Copper-catalyzed oxidative hydrosulfonylation of alkynes using sodium sulfinates in air

Article abstract of DOI:10.1055/s-0031-1290934

Copper-catalyzed hydrosulfonylations of alkynes can be carried out using sodium sulfinates in air. The procedure affords syn-selectively (E)-alkenyl sulfones in good yields. Then, both terminal and internal alkynes are available. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290934

LETTER
▌1245
lCettoerpper-Catalyzed Oxidative Hydrosulfonylation of Alkynes Using Sodium
Sulfinates in Air
Copper-Catalyzed Oxidative Hydrosulfonylation of Alkynes
Nobukazu Taniguchi*
Department of Chemistry, Fukushima Medical University, Fukushima 960-1295, Japan
Fax +81(24)5471369; E-mail: taniguti@fmu.ac.jp
Received: 19.01.2012; Accepted after revision: 09.03.2012
tion of sodium sulfinates (cycle A). Alkenyl sulfones can
Abstract: Copper-catalyzed hydrosulfonylations of alkynes can be
be obtained anti-selectively.
carried out using sodium sulfinates in air. The procedure affords
syn-selectively (E)-alkenyl sulfones in good yields. Then, both ter-
minal and internal alkynes are available.
But, as shown in cycle B, a metal-catalyzed syn-addition
to alkynes has not been reported yet.
Key words: (E)-alkenyl sulfone, hydrosulfonylation, copper cata-
lyst, alkyne, sodium sulfinate
For a successful catalytic cycle, controls of two oxidative
processes are required, which are as follows: (1) the sup-
pression of the oxidation of sulfonyl anion, and, (2) the
oxidation of a copper–alkenyl intermediate formed after a
sulfonylation of alkynes.
Organosulfur preparations by transition-metal catalysts
are important methodologies, and numerous procedures
have been reported so far.1 The compounds thus obtained
have found widespread utilization as intermediates or re-
agents in organic syntheses.2
As an approach to solve these problems, the reactivities of
copper salts were investigated. From many experiments, it
was found that a copper-catalyzed reaction of alkynes
with sodium sulfinates affords syn-additive products un-
der oxidative condition. The methodology is described
herein.
Alkenyl sulfones can also be prepared by various meth-
ods, particularly by Michael additions, Horner–Emmons
reactions and metal-catalyzed cross-couplings.3
Initially, the optimum conditions were investigated for the
reaction of phenylacetylene (1a) with 4-MeC6H4SO2Na
(2b; Table 1). When the reaction was performed using
CuI–bpy in acetic acid, the production of the correspond-
ing product 3ab was not observed at all (entry 1). The re-
action using 2,2′-bis(2-oxazoline) (L2) gave 3ab in 10%
yield (entry 2). Moreover, the addition of DMF with H2O
increased the yield of 3ab to 51%, and β-keto sulfone 4ab
was also obtained in 10% yield (entry 3).
As a general rule, in order to prepare these compounds
from alkynes and sodium sulfinates, alkynes have to pos-
sess electron-withdrawing groups. Therefore, normal al-
kynes are not feasible.4 In order to use these inactivated
alkynes, it is necessary for oxidations of sulfonyl anions
to take place with stoichiometric oxidants.5,6
Regrettably, a sulfonylation of alkynes without the forma-
tion of sulfonyl cations or radicals as intermediates has
not been explored to date.
Fortunately, a combination of Cu(I)Cl with trans-N,N′-di-
para-tosyl-1,2-cyclohexanediamine (L3) afforded 3ab in
80–83% yields with a trace amount of 4ab (entries 6 and
7). Similarly, the use of L2 or Cu(II)Cl2 also gave nice re-
sults (entries 8 and 9).
A copper-catalyzed synthesis of (E)-β-haloalkenyl sul-
fones using alkynes with sodium sulfinates (Scheme 1)
was recently reported.7 The reaction proceeds via the for-
mation of sulfonyl cations by a copper-catalyzed oxida-
SO2R1
R2
H
SO2R1
R2
R2
X
anti-addition
syn-addition
R1SO2
X
R2
cat. Cu
[O]
cat. Cu
A
H+
[O]
B
cat. Cu
R2
R2
Cu
R2
SO2R1
R2
R1SO2-Cu
X–
R1SO2
or
R2
R2
1
•
R SO2
Scheme1 Strategy for (E)-alkenyl sulfone synthesis
SYNLETT 2012, 23, 1245–1249
Advanced online publication: 26.04.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0031-1290934; Art ID: ST-2012-U0057-L
© Georg Thieme Verlag Stuttgart · New York

1246
N. Taniguchi
LETTER
Table 1 Investigation of Suitable Conditiona
However, reactions using CuBr2 and Cu(OAc)2 catalysts
gave lower yields (entries 10 and 11). The reaction in the
absence of a copper catalyst gave 4ab in 17% yield with-
out the production of 3ab (entry 12).
SO2C6H4Me-4
Ph
Ph
4-MeC6H4SO2Na 2b,
cat. [Cu]-L
3ab
Ph
+
solvent, 60 °C, air, 18 h
1a
O
Thus, the catalytic process achieved by the combination
of copper chlorides (CuCl or CuCl2) with ligands (L2 or
L3), and other copper salts [CuI, CuBr2 or Cu(OAc)2]
could not promote the reaction satisfactorily.
SO2C6H4Me-4
4ab
NHTs
O
N
O
N
On the basis of above developed method, the hydrosulfo-
nylation of various alkynes was then surveyed (Table 2).8
The procedure afforded the expected (E)-alkenyl sulfones
3 from terminal alkynes in excellent yields (entries 1–11).
N
N
NHTs
L1
L2
L3
3ab/4abb
Entry CuX–L
(1:1, 5 mol%)
Solvent
3ab
(%)c
Yields of reactions using alkyl acetylenes decreased to
38–60% and a trace amount of β-keto sulfone was ob-
served as by-product (entries 12–15). The reactivities of
alkyl acetylenes were slightly lower than those of aryl al-
kynes. Unfortunately, the reaction using 1-octyne hardly
proceeded (entry 16).
1d
2d
3d
4
CuI–L1
AcOH (0.3 mL)
AcOH (0.3 mL)
–
0
10
51
50
55
80
83
83
80
50
50
0
CuI–L2
83:17
83:17
83:17
83:17
95:5
95:5
95:5
95:5
91:9
83:17
AcOH–DMF–H2Oe
AcOH–DMF–H2Oe
AcOH–DMF–H2Oe
AcOH–DMF–H2Oe
AcOH–DMI–H2Oe
AcOH–DMI–H2Oe
AcOH–DMI–H2Oe
AcOH–DMI–H2Oe
AcOH–DMI–H2Oe
AcOH–DMI–H2Oe
CuI–L2
CuI–L2
In this procedure, not only terminal alkynes but also inter-
nal alkynes were feasible (entries 17–20).
5
CuI–L3
The stereochemistries of alkenyl sulfones 3 in entries 17
and 18 were determined by comparison with the 1H NMR
data of (Z)-alkenyl sulfone 39 or with the reported data3i
(Scheme 2).
6
CuCl–L3
CuCl–L3
CuCl–L2
CuCl2–L2
CuBr2–L2
Cu(OAc)2–L2
none
7
8
1. Pd(PPh3)4, MeONa, DMF,
100 °C, 18 h
R
Br
9
2. MCPBA, CH2Cl2
0 °C, 1 h
SC6H4Me-4
Ph
10
5
11
12
R
Ha
Ph
SO2C6H4Me-4
R
Hb
Ph
0:100f
SO2C6H4Me-4
a Reaction conditions: A mixture of 1a (0.3 mmol) 2b (0.33 mmol)
and Cu-L catalyst (5 mol%) was treated in AcOH or/and DMF, DMI,
H2O.
(Z)-3
(E)-3
Ha
δ
Hb
δ
b The ratio was determined by 1H NMR.
c Isolated yield after silica gel chromatography.
d The reaction was performed at 100 ºC.
e AcOH (0.1 mL), DMF or DMI (0.1 mL) and H2O (0.1 mL) were
used.
R = Me (3kb) 7.02
R = Et (3lb)
7.79
7.79
6.99
f Compound 4ab was obtained in 17% yield.
Scheme 2 Determination of stereochemistry
Table 2 Copper-Catalyzed Hydrosulfonylation of Alkynes Using Sodium Sulfinatesa
R3SO2Na 2,
SO2R3
CuCl-L2 (1:1, 5 mol%)
R1
R2
R1
AcOH, DMI, H2O,
60 °C, air, 18 h
R2
3
1
3 (%)b
Entry
1
1
2
SO2Ph
1a
3aa
85
Ph
Ph
Ph
Ph
SO2C6H4Me-4
SO2C6H4OMe-4
2
3
1a
1a
3ab
3ac
83
80
Synlett 2012, 23, 1245–1249
© Georg Thieme Verlag Stuttgart · New York

LETTER
Copper-Catalyzed Oxidative Hydrosulfonylation of Alkynes
1247
Table 2 Copper-Catalyzed Hydrosulfonylation of Alkynes Using Sodium Sulfinatesa (continued)
R3SO2Na 2,
SO2R3
CuCl-L2 (1:1, 5 mol%)
R1
R2
R1
AcOH, DMI, H2O,
60 °C, air, 18 h
R2
3
1
3 (%)b
Entry
4
1
2
SO2C6H4Cl-4
SO2C6H4F-4
SO2C6H4NHAc-4
SO2Me
1a
3ad
75
Ph
Ph
Ph
5
6
1a
1a
1a
1b
1c
1d
3ae
3af
71
72
84
80
91
73
7
3ag
3bb
3cb
3db
Ph
SO2C6H4Me-4
4-MeC6H4
4-MeOC6H4
4-FC6H4
8
4-MeC6H4
SO2C6H4Me-4
SO2C6H4Me-4
SO2C6H4Me-4
9
4-MeOC6H4
4-FC6H4
10
11
12
1e
1f
3eb
3fb
88
51
N
N
HO
HO
Ph
SO2C6H4Me-4
Ph
SO2C6H4Me-4
HO
HO
13
14
1g
1h
3gb
3hb
60
SO2C6H4Me-4
SO2C6H4Me-4
50c
38d
trace
80
15
16
17
1i
3ib
3jb
3kb
SO2C6H4Me-4
SO2C6H4Me-4
n-Hex
1j
1k
n-Hex
Ph
Ph
SO2C6H4Me-4
SO2C6H4Me-4
Ph
Ph
Ph
Et
18
1l
3lb
70
Et
Ph
Ph
19
20
21
1m
1n
1o
3mb
3ab
3ob
48
76e
0f
Ph
SO2C6H4Me-4
SO2C6H4Me-4
Ph
TMS
Ph
n-Pr
n-Pr
n-Pr
n-Pr
a Reaction conditions: A mixture of 1a (0.3 mmol), 2b (0.33 mmol) and Cu–L2 catalyst (5 mol%) was treated in AcOH (0.1 mL), DMI (0.1
mL) and H2O (0.1 mL).
b Isolated yield after silica gel chromatography.
c Reaction time: 36 h.
d Reaction time: 66 h.
e Compound 3ab was obtained.
f Complex mixtures were obtained.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 1245–1249

1248
N. Taniguchi
LETTER
Although the reaction of 4-octyne (lo) gave complex mix-
tures, the expected alkenyl sulfone 3 was not detected at
all (entry 21). However, compound 6 could be synthesized
in 31% yield by the development of the reaction condition
(Scheme 3).
cat. CuCl-L2 (5 mol%)
trans-3ab
cis-3ab +
Ph
SO2C6H4Me-4
cis-3ab
AcOH, DMF, H2O, air,
60 °C, 36 h
98%
cis/trans = 91:9
Scheme6 Investigation of the isomerization
4-MeC6H4SO2Na 2b,
CuCl-L3 (1:1, 5 mol%),
sulfonyl radicals 13 are formed by the oxidation of copper
catalyst and oxygen, a reaction with alkynes gives alkenyl
sulfones. Investigation of the detailed process is now in
progress.
SO2C6H4Me-4
n-Pr
n-Pr
AcOH, DMF, H2O,
air, 40 °C
O
n-Pr
6 (31%)
1o
Scheme 3 Hydrosulfonylations of 4-octyne
SO2R2
R2SO2Na
R1
3
2
H2O
To elucidate the reaction mechanism, a reaction in the ab-
sence of oxygen was carried out. When a mixture of 1-
pheny-1-propyne (1k) with 4-MeC6H4SO2Na (2b) was
treated under a nitrogen atmosphere, the corresponding al-
kenyl sulfone 3kb was obtained in only 12% yield
(Scheme 4). This result shows that the copper-catalyzed
hydrosulfonylation of alkynes requires the presence of ox-
ygen.
CuIXLn
R2SO2 CuIIXLn
H+
8
12
8
1
NaX
CuIIXLn
HX, O2
R2SO2
SO2R2
R2SO2 CuILn
B
A
13
R1
9
11
R1
CuILn
H2O
1
SO2R2
SO2R2
R1
R1
4-MeC6H4SO2Na,
CuCl-L2 (1:1, 5 mol%),
HX, O2
14
3
10
SO2C6H4Me-4
H2O
Ph
Ph
AcOH, DMF, H2O,
60 °C, under N2
1k
3kb (12%)
Scheme 4 Reaction carried out in the absence of oxygen
Scheme 7 A plausible reaction mechanism
Then, a stoichiometric reaction was examined (Scheme
5). When a stoichiometric amount of CuCl was employed,
the reaction afforded alkenyl sulfone 3kb in 25% yield.
The ratio of E and Z product was found to be 62:38. Sim-
ilarly, when the resulting solution was treated in air, the
production of 3kb increased to 74% yield, and the ratio of
E and Z product changed to 86:14.
A gram-scale hydrosulfonylation was then investigated;
experiments are shown in Table 3. When a mixture of al-
kynes 1 (10 mmol) and 4-MeC6H4SO2Na (11 mmol) was
treated with CuI–2,2′-bis(2-oxazoline) (L2) catalyst, the
corresponding (E)-alkenyl sulfones 3 were obtained in
good yields.10 Thus, the procedure could be applied as a
practical reaction.
Finally, the isomerization of cis-alkenyl sulfone 3ab was
investigated (Scheme 6). After the treatment of cis-3ab at
60 ºC, the ratio of cis- and trans-isomer became 91:9.
Thus, the progress of isomerization was very slow.
In conclusion, a copper-catalyzed oxidative hydrosulfo-
nylation of alkynes with sodium sulfinates in air has been
achieved. The procedure proceeded syn-selectively, and
could produce (E)-alkenyl sulfones from terminal or inter-
nal alkynes. Thus, the stereochemistry was controlled by
the use of CuCl–2,2′-bis(2-oxazoline) catalyst.
From these results, a plausible mechanism is considered
as follows (Scheme 7). In process A, R2SO2-CuILn 9 is
initially produced from a copper salt and sodium sulfinate.
After an addition of 9 to alkynes, the oxidation of interme-
diate 10 gives alkenyl sulfone in the presence of acetic ac-
id, and copper(I) catalyst is reproduced. In process B, after
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.onmornifIatngonimSorfniturItagponiSutpor
4-MeC6H4SO2Na,
CuCl-L2 (100 mol%)
SO2C6H4Me-4
+
1k
AcOH, DMF, H2O, 60 °C,
18 h, under N2
Ph
Ph
SO2C6H4Me-4
(E)-3kb
(Z)-3kb
25%
E/Z = 62:38
1. 4-MeC6H4SO2Na,
CuCl-L2 (100 mol%)
1k
(Z)-3kb
+
(E)-3kb
AcOH, DMF, H2O,
74%
E/Z = 86:14
60 °C, 18 h, under N2
2. 60 °C, 18 h, air
Scheme5 A reaction using a stoichiometric amount of copper(I) chloride
Synlett 2012, 23, 1245–1249
© Georg Thieme Verlag Stuttgart · New York

LETTER
Copper-Catalyzed Oxidative Hydrosulfonylation of Alkynes
1249
(4) Harwood, L. M.; Julia, M.; Thuillier, G. L. Tetrahedron
1980, 36, 2483.
Table 3 Large-Scale Hydrosulfonylations
4-MeC6H4SO2Na,
(5) (a) Katrun, P.; Chiampanichayakul, S.; Korworapan, K.;
Pohmakotr, M.; Reutrakul, V.; Jaipetch, T.; Kuhakarn, C.
Eur. J. Org. Chem. 2010, 5633. (b) Nair, V.; Augustine, A.;
Suja, T. D. Synthesis 2002, 2259. (c) Mochizuki, T.;
Hayakawa, S.; Narasaka, K. Bull. Chem. Soc. Jpn. 1996, 69,
2317.
SO2C6H4Me-4
CuCl-L2 (1:1, 5 mol%)
R1
R1
R2
R2
3
AcOH (3 mL), DMI (3 mL),
H2O (3 mL), 60 °C, air, 18 h
1
(10 mmol)
3 (%)a
Entry
1
(6) (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.
R1 = Ph, R2 = H; 1a
1
2
78
75
R1 = Ph, R2 = Me; 1k
(7) Taniguchi, N. Synlett 2011, 1308.
(8) Typical Procedure for Hydrosulfonylation of Alkynes:
To a mixture of CuCl (1.5 mg, 0.015 mmol), 2,2′-bis(2-
oxazoline) (2.1 mg, 0.015 mmol), and PhSO2Na (2a; 54.2
mg, 0.33 mmol), in DMSO (0.1 mL), H2O (0.1 mL) and
AcOH (0.1 mL) was added phenylacetylene (1a; 30.6 mg,
0.3 mmol), and the mixture was stirred at 60 ° C for 18 h in
air. After the residue was dissolved in Et2O, the solution was
washed with H2O and sat. NaCl and dried over anhyd
MgSO4. Chromatography on silica gel (40% Et2O–hexane)
gave phenyl (E)-2-phenylethenyl sulfone (3aa; 61.8 mg,
85%). 1H NMR (270 MHz, CDCl3): δ = 7.96 (d, J = 8.2 Hz,
2 H), 7.68 (d, J = 15.5 Hz, 1 H), 7.30–7.58 (m, 8 H), 6.87 (d,
J = 15.5 Hz, 1 H). 13C NMR (67.5 MHz, CDCl3): δ = 142.4,
140.6, 133.3, 132.2, 131.1, 129.3, 128.9, 128.5, 127.6,
127.2. IR (CHCl3): 1613, 1447, 1306, 1146 cm–1. Anal.
Calcd for C14H12O2S: C, 68.83; H, 4.95. Found: C, 68.56; H,
5.02.
a Isolated yields after silica gel chromatography.
References
(1) For selected reviews, see: (a) Beletskaya, I. P.; Ananikov,
V. P. Chem. Rev. 2011, 111, 1596. (b) Partyka, D. V. Chem.
Rev. 2011, 111, 1529. (c) Ley, S. V.; Thomas, A. W. Angew.
Chem. Int. Ed. 2003, 42, 5400. (d) Kondo, T.; Mitsudo, T.
Chem. Rev. 2000, 100, 3205. (e) Lipshutz, B. H. In
Comprehensive Organometallic Chemistry II, Vol. 12; Abel,
E. W.; Stone, F. G. A.; Wilkinson, G., Eds.; Chap 3.2;
Pergamon Press Ltd: New York, 1995. (f) Metzner, P.;
Thuillier, A. Sulfur Reagents in Organic Synthesis;
Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W., Eds.;
Academic Press: San Diego, 1994.
(2) For selected papers, see: (a) Lebrun, M.-E.; Marquand, P. L.;
Berthelette, C. J. Org. Chem. 2006, 71, 2009. (b) Mauleón,
P.; Alonso, I.; Rodríguez, M.; Rivero, M. R.; Carretero, J. C.
J. Org. Chem. 2007, 72, 9924. (c) Enders, D.; Frank, S.;
Raabe, G.; Runsink, J. Eur. J. Org. Chem. 2000, 879.
(d) Murphy, J. J.; Quintard, A.; McArdle, P.; Alexakis, A.;
Steplens, J. C. Angew. Chem. Int. Ed. 2011, 50, 5095.
(e) Oishi, S.; Hatano, K.; Tsubouchi, A.; Takeda, T. Chem.
Commun. 2011, 47, 11639.
(3) (a) Posner, G. H.; Brunelle, D. J. J. Org. Chem. 1972, 37,
3547. (b) 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. (c) Battace, A.; Zair, T.;
Doucet, H.; Santelli, M. Synthesis 2006, 3495. (d) Cacchi,
S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M.; Bernini, R.
J. Org. Chem. 2004, 69, 5608. (e) Bian, M.; Xu, F.; Ma, C.
Synthesis 2007, 2951. (f) Guan, Z.-H.; Zuo, W.; Zhoo, L.-B.;
Ren, Z.-H.; Liang, Y.-M. Synthesis 2007, 1465.
(9) These (Z)-alkenyl sulfones were prepared according to
reported papers. See: (a) Taniguchi, N. Tetrahedron 2009,
65, 2728. (b) Taniguchi, N. Synlett 2008, 849. (c) Zask, A.;
Helquist, P. J. Org. Chem. 1978, 43, 1619. (d) Bäckvall,
J.-E.; Ericsson, A. J. Org. Chem. 1994, 59, 5850.
(10) Typical Procedure for Gram-Scale Hydrosulfonylation
of Alkynes: To a mixture of CuCl (49.5 mg, 0.5 mmol), 2,2′-
bis(2-oxazoline) (70.1 mg, 0.5 mmol), and 4-MeC6H4SO2Na
(2b; 1.9 g, 11 mmol), in DMSO (3 mL), H2O (3 mL) and
AcOH (3 mL) was added phenylacetylene (1a; 10.0 g, 10.0
mmol), and the mixture was stirred at 60 °C for 18 h in air.
After the residue was dissolved in Et2O, the solution was
washed with H2O and sat. NaCl and dried over anhyd
MgSO4. Chromatography on silica gel (40% Et2O–hexane)
gave 4-tolyl (E)-2-phenylethenyl sulfone (3ab; 1.78 g,
78%). 1H NMR (270 MHz, CDCl3): δ = 7.83 (d, J = 8.2 Hz,
2 H), 7.65 (d, J = 15.5 Hz, 1 H), 7.45–7.49 (m, 2 H), 7.32–
7.40 (m, 5 H), 6.85 (d, J = 15.5 Hz, 1 H), 2.43 (s, 3 H). 13
C
(g) Kamigata, N.; Sawada, H.; Kobayashi, M. J. Org. Chem.
1983, 48, 3793. (h) Huang, X.; Duan, D.; Zheng, W. J. Org.
Chem. 2003, 69, 1958. (i) Zoller, T.; Ugeuen, D. Eur. J. Org.
Chem. 1999, 1545. (j) Kamigata, N.; Narushima, T.;
Sawada, H.; Kobayashi, M. Bull. Chem. Soc. Jpn. 1984, 57,
1421.
NMR (67.5 MHz, CDCl3): δ = 144.3, 141.9, 137.8, 132.4,
131.1, 129.9, 129.0, 128.5, 127.7, 127.6, 21.5. IR (CHCl3):
1614, 1449, 1302, 1145 cm–1. Anal. Calcd for C15H14O2S: C,
69.74; H, 5.46. Found: C, 69.38; H, 5.46.
g
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Synlett 2012, 23, 1245–1249

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