14
Chemistry Letters Vol.36, No.1 (2007)
A Convenient, Catalyst-free Cross-coupling Reaction of ꢀ-Sulfur-substituted Alkylstannanes
with Acid Chlorides Leading to ꢀ-Sulfur-substituted Ketones
Hirotaka Kagoshimaà and Naoshi Takahashi
Center for Instrumental Analysis, Ibaraki University, 2-1-1 Bunkyo, Mito 310-8512
(Received September 20, 2006; CL-061092; E-mail: hkago@mx.ibaraki.ac.jp)
Table 1. Optimization of reaction conditionsa
A thermal cross-coupling reaction of ꢀ-sulfur-substituted al-
kylstannanes with acid chlorides is described. A range of sub-
strates can be used for the present reaction and the reaction pro-
ceeds by just mixing two components under reflux in mesitylene
to give the corresponding ꢀ-sulfur-substituted ketones in good
yields.
O
SCOPh
O
conditions
+
n
Ph
Sn Bu
Ph
Cl
3
SCOPh
1a
2a
3a
Entry
1
Conditions
Yield/%
33
PdCl2(PPh3)2 (4 mol %), CuCN
(8 mol %), toluene, 75 ꢀC, 24 h
CuCN (8 mol %), toluene, 75 ꢀC, 24 h
Cu(OTf)2 (8 mol %), toluene, 75 ꢀC, 6 h
toluene, 75 ꢀC, 24 h
toluene, reflux, 24 h
mesitylene, reflux, 1 h
dioxane, reflux, 24 h
N,N-dimethylformamide, reflux, 6 h
Transition-metal-catalyzed cross-coupling reactions of
organometallic compounds with organic electrophiles are very
powerful methods for the construction of carbon–carbon bonds.1
Significant synthetic and mechanistic progress in this area has
been made during the past few decades.
The Stille cross-coupling reaction is one of the most useful
and well-documented cross-coupling reactions.2 The ease of
accessibility of various organostannanes, the mildness of the
reaction conditions, and the tolerance of functional groups make
it possible to build up complex molecules. As a consequence of
extensive studies on the Stille cross-coupling reaction, it has
been shown that various kinds of stannane/electrophile combi-
nations can be applied to the coupling reaction, and these advan-
ces enhance synthetic utility of the reaction.
ꢀ-Heteroatom-substituted alkylstannanes are one of the
most attractive nucleophiles in the Stille cross-coupling reaction
because an alkyl chain with an ꢀ-heteroatom functionality can
be introduced into the products. In this regard, it has been dem-
onstrated that ꢀ-oxygen- and nitrogen-substituted alkylstan-
nanes undergo the coupling reaction with various organic halides
to afford the corresponding coupling products.3–6
Recently, we have devoted considerable effort to expanding
the scope of the reactions using ꢀ-heteroatom-substituted alkyl-
stannenes and alkylsilanes as nucleophiles,7 and reported that
ꢀ-sulfur-substituted alkylstannenes react with imines to give
1,2-amino sulfide derivatives.7b Here, we have anticipated
that ꢀ-sulfur-substituted alkylstannanes would react with acid
chlorides as electrophiles under the proper conditions to produce
ꢀ-sulfur-substituted ketones, which are useful intermediates in
organic synthesis.8 In this paper, we will present a convenient,
catalyst-free cross-coupling reaction of ꢀ-sulfur-substituted
alkylstannanes with acid chlorides.
2
3
4
5
6
7
8
60
22
16
77
87
64
0
aMolar ratio; 1a:2a = 1.2:1.0.
reaction. Accordingly, heating the reaction mixture of 1a and
2a in toluene at 75 ꢀC for 24 h in the absence of the catalyst
furnished 3a in 16% yield although a considerable amount of
2a remained unchanged (Entry 4). This result prompted us to
further investigate the cross-coupling reaction under catalyst-
free conditions because the reaction can be conveniently carried
out. To overcome the low reactivity of 2a, the reaction was per-
formed under reflux in different solvents (Entries 5–8). Reflux-
ing a mixture of 1a and 2a in toluene afforded 3a in 77% yield
although the reaction was still sluggish (Entry 5). Gratifyingly, it
was found that the use of mesitylene as a solvent could further
improve both the yield and the reaction rate (Entry 6). Polar
solvents such as dioxane and N,N-dimethylformamide proved
to be less effective for this reaction (Entries 7 and 8).
With the optimized conditions (reflux in mesitylene, Entry
6, Table 1), we then examined the effect of substituents of stan-
nanes.9 As summarized in Table 2, various stannanes could be
used for the coupling reaction. When an acetyl-substituted stan-
nane 2b was allowed to react with 1a, the corresponding product
3b was obtained in 80% yield (Entry 2). The ethoxythiocarbon-
yl-substituted stannanes 2c produced 3c in 85% yield (Entry 3)
whereas N,N-diethylthiocarbamoyl-substituted stannanes 2d af-
forded 3d in somewhat lower yield (68%, Entry 4). Stannanes
having either a phenyl or methyl group on the sulfur, such as
2e and 2f, were found to be inferior to 2a–2d (Entries 5 and
6). From these results, higher reactivity of 2a–2d compared to
2e and 2f could be attributed to intramolecular coordination of
the carbonyl oxygen or the thiocarbonyl sulfur to the tin atom,
which makes the stannanes more nucleophilic. Next, we tested
the reactions of stannanes bearing an isopropyl or a phenyl group
at the ꢀ-carbon with 1a. As a result, 3g and 3h were obtained in
87 and 84% yield, respectively (Entries 7 and 8). In addition, an
At first, we examined the reaction of ꢀ-sulfur-substituted al-
kylstannanes 2a with benzoyl chloride (1a) under the conditions
reported by Falck et al.,5b and it was found that the desired cross-
coupling reaction occurred and the corresponding ꢀ-sulfur-sub-
stituted ketone 3a was obtained in 33% yield (Table 1, Entry 1).
It is interesting that CuCN alone could catalyze the reaction
and improve the yield (Entry 2). On the other hand, the use of
Cu(OTf)2, which is the most effective mediator in our previous
reports,7 did not give a good result in the present case (Entry 3).
During subsequent examination of reaction conditions, however,
we noticed that the catalyst was not necessarily required for the
Copyright Ó 2007 The Chemical Society of Japan
Kagoshima, Hirotaka
