Unexpected hydrobromic acid-catalyzed C-C bond-forming reactions and facile synthesis of coumarins and benzofurans based on ketene dithioacetals

Article abstract of DOI:10.1002/chem.201002107

Hydrobromic acid was found to be a unique catalyst in C-C bond-forming reactions with ketene dithioacetals. Distinctly different from other acids (including Lewis and Bronsted acids), the remarkable catalytic performance of hydrobromic acid in catalytic a

Full text of DOI:10.1002/chem.201002107

DOI: 10.1002/chem.201002107
À
Unexpected Hydrobromic Acid-Catalyzed C C Bond-Forming Reactions
and Facile Synthesis of Coumarins and Benzofurans Based on Ketene
DithioACTHNUTRGENUGaN cetals
Hongjuan Yuan, Mang Wang,* Yingjie Liu, Lili Wang, Jun Liu, and Qun Liu*[a]
À
Abstract: Hydrobromic acid was found
bonyl compounds 2a–l gave polyfunc-
tionalized penta-1,4-dienes 3 or conju-
gated dienes 4 in good to excellent
yields. The reaction tolerated a broad
range of substituents on both the
ketene dithioacetals 1 and the carbonyl
compounds 2. Application of this effi-
cient C C bond-forming method gener-
ated coumarins 5 and benzofurans 7
under mild, metal-free conditions by
hydrobromic acid-catalyzed reactions
of 1 with salicylaldehydes 2m–o and p-
quinones 6a–d, respectively. A new re-
active species, a sulfur-stabilized carbo-
nium ylide, formed depending on the
nature of the counterion, and this was
proposed as the key intermediate in
the unique catalysis of hydrobromic
acid.
À
to be a unique catalyst in C C bond-
forming reactions with ketene dithioa-
cetals. Distinctly different from other
acids (including Lewis and Brønsted
acids), the remarkable catalytic perfor-
mance of hydrobromic acid in catalytic
amounts was observed in the “acid”-
catalyzed reactions of readily available
functionalized ketene dithioacetals 1
with various electrophiles. Under the
catalysis of 0.1 equivalents of hydro-
bromic acid, the reaction of 1 with car-
À
À
Keywords: C H activation · C C
coupling
·
hydrobromic acid
·
oxygen heterocycles
mechanisms
·
reaction
Introduction
À
C H functionalization leading
À
to C C bond formation has
been a longstanding goal in or-
ganic synthesis and is an area of
rapid growth that will continue
to push the limits of chemical
À
reactivity because C H bonds
can be viewed as being a ubiq-
uitous functional group.[1–3] As
À
Scheme 1. C C bond formation reaction of functionalized ketene dithio
N
versatile organic intermedi-
ates,[4,5] the a-C H functionali-
À
zation of ketene dithioacetals 1
(Scheme 1, FG=Functional Group) has become an attrac-
tive transformation due to the formation of more densely
functionalized molecules with synthetic potential.[6–9] It was
À
reported that the C C bond formation reaction of 1 and
acid-activated aldehydes can give the corresponding adducts
efficiently (Scheme 1, conventional activation mode).[7,8] As
part of our studies on ketene dithioacetal chemistry,[5a–e,8,9]
we found that this kind of reaction was highly catalyst de-
pendent.[8,9] In contrast to reactions promoted by BF3·Et2O
[a] H. Yuan, Prof. M. Wang, Y. Liu, L. Wang, Dr. J. Liu, Prof. Q. Liu
Department of Chemistry
Northeast Normal University
Changchun, 130024 (P. R. China)
Fax : (+86)431-850-99759
E-mail: wangm452@nenu.edu.cn
liuqun@nenu.edu.cn
(50 mol%),[7a]
EtAlCl2
or
TiCl4
(120 mol%),[8a–c] which would be consistent with the activa-
tion of aldehydes by Lewis or Brønsted acids with high cata-
lyst loadings, the reactions of 1 with aldehydes under the
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002107.
13450
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Chem. Eur. J. 2010, 16, 13450 – 13457

FULL PAPER
À
catalysis of CuBr2 were shown to involve a-C H activation
Results and Discussion
of ketene dithioacetals 1 (Scheme 1, nonconventional activa-
tion mode).[9] Notably, in the latter cases, a wider range of
substrates, including both ketene dithioacetals and electro-
philes, are scalable with low catalyst loadings (10 mol%).[9]
The significant acceleration of the CuBr2/BF3·Et2O cocata-
lyzed reaction of 1 with aldehydes (Table 1, entry 7 vs. en-
tries 1 and 6)[9b] seemed to give further support to the activa-
tion of 1 by CuBr2.
Preparation of functionalized ketene dithioacetals 1: Ac-
cording to the procedures reported previously,[8d] ketene di-
thioacetals 1a–l were prepared through a two-step process
involving the preparation of a-acetyl ketene dithioacetals,
starting from the corresponding active methylene com-
pounds, carbon disulfide, and alkyl halides in the presence
of K2CO3 catalyzed by tetrabutylammonium bromide
(TBAB) in water, followed by acid/base-promoted deacyla-
tion. The results are summarized in Scheme 2.
Table 1. Comparison of catalysts.[a]
Entry
Catalyst [equiv]
t [h]
Yield [%][b]
1
2
3
4
5
6
7
8
CuBr2 (0.1)
TiCl4 (1.2)
TiCl4 (0.5)
CuBr (1.0)
CuCl2 (0.1)
BF3·Et2O (0.1)
CuBr2 (0.1)/BF3·Et2O (0.1)
HBr (0.1, 46% aqueous)
HBr (0.1, 36% aqueous)
HCl (0.1, 36% aqueous)
HI (0.1, 45% aqueous)
HI (0.1, 36% aqueous)
H2SO4 (0.1, concentrated)
PTS (0.1)
12
2
98[9a]
93[8c]
46
10
24
48
35
2
[c][9a]
–
45[9a]
70[9b]
98[9b]
98
3
3
9
98
trace
8
10
11
12
13
14
15
16
24
24
24
24
24
24
24
trace
trace
7
[c]
TFA (0.1)
HOAc (0.1, glacial)
–
–
[c]
[a] Reaction conditions: 1a (1 mmol), 2a (0.5 mmol), MeCN (5 mL),
room temperature. [b] Isolated yield based on 2a. [c] No reaction.
Scheme 2. Preparation of functionalized ketene dithioacetals 1.
However, in the course of our continuing research, we
became aware that the HBr, generated in situ in the CuBr2-
À
catalyzed C C bond-forming reaction, played a crucial role
The remarkable catalytic performance of HBr in the “acid”-
À
in the activation of ketene dithioacetals. Furthermore, in
contrast to other acids (including various Lewis and Brønst-
ed acids), the remarkable catalytic performance of HBr in
catalytic amounts was observed in this kind of “acid”-cata-
lyzed reaction. Accordingly, the formation of a new reactive
species, a sulfur-stabilized carbonium ylide, depending on
the nature of the counterion, is proposed as the key inter-
mediate in the unique catalysis of HBr. Herein, we report a
novel catalytic method that involves several new chemical
aspects, including: 1) the unusual catalytic power of HBr in
catalyzed C C bond-forming reaction of ketene dithioacetal
1a and 4-chlorobenzaldehyde (2a): It was found that the re-
action of a-cyano ketene cyclic dithioacetal 1a (1 mmol)
with 4-chlorobenzaldehyde 2a (0.5 mmol) catalyzed by
CuBr2 (10 mol%) at room temperature in acetonitrile
(5 mL) for 12 h, gave the 2:1 adduct, penta-1,4-diene 3a, in
98% yield (Table 1, entry 1).[9a] With shorter reaction times
(2 h), under similar conditions, 3a was produced in 93%
yield with TiCl4 (120 mol%) as the promoter (Table 1,
entry 2).[8c] The yield of 3a was lower (46%) when substoi-
chiometric amounts of TiCl4 (50 mol%) was used even after
longer reaction times (10 h; Table 1, entry 3). By compari-
son, no reaction was observed with CuBr (100 mol%) as the
promoter (Table 1, entry 4).[9a] When catalyzed by CuCl2
(10 mol%) or BF3·Et2O (10 mol%) at room temperature for
48 or 35 h, 3a was afforded only in 45 and 70% yield, re-
spectively (Table 1, entries 5 and 6).[9a,b] Notably, with CuBr2
(10 mol%) and BF3·Et2O (10 mol%) as cooperative cata-
lyst, the reaction was significantly accelerated (Table 1,
entry 7 vs. entries 1 and 6). Taken together, the above results
À
the C C bond forming reaction, which is recognized and
evaluated for the first time; 2) a new reaction mechanism in-
volving anion-catalyzed C C bond formation; and 3) the
successful application of this approach to the efficient syn-
thesis of useful coumarins and benzofurans. This approach
À
À
has the potential to develop the fields of both C C bond-
forming reactions and anion catalysis.
Chem. Eur. J. 2010, 16, 13450 – 13457
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13451

M. Wang, Q. Liu et al.
[a]
À
Table 2. HBr-catalyzed C C bond formation of 1 with 2.
(Table 1, entries 1–7) suggest that CuBr2 is a more effective
catalyst than TiCl4, BF3·Et2O, CuCl2, or CuBr, and that
CuBr2 plays a double role in both the activation of the car-
À
bonyl electrophiles and of the a-C H bond of the ketene di-
thioacetals.[8c,9]
Although the experimental results (Table 1, entries 1–7)
suggest that CuBr2 is a more effective catalyst[6] than the
Entry
1
FG
R or
R/R
2
R’
R’’
3
t
Yield
[h] [%][b]
other Lewis acids tested[7,8] in the C C bond formation reac-
À
1
2
3
4
5
6
7
8
1a CN
1a CN
1a CN
1a CN
1a CN
1a CN
1a CN
1a CN
1a CN
1b CN
1c CO2Et
1d MeCO
1e PhCO
1a CN
1a CN
1a CN
A
H
H
H
H
H
H
H
H
H
H
H
H
H
3a
3b
3c
3d
3e
3 f
3g
3h
3i
4
4
3
1
4
4
2
6
7
98
93
98
91
89
85
90
80
85
tion based on ketene dithioacetals, the reaction mechanism
has not yet been elucidated because no detailed information
has previously been made available. To gain insight into the
mechanism, we examined the catalytic activity of HBr,
which was generated during the reaction of 1 and aldehydes
during the catalysis by CuBr2.[9a] Surprisingly, the adduct 3a
could be obtained in excellent yield by using HBr (46% or
36% aqueous, 10 mol%) as the catalyst. In this case, the re-
action time was shortened to 3 h to give excellent yields
under otherwise identical conditions (Table 1, entries 8 and
9 vs. entry 1). To better understand the origins of the ob-
served catalysis, we evaluated the influence of other protic
acids. As a comparison, interestingly, HCl (36% aqueous,
10 mol%) and HI (45% or 36% aqueous, 10 mol%) both
proved to be less effective than HBr; in both cases, very
small or trace amounts of 3a were formed even after ex-
tended reaction times (Table 1, entries 10–12).
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
9
A
H
10
11
12
13
14[c]
15[d]
16[d]
Et
G
2a 4-ClC6H4
3j
3k
3l
20 50
94
15 68
1
AHCTUNGTRENNUNG
G
3m 15 60
G
Me 3n 24 51
4a 18 52
N
ACHTUNGTRENNUNG
A
G
4b 20 64
[a] Reaction conditions: 1 (1 mmol), 2 (0.5 mmol), HBr (46% aqueous,
0.05 mmol), MeCN (5 mL), room temperature. [b] Isolated yield based
on 2. [c] Reaction performed at 608C. [d] Reaction conditions: 1a
(1 mmol), 2k or 2l (1 mmol), HBr (46% aqueous, 0.1 mmol), MeCN
(5 mL), room temperature.
Combining the above results (Table 1, entries 1–12) with
those obtained by Minami and co-workers,[7] highlights the
remarkable catalytic performance of HBr and indicates
(Table 2, entries 8 and 9), with 1a all proceed smoothly to
give the corresponding adducts 3a–i in excellent yields. In
addition, we also found that the reaction could tolerate acy-
clic alkylthio (Table 2, entry 10) groups as well as various a-
EWG groups (EWG=electron-withdrawing group; Table 2,
entries 11–13) on 1 and led to the corresponding adducts
3j–m in good to excellent yields. An explorative study using
other electrophiles showed that the reaction of 1a with ace-
tone 2j for 24 h at elevated temperature gave the adduct 3n
in 51% yield (Table 2, entry 14). The reactions of 1a with
cyclopentanone 2k and cyclohexanone 2l led to the forma-
tion of conjugated dienes 4a and 4b in good yields, respec-
that: 1) HBr is
a more effective catalyst than CuBr2
(Table 1, entry 8 vs. entry 1), 2) the HBr generated during
the CuBr2-catalyzed reaction of 1 and aldehydes[9a] should
play the crucial role in the activation of 1, and 3) the bro-
mide anion is more than a spectator in this “acid” catalyzed
reaction (Table 1, entries 8 and 9 vs. entries 10–12). Consid-
ering the substantial contribution made by the bromide
2
À
anion to the a-Csp H bond activation of ketene dithioace-
tals, the catalytic performance of other protic acids was fur-
ther investigated. We found that HBr is unique because, in
addition to HCl and HI (Table 1, entries 10–12), concentrat-
ed sulfuric acid (10 mol%) and 4-methylbenzenesulfonic
acid (PTS, 10 mol%) were also less effective catalysts
(Table 1, entries 13 and 14); trifluoroacetic acid (TFA, 10
mol%) and glacial acetic acid (10 mol%) were ineffective
catalysts for the reaction of 1a with 2a (Table 1, entries 15
and 16).
À
tively, through consecutive C C coupling and dehydration
(Table 2, entries 15 and 16).
Synthesis of coumarins 5 through the reaction of ketene di-
ethylthioacetals 1 and salicylaldehydes 2 catalyzed by HBr:
As described above, we have developed an efficient C C
À
bond-forming reaction under the catalysis of HBr. As a
comparison with our previous work,[9a] we applied the ap-
proach to the synthesis of coumarins, which are frequently
occurring structural subunits in numerous natural products
with interesting biological activities.[10] As shown in
Scheme 3, when salicylaldehydes 2m–o (1 mmol) were se-
lected as electrophiles to react with ketene diethylthioace-
tals 1b (1 mmol), 1 f (1 mmol), 1g (1 mmol), or 1h (1 mmol)
under the catalysis of HBr (46% aqueous, 10 mol%) in ace-
tonitrile (5 mL), 3-substituted coumarin derivatives 5a–i
were obtained in high yields. Notably, none of the desired
product 5c was detected when the reaction of 1 f and 2m
À
HBr-catalyzed C C bond formation of ketene dithioacetals
1 with carbonyl compounds 2: Under the reaction conditions
detailed in Table 1, entry 8, a series of experiments were
performed, the results of which are summarized in Table 2.
It is clear that the reactions of a range of aldehydes, includ-
ing benzaldehyde (Table 2, entry 2), aromatic aldehydes
having both electron-withdrawing (Table 2, entries 1 and 3)
and electron-donating (Table 2, entry 4) substituents, hetero-
aromatic aldehydes (Table 2, entries 5 and 6), an a,b-unsatu-
rated aldehyde (Table 2, entry 7), and aliphatic aldehydes
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Synthesis of Coumarins and Benzofurans
FULL PAPER
zoquinone 6a (1.5 mmol) with ketene dimethylthioacetal 1k
(1 mmol) catalyzed by HBr (46% aqueous, 10 mol%) in
acetonitrile (5 mL), led to the formation of benzofuran 7b
in 62% yield after heating the reaction mixture to reflux for
6 h. In contrast, HCl (36% aqueous, 10 mol%) and HI
(45% aqueous, 10 mol%) were found to be either ineffec-
tive or less effective as catalysts for this procedure under
identical reaction conditions (Scheme 4). The synthetic
method was then successfully employed to prepare the cor-
responding benzofurans 7c–j in 16–66% yields. Moreover,
À
the higher efficiency of HBr as a catalyst in this kind of C
C coupling and sequential cyclization was also clearly ob-
served when 1j and 6b were used as substrates (Scheme 4,
catalytic synthesis of 7 f).
Proposed reaction mechanism: The above results (Tables 1
and 2, and Schemes 3 and 4) suggest that: 1) HBr is a more
efficient catalyst than either Lewis acids (e.g., TiCl4,
BF3·Et2O, or CuBr2) or protic acids (e.g., HCl, HI, H2SO4,
PTS, or TFA); 2) the origins of the unexpected catalytic ac-
À
tivity of CuBr2 for the C C bond formation reaction of
functionalized ketene dithioacetals 1 with aldehydes 2 do
indeed stem from the HBr generated during the reactions;[9]
and, most importantly 3) the bromide anion plays a crucial
role in the reaction by enhancing the nucleophilicity of the
functionalized ketene dithioacetals 1 (Table 1, entries 8 and
9 vs. entries 10–16). These observations provide new insights
À
into the mechanism of the C C bond formation reaction
with functionalized ketene dithioacetals 1 (Scheme 5).
It is easy to understand that in reactions catalyzed (or
promoted) by Lewis acids, such as EtAlCl2, BF3·Et2O, and
À
TiCl4, C C bond formation could result from nucleophilic
Scheme 3. Synthesis of coumarins 5 through the reaction of ketene di-
ACHTUNGTRENNUNGethylthioacetals 1 and salicylaldehydes 2 catalyzed by HX.
attack of a ketene dithioacetal 1 on a Lewis acid activated
aldehyde C (Scheme 5, Path A).[7,8] Because CuBr2 is a
weaker Lewis acid than EtAlCl2, BF3·Et2O, or TiCl4,[11] ac-
cording to the conventional activation mode, the rate of
CuBr2-catalyzed reaction of 1 with 2 should be slower, and
similar to that catalyzed by CuCl2 (Table 1, entry 5). Howev-
er, in the case of CuBr2-catalyzed reaction of 1 and 2,[9a] the
unexpected rate increase cannot be explained unless the
HBr, generated during the reaction, is taken into consider-
ation. In fact, the present results suggest that HBr is a true
was performed with HCl (36% aqueous, 10 mol%) or HI
(45% aqueous, 10 mol%) as catalysts (Scheme 3). Similarly,
a remarkable catalytic performance of HBr was observed
with 1h and 2m as substrates (Scheme 3, catalytic synthesis
of 5h). When the reaction of 1g and 2o was selected to in-
vestigate the catalytic performance of HX (X=Br, Cl, and
I) in this process (Scheme 3, catalytic synthesis of 5 f), it was
found that 5 f was isolated in 85% yield under the catalysis
of HBr, whereas no reaction was detected with HCl as cata-
lyst and a lower yield of 5 f was obtained with HI as cata-
lyst.
À
catalyst in the CuBr2-catalyzed C C bond forming reaction
of 1,[9] and that this HBr-catalyzed reaction involves a very
different mechanism to the conventional version.[7,8] Thus, a
new mechanism is proposed that takes into account the ef-
fects of the bromide anion. As depicted in Scheme 5,
Path B, the reaction of 1 with aldehyde 2 is presumably initi-
ated by the protonation of the polarized C=C bond of 1 to
form intermediate A,[5f,12,13] in which the a-proton adjacent
to two electron-withdrawing groups (FG and RS+ =CSR) is
highly acidic. Thus, base-assisted (BrÀ) deprotonation of A
should take place smoothly and further transform A into
Synthesis of benzofurans 7 through the reaction of ketene
diethylthioacetals 1 and p-quinones 6 catalyzed by HBr: Re-
cently, we reported that benzofurans 7 can be easily pre-
pared by the reaction of CuBr2-activated ketene dimethylth-
ioacetals 1 with BF3·Et2O-activated p-quinones 6.[9b] In con-
trast, under the same conditions, no reaction was detected in
the absence of BF3·Et2O.[9b] In this study, we found that all
the reactions of 1 with 6, except for the reaction between 1i
and 6a, could also afford benzofurans 7 under the catalysis
of only HBr (10 mol%). For example, the reaction of p-ben-
the carbon anion intermediate B through selective forma-
tion of the S Br bond. Alternative mesomeric structures
[14]
À
of B, such as B’, B’’, and B’’’, also suggest that a sulfur-stabi-
lized carbonium ylide[15–17] (B’’’), which is a far better carbon
Chem. Eur. J. 2010, 16, 13450 – 13457
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13453

M. Wang, Q. Liu et al.
Scheme 4. Synthesis of benzofurans 7 through the reaction of ketene diethylthioacetals 1 and p-quinones 6 catalyzed by HX.
Conclusion
À
We have shown that HBr is a unique catalyst for C C bond
formation reactions involving functionalized ketene dithioa-
cetals 1. Our conclusions are supported by the rate increase
relative to those catalyzed (or promoted) by CuBr2 and se-
lected Lewis or Brønsted acids, and by the wide range of
substrates that can be used for functionalized ketene di-
thioacetals and carbon electrophiles. Accordingly, a variety
of products, such as polyfunctionalized penta-1,4-dienes 3,
conjugated dienes 4, coumarins 5, and benzofurans 7, were
synthesized successfully under mild, metal-free conditions.
A new mechanism is proposed for the unique catalysis of
HBr, which involves the generation of a strong nucleophilic
species, a sulfur-stabilized carbonium ylide. Further studies
are in progress.
Scheme 5. Proposed reaction mechanism.
nucleophile than polarized ketene dithioacetal 1, is involved
À
and that it is, in fact, this species that induces this initial C
C formation reaction. The proposed mechanism thus in-
volves activation of both the ketene dithioacetal 1 and the
electrophile by a bromide anion and a proton, respectively,
and indicates that HBr plays a cocatalytic role (Scheme 5,
Path B). In addition, this description provides a better ex-
planation for the results given in Table 1 (in particular, com-
pare entry 1 vs. entries 2–6; entries 8 and 9 vs. entries 10–16;
entry 1 vs. entry 7; and reference [9]).
Experimental Section
General: All reagents were purchased from commercial sources and used
directly, unless otherwise indicated. Flash column chromatography was
carried out by using 300–400 mesh silica gel under increased pressure.
All reactions were monitored by TLC, which was performed on precoat-
1
ed aluminum sheets of silica gel 60 (F254). H NMR and 13C NMR spectra
were recorded at ambient temperature with Varian 500 MHz and
125 MHz instruments, respectively, using TMS as internal standard. All
shifts are given in ppm. IR spectra (KBr) were recorded with a Magna-
560 FTIR spectrophotometer in the range of 400–4000 cmÀ1. Mass spec-
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Synthesis of Coumarins and Benzofurans
FULL PAPER
tra were measured with an Agilient 1100 LCMSD spectrometer. Elemen-
tal analyses were obtained with a VarioEL analyzer.
C11H10N2S4 (298.3): C 44.26, H 3.38, N 9.39; found: C 44.40, H 3.31, N
9.36.
Typical procedure for the preparation of 1; Synthesis of 1d:[8d] CS2
(0.73 mL, 12 mmol) was added under stirring to a solution of pentane-
2,4-dione (1 mL, 10 mmol), K2CO3 (3.45 g, 25 mmol), and TBAB
(321 mg, 1 mmol) in water (15 mL) at room temperature. After stirring at
room temperature for 1 h, 1,2-dibromoethane (0.87 mL, 10 mmol) was
added dropwise within 15 min. The resulting mixture was stirred for 8 h
at room temperature then the precipitated solid was collected by filtra-
tion, washed with water (3ꢁ25 mL), and dried under vacuum to afford 3-
(1,3-dithiolan-2-ylidene)pentane-2,4-dione (1.96 g, 97%) as a white solid.
Concentrated H2SO4 (1.1 mL, 20 mmol) was added to a solution of the
latter (1.01 g, 5 mmol) in CH2Cl2 (50 mL) at 08C, and the mixture was al-
lowed to warm to room temperature and stirred for 10 h. The mixture
was poured onto saturated NaCl ice-water (50 mL) under stirring then
the mixture was neutralized with aqueous Na2CO3 and extracted with
CH2Cl2 (3ꢁ20 mL). The combined organic phase was washed with water
(3ꢁ15 mL), dried (MgSO4) and concentrated in vacuo. The crude prod-
uct was purified by flash chromatography (silica gel; petroleum ether/di-
ethyl ether=2:1, v/v) to give 1d (750 mg, 94%) as a white solid.
Compound 3j:[9a] White solid; 1H NMR (500 MHz, CDCl3): d=1.25–1.28
(m, 6H), 1.31–1.35 (m, 6H), 2.94–3.03 (m, 8H), 5.61 (s, 1H), 7.24 (d, J=
8.5 Hz, 2H), 7.35 ppm (d, J=8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3):
d=14.9 (2C), 15.6 (2C), 29.2 (2C), 30.4 (2C), 49.5, 116.4 (2C), 117.3 (2C),
129.2 (2C), 129.5 (2C), 133.9, 136.5, 156.9 ppm (2C).
1
Compound 3k:[9a] Pink solid; H NMR (500 MHz, CDCl3): d=0.98 (t, J=
7.0 Hz, 6H), 3.33ACTHUNTGRNEUNG(s, 8H), 3.97–4.00 (m, 4H), 5.42 (s, 1H), 7.11 (d, J=
8.5 Hz, 2H), 7.18 ppm (d, J=8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3):
d=14.0 (2C), 37.5 (2C), 38.5 (2C), 53.7 (2C), 60.5, 117.1, 127.9 (2C),
130.0 (2C), 131.8, 140.5 (2C), 161.1 (2C), 166.7 ppm (2C).
Compound 3l:[8a] Yellowish solid; 1H NMR (500 MHz, CDCl3): d=1.93
(s, 6H), 3.24–3.29 (m, 8H), 5.69 (s, 1H), 7.15 (d, J=8.0 Hz, 2H),
7.28 ppm (d, J=8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3): d=29.1 (2C),
37.5 (2C), 37.9 (2C), 53.5, 124.4, 129.3 (2C), 130.7 (2C), 133.4 (2C), 139.9,
163.9 (2C), 195.8 ppm (2C).
Compound 3m:[9a] Yellow solid; 1H NMR (500 MHz, CDCl3): d=3.15–
3.19 (m, 6H), 3.27–3.28 (m, 2H), 5.56 (s, 1H), 7.21 (d, J=8.5 Hz, 2H),
7.31–7.32 (m, 4H), 7.39–7.41 (m, 4H), 7.55 ppm (d, J=7.0 Hz, 4H);
13C NMR (125 MHz, CDCl3): d=37.8 (2C), 38.4 (2C), 56.3, 125.2 (2C),
128.1 (2C), 128.3 (4C), 128.7 (4C), 130.5 (2C), 131.6 (2C), 138.2 (2C),
138.6 (2C), 154.9 (2C), 195.1 ppm (2C).
Synthesis of polyfunctionalized penta-1,4-dienes 3; Typical procedure
with 1a and 2a: HBr in acetonitrile (4 mL, 0.0125 m, 0.05 mmol) was
added to a solution of 1a (143 mg, 1 mmol) and 2a (70 mg, 0.5 mmol) in
acetonitrile (1 mL) at room temperature. The reaction mixture was
stirred for 3 h (reaction monitored by TLC) and then poured onto ice-
water (20 mL). The precipitate was collected by filtration, washed with
water (3ꢁ50 mL), and dried in vacuo to afford the product 3a (199 mg,
98%) as a white solid.
Compound 3n:[8c] Yellow solid; 1H NMR (500 MHz, DMSO): d=3.36 (s,
6H), 3.49–3.64 ppm (m, 8H); 13C NMR (125 MHz, DMSO): d=26.7
(2C), 31.2 (2C), 37.6 (2C), 42.3, 99.9 (2C), 118.7 (2C), 165.0 ppm (2C).
Synthesis of dienes 4a; Typical procedure with 1a and 2k: HBr in aceto-
nitrile (4 mL, 0.025 m, 0.1 mmol) was added to a solution of 1a (143 mg,
1 mmol) and 2k (0.088 mL, 1 mmol) in acetonitrile (1 mL) at room tem-
perature. The reaction was allowed to proceed at room temperature until
completion (18 h). The mixture was quenched with ice-water (20 mL),
then extracted with CH2Cl2 (3ꢁ20 mL). The combined organic extracts
were washed with water, dried (Na2SO4), filtered, and concentrated. The
residue was purified by flash chromatography on silica gel (petroleum
ether/diethyl ether=9:1, v/v) to give conjugated dienes 4a (108 mg,
52%) as a colorless oil.
Compound 4a: Colorless oil; 1H NMR (500 MHz, CDCl3): d=1.91–1.97
(m, 2H), 2.47–2.50 (m, 2H), 2.68–2.71 (m, 2H), 3.48–3.50 (m, 2H), 3.57–
3.59 (m, 2H), 5.97 ppm (s, 1H); 13C NMR (125 MHz, CDCl3): d=23.6,
33.5, 35.3, 37.6, 40.7, 96.7, 118.7, 131.1, 137.6, 159.1 ppm; ES-MS: m/z
calcd. 209; found 210 [M+1]+; elemental analysis calcd (%) for
C10H11NS2 (209.2): C 57.38, H 5.30, N 6.69; found: C 57.20, H 5.39, N
6.75.
Compound 4b: Colorless oil; 1H NMR (500 MHz, CDCl3): d=1.59–1.63
(m, 2H), 1.67–1.69 (m, 2H), 2.14–2.15 (m, 2H), 2.22 (s, 2H), 3.48–3.49
(m, 4H), 5.90 ppm (s, 1H); 13C NMR (125 MHz, CDCl3): d=21.6, 22.5,
25.4, 27.5, 37.7, 39.2, 100.6, 118.2, 129.8, 133.3, 159.3 ppm; ES-MS: m/z
calcd. 223; found 224 [M+1]+; elemental analysis calcd (%) for
C11H13NS2 (223.2): C 59.15, H 5.87, N 6.27; found: C 59.01, H 5.96, N
6.35.
1
Compound 3a:[8c] White solid; H NMR (500 MHz, CDCl3): d=3.53–3.60
(m, 8H), 4.51 (s, 1H), 7.29 (d, J=8.5 Hz, 2H), 7.35 ppm (d, J=8.5 Hz,
2H); 13C NMR (125 MHz, CDCl3): d=38.4 (2C), 40.1 (2C), 52.5, 96.3
(2C), 117.3 (2C), 129.2, 129.4 (2C), 134.2 (2C), 135.7, 165.1 ppm (2C).
1
Compound 3b:[8c] White solid; H NMR (500 MHz, CDCl3): d=3.55–3.56
(m, 8H), 4.54 (s, 1H), 7.32–7.37 ppm (m, 5H); 13C NMR (125 MHz,
CDCl3): d=38.3 (2C), 39.9 (2C), 53.1, 96.6 (2C), 117.4 (2C), 127.9, 128.2
(2C), 128.9 (2C), 137.1, 164.7 ppm (2C).
Compound 3c:[8c] Yellowish solid; 1H NMR (500 MHz, CDCl3): d=3.56–
3.63 (m, 8H), 4.64 (s, 1H), 7.54 (d, J=8.5 Hz, 2H), 8.23 ppm (d, J=
8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): d=38.8 (2C), 40.4 (2C), 52.8,
95.2 (2C), 117.2 (2C), 124.4, 129.3 (2C), 144.6 (2C), 147.9, 166.7 ppm
(2C).
Compound 3d:[8c] Yellow solid; 1H NMR (500 MHz, CDCl3): d=3.54–
3.58 (m, 8H), 3.80 (s, 3H), 4.48 (s, 1H), 6.90 (d, J=8.0 Hz, 2H),
7.28 ppm (d, J=8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3): d=38.3 (2C),
40.0 (2C), 52.5, 55.2, 97.3 (2C), 114.3 (2C), 117.5 (2C), 129.2 (2C), 159.4
(2C), 164.1 ppm (2C).
Compound 3e:[8c] Red solid; 1H NMR (500 MHz, CDCl3): d=3.54–3.60
(m, 8H), 4.66 (s, 1H), 6.37–6.40 (m, 2H), 7.43–7.44 ppm (m, 1H);
13C NMR (125 MHz, CDCl3): d=38.7 (2C), 40.3 (2C), 47.7, 94.7 (2C),
108.9, 111.0, 117.3 (2C), 143.4, 149.5, 165.5 ppm (2C).
Compound 3 f:[8c] Brown solid; 1H NMR (500 MHz, CDCl3): d=3.56–
3.59 (m, 8H), 4.80 (s, 1H), 7.01–7.03 (m, 1H), 7.11–7.12 (m, 1H), 7.28–
7.29 ppm (m, 1H); 13C NMR (125 MHz, CDCl3): d=38.3 (2C), 40.0 (2C),
48.4, 96.5 (2C), 116.9, 125.5, 126.3 (2C), 127.3, 139.4, 164.9 ppm (2C).
Synthesis of 3-substituted 2H-chromen-2-ones 5; Typical procedure with
1h and 2m: HBr in acetonitrile (4 mL, 0.025 m, 0.1 mmol) was added to
a stirred solution of 2m (0.12 mL, 1.1 mmol) and 1h (252 mg, 1 mmol) in
MeCN (1 mL) at room temperature. The reaction was allowed to pro-
ceed at room temperature until completion (1 h). The mixture was
quenched with aqueous NaHCO3 (10 mL, 5%), then extracted with
CH2Cl2 (3ꢁ10 mL). The combined organic extracts were washed with
water, dried (Na2SO4), filtered, and concentrated in vacuo to afford the
pure product 5h (212 mg, 85%) as a white solid.
Compound 3g:[9a] White solid; 1H NMR (500 MHz, CDCl3): d=3.55 (s,
8H), 4.40 (d, J=6.0 Hz, 1H), 6.10–6.16 (m, 2H), 7.26–7.37 ppm (m, 5H);
13C NMR (125 MHz, CDCl3): d=38.3 (2C), 39.3, 39.5, 52.4, 97.2, 98.7,
116.4, 117.8, 126.8, 127.6, 127.8 (2C), 128.8 (2C), 128.9, 139.3, 161.2,
161.7 ppm.
1
1
Compound 3h:[9a] White solid; H NMR (500 MHz, CDCl3): d=1.46–1.48
Compound 5a:[9a] White solid; H NMR (500 MHz, CDCl3): d=7.41–7.44
(m, 3H), 3.32–3.34 (m, 1H), 3.53–3.58 ppm (m, 8H); 13C NMR
(125 MHz, CDCl3): d=18.3, 38.2 (2C), 39.8 (2C), 42.2, 98.0 (2C), 117.1
(2C), 162.8 ppm (2C).
(m, 2H), 7.62–7.64 (m, 1H), 7.72–7.76 (m, 1H), 8.30 ppm (s, 1H);
13C NMR (125 MHz,CDCl3): d=103.5, 113.7, 117.3, 117.6, 125.9, 129.5,
135.7, 152.0, 154.8, 156.6 ppm.
1
1
Compound 3i: White solid; mp 162–1648C; H NMR (500 MHz, CDCl3):
Compound 5b:[9a] Yellow solid; H NMR (500 MHz, DMSO): d=7.54 (d,
d=3.27 (s, 2H), 3.56–3.59 ppm (m, 8H); 13C NMR (125 MHz, CDCl3):
d=38.4, 38.6 (2C), 39.8 (2C), 91.6 (2C), 109.7 (2C), 118.2 ppm (2C); ES-
MS: m/z calcd. 298; found 299 [M+1]+; elemental analysis calcd (%) for
J=9.0 Hz, 1H), 7.81–7.83 (m, 1H), 7.89 (d, J=2.5 Hz, 1H), 8.84 ppm (s,
1H); 13C NMR (125 MHz, DMSO): d=103.6, 114.3, 118.8, 118.9, 128.7,
129.1, 134.8, 152.1, 152.7, 156.5 ppm.
Chem. Eur. J. 2010, 16, 13450 – 13457
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
13455

M. Wang, Q. Liu et al.
Compound 5c:[9a] White solid; 1H NMR (500 MHz, CDCl3): d=1.42 (t,
J=7.0 Hz, 3H), 4.40–4.44 (m, 2H), 7.32–7.37 (m, 2H), 7.61–7.67 (m,
2H), 8.54 ppm (s, 1H); 13C NMR (125 MHz, CDCl3): d=14.2, 61.9, 116.7,
117.8, 118.2, 124.8, 129.5, 134.3, 148.6, 155.1, 156.7, 163.0 ppm.
Compound 5d:[9a] Yellow solid; 1H NMR (500 MHz, DMSO): d=1.41 (t,
J=7.0 Hz, 3H), 4.40–4.45 (m, 2H), 7.32 (d, J=8.5 Hz, 1H), 7.58–7.60 (m,
2H), 8.44 ppm (s, 1H); 13C NMR (125 MHz, DMSO) d=14.1, 62.1, 118.2,
118.8, 119.4, 128.4, 130.0, 134.0, 147.0, 153.4, 155.9, 162.6 ppm.
Compound 5e:[9a] Yellow solid; 1H NMR (500 MHz, CDCl3): d=1.42 (t,
J=7.0 Hz, 3H), 3.87 (s, 3H), 4.40–4.44 (m, 2H), 7.00 (d, J=3.0 Hz , 1H),
7.22–7.24 (m, 1H), 7.29 (d, J=9.0 Hz, 1H), 8.48 ppm (s, 1H); 13C NMR
(125 MHz, CDCl3): d=14.2, 55.9, 61.9, 109.8, 110.7, 117.9, 118.2, 122.6,
148.3, 149.8, 156.3, 156.9, 163.2 ppm.
Compound 5 f:[9a] Yellow solid; 1H NMR (500 MHz, DMSO): d=2.57 (s,
3H), 7.49 (d, J=9.0 Hz, 1H), 7.75–7.77 (m, 1H), 8.06 (d, J=2.0 Hz, 1H),
8.59 ppm (s, 1H). 13C NMR (125 MHz, DMSO): d=30.0, 118.2, 119.6,
125.4, 128.6, 129.5, 133.8, 145.7, 153.2, 158.0, 195.0 ppm.
14.7 (2C), 60.9, 110.2, 113.0, 113.6, 117.9, 125.6, 148.3, 152.4, 161.1,
163.7 ppm.
Compound 7g:[9b] White solid; 1H NMR (500 MHz, DMSO): d=1.33 (t,
J=7.0 Hz, 3H), 2.65 (s, 3H), 4.32 (q, J=7.0 Hz, 2H), 7.14 (s, 1H),
10.54 ppm (s, 1H); 13C NMR (125 MHz, DMSO): d=14.6, 14.7, 61.6,
98.6, 102.0, 112.6, 115.4, 127.5, 146.2, 152.8, 160.5, 162.5 ppm.
Compound 7h:[9b] White solid; 1H NMR (500 MHz, DMSO): d=2.55 (s,
3H), 7.20 (s, 1H), 7.53 (t, J=7.5 Hz, 2H), 7.69 (t, J=7.0 Hz, 1H), 7.82
(d, J=7.0 Hz, 2H), 10.58 ppm (s, 1H); 13C NMR (125 MHz, DMSO): d=
15.9, 97.9, 101.7, 115.8, 121.5, 128.5, 129.0 (2C), 129.4 (2C), 134.1, 137.8,
145.9, 151.9, 154.4, 189.6 ppm.
Compound 7i:[9b] White solid; 1H NMR (500 MHz, DMSO): d=1.38 (t,
J=7.0 Hz, 3H), 2.78 (s, 3H), 4.33 (q, J=7.0 Hz, 2H), 7.34 (s, 1H), 7.48
(t, J=8.0 Hz, 1H), 7.63 (t, J=7.5 Hz, 1H), 8.11 (d, J=8.0 Hz, 1H), 8.20
(d, J=8.5 Hz, 1H), 10.26 ppm (s, 1H); 13C NMR (125 MHz, DMSO): d=
13.4, 14.9, 60.7, 100.1, 108.7, 119.5, 120.7, 122.6, 123.0, 123.8, 124.8, 127.9,
144.4, 151.2, 160.8, 163.6 ppm.
Compound 7j:[9b] White solid; 1H NMR (500 MHz, DMSO): d=2.59 (s,
3H), 2.80 (s, 3H), 7.39 (s, 1H), 7.48–7.51 (m, 1H), 7.62–7.65 (m, 1H),
8.13 (d, J=8.0 Hz, 1H), 8.20 (d, J=8.5 Hz, 1H), 10.25 ppm (s, 1H);
13C NMR (125 MHz, DMSO): d=13.6, 30.3, 99.8, 118.0, 119.1, 120.1,
122.0, 122.1, 123.2, 124.4, 127.4, 144.0, 150.8, 160.0, 192.3 ppm.
Compound 5g:[9a] Yellow solid; 1H NMR (500 MHz, DMSO): d=2.57 (s,
3H), 3.80 (s, 3H), 7.32 (t, J=2.5 Hz, 1H), 7.39 (d, J=9.0 Hz, 1H), 7.48
(d, J=2.5 Hz, 1H), 8.58 ppm (s, 1H); 13C NMR (125 MHz, DMSO): d=
30.1, 55.8, 112.2, 117.2, 118.6, 122.4, 124.5, 146.9, 149.1, 155.8, 158.6,
195.2 ppm.
Compound 5h:[9a] White solid; 1H NMR (500 MHz, CDCl3): d 7.35–7.38
(m, 1H), 7.42 (d, J=8.5 Hz, 1H), 7.48–7.51 (m, 2H), 7.61–7.68 (m, 3H),
7.89 (d, J=8.0 Hz, 2H), 8.09 ppm (s, 1H); 13C NMR (125 MHz, CDCl3) d
116.9, 118.1, 124.9, 126.9, 128.6, 129.2 (2C), 129.6 (2C), 133.6, 133.8,
136.2, 145.5, 154.7, 158.4, 191.6 ppm.
Compound 5i:[9a] White solid; 1H NMR (500 MHz, DMSO): d=3.82 (s,
3H), 7.32–7.34 (m, 1H), 7.42–7.45 (m, 2H), 7.55 (t, J=7.5 Hz, 2H), 7.69
(t, J=7.5 Hz, 1H), 7.92 (t, J=7.0 Hz, 2H), 8.36 ppm (s, 1H); 13C NMR
(125 MHz, DMSO): d=55.8, 111.6, 117.5, 118.7, 121.3, 126.6, 128.8 (2C),
129.5 (2C), 133.9, 136.1, 145.2, 148.6, 155.8, 158.2, 191.8 ppm.
Acknowledgements
Financial support of this research by NNSFC (20872015/20972029) and
the Fundamental Research Funds for the Central Universities (NENU-
STC08007/07007) is gratefully acknowledged.
Synthesis of benzofurans 7; Typical procedure with 1k and 6a: HBr in
acetonitrile (4 mL, 0.025 m, 0.1 mmol) was added to a stirred solution of
1k (162 mg, 1.0 mmol) and 6a (162 mg, 1.5 mmol) in MeCN (1 mL) at
room temperature. The reaction mixture was heated at reflux for 6 h,
until the starting material 1k was consumed (reaction monitored by
TLC). The resulting mixture was poured into saturated aqueous NaCl
(20 mL), neutralized with aqueous NaHCO3 and extracted with CH2Cl2
(3ꢁ20 mL). The combined organic phase was washed with water (3ꢁ
20 mL), dried (MgSO4) and concentrated in vacuo to yield the crude
product, which was purified by silica gel chromatography (petroleum
ether/diethyl ether=5:1, v/v) to give 7b (138 mg, 62%) as a white solid.
Compound 7b:[9b] White solid; 1H NMR (500 MHz, DMSO): d=2.52 (s,
3H), 2.66 (s, 3H), 6.71 (dd, J=2.5, 9.0 Hz, 1H), 7.20 (d, J=2.5 Hz, 1H),
7.40 (d, J=9.0 Hz, 1H), 9.50 ppm (s, 1H); 13C NMR (125 MHz, DMSO):
d=13.1, 30.3, 105.5, 111.2, 111.9, 116.4, 126.7, 148.8, 154.7, 162.8,
192.0 ppm.
Compound 7c:[9b] White solid; 1H NMR (500 MHz, DMSO): d=1.34 (t,
J=7.5 Hz, 3H), 2.66 (s, 3H), 4.29 (q, J=7.0 Hz, 2H), 6.69 (dd, J=2.5,
9.0 Hz, 1H), 7.18 (d, J=2.5 Hz, 1H), 7.39 (d, J=9.0, 1H), 9.43 ppm (s,
1H); 13C NMR (125 MHz, DMSO): d=13.2, 14.8, 60.6, 105.7, 107.3,
111.6, 112.4, 127.4, 149.2, 155.1, 163.3, 163.5 ppm.
Compound 7d:[9b] Yellow solid; 1H NMR (500 MHz, DMSO): d=2.63 (s,
3H), 6.56 (d, J=2.0 Hz, 1H), 6.70 (dd, J=2.0, 9.0 Hz, 1H), 7.43 (d, J=
9.0 Hz, 1H), 7.56 (t, J=7.5 Hz, 2H), 7.65–7.70 (m, 3H), 9.37 ppm (s,
1H); 13C NMR (125 MHz, DMSO): d=13.5, 105.1, 111.3, 112.4, 116.1,
127.0, 128.2 (2C), 128.7 (2C), 132.3, 139.1, 148.9, 154.3, 163.3, 189.7 ppm.
[1] a) S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M.
Sonoda, N. Chatani, Nature 1993, 366, 529; b) R. J. Phipps, M. J.
Gaunt, Science 2009, 323, 1593; c) J.-Y. Cho, M. K. Tse, D. Holmes,
R. E. Maleczka, Jr., M. R. Smith III, Science 2002, 295, 305; d) K.
Godula, D. Sames, Science 2006, 312, 67; e) C.-J. Li, Acc. Chem. Res.
2009, 42, 335.
2
À
[2] For selected examples on oxygen-directed Csp H activation, see:
a) T. Satoh, Y. Kawamura, M. Miura, M. Nomura, Angew. Chem.
1997, 109, 1820; Angew. Chem. Int. Ed. Engl. 1997, 36, 1740; b) K.
Tsuchikama, Y. Kuwata, Y.-k. Tahara, Y. Yoshinami, T. Shibata,
Org. Lett. 2007, 9, 3097; c) K. Tanaka, Y. Otake, A. Wada, K. Nogu-
chi, M. Hirano, Org. Lett. 2007, 9, 2203.
[3] For selected examples on nitrogen-directed Csp H activation, see:
2
À
a) D. A. Colby, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc.
2006, 128, 5604; b) X. Chen, X.-S. Hao, C. E. Goodhue, J.-Q. Yu, J.
Am. Chem. Soc. 2006, 128, 6790; c) H.-Q. Do, O. Daugulis, J. Am.
Chem. Soc. 2007, 129, 12404; d) I. ꢂzdemir, S. Demir, B. Cetinkaya,
C. Gourlaouen, F. Maseras, C. Bruneau, P. H. Dixneuf, J. Am.
Chem. Soc. 2008, 130, 1156; e) M. Kim, J. Kwak, S. Chang, Angew.
Chem. 2009, 121, 9097; Angew. Chem. Int. Ed. 2009, 48, 8935.
[4] a) R. K. Dieter, Tetrahedron 1986, 42, 3029; b) H. Junjappa, H. Ila,
C. V. Asokan, Tetrahedron 1990, 46, 5423.
[5] a) X. Bi, D. Dong, Q. Liu, W. Pan, L. Zhao, B. Li, J. Am. Chem.
Soc. 2005, 127, 4578; b) D. Dong, X. Bi, Q. Liu, F. Cong, Chem.
Commun. 2005, 3580; c) J. Tan, X. Xu, L. Zhang, Y. Li, Q. Liu,
Angew. Chem. 2009, 121, 2912; Angew. Chem. Int. Ed. 2009, 48,
2868; d) M. Wang, F. Han, H. Yuan, Q. Liu, Chem. Commun. 2010,
46, 2247; e) Y. Li, X. Xu, J. Tan, P. Liao, J. Zhang, Q. Liu, Org. Lett.
2010, 12, 244; f) H. Yu, Z. Yu, Angew. Chem. 2009, 121, 2973;
Angew. Chem. Int. Ed. 2009, 48, 2929; g) P. P. Singh, A. K. Yadav, H.
Ila, H. Junjappa, J. Org. Chem. 2009, 74, 5496; h) H. S. P. Rao, K.
Vasantham, J. Org. Chem. 2009, 74, 6847; i) M. Hagimori, S. Matsui,
N. Mizuyama, K. Yokota, J. Nagaoka, Y. Tominaga, Eur. J. Org.
Chem. 2009, 5847; j) X. Gao, C. Di, Y. Hu, X. Yang, H. Fan, F.
Zhang, Y. Liu, H. Li, D. Zhu, J. Am. Chem. Soc. 2010, 132, 3697;
Compound 7e:[9b] White solid; 1H NMR (500 MHz, DMSO): d=1.74 (s,
3H), 2.40 (s, 3H), 2.52 (s, 3H), 6.70 (s, 1H), 7.54 (t, J=7.5 Hz, 2H), 7.68
(t, J=7.5 Hz, 1H), 7.78 (d, J=7.0 Hz, 2H), 9.12 ppm (s, 1H); 13C NMR
(125 MHz, DMSO): d=13.2, 15.0, 16.1, 112.1, 114.7, 118.5, 121.6, 127.0,
129.5 (2C), 129.7 (2C), 134.2, 138.6, 148.4, 152.0, 154.0, 191.8 ppm.
Compound 7 f:[9b] White solid; 1H NMR (500 MHz, DMSO): d=1.32 (t,
J=7.0 Hz, 3H), 2.34 (s, 6H), 2.63 (s, 3H), 4.28 (d, J=7.0 Hz, 2H), 6.62
(s, 1H), 9.08 ppm (s, 1H); 13C NMR (125 MHz, DMSO): d=13.4, 13.8,
13456
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 13450 – 13457

Synthesis of Coumarins and Benzofurans
FULL PAPER
k) S. Yoshida, H. Yorimitsu, K. Oshima, Org. Lett. 2009, 11, 2185;
l) S. Yoshida, H. Yorimitsu, K. Oshima, Org. Lett. 2007, 9, 5573.
[6] a) T. Minami, T. Okauchi, H. Matsuki, M. Nakamura, J. Ichikawa,
M. Ishida, J. Org. Chem. 1996, 61, 8132; b) R. Kouno, T. Okauchi,
M. Nakamura, J. Ichikawa, T. Minami, J. Org. Chem. 1998, 63, 6239.
[7] a) T. Okauchi, T. Tanaka, T. Minami, J. Org. Chem. 2001, 66, 3924;
b) S. Yahiro, K. Shibata, T. Saito, T. Okauchi, T. Minami, J. Org.
Chem. 2003, 68, 4947.
(0.5 mL) at ambient temperature. The deuterated 1a was detected
by 1H NMR spectroscopic analysis. Comparing the 1H NMR spectra
of 1a and 1a-D at different times, it is observed that there were
clear changes in the ratio of the peak area at d=3.58 and 5.43 ppm
(see the 1H NMR spectra in the Supporting Information for this ex-
periment). The stepwise decrease in the peak area at d=5.43 ppm
indicates that the a-hydrogen of
1a is gradually deuterated under
[8] a) Y. Yin, M. Wang, Q. Liu, J. Hu, S. Sun, J. Kang, Tetrahedron Lett.
2005, 46, 4399; b) S. Sun, Q. Zhang, Q. Liu, J. Kang, Y. Yin, D. Li,
D. Dong, Tetrahedron Lett. 2005, 46, 6271; c) Q. Zhang, Y. Liu, M.
Wang, Q. Liu, J. Hu, Y. Yin, Synthesis 2006, 3009; d) Z. Fu, M.
Wang, Y. Ma, Q. Liu, J. Liu, J. Org. Chem. 2008, 73, 7625; e) Y. Ma,
M. Wang, D. Li, B. Bekturhun, J. Liu, Q. Liu, J. Org. Chem. 2009,
74, 3116.
the acidic conditions. This experi-
ment thus provides evidence for
the transformation of 1 into inter-
mediate
A
as described in
Scheme 5.
[14] M. Gonsior, I. Krossing, Chem.
Eur. J. 2004, 10, 5730.
[9] a) H.-J. Yuan, M. Wang, Y.-J. Liu, Q. Liu, Adv. Synth. Catal. 2009,
351, 112; b) Y. Liu, M. Wang, H. Yuan, Q. Liu, Adv. Synth. Catal.
2010, 352, 884; c) D. Liang, M. Wang, B. Bekturhun, B. Xiong, Q.
Liu, Adv. Synth. Catal. 2010, 352, 1593.
[10] a) R. O. Kennedy, R. D. Tharnes, Coumarins: Biology Application
and Mode of Action, Wiley, New York, 1997; b) R. D. H. Murray, J.
Mendez, S. A. Brown, The Natural Coumarins: Occurrence Chemis-
try and Biochemistry, Wiley, New York, 1982.
[15] a) A. Fꢃrstner, M. Alcarazo, R.
Goddard, C. W. Lehmann, Angew. Chem. 2008, 120, 3254; Angew.
Chem. Int. Ed. 2008, 47, 3210; b) O. Kaufhold, F. E. Hahn, Angew.
Chem. 2008, 120, 4122; Angew. Chem. Int. Ed. 2008, 47, 4057; c) V.
Lavallo, C. A. Dyker, B. Donnadieu, G. Bertrand, Angew. Chem.
2009, 121, 1568; Angew. Chem. Int. Ed. 2009, 48, 1540.
[16] For the formation and reaction of nonclassical carbonium ylide, see:
ˇ
a) K. Vyakaranam, S. Kçrbe, H. Divisovꢄ, J. Michl, J. Am. Chem.
[11] a) W. B. Jensen, Chem. Rev. 1978, 78, 1; b) G. A. Olah, S. Kobayashi,
M. Tashiro, J. Am. Chem. Soc. 1972, 94, 7448.
Soc. 2004, 126, 15795; b) K. Vyakaranam, Z. Havlas, J. Michl, J. Am.
Chem. Soc. 2007, 129, 4172.
[12] a) D. Dong, Y. Ouyang, H. Yu, Q. Liu, J. Liu, M. Wang, J. Zhu, J.
Org. Chem. 2005, 70, 4535; b) Q. Liu, G. Che, H. Yu, Y. Liu, J.
Zhang, Q. Zhang, D. Dong, J. Org. Chem. 2003, 68, 9148.
[13] The hydrobromic acid-catalyzed hydrogen–deuterium exchange re-
action of 1a with heavy water was performed: D2O (0.025 mL) was
added to a solution of 1a and HBr (0.025 mL, 1.4 equiv) in CD3CN
[17] a) O. I. Kolodiazhnyi, Phosphorus Ylides: Chemistry and Application
in Organic Synthesis, Wiley-VCH, Weinheim, 1999; b) Nitrogen
Oxygen and Sulfur Ylide Chemistry (Ed.: S. J. Clark), Oxford Uni-
versity Press, Oxford, 2002.
Received: July 23, 2010
Published online: October 7, 2010
Chem. Eur. J. 2010, 16, 13450 – 13457
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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