Sequential Sonogashira/carbopalladative cyclization/Suzuki reactions catalyzed by a single palladium source by using protected homopropargyl alcohol

Article abstract of DOI:10.1002/ejoc.201000515

A novel cascade combination reaction catalyzed by a single palladium source for the synthesis of various indene derivatives is reported, The approach involved sequential Sonogashira/carbopalladative cyclization/Suzuki coupling reactions by using three readily available components, such as homopropargyl alcohol, aryl iodides or aryl bromides, and arylboronic acids. The overall domino reaction yields were up to 70%.

Full text of DOI:10.1002/ejoc.201000515

FULL PAPER
DOI: 10.1002/ejoc.201000515
Sequential Sonogashira/Carbopalladative Cyclization/Suzuki Reactions
Catalyzed by a Single Palladium Source by Using Protected Homopropargyl
Alcohol
Xin Wang,[a] Lingyan Liu,*[a] Weixing Chang,[a] and Jing Li*[a]
Keywords: Alkynes / Palladium / Cross-coupling / Cyclization / Domino reactions
A novel cascade combination reaction catalyzed by a single
palladium source for the synthesis of various indene deriva-
tives is reported. The approach involved sequential Sonoga-
shira/carbopalladative cyclization/Suzuki coupling reactions
by using three readily available components, such as homo-
propargyl alcohol, aryl iodides or aryl bromides, and aryl-
boronic acids. The overall domino reaction yields were up to
70%.
construction of various 2,5-disubstituted-3-bromofurans
starting from protected homopropargyl alcohol.[5] As a
continuation of our ongoing work on the further applica-
tion of homopropargyl alcohols, which can be easily ob-
tained by Barbier-type propargylation of aldehydes,[6] we
designed a novel cascade combination involving a Sonoga-
shira/carbopalladative cyclization/Suzuki sequential reac-
tion by using ortho-bromo-substituted homopropargyl
alcohol, which is relatively easily available and stable com-
pared to the ortho-iodophenylhomopropargyl alcohol. The
underlying principle of our approach is shown in Scheme 1.
The Sonogashira coupling of protected homopropargyl
alcohol 1 with aryl halide 2 in the presence of a palladium
catalyst should give the disubstituted arylalkyne 5, which
would further react with arylboronic acid 3 to yield target
compound 4 through a sequence of intramolecular car-
bopalladation/cyclization/Suzuki coupling (Scheme 1). By
following this protocol and with simple variations in the
structure of some of the starting materials, it would be very
easy to access small libraries of differently substituted in-
dene derivatives. Moreover, to the best of our knowledge,
there are no reports on the synthesis of indene derivatives
from homopropargyl alcohol derivatives through Sonoga-
shira/carbopalladative cyclization/Suzuki multistep sequen-
tial transformations.
Introduction
Arylalkynes play an important role as building blocks in
many synthetic transformations and are common units of
natural products, new materials, and pharmaceuticals.[1] In
the field of alkyne chemistry, palladium-catalyzed domino
reactions have attracted great interest and enabled the rapid
establishment of molecular complexity in the total synthesis
of complex natural products with minimized separation/
purification efforts. Among such approaches, heteroaryl-
alkyne are widely used with (hetero)aryl bromides or io-
dides for the synthesis of arylheterocyclic compounds by
intramolecular Heck reaction involving terminations of in-
sertion cascades as Sonogashira, Suzuki–Miyaura, or Heck
cross-coupling reactions.[2] Zhu and co-workers reported a
novel approach based on the multicomponent reaction con-
cept by using a palladium-catalyzed domino Sonogashira/
carbopalladation/C–H activation/C–C bond forming se-
quence for the synthesis of 3-arylidene oxindoles.[3] In com-
parison, few reports are concerned about the domino reac-
tions of simple (alkyl)arylalkynes which are readily available
for the synthesis of (benzo)carbocycles. Carbocycles are ex-
tremely important as basic skeletons of many biologically
active natural products with specific structures. The synthe-
sis of these carbocycles remains a challenge. Typical exam-
ples reported in the literature described the preparation of
alkylidene indenols containing five-membered carbocycles
by an intramolecular domino cyclocarbopalladation of al-
kynes following a Suzuki–Miyaura cross-coupling termina-
tion.[4] Recently, we developed an efficient method for the
[a] State Key Laboratory and Research Insititute of Elemento-
Organic Chemsitry,
Nankai University, Tianjin 300071, P. R. China
Fax: +86-22-23506057
E-mail: liulingyan@nankai.edu.cn
lijing@nankai.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000515.
Scheme 1. Proposed three-component cascade reaction.
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X. Wang, L. Liu, W. Chang, J. Li
Table 1. Screening the intramolecular cyclization.[a]
FULL PAPER
Results and Discussion
To probe the viability of the envisioned entire cascade
reaction, we examined the reaction conditions step by step.
The key step in these reactions is the syn addition of aryl-
palladium halide to the triple bond, which affords an inter-
mediate that can participate in a wide variety of useful syn-
thetic processes. Furthermore, the combination of mechan-
istically distinct reactions by a single catalyst is by far less
developed owing to the specificity of each catalytic system
to each individual reaction. Thus, in our initial studies, dif-
ferent bases were screened in the presence of the palladium
catalyst to determine the optimal conditions for the first
Sonogashira coupling reaction step (Table 1). Intriguingly,
when HCOONa was used as a base, cyclization product 7
was observed. Thus, we considered the process shown in
Scheme 2 as a potentially useful approach for the synthesis
of indene derivative (Table 1, Entry 7). It should be noted
that the termination of insertion cascades by using
HCOONa to provide reductive protons has remained unex-
plored to date. The displacement of the Pd–Br bond in in-
termediate 6 by HCOO- afforded new intermediate A,
which could further undergo decarboxylation to afford [H-
Pd-C] species B. Intermediate B made the entire catalysis
cycle complete through reductive elimination to finally yield
target 7 (Scheme 1). Thus, the formation of intermediate B
was the key step of the projected cyclization. For example,
in the presence of other bases, no cyclization product was
obtained due to the lack of a β-hydride elimination pathway
for the PdII intermediate to recycle Pd0 complexes (Table 1,
Entries 3–6, 8, and 9) even when the reaction temperature
was increased (Table 1, Entries 1and 2). In addition, when
using the mixed solvents DMF/H2O, we obtained trace
amounts of the cyclic product (Table 1, Entry 10). This
demonstrated that water had a great influence on this reac-
tion.
Entry
Base
T [°C]
Yield [%][b]
1
2
3
4
5
6
7
8
NaHCO3
NaOAc
NaHCO3
NaOAc
130
130
80
80
80
80
80
80
80
–
–
–
–
–
–
74
–
K2CO3
CH3ONa
HCOONa
N(C2H5)3
piperidine
HCOONa
9
–
10[c]
80
trace
[a] Reaction was carried out with the alcohol (0.2 mmol), 2
(0.21 mmol), the palladium catalyst (5 mol-%), and PPh3 (8 equiv.)
in piperidine (2 mL) at 80 °C under an atmosphere of N2 for 12 h.
[b] Isolated yield. [c] Using the mixed solvents DMF/H2O, 9:1.
Preliminary investigations confirmed the viability of cy-
clocarbopalladation in the presence of the same palladium
catalyst system that is optimal for the first Sonogashira cou-
pling step. Notably, the indene skeleton of product 7 is pres-
ent in a large number of drug candidates possessing inter-
esting biological activities.[7] Such molecules are also used
as ligands in metallocene complexes, especially group IV
metallocene complexes used in the area of catalytic olefin
polymerization.[8] With this promising result in hand, we
defined an efficient catalytic system for the entire sequence,
starting from readily available protected ortho-bromophen-
ylhomopropargyl alcohol (1), phenyl iodide (2), and para-
Scheme 2. Carbopalladative cyclization of protected homoprop-
argyl alcohol.
methoxyphenylboronic acid (3a). By this reaction in the also resulted in the corresponding product with a similar
presence of a suitable palladium catalyst, highly substituted yield when only PPh3 and K2CO3 were added without any
indene derivative 4a could be afforded. To improve the total additional palladium catalyst in the second step after the
yield of this sequential reaction, we attempted to vary the Sonogashira coupling (Table 2, Entry 5). We were intrigued
palladium source at different stages, one for the Sonoga- enough by this result to explore the use of a single palla-
shira coupling and the other for the successive carbopallad- dium catalyst in mechanistically distinct reactions. By using
ative cyclization/Suzuki sequence. Regardless, the tandem piperidine and K2CO3 as bases at different stages, only
reaction proceeded smoothly whether catalyzed by the same 10 mol-% Pd(OAc)2/PPh3 (1:8) with 5 mol-% CuI, neces-
palladium source or by different palladium sources sary for the Sonogashira step, could catalyze the whole re-
(Table 2, Entries 1–4). Even more interestingly, the reaction action sequence successfully with 59% yield (Table 2, En-
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Sequential Sonogashira/Carbopalladative Cyclization/Suzuki Reactions
try 6). The reaction has unaffected by reducing the loading tion produced the highest yield of 70% (Table 3, Entry 9).
of Pd(OAc)2 to 5 mol-%, yielding 60% of the product These corresponding new indene derivatives products have
(Table 2, Entry 7). Adjusting the Pd(OAc)2/PPh3 ratio from single Z or E structures with different substitutions on the
1:8 to 1:4 resulted in a decrease in the yield to 46% (Table 1, aromatic rings. Nevertheless, as for the o-substitution of R1
Entry 8). By further reducing the loading of Pd(OAc)2 to or R2 in the aromatic halide or arylboronic acid, this tan-
3 mol-%, only 42% product was obtained (Table 2, En- dem reaction was either sluggish or complicated. This may
try 9). After optimization, we found that 5 mol-% of be attributed to steric hindrance. When p-substitution R1
Pd(OAc)2/PPh3 (1:8) gave the best results with 60% yield was an electron-donating group, such as p-CH3, a trace
for the entire cascade reaction sequence, although other dif- amount of the product was obtained.
ferent palladium catalysts [e.g., Pd(CH3CN)2Cl2, Pd-
(PPh3)4, and PdCl2] were also successful in this procedure.
Table 3. Scope of the tandem reaction of aryl iodides and aryl-
boronic acids.[a]
As such consecutive processes avoid the use of higher
amounts of expensive palladium catalysts and avoids time
consuming and costly purification processes, they are in-
herently environmentally benign and atom economic com-
pared to the step-by-step reactions, although herein the
overall yield by this cascade reaction (yield 60%) has no
advantageous over that of the traditional step-by-step reac-
tions [Sonogashira coupling, 10 mol-% Pd(OAc)2/PPh3
(1:2), yield 84%; cyclocarbopalladation/Suzuki coupling,
10 mol-% Pd(OAc)2/PPh3 (1:2), yield 83%].
Entry
R1
R2
Yield [%][b]
Table 2. A survey of reaction conditions.[a]
1
2
3
4
5
6
7
8
9
H
H
H
p-F
p-F
p-F
H
p-CO2CH3
p-OCH3 (3a)
H
p-CO2CH3
p-OCH3
H
44
34
60
50
46
67
58
48
70
p-COCH3
p-COCH3
p-COCH3
p-CO2CH3
p-OCH3
[a] General conditions: All reactions were carried out under an at-
mosphere of argon by using 1 (1.2 equiv.), ArI (1.0 equiv.), CuI
(5 mol-%), Pd(OAc)2 (5 mol-%), PPh3 (40 mol-%), and piperidine
(3.0 equiv.) in DMF (2 mL) at 80 °C for 12 h; then K2CO3
(3.0 equiv.) and ArB(OH)2 (3.0 equiv.) were added, followed by
heating at 80 °C. [b] Isolated yield.
Entry
Sonogashira (mol-%)
Pd(PPh3)4 (10)
Successive
sequence (mol-%)
Yield[b]
[%]
1
2
3
4
5
6
7
8
9
Pd(OAc)2/PPh3 (10:20)
59
55
59
58
55
59
60
46
42
Pd(CH3CN)2Cl2/PPh3 (10:80) Pd(OAc)2/PPh3 (10:20)
Pd(OAc)2/PPh3 (10:80)
Pd(OAc)2/PPh3 (10:80)
Pd(OAc)2/PPh3 (10:80)
Pd(OAc)2/PPh3 (10:80)
Pd(OAc)2/PPh3 (5:40)
Pd(OAc)2/PPh3 (5:20)
Pd(OAc)2/PPh3 (3:24)
Pd(OAc)2/PPh3 (10:20)
Compared to aryl iodides, aryl bromides have many ad-
vantages, including that they are widely commercially avail-
able at a low price. Thus we attempted to use aryl bromides
instead of aryl iodides in the reaction. We found that the
same product was made in 40% yield (Table 4, Entry 1). KI
was added to the reaction in an attempt to enhance the
reaction yield. However, the yield remained unchanged
(36%) when adding KI (20 mol-%) at the beginning of the
reaction (Table 4, Entries 2 and 3). However, after the Son-
ogashira coupling reaction, KI (20 mol-%) was added in ad-
dition to K2CO3 (3.0 equiv.), and the reaction yield in-
Pd(OAc)2 (10)
PPh3 (20)
–
–
–
–
[a] All reactions were carried out under an atmosphere of argon by
using 1 (1.2 equiv.), 2 (1.0 equiv.), Pd catalyst, CuI (5 mol-%), and
piperidine (3.0 equiv.) in DMF (2 mL) for 12 h at 80 °C. Then cata-
lyst, base, and 3a were added, followed by heating at 80 °C for 20 h.
[b] Isolated yield.
Encouraged by the efficiency of the reaction protocol de- creased to 57% (Table 4, Entry 3). The reason for this re-
scribed above, different substituted aryl iodides and aryl- mains unexplained to date. In addition, we also tested the
boronic acids were examined to probe the scope and limita- loading of KI, but no improvement was observed by in-
tion of this new three-component reaction (Table 3). As creasing or decreasing the amount of KI (Table 4, En-
summarized in Table 3, a variety of arylboronic acids sub- tries 5–7).
stituted by an electron-donating or an electron-withdrawing
The scope of the reaction was also surveyed by probing
group were tolerated in moderate yields. In the cases of the changes in the aryl bromides and the substituted phenyl
same R1 group, phenylboronic acids bearing an electron- boronic acid substrates; the results are listed in Table 5. The
donating group produced a higher yield than those with an outcome of this three-component reaction was influenced
electron-withdrawing group. Furthermore, when R1 and R2 by the electronic properties of the phenylboronic acids, and
were p-COCH3 and p-OCH3 groups, respectively, the reac- a variety of products were synthesized in moderate levels or
Eur. J. Org. Chem. 2010, 5391–5396
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X. Wang, L. Liu, W. Chang, J. Li
FULL PAPER
Table 4. Screening reaction conditions of aryl bromides.[a]
strate, which makes it easier to form the [ArPdX] intermedi-
ate (for Suzuki reaction) when KI (20 mol-%) was added.
To challenge the methodology further, we also investi-
gated the Sonogashira/carbopalladative cyclization/Stille
coupling cascade sequence. By employing phenyltributyltin
and CsF (1.2 equiv.), we obtained the desired product in
44% yield under the previously optimized conditions
(Scheme 3). According to this result, we believe that the pri-
mary factor affecting the reaction yield is the efficiency of
the Stille coupling.
Entry
Sonogashira
(mol-%)
Successive
sequence (mol-
%)
Yield[b]
[%]
1
2
3
4
5
6
7
Pd(OAc)2/PPh3 (5:40)
Pd(OAc)2/PPh3 (5:40), KI (20)
Pd(OAc)2/PPh3 (5:40)
Pd(OAc)2/PPh3 (5:40)
Pd(OAc)2/PPh3 (5:40)
Pd(OAc)2/PPh3 (5:40)
Pd(OAc)2/PPh3 (5:40)
–
–
40
36
57
39
47
32
50
KI (20)
Pd(OAc)2 (5)
KI (40)
KI (50)
KI (10)
[a] All reactions were carried out under an atmosphere of argon by
using 1 (1.2 equiv.), 2a (1.0 equiv.), Pd(OAc)2 (5 mol-%), CuI
(5 mol-%), and piperidine (3 equiv.) in DMF (2 mL) for 12 h at
80 °C. Then the base, additive, and 3a were added into the above
reaction mixture, followed by heating at 80 °C for 20 h. [b] Isolated
yield.
Scheme 3. Sonogashira-carbopalladative cyclization-Stille reaction.
Conclusions
In conclusion, we developed a sequential reaction involv-
ing multi carbon–carbon bond formation by using pro-
tected homopropargyl alcohol in the presence of a single
Pd(OAc)2/triphenylphosphane catalytic system with good
yields under mild conditions. The methodology that we de-
scribed consists of Sonogashira/carbopalladative cycliza-
tion/Suzuki or Stille coupling reactions, leading to an ef-
ficient method to construct various indene derivatives, and
this is the first report of such a cascade combination. More-
over, the wide tolerance of various substituents in the sub-
strates and easy procedure to access the products efficiently
from readily available starting materials may imply a poten-
tial synthetic application. Further experiments designed to
explore the reaction scope are currently underway.
somewhat higher yields. When R1 = p-COCH3 and R2 =
H, the reaction resulted in the best yield of 69% (Table 5,
Entry 7). Among these results, some of the yields of the
products were slightly higher than those obtained for iodo-
benzene (Table 5, Entries 1 and 7). This may be due to fa-
vorable Br/I exchange on the ortho-bromide of the sub-
Table 5. Scope of the tandem reaction of aryl bromides and aryl-
boronic acids.[a]
Experimental Section
General: All reagents were obtained from commercial suppliers and
were used without further purification. DMF was distilled from
CaH2, ethyl acetate (anhydrous, 99.9%) was used as received. 1H
NMR and 13C NMR spectra were obtained with a Bruker 400-AM
spectrometer in CDCl3. High-resolution mass spectra were deter-
mined with a Bruker Daltonics APEXII 47e FT-ICR spectrometer.
Entry
R1
R2
Yield [%][b]
1
2
3
4
5
6
7
8
9
H
H
H
p-F
p-F
H
p-CO2CH3
p-OCH3 (3a)
H
p-CO2CH3
p-OCH3
H
57
38
57
57
45
65
69
45
68
General Procedure: To the solution of [1-(2-bromophenyl)but-3-yn-
yloxy](tert-butyl)dimethylsilane in anhydrous DMF in a Schlenk
flask under an atmosphere of nitrogen was added Pd(OAc)2
(2.2 mg, 5 mol-%), PPh3 (21 mg, 40 mol-%), and piperidine (51 mg,
0.6 mmol). The mixture was stirred vigorously at room temperature
for 2 h. After addition of iodobenzene (40.8 mg, 0.2 mmol), the
mixture was heated to 80 °C for 12 h until iodobenzene was totally
consumed, as indicated by TLC. The mixture was cooled to room
temperature. K2CO3 (82.8 mg, 0.6 mmol) and 4-methoxyphenyl-
boronic acid (91.2 mg, 0.6 mmol) were added to the reaction sys-
tem. Then the mixture was warmed to 80 °C for another 20 h. After
p-F
p-COCH3
p-COCH3
p-COCH3
p-CO2CH3
p-OCH3
[a] General conditions: All reactions were carried out under an at-
mosphere of argon by using 1 (1.2 equiv.), ArI (1.0 equiv.), CuI
(5 mol-%), Pd(OAc)2 (5 mol-%), PPh3 (40 mol-%), and piperidine
(3.0 equiv.) in DMF (2 mL) at 80 °C for 12 h; then K2CO3
(3.0 equiv.), KI (20 mol-%), and ArB(OH)2 (3.0 equiv.) were added,
followed by heating at 80 °C. [b] Isolated yield.
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Sequential Sonogashira/Carbopalladative Cyclization/Suzuki Reactions
the reaction was complete, the mixture was quenched with brine
(10 mL) and extracted with EtOAc (3ϫ10 mL). The combined or-
ganic layer was washed with brine and dried with anhydrous
Na2SO4. The solvent was removed in vacuo, and the residue was
purified by column chromatography to afford the white solid
(266 mg, yield 60%).
(m, 2 H), 3.69 (s, 3 H), 5.15 (t, J = 6.53 Hz, 1 H), 6.38 (d, J =
7.90 Hz, 1 H), 6.72–7.09 (m, 9 H), 7.21 (d, J = 7.51 Hz, 1 H), 7.34
(d, J = 8.82 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
–5.64, –5.37, 17.18, 24.88, 45.49, 54.15, 72.90, 113.07, 113.82 (d, J
= 21.25 Hz), 122.98, 123.70, 126.13, 126.67, 129.86 (d, J =
7.92 Hz), 130.02, 133.35, 133.66, 134.94, 138.79, 147.82, 157.85,
149.21, 160.51 (d, J = 254.89 Hz) ppm. HRMS: calcd. for
C29H33FO2Si 460.22339; found 460.22399.
tert-Butyl[3-(diphenylmethylene)-2,3-dihydro-1H-inden-1-yloxy]di-
1
methylsilane: H NMR (400 MHz, CDCl3): δ = 0.14 (s, 3 H), 0.19
(s, 3 H), 0.98 (s, 9 H), 2.94–3.21 (m, 2 H), 5.30 (t, J = 6.57 Hz, 1
H), 6.41 (d, J = 7.91 Hz, 1 H), 6.92 (t, J = 7.58 Hz, 1 H), 7.18 (t,
J = 7.38 Hz, 1 H), 7.24–7.37 (m, 11 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = –5.63, –5.35, 17.19, 24.89, 45.34, 72.90, 125.73, 126.09,
(E)-1-(4-{[3-(tert-Butyldimethylsilyloxy)-2,3-dihydro-1H-inden-1-
yli-dene](phenyl)methyl}phenyl)ethanone: 1H NMR (400 MHz,
CDCl3): δ = –0.05 (s, 3 H), 0.00 (s, 3 H), 0.78 (s, 9 H), 2.42 (s, 3
H), 2.75–3.00 (m, 2 H), 5.11 (t, J = 6.41 Hz, 1 H), 6.22 (d, J =
126.14, 126.76, 126.97, 127.68, 128.22, 128.91, 134.78, 135.18, 7.92 Hz, 1 H), 6.74 (t, J = 7.62 Hz, 1 H), 6.99–7.19 (m, 9 H), 7.74
138.75, 141.53, 142.18, 147.91 ppm. HRMS: calcd. for C28H32OSi (d, J = 8.28 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
412.22224; found 412.22267.
–4.57, –4.29, 18.24, 25.93, 29.73, 46.47, 73.86, 124.13, 125.04,
127.28, 127.55, 128.21, 128.33, 128.94, 129.46, 129.99, 134.76,
135.37, 138.06, 139.39, 141.88, 148.19, 149.22, 197.69 ppm.
HRMS: calcd. for C30H34O2Si 454.23281; found 454.23224.
(Z)-Methyl-4-{[3-(tert-Butyldimethylsilyloxy)-2,3-dihydro-1H-
inden-1-ylidene](phenyl)methyl}benzoate: 1H NMR (400 MHz,
CDCl3): δ = 0.00 (s, 3 H), 0.05 (s, 3 H), 0.83 (s, 9 H), 2.80–3.06
(m, 2 H), 3.81 (s, 3 H), 5.15 (t, J = 6.43 Hz, 1 H), 6.29 (d, J = (Z)-Methyl-4-{(4-Acetylphenyl)[3-(tert-butyldimethylsilyloxy)-2,3-
7.84 Hz, 1 H), 6.78 (t, J = 7.58 Hz, 1 H), 7.03–7.24 (m, 9 H), 7.88 dihydro-1H-inden-1-ylidene]methyl}benzoate: 1H NMR (400 MHz,
(s, 1 H), 7.90 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
CDCl3): δ = 0.05 (s, 3 H), 0.00 (s, 3 H), 0.77 (s, 9 H), 2.41 (s, 3 H),
–4.56, –4.29, 18.24, 25.95, 46.65, 52.14, 73.84, 124.22, 124.81, 2.76–3.00 (m, 2 H), 3.74 (s, 3 H), 5.11 (t, J = 6.41 Hz, 1 H), 6.24
127.11, 127.30, 128.20, 128.92, 129.33, 130.09, 130.20, 134.71, (d, J = 7.78 Hz, 1 H), 6.74 (t, J = 7.55 Hz, 1 H), 7.00–7.20 (m, 6
137.28, 139.25, 142.61, 147.54, 149.25, 167.08 ppm. HRMS: calcd.
for C30H34O3Si 470.22772; found 470.22732.
H), 7.74 (d, J = 7.82 Hz, 2 H), 7.85 (d, J = 7.75 Hz, 2 H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = –4.56, –4.29, 18.22, 25.93, 29.73,
46.71, 52.16, 73.75, 124.31, 124.97, 127.42, 128.33, 128.73, 129.27,
129.51, 130.23, 130.35, 133.64, 135.62, 138.85, 139.04, 146.77,
147.47, 149.49, 197.52, 166.87 ppm. HRMS: calcd. for C32H36O4Si
512.23829; found 512.23855.
(Z)-tert-Butyl{3-[(4-methoxyphenyl)(phenyl)methylene]-2,3-dihydro-
1H-inden-1-yloxy}dimethylsilane: 1H NMR (400 MHz, CDCl3): δ =
0.00 (s, 3 H), 0.05 (s, 3 H), 0.84 (s, 9 H), 2.82 (dd, J = 6.9, 15.1 Hz,
1 H), 3.02 (dd, J = 6.9, 15.2 Hz, 1 H), 3.71 (s, 3 H), 5.15 (t, J =
6.5 Hz, 1 H), 6.38 (d, J = 7.9 Hz, 1 H), 6.74–7.44 (m, 13 H) ppm.
(Z)-1-(4-{[3-(tert-Butyldimethylsilyloxy)-2,3-dihydro-1H-inden-
13C NMR (100 MHz, CDCl3): δ = –5.64, –5.36, 17.18, 24.89, 45.46, 1-ylidene](4-methoxyphenyl)methyl}phenyl)ethanone: 1H NMR
54.16, 72.96, 113.00, 122.94, 123.74, 125.68, 126.08, 126.62, 126.91,
(400 MHz, CDCl3): δ = 0.00 (s, 3 H), 0.05 (s, 3 H), 0.83 (s, 9 H),
128.26, 130.07, 133.91, 134.40, 134.87, 138.95, 142.49, 147.85, 2.36 (s, 3 H), 2.82–3.06 (m, 2 H), 3.59 (s, 3 H), 5.16 (t, J = 6.21 Hz,
157.74 ppm. HRMS: calcd. for C29H34O2Si 442.23281; found
442.23288.
1 H), 6.42 (d, J = 7.90 Hz, 1 H), 6.68–7.25 (m, 9 H), 7.31 (d, J =
8.31 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = –4.56, –4.26,
18.20, 25.97, 29.59, 46.63, 55.03, 73.99, 114.30, 124.18, 125.07,
126.52, 127.32, 128.17, 129.52, 131.18, 134.19, 134.56, 135.38,
137.80, 139.69, 148.47, 149.22, 159.16, 196.99 ppm. HRMS: calcd.
for C31H36O3Si 484.24337; found 484.24373.
(E)-tert-Butyl{3-[(4-fluorophenyl)(phenyl)methylene]-2,3-dihydro-
1H-inden-1-yloxy}dimethylsilane: 1H NMR (400 MHz, CDCl3): δ =
0.10 (s, 3 H), 0.15 (s, 3 H), 0.93 (s, 9 H), 2.87–3.14 (m, 2 H), 5.26
(t, J = 6.45 Hz, 1 H), 6.38 (d, J = 6.38 Hz, 1 H), 6.84 (t, J =
7.60 Hz, 1 H), 6.93 (t, J = 8.67 Hz, 2 H), 7.08–7.33 (m, 9 H) ppm.
13C NMR (100 MHz, CDCl3): δ = –5.66, –5.38, 17.12, 24.86, 45.36,
72.81, 113.95 (d, J = 21.26 Hz), 122.99, 123.73, 126.10, 126.24,
126.82, 127.71, 128.81, 129.81 (d, J = 7.93 Hz), 135.27, 133.66,
138.14 (d, J = 3.23 Hz), 138.54, 141.26, 147.85, 160.48 (d, J =
246.64 Hz) ppm. HRMS: calcd. for C28H31FOSi 430.21282; found
430.21222.
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the 1H and 13C NMR spectra of selected com-
pounds.
Acknowledgments
We are grateful for financial support from the National Natural
Science Foundation of China (grants 20421202 and 20372033).
(E)-Methyl-4-{[3-(tert-Butyldimethylsilyloxy)-2,3-dihydro-1H-inden-
1
1-ylidene](4-fluorophenyl)methyl}benzoate: H NMR (400 MHz,
CDCl3): δ = 0.00 (s, 3 H), 0.05 (s, 3 H), 0.82 (s, 9 H), 2.77–3.03
(m, 2 H), 3.77 (s, 3 H), 5.16 (t, J = 6.42 Hz, 1 H), 6.29 (d, J =
7.94 Hz, 1 H), 6.76 (t, J = 7.57 Hz, 1 H), 6.86 (t, J = 8.70 Hz, 2
H), 7.02–7.24 (m, 6 H), 7.87 (s, 1 H), 7.89 (s, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = –4.59, –4.32, 18.23, 25.91, 46.66, 52.15,
73.76, 115.14 (d, J = 21.38 Hz), 124.23, 124.74, 127.32, 128.31,
129.04, 130.12, 130.96 (d, J = 7.98 Hz), 133.61, 137.42, 138.60 (d,
J = 3.28 Hz), 139.05, 147.24, 149.21, 161.73 (d, J = 247.07 Hz),
167.00 ppm. HRMS: calcd. for C30H33FO3Si 488.21830; found
488.21800.
[1] a) M. G. Organ, H. Ghasemi, J. Org. Chem. 2004, 69, 695–700;
b) N. Ohyabu, T. Nishikawa, M. Isobe, J. Am. Chem. Soc. 2003,
125, 8798–8805; c) J. M. Altenburger, G. Y. Lassalle, M. Ma-
trougui, D. Galtier, J. C. Jetha, Z. Bocskei, C. N. Berry, C.
Lunven, J. Lorrain, J. P. Herault, P. Schaeffer, S. E. O’Connor,
J. M. Herbert, Bioorg. Med. Chem. 2004, 12, 1713–1730; d) W.-
M. Dai, K.-W. Lai, A. Wu, W. Hamaguchi, M. Y. H. Lee, L.
Zhou, A. Ishii, S. Nishimoto, J. Med. Chem. 2002, 45, 758–
761; e) S. H. Lee, T. Nakamura, T. Tsutsui, Org. Lett. 2001, 3,
2005–2007.
[2] a) D. M. DЈSouza, F. Rominger, T. J. J. Müller, Angew. Chem.
Int. Ed. 2005, 44, 153–158; b) W. S. Cheung, R. J. Patch, M. R.
Player, J. Org. Chem. 2005, 70, 3741–3744; c) R. Yanada, S.
Obika, T. Inokuma, K. Yanada, M. Yamashita, S. Ohta, Y.
(E)-tert-Butyl{3-[(4-Fluorophenyl)(4-methoxyphenyl)methylene]-2,3-
dihydro-1H-inden-1-yloxy}dimethylsilane: 1H NMR (400 MHz,
CDCl3): δ = 0.00 (s, 3 H), 0.05 (s, 3 H), 0.83 (s, 9 H), 2.74–2.99
Eur. J. Org. Chem. 2010, 5391–5396
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5395

X. Wang, L. Liu, W. Chang, J. Li
FULL PAPER
Takemoto, J. Org. Chem. 2005, 70, 6972–6975; d) M. Arthuis,
R. Pontikis, J.-C. Florent, Tetrahedron Lett. 2007, 48, 6397–
6400.
awa, K. Terada, Y. Kurusu, Chem. Commun. 1998, 2025–2026;
c) Q. R. Li, C. Z. Gu, H. Yin, Chin. J. Chem. 2006, 1, 72–78;
d) A. Kundu, S. Prabhakar, M. Vairamani, S. Roy, Organome-
tallics 1999, 18, 2782–2785.
a) S. Hagishita, M. Yamada, K. Shirahase, T. Okada, Y. Mu-
rakami, Y. Ito, T. Matsuura, M. Wada, T. Kato, J. Med. Chem.
1996, 39, 3636–3658; b) J. Palm, K. P. Boegesoe, T. Liljefors, J.
Med. Chem. 1993, 36, 2878–2885; c) N. J. Clegg, S. Paruthiyil,
D. C. Leitman, T. S. Scanlan, J. Med. Chem. 2005, 48, 5989–
6003; d) D. T. Witiak, S. V. Kakodkar, G. E. Brunst, J. R. Bal-
dwin, R. G. Rahwan, J. Med. Chem. 1978, 21, 1313–1315; e)
H. Gao, J. A. Katzenellenbogen, R. Garg, C. Hansch, Chem.
Rev. 1999, 99, 723–744.
[3] a) A. Pinto, L. Neuville, P. Retailleau, J. Zhu, Org. Lett. 2006,
8, 4927–4930; b) A. Pinto, L. Neuville, J. Zhu, Angew. Chem.
Int. Ed. 2007, 46, 3291–3295.
[7]
[4] a) L. F. Tietze, K. Kahle, T. Raschke, Chem. Eur. J. 2002, 8,
401–407; b) S.-H. Min, S. J. Pang, C. G. Cho, Tetrahedron Lett.
2003, 44, 4439–4442; c) C. H. Oh, Y. M. Lim, Tetrahedron Lett.
2003, 44, 267–270; d) B. Salem, E. Delort, P. Klotz, J. Suffert,
J. Org. Lett. 2003, 5, 2307–2310; e) E. Marchal, J. F. Cupif, P.
Uriac, P. Weghe, Tetrahedron Lett. 2008, 49, 3713–3715; f) L.-
N. Guo, X.-H. Duan, J. Hu, H.-P. Bi, X.-Y. Liu, Y.-M. Liang,
Eur. J. Org. Chem. 2008, 1418–1425.
[5] X. Wang, L.-Y. Liu, J. Li, Sci. China Ser. B: Chem. 2009, 52,
1314–1320.
[6] a) A. S. Y. Lee, S. F. Chu, Y. T. Chang, S. H. Wang, Tetrahedron
Lett. 2004, 45, 1551–1553; b) Y. Masuyama, A. Ito, M. Fukuz-
[8] H. G. Alt, A. Koeppl, Chem. Rev. 2000, 100, 1205–1222.
Received: April 15, 2010
Published Online: August 16, 2010
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