CL-150444
Received: May 8, 2015 | Accepted: May 18, 2015 | Web Released: May 26, 2015
Rhodium-catalyzed Direct Coupling of Benzothioamides
with Alkenes and Alkynes through Directed C-H Bond Cleavage
Yuki Yokoyama,1 Yuto Unoh,1,2 Rebekka Anna Bohmann,1,3 Tetsuya Satoh,*1,2,4 Koji Hirano,1 Carsten Bolm,3 and Masahiro Miura*1
1Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871
2JST, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012
3Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52056 Aachen, Germany
4Department of Chemistry, Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585
(E-mail: satoh@sci.osaka-cu.ac.jp)
Table 1. Reaction of N,N-diisopropylbenzothioamide (1a) with
styrene (2a)a
Rhodium-catalyzed direct coupling of benzothioamides with
alkenes proceeds smoothly involving ortho-C-H bond cleavage.
The thioamides also couple with alkynes under similar
conditions accompanied by desulfurization and C-N bond
cleavage to produce indenone derivatives.
S
S
[Cp*Rh(MeCN)3][SbF6]2
Cu(OAc)2•H2O
NPri2
NPri2
Ph
+
Ph
1a
2a
3a
Entry
Solvent
Temp./°C
Yield of 3ab/%
The direct coupling of aromatic substrates with alkenes and
alkynes involving C-H bond cleavage provides atom- and step-
economical routes for synthesizing π-conjugated molecules.1
One of the most important modes for C-H bond cleavage is a
functional group-directed version, which enables the regiose-
lective cleavage and functionalization of ubiquitous C-H
bonds.2 In this kind of reaction, oxygen- and nitrogen-containing
functional groups such as carbonyl, hydroxy, and imino groups
are frequently employed as the directing groups. Contrastingly,
the use of sulfur-containing groups3 such as thiocarbonyls and
thiols has been far less explored, probably due to their tight
coordination to the metal center of catalysts to render the
couplings less efficient. Recently, we1o,4 and others1a,1e,1f have
shown that Cp*-rhodium(III) complexes are versatile catalysts
for the direct coupling of a wide range of aromatic substrates
possessing various directing groups with unsaturated com-
pounds. Under rhodium catalysis, even some sulfur-containing
groups such as sulfinyl,5a sulfonyl,5b dithiane,5c and sulfoximi-
doyl5d-5g groups have been demonstrated to be effectively
utilizable as directing groups. During our further studies, we
succeeded in expanding the rhodium-catalyzed direct coupling
procedure to a thiocarbonyl family of substrates, i.e. benzo-
thioamides. Since aromatic thioamides are known to show a
variety of bioactive properties,6 their new, effective modification
methods are of importance in pharmaceutical and agrochemical
fields. In this work, we found that the treatment of benzothio-
amides with alkenes efficiently affords ortho-alkenylated prod-
ucts through C-H bond cleavage. Furthermore, we observed an
unexpected annulation reaction with alkynes accompanied by
desulfurization and C-N bond cleavage to produce indenone
derivatives. These new findings are described herein.
1
2
3
4
5
6
7
8
9c
10d
dioxane
dioxane
dioxane
PhCl
diglyme
toluene
DMSO
DMF
100
80
91 (79)
72
74
51
69
58
10
74
70
120
100
100
100
100
100
100
100
dioxane
dioxane
82
aReaction conditions: 1a (0.25 mmol), 2a (1 mmol), [Cp*Rh(MeCN)3]-
[SbF6]2 (0.01 mmol), Cu(OAc)2¢H2O (0.5 mmol), solvent (3 mL) under
N2 for 4 h, unless otherwise noted. GC yield based on the amount of
1a used. Value in parentheses indicates yield after isolation. AgOAc
(0.5 mmol) was used in place of Cu(OAc)2¢H2O. dWith 2a (0.5 mmol).
b
c
(Entries 4-8). A typical silver oxidant, AgOAc, was less effective
than Cu(OAc)2¢H2O (Entry 9). The amount of 2a could be
reduced to 0.5 mmol to provide 3a in 82% yield (Entry 10).
We next examined the reactions of thioamide 1a with
various alkenes 2b-2g under the conditions employed for
Entry 10 in Table 1 (Table 2). In cases using 4-substituted
styrenes 2b and 2c and 2-vinylnaphthalene (2d), the corre-
sponding ortho-alkenylated products 3b-3d were obtained in
63-74% yields (Entries 1-3). The use of 1 mmol of 2 gave
slightly better results in these reactions. Butyl- (2e) and
cyclohexyl (2f) acrylates coupled with 1a smoothly under the
standard conditions to produce 3e and 3f in good yields (Entries
4 and 5). The reaction with acrylamide 2g gave 3g in moderate
yield (Entry 6). 4- and 3-Substituted benzothioamides 1b-1f
underwent ortho-alkenylation upon treatment with 2e to give
products 3h-3l (Entries 7-11). In contrast, the reaction of 2-
substituted benzothioamide 1g was sluggish, probably due to
steric reasons. Thus, even after heating at 120 °C for 24 h, the
yield of 3m was 20% (Entry 12). Under the relatively harsh
conditions, a non-negligible E-Z isomerization of 3m was
observed. The alkenylation of 2-naphthothioamide 1h took place
regioselectively at the sterically less hindered position to give 3n
as a single major product (Entry 13).
In an initial attempt, N,N-diisopropylbenzothioamide (1a)
(0.25 mmol) was treated with styrene (2a) (1 mmol) in the pres-
ence of [Cp*Rh(MeCN)3][SbF6]2 (0.01 mmol) and Cu(OAc)2¢
H2O (0.5 mmol) in dioxane at 100 °C under N2 for 4 h. As a
result, the thioamide-directed C-H alkenylation took place
efficiently at the ortho-position to produce vinylarene 3a in
91% yield (Entry 1 in Table 1). Decreasing and increasing the
temperature to 80 and 120 °C somewhat reduced the yield of 3a
(Entries 2 and 3). In other solvents, including PhCl, diglyme,
toluene, DMSO, and DMF, the reaction was relatively sluggish
© 2015 The Chemical Society of Japan
Yokoyama, Yuki
