).
These experiments suggest that oxygen is necessary for
promotions of these procedures. In addition, it seems that
disproportionations of copper complexes also proceed.9,14
(d) Hoogenboom, B. E.; El-Faghi, M. S.; Fink, S. C.; Ihrig,
P. I.; Langsjoen, A. N.; Linn, C. J.; Maehling, K. L. J. Org.
Chem. 1975, 40, 880. (e) Posner, G. H.; Brunelle, D. J.
J. Org. Chem. 1972, 37, 3547.
From these results, reaction mechanisms are considered as
follows (Scheme 3). At first step, after Cu(II) was pro-
duced by the oxidation of Cu(I) or the disproportionation,
sulfonyl radicals or cations were afforded by Cu(II).15
Consequently, herein produced sulfonyl activators afford-
(5) (a) Beaulieu, C.; Guay, D.; Wang, Z.; Evans, D. A.
Tetrahedron Lett. 2004, 45, 3233. (b) Baskin, J. M.; Wang,
Z. Org. Lett. 2002, 4, 4423. (c) Suzuki, H.; Abe, H.
Tetrahedron Lett. 1995, 36, 6239.
Synlett 2011, No. 9, 1308–1312 © Thieme Stuttgart · New York

1312
N. Taniguchi
LETTER
(6) (a) Perrlmutter, P. Conjugate Addition Reactions in Organic
Synthesis; Baldwin, J. L.; Magnus, F. P. D., Eds.; Pergamon
Press: Oxford, 1992. (b) Ochiai, M.; Kitagawa, Y.;
Toyonari, M.; Uemura, K.; Oshima, K.; Shiro, M. J. Org.
Chem. 1997, 62, 8001.
(7) (a) Battace, A.; Zair, T.; Doucet, H.; Santelli, M. Synthesis
2006, 3495. (b) Cacchi, S.; Fabrizi, G.; Goggiamani, A.;
Parisi, L. M.; Bernini, R. J. Org. Chem. 2004, 69, 5608.
(c) Bian, M.; Xu, F.; Ma, C. Synthesis 2007, 2951.
(8) (a) Nair, V.; Augustine, A.; Suja, T. D. Synthesis 2002,
2259. (b) Mochizuki, T.; Hayakawa, S.; Narasaka, K. Bull.
Chem. Soc. Jpn. 1996, 69, 2317.
133.3, 132.2, 131.1, 129.3, 128.9, 128.5, 127.6, 127.2. IR
(CHCl3): 3061, 3025, 1613, 1447, 1306 cm–1. Anal. Calcd
for C14H12O2S: C, 68.83; H, 4.95. Found: C, 68.75; H, 5.13.
(12) The stereochemistry of these compounds was determined by
the comparison with references or authentic samples.
Compounds 7cb, 7db, (Z)-3hb, and (Z)-3ib were prepared
by oxidation of the corresponding alkenyl sulfides using
MCPBA. For the preparation of alkenyl sulfides, see:
Taniguchi, N. Tetrahedron 2009, 65, 2782; see ref. 15a.
(13) Typical Procedure of b-Haloalkenyl Sulfones Using
Alkynes
To a mixture of CuI (4.6 mg, 0.024 mmol), bpy (3.7 mg,
0.024 mmol), PhSO2Na (2a, 59.4 mg, 0.33 mmol), and KBr
(39.3 mg, 0.33 mmol) in AcOH (0.3 mL) was added
phenylacetylene 1a (30.6 mg, 0.3 mmol), and the mixture
was stirred at 100 °C for 18 h in air. After the residue was
dissolved in Et2O, the solution was washed with sat.
NaHCO3, H2O, and sat. NaCl and dried over anhyd MgSO4.
Chromatography on silica gel (40% Et2O–hexane) gave (E)-
1-phenylsulfonyl-2-bromo-2-phenylethene (7aa, 60.7 mg,
63%). 1H NMR (270 MHz, CDCl3): d = 7.61–7.51 (m, 3 H),
7.42–7.30 (m, 7 H), 7.17 (s, 1 H). 13C NMR (67.5 MHz,
CDCl3): d = 140.2, 138.7, 135.9, 134.1, 133.5, 130.4, 128.9,
128.5, 127.9, 127.7. IR (CHCl3): 3056, 1611, 1590, 1446,
1324 cm–1. Anal. Calcd for C14H11O2SBr: C, 52.03; H, 3.43.
Found: C, 51.42; H, 3.17.
(9) (a) Amiel, Y. J. Org. Chem. 1971, 36, 3697. (b) Truce,
W. E.; Larry, C. T.; Christensen, L. W.; Bavry, R. H. J. Org.
Chem. 1970, 35, 4217.
(10) (a) Taniguchi, N. J. Org. Chem. 2006, 71, 7874.
(b) Taniguchi, N. J. Org. Chem. 2007, 72, 1241.
(c) Taniguchi, N. Eur. J. Org. Chem. 2010, 2670.
(11) Typical Procedure of Alkenyl Sulfones Using Alkenes
To a mixture of CuI (4.6 mg, 0.024 mmol), bpy (3.7 mg,
0.024 mmol), PhSO2Na (2a, 59.4 mg, 0.33 mmol), and KI
(24.9 mg, 0.15 mmol) in DMSO (0.15 mL) and AcOH (0.15
mL) was added styrene 1a (31.2 mg, 0.3 mmol), and the
mixture was stirred at 100 °C for 18 h in air. After the residue
was dissolved in Et2O, the solution was washed with sat.
NaHCO3, H2O, and sat. NaCl and dried over anhyd MgSO4.
Chromatography on silica gel (30% Et2O–hexane) gave
phenyl (E)-2-phenylethenyl sulfone (3aa, 68.7 mg, 94%).
1H NMR (270 MHz, CDCl3): d = 7.96–7.93 (m, 2 H), 7.68
(d, J = 15.5 Hz, 1 H), 7.58–7.30 (m, 8 H), 6.87 (d, J = 15.5
Hz, 1 H). 13C NMR (67.5 MHz, CDCl3): d = 142.4, 140.6,
(14) In the presence of the proton, the disproportionation of
copper ion easily proceeds, see ref. 12.
(15) (a) Amiel, Y. J. Org. Chem. 1974, 39, 1974. (b) Amiel, Y.
J. Org. Chem. 1970, 36, 3691.
Synlett 2011, No. 9, 1308–1312 © Thieme Stuttgart · New York