Copper-catalyzed cross-coupling reaction of α-sulfur-substituted alkylstannanes with acid chlorides

Article abstract of DOI:10.1016/j.tetlet.2013.06.088

Copper compounds were found to catalyze the cross-coupling reaction of α-sulfur-substituted alkylstannanes with acid chlorides. Under the optimized conditions (CuF₂ (1 mol %), 1,4-dioxane, 102 C), various substrates coupled to afford the corres

Full text of DOI:10.1016/j.tetlet.2013.06.088

Tetrahedron Letters 54 (2013) 4558–4560
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Tetrahedron Letters
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Copper-catalyzed cross-coupling reaction of a-sulfur-substituted
alkylstannanes with acid chlorides
⇑
Hirotaka Kagoshima , Naoshi Takahashi
Center for Instrumental Analysis, Ibaraki University, 2-1-1 Bunkyo, Mito, Ibaraki 310-8512, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Copper compounds were found to catalyze the cross-coupling reaction of
annanes with acid chlorides. Under the optimized conditions (CuF2 (1 mol %), 1,4-dioxane, 102 °C), vari-
a-sulfur-substituted alkylst-
Received 13 May 2013
Revised 13 June 2013
Accepted 17 June 2013
Available online 26 June 2013
ous substrates coupled to afford the corresponding
a
-sulfur-substituted ketones in good yields.
Ó 2013 Elsevier Ltd. All rights reserved.
This Letter is dedicated to Professor Teruaki
Mukaiyama in celebration of the 40th
anniversary of the Mukaiyama aldol
reaction
Keywords:
Cross-coupling reaction
Copper catalyst
a-Sulfur-substituted alkylstannanes
Acid chlorides
a-Sulfur-substituted ketones
The palladium-catalyzed coupling reaction between organost-
and products. To address this issue, we have studied cross-
coupling reactions in the presence of a catalyst, which would en-
able the reactions to take place under milder conditions. Herein,
we describe a copper-catalyzed method for the cross-coupling of
annanes and organic electrophiles to form carbon–carbon bonds
(the Stille reaction) is one of the most widely used transition-
metal-catalyzed reactions.1 Although it has been demonstrated
that various combinations of stannane and organic electrophile
can undergo cross-coupling reactions, such reactions with alkylst-
annanes are limited,2 probably due to their low nucleophilicity
compared with aryl-, alkenyl-, and allylstannanes. As a result,
although simple alkyl groups have often been incorporated as
residual ligands, their use often leads to the transfer of other more
labile ligands from tin. In contrast, alkylstannanes possessing het-
a-sulfur-substituted alkylstannanes with acid chlorides.
Catalyst activity was initially assessed by coupling the
a
-sulfur-
substituted alkylstannane 2a4 (0.10 mmol) with benzoyl chloride
(1a) (0.12 mmol) under various conditions (Table 1). Table 1 also
includes a few of our previously reported results4 for comparison.
The reaction was initially carried out under the conditions de-
scribed by Falck and co-workers3e. Thus, the reaction conducted
with 4 mol % of PdCl2(PPh3)2 and 8 mol % of CuCN in toluene at
eroatoms such as oxygen and nitrogen at the a-position have been
shown to have sufficient nucleophilicity and, as such, have often
been used in the Stille and related coupling reactions catalyzed
or mediated by transition metals other than palladium.2h,i,3 In this
75 °C for 24 h led to the corresponding a-sulfur-substituted ketone
3a in 33% yield (entry 1). We subsequently found that CuCN alone
could catalyze the coupling reaction to give better results and that
the presence of the palladium catalyst was detrimental to the reac-
tion (60%, entry 2). A similar retardation effect caused by palladium
regard, we have previously reported that
a-sulfur-substituted alk-
ylstannanes can couple with acid chlorides to afford the corre-
sponding
a
-sulfur-substituted ketones by heating under catalyst-
compounds has been observed in the coupling reactions of a-oxy-
free conditions.4 Although these coupling reactions proceeded
smoothly upon simply mixing the two components in refluxing
mesitylene, a lower reaction temperature is preferable in order to
prevent possible thermal decomposition of the starting materials
gen-substituted alkylstannanes with acid chlorides.3f This observa-
tion prompted us to examine the effect of copper catalysts in
greater detail. An extensive study in this respect revealed that
the coupling reactions could be catalyzed by various copper com-
pounds. As can been seen from entries 3 to 9, both copper(I) and
copper(II) halides catalyzed the reactions to produce 3a in moder-
ate to good yields. Among the copper compounds examined, the
⇑
Corresponding author. Tel./fax: +81 29 228 8091.
E-mail address: hkago@mx.ibaraki.ac.jp (H. Kagoshima).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.06.088

H. Kagoshima, N. Takahashi / Tetrahedron Letters 54 (2013) 4558–4560
4559
Table 1
Table 2
Optimization of the reaction conditions
Effect of substituents of stannanes 2
SR1
SnnBu3
1a (0.12 mmol) 2 (0.10 mmol)
O
O
O
O
SCOPh
SnnBu3
CuF2 (1 mol%)
conditions
R2
SR1
+
+
R2
Ph
Ph
Ph
Cl
Ph
Cl
1,4-dioxane
102 °C
SCOPh
3
1a
2a
3a
(0.12 mmol)
(0.10 mmol)
Entry
2
Time (h)
3
Yield (%)
Entry Catalyst
Solvent
Toluene
Temp
(°C)
Time
(h)
Yield (%)
R1
R2
1a
PdCl2(PPh3)2/
75
24
33
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
COPh
COMe
CSOEt
CSNEt2
Ph
nPr
nPr
nPr
nPr
nPr
nPr
iPr
Ph
H
4
6
2
3
9
24
6
3
3a
3b
3c
3d
3e
3f
3g
3h
3i
80
76
92
94
52
48
80
84
82
CuCNb
CuCNc
CuIc
2a
3
4
5
6
7
8
9
10
11
12
13
14
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Benzene
THF
75
75
75
75
75
75
75
75
75
24
24
24
24
24
24
24
24
24
9
60
50
67
57
32
47
50
70
70
CuBrc
CuClc
CuFc
Me
COPh
COPh
COPh
c
CuBr2
c
CuCl2
CuF2
CuF2
CuF2
CuF2
CuF2
6
c
d
d
110
80
66
77
67
d
24
24
4
and 6). Next, the effect of the R2 substituent in the stannanes
was examined. Gratifyingly, all stannanes employed here (2g–i)
effectively coupled with 1a to give the corresponding products
3g–i in good yields (entries 7–9).
d
47
d
CuF2
1,4-
Dioxane
1,4-
102
80 (78)e
15
none
102
4
23
Dioxane
As summarized in Table 3, the copper-catalyzed cross-coupling
reactions of 2a with various acid chlorides 1 were conducted under
the optimized conditions. The reaction of aromatic acid chlorides
bearing an electron-donating or -withdrawing group at the para
position, such as 1b and 1c, with 1a led to adducts 3j and 3k in
good yields of 70% and 66%, respectively (entries 2 and 3). In addi-
tion, a heteroaromatic acid chloride 1d could also be used in the
coupling reaction (60%, entry 4). The range of electrophiles is not
limited to aromatic acid chlorides. Thus, aliphatic acid chlorides
such as octanoyl chloride (1e), phenylacetyl chloride (1f), and
cyclohexanecarbonyl chloride (1g) coupled with 1a to provide
the desired products (entries 5–7).
a
b
c
See Ref. 4.
PdCl2(PPh3)2 (4 mol %), CuCN (8 mol %).
8 mol %.
1 mol %.
d
E
Compound 1a (1.2 mmol), 2a (1.0 mmol).
use of CuF2 (8 mol %) provided the highest yield (70%, entry 9).
Furthermore, the catalyst loading could be reduced to 1 mol % with
no effect on the yield (70%, entry 10). At higher temperatures
(110 °C), the reaction was complete within 9 h, giving 3a in a some-
what improved yield (77%, entry 11). Finally, we examined the effect
of solvents (entries 11–14). Although each reaction was performed
at a different temperature, it is apparent that 1,4-dioxane (80%, en-
try 14) is preferable from a yield, reaction temperature, and reaction
time viewpoint in comparison with toluene, benzene, and THF. The
reaction is practically useful because a larger-scale synthesis
(1.0 mmol scale) of 3a was realized (78%). Since it was possible that
the reaction could have proceeded thermally rather than catalyti-
cally, we conducted the reaction in 1,4-dioxane at 102 °C for 4 h in
the absence of CuF2 (Entry 15). This led to 3a in a much lower yield
of 23%, thus allowing us to estimate that approximately three-quar-
ters of the reaction product of entry 14 was obtained as a result of
CuF2 catalysis and the remaining quarter thermally. Thus, although
the present reaction using CuF2 is not fully catalytic, we refer to the
reaction as ‘catalytic’ throughout this Letter as the catalytic pathway
clearly dominates over the thermal pathway.
At present, reaction mechanism including the role of copper
catalysts is not clear. One of the tentatively proposed mechanisms,
which is based on the mechanistic proposal for the CuCN-catalyzed
cross-coupling reaction of
a-oxygen-substituted alkylstannanes
with organohalides reported by Falck,3f is outlined in Figure 1. It
is likely that the Cu(I) species is the active catalyst since both
Cu(I) and Cu(II) compounds catalyzed the reaction. Thus, the Cu(II)
catalyst used in the coupling reaction would be reduced to Cu(I) by
the a-sulfur-substituted alkylstannane 2 as a reducing reagent, en-
abling entry into the catalytic cycle. Next, transmetallation be-
Table 3
Copper-catalyzed cross-coupling reactions of 2a
O
O
SCOPh
SnnBu3
CuF2 (1 mol%)
R3
+
R3
Cl
Once the optimal reaction conditions (CuF2 (1 mol %), 1,4-diox-
1,4-dioxane
102 °C
ane, 102 °C) had been identified, the scope of the coupling reaction
was investigated. First, the couplings of
SCOPh
1 (0.12 mmol) 2a
3
(0.10 mmol)
a-sulfur-substituted alk-
ylstannanes 24 bearing various substituents on the sulfur atom
with benzoyl chloride (1a) were examined; the results are summa-
rized in Table 2.5 The reaction of an acetyl-substituted alkylstann-
ane 2b with 1a also proceeded smoothly to afford 3b in 76% yield
(entry 2). More efficient cross-couplings were obtained with
ethoxythiocarbonyl- and N,N-diethylthiocarbamoyl-substituted
alkylstannanes 2c,d (92% and 94%, respectively, Entries 3 and 4).
In contrast, the use of phenyl- and methyl-substituted alkylstann-
anes 2e,f, which had been suitable for the copper(II) triflate-
mediated addition to imines,6 resulted in lower yields (entries 5
Entry
1
Time (h)
3
Yield (%)
R3
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
Ph
4
4
9
18
8
3
3a
3j
3k
3l
3m
3n
3o
80
70
66
60
59
58
66
p-MeOC6H4
p-ClC6H4
2-Furyl
nC7H15
Bn
1g
cC6H11
10

4560
H. Kagoshima, N. Takahashi / Tetrahedron Letters 54 (2013) 4558–4560
References and notes
Cu(II)X2
Cu(I)X
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Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 4704–4734; (d) Echavarren, A.
M.; Cardenas, D. J. In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de
Meijere, A.; Diederich, F., Eds.; Wiley-VCH: New York, 2004; Vol. 1, Chapter 1.;
(e) Mitchell, T. N. In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de
Meijere, A.; Diederich, F., Eds.; Wiley-VCH: New York, 2004; Vol. 1, Chapter 3.
2. (a) Kosugi, M.; Shimizu, Y.; Migita, T. Chem. Lett. 1977, 1423–1424; (b) Milstein,
D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636–3638; (c) Milstein, D.; Stille, J. K. J.
Am. Chem. Soc. 1979, 101, 4981–4991; (d) Milstein, D.; Stille, J. K. J. Am. Chem. Soc.
1979, 101, 4992–4998; (e) Milstein, D.; Stille, J. K. J. Org. Chem. 1979, 44, 1613–
1618; (f) Kende, A. S.; Roth, B.; Sanfilippo, P. J.; Blacklock, T. J. J. Am. Chem. Soc.
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Labadie, J. W.; Tueting, D.; Stille, J. K. J. Org. Chem. 1983, 48, 4634–4642; (j) Scott,
W. J.; Crisp, G. T.; Stille, J. K. J. Am. Chem. Soc. 1984, 106, 4630–4632; (k) Farina, V.;
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Chem. Soc. 1994, 116, 1–5; (f) Falck, J. R.; Bhatt, R. K.; Ye, J. J. Am. Chem. Soc. 1995,
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R4
O
R2
R3
S
Y
S
R4
R2
SnnBu3
2
Y
3
O
R4
nBu3SnX
R3
Cl
S
Y
1
R2
4 (Y= O, S)
Cu(I)
Figure 1. Tentatively proposed mechanism for the copper-catalyzed cross-coupling
reaction.
tween Cu(I) and 2 would occur to give a coordinatively stabilized
organocopper(I) species 4. The fact that the use of 2a–d, g–i gave
superior results compared with 2e,f (see Table 2) implies impor-
tance of intramolecular complexation in order to stabilize 4. Then,
4 would couple with the acid chloride 1 to furnish the desired
product 3 and Cu(I), which reenter into the catalytic cycle.
In conclusion, we have developed a copper-catalyzed cross-
4. Kagoshima, H.; Takahashi, N. Chem. Lett. 2007, 36, 14–15.
coupling reaction of a-sulfur-substituted alkylstannanes with acid
5. A typical experimental procedure (Table 2, entry 1): To a mixture of CuF2 (0.1 mg,
0.001 mmol) and 2a (48 mg, 0.10 mmol) in 1,4-dioxane (2.5 mL) was added 1a
(17 mg, 0.12 mmol) in 1,4-dioxane (0.5 mL) at room temperature. After being
stirred for 4 h at 102 °C, the resulting mixture was allowed to cool to room
temperature, and then passed through a silica gel short column. The crude
product was purified by TLC (AcOEt:hexane = 1:10) to give the corresponding
product 3a (24 mg, 80%).
chlorides. The reaction can be carried out under milder conditions
than for the thermal cross-coupling reaction reported by us
previously4 while maintaining a reasonable reaction rate and com-
parable yields. In addition, a range of a-sulfur-substituted alkylst-
annane/acid chloride combinations can be used in the reaction.
6. Kagoshima, H.; Takahashi, N. Chem. Lett. 2004, 33, 962–963.
Further studies in this respect are currently underway.