Conjugate addition of α-sulfur-substituted alkylstannanes to α,β-unsaturated ketones mediated by a copper(II) triflate and chlorotrimethylsilane combination

Article abstract of DOI:10.1246/cl.130284

The copper(II) triflate and chlorotrimethylsilane combination was found to be effective for the conjugate addition of α-sulfur-substituted alkylstannanes to α,β-unsaturated ketones. Thus, the corresponding γ-sulfur-substituted ketones were obtained in goo

Full text of DOI:10.1246/cl.130284

doi:10.1246/cl.130284
Published on the web May 30, 2013
869
Conjugate Addition of ¡-Sulfur-substituted Alkylstannanes to ¡,¢-Unsaturated Ketones
Mediated by a Copper(II) Triflate and Chlorotrimethylsilane Combination
Hirotaka Kagoshima* and Takeshi Yahagi
Center for Instrumental Analysis, Ibaraki University, 2-1-1 Bunkyo, Mito, Ibaraki 310-8512
(Received April 2, 2013; CL-130284; E-mail: hkago@mx.ibaraki.ac.jp)
The copper(II) triflate and chlorotrimethylsilane combina-
tion was found to be effective for the conjugate addition of
¡-sulfur-substituted alkylstannanes to ¡,¢-unsaturated ketones.
Thus, the corresponding £-sulfur-substituted ketones were
obtained in good yields.
successful conjugate addition reaction of ¡-sulfur-substituted
alkylstannanes to ¡,¢-unsaturated ketones mediated by a
copper(II) triflate and chlorotrimethylsilane combination. It is
noted that Falck et al. reported the copper(I) cyanide-catalyzed
conjugate addition of ¡-oxygen-substituted alkylstannanes.7
In addition, Narasaka et al. reported the photoinduced, radical
conjugate addition of ¡-sulfur-substituted alkylstannanes.6
However, to date, there have been no examples for the metal-
catalyzed or -mediated version using ¡-sulfur-substituted alkyl-
stannanes.
To optimize the reaction conditions, the reaction of
2-cyclohexen-1-one (1a) with ¡-sulfur-substituted alkylstannane
2a was performed under various settings (Table 1). First, the
conditions described by Falck et al.7 were tested. Treatment of
1a (1.0 equiv) with 2a (1.0 equiv) in the presence of CuCN
(0.08 equiv) and Me3SiCl (2.5 equiv) in 1,2-dimethoxyethane
(DME) at room temperature for 1 h afforded no desired product
3a, although 2a was completely consumed (Entry 1). Following
this, a wide range of copper compounds were surveyed and it
was found that the use of Cu(OTf)2 in CH2Cl2 promoted the
conjugate addition to give 3a in a 10% yield (Entry 2). Other
copper compounds such as CuCl, CuBr, CuI, CuCl2, CuBr2, and
Cu(OAc)2 were not effective, and no yield of 3a was obtained.
Next, in order to improve the yield of 3a, we examined the effect
of the molar ratio of 1a, 2a, Cu(OTf)2, and Me3SiCl (Entries
3-5). When the Cu(OTf)2 loading was increased to 1.0 equiv,
significant improvement of the yield was attained (74%,
Entry 3). Further increasing the loading of Cu(OTf)2 did not
have a beneficial effect. It was observed that the loading of
Me3SiCl could be lowered to 1.2 equiv while maintaining a good
yield (76%, Entry 4). However, the reaction without Me3SiCl
led to a decrease in the yield of 3a (41%, Entry 5). Furthermore,
The conjugate addition of organometallic reagents to
¡,¢-unsaturated carbonyl compounds is a powerful tool for
the construction of carbon-carbon bonds at the ¢-position.
Numerous procedures using organometallic reagents as nucle-
ophiles have been developed and reported.1 Among various
organometallic reagents, organostannanes have been widely
used due to their ready availability, stability to air and moisture,
and tolerance by a wide range of functional groups. Therefore,
conjugate additions of aryl-,2a-2i alkenyl-,2g-2o and allylstanna-
nes2p,2q to ¡,¢-unsaturated carbonyl compounds have been well
documented. In contrast, alkylstannanes have been rarely used
for the conjugate addition because of their lower nucleophilicity
relative to aryl-, vinyl-, and allylstannanes. A particularly
favorable case involves the intramolecular conjugate addition of
cyclic ¡,¢-unsaturated ketones which possess a trimethylstannyl
moiety, leading to the corresponding bicyclic ketones.3
As a part of our continuing interest in the development of
new carbon-carbon bond-forming reactions, we have devoted
considerable effort to expanding the scope of reactions using
¡-heteroatom-substituted alkylstannanes as nucleophiles and
found that these stannanes have sufficient nucleophilicity under
the proper conditions.4 Here, we have anticipated that the
conjugate addition of ¡-sulfur-substituted alkylstannanes to
¡,¢-unsaturated ketones would produce the corresponding
£-sulfur-substituted ketones.5,6 Herein, we wish to describe a
Table 1. Optimization of the reaction conditions
copper compound
Me3SiCl
O
O
SMe
+
SnnBu3
solvent, rt
1a
2a
3a
SMe
Copper
compound/equiv
Diastereomer
ratioc
Entry
Me3SiCl/equiv
Solvent
Time/h
Yield/%
1a
2a
3a
4a
5a
6b
7b
8b
CuCN/0.08
Cu(OTf)2/0.08
Cu(OTf)2/1.0
Cu(OTf)2/1.0
Cu(OTf)2/1.0
Cu(OTf)2/1.0
Cu(OTf)2/1.0
Cu(OTf)2/1.0
b
2.5
2.5
2.5
1.2
0
1.2
1.2
1.2
DME
1
1
0
10
74
76
41
quant.
68
49
®
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
ether
49:51
50:50
49:51
48:52
49:51
49:51
50:50
0.5
0.5
0.5
0.5
0.5
0.5
THF
aMolar ratio; 1a:2a = 1.0:1.0. Molar ratio; 1a:2a = 1.0:1.5. Determined by 100 MHz 13C NMR.
c
Chem. Lett. 2013, 42, 869-870
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

870
Table 2. Conjugate addition of ¡-sulfur-substituted alkylstan-
nanes to ¡,¢-unsaturated ketones mediated by the copper(II)
triflate and chlorotrimethylsilane combination
Having
optimized
the
reaction
conditions
(1:2:Cu(OTf)2:Me3SiCl = 1.0:1.5:1.0:1.2, CH2Cl2, rt, Entry 6,
Table 1), we then explored the scope of the reaction (Table 2).8
First, various ¡-sulfur-substituted alkylstannanes with different
substitution patterns were subjected to the conjugate addition to
1a (Entries 1-5). The reaction of phenylsulfanyl-substituted
alkylstannane 2b also proceeded smoothly to give 3b in a 93%
yield (Entry 2). Not only 2a and 2b but also 2c-2e, which have
different substituents on the ¡-carbon atom, were able to be
employed in the reaction (Entries 3-5). Next, the reactions of 2a
with cyclic and acyclic ¡,¢-unsaturated ketones were examined.
The conjugate addition products from 1b and 1c were obtained
in good yields (89% and 62%, respectively, Entries 6 and 7). In
contrast, the use of 1d afforded 3h in a lower yield (19%) most
likely due to the steric hindrance provided by the ¢-methyl
group (Entry 8). Acyclic ¡,¢-unsaturated ketones such as 1e and
1f also reacted with 2a to give the corresponding products in
good yields (Entries 9 and 10).
In conclusion, we have presented the copper(II) triflate and
chlorotrimethylsilane combination-mediated conjugate addition
of ¡-sulfur-substituted alkylstannanes to ¡,¢-unsaturated ke-
tones. The present reaction provides a new, facile method for the
synthesis of £-sulfur-substituted ketones. Development of new
carbon-carbon bond-forming reactions of ¡-sulfur-substituted
alkylstannanes with other electrophiles is in progress.
Cu(OTf)2 (1.0 equiv)
Me3SiCl (1.2 equiv)
CH2Cl2, rt, 0.5 h
α,β-unsaturated
ketone
1 (1.0 equiv)
α-sulfur-substituted
alkylstannane
product
3
+
2 (1.5 equiv)
Yield/%
Entry
1
1
2
3
(Diastereomer ratioa)
O
O
SMe
SnnBu3
2a
quant.
(49:51)
1a
1a
3a
3b
3c
SMe
O
O
O
SPh
93
(44:56)
2
3
SnnBu3
2b
SPh
SMe
SMe
SnnBu3
2c
82
(45:55)
1a
1a
SMe
44
(35:65)
4
5
Ph
SnnBu3
Ph
SMe
2d
SMe
SnnBu3
3d
3e
O
O
66
(—)
This paper is dedicated to Professor Teruaki
Mukaiyama in celebration of the 40th anniversary of the
Mukaiyama aldol reaction.
1a
SMe
2e
O
References and Notes
89
(46:54)
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O
O
O
62
(46:54)
2a
2a
1c
3g
SMe
O
19
(37:63)
8
1d
3h
3i
SMe
SMe
SMe
O
Ph
83
(46:54)
2a
2a
9
Ph
Ph
O
Ph
Ph
1e
O
3
4
Me
90
(47:53)
10
Me
Ph
1f
3j
5
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A typical experimental procedure (Table 2, Entry 1): To a mixture of 1a
(10 ¯L, 0.10 mmol), Cu(OTf)2 (36 mg, 0.10 mmol), and Me3SiCl (15 ¯L,
0.12 mmol) in CH2Cl2 (1 mL) was added 2a (59 mg, 0.15 mmol) in
CH2Cl2 (0.5 mL) at room temperature. After being stirred for 0.5 h at this
temperature, the reaction was quenched with saturated aqueous NaHCO3.
After a usual work up, the crude product was purified by TLC
(AcOEt:hexane = 1:10) to give the corresponding product 3a (20 mg,
quant., diastereomer ratio = 49:51).
when an excess amount of 2a (1.5 equiv) was employed, 3a
could be obtained quantitatively (Entry 6). Finally, a survey of
the solvents revealed that the use of CH2Cl2 gave better results
than that of coordinating solvents such as ether and THF (Entries
7 and 8). In all cases described above, the reactions were non-
diastereoselective.
Chem. Lett. 2013, 42, 869-870
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/