Palladium-catalyzed synthesis of benzosilolo[2,3- b ]indoles via cleavage of a C(sp3)-Si bond and consequent intramolecular C(sp 2)-Si coupling

Article abstract of DOI:10.1021/ja2024959

An efficient process involving Pd-catalyzed selective cleavage of a C(sp³)-Si bond and consequent intramolecular C(sp²)-Si coupling has been developed, affording benzosilolo[2,3-b]indoles as a new type of silicon-bridged polyheteroarene in excellent yields. Aldehyde was found for the first time to be able to promote the efficiency of the catalytic process remarkably.

Full text of DOI:10.1021/ja2024959

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Palladium-Catalyzed Synthesis of Benzosilolo[2,3-b]indoles via
Cleavage of a C(sp3)ꢀSi Bond and Consequent Intramolecular
C(sp2)ꢀSi Coupling
Yun Liang,†,‡ Shaoguang Zhang,† and Zhenfeng Xi*,†,§
†Beijing National Laboratory for Molecular Sciences and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the
Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China
‡Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Hunan Normal University,
Changsha, Hunan 410081, China
§State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai 200032, China
S Supporting Information
b
results in the first efficient synthesis of benzosilolo[2,3-b] indoles, a
new type of silicon-bridged polyheteroarene.11,12 In addition, for
ABSTRACT: An efficient process involving Pd-catalyzed
selective cleavage of a C(sp3)ꢀSi bond and consequent
the first time, aldehyde has been found to be able to promote the
intramolecular C(sp2)ꢀSi coupling has been developed,
efficiency of the catalytic process remarkably.
affording benzosilolo[2,3-b]indoles as a new type of silicon-
bridged polyheteroarene in excellent yields. Aldehyde was
found for the first time to be able to promote the efficiency
of the catalytic process remarkably.
We have recently been studying the preparation and synthetic
applications of polyfunctional conjugated compounds such as
polyhalo compounds, aiming at utilizing the cooperative effect
among functional groups on the conjugated systems.13 During
our studies of the Pd-catalyzed reaction of polyhalo compounds
with amines, we found that when 1a was treated with p-toluidine
(Scheme 2), the indole derivative 2a was obtained in 87%
isolated yield.14 Surprisingly, the benzosilolo[2,3-b] indole deri-
vative 3a was also obtained in 7% isolated yield, and its structure
was confirmed by X-ray structural analysis (Figure 1). We assumed
that 3a might be the result of continuous intramolecular coupling
of 2a under the Pd-catalyzed reaction conditions. To test this
hypothesis, we investigated the Pd-catalyzed intramolecular
coupling of (20-bromobiphen-2-yl)trimethylsilane (4a) as a
model compound (Scheme 3). Gratifyingly, screening of various
reaction conditions [see the Supporting Information (SI) for details]
revealed the optimal reaction conditions, and the expected
dibenzosilole 5a was obtained in 82% isolated yield (Scheme 3).
LiOt-Bu was found to be the most effective base in this reaction.
Other bases (e.g., Cs2CO3, CsF, K2CO3, NaOAc, KOt-Bu, and
LiOMe) afforded either low yields or mixtures of products. To our
surprise, we found that the addition of an aldehyde could remarkably
increase the yields of the products (see the SI for details).
Since such a selective cleavage of the C(sp3)ꢀSi bond and the
consequent intramolecular C(sp2)ꢀSi coupling process was
unprecedented, we next investigated the effect of substituents
on the silicon center, expecting the chemoselective cleavage of a
C(sp3)ꢀSi bond.5,10 As summarized in Scheme 3, the C(Me)ꢀ
Si bond was always selectively cleaved in the cases of SiMe2Et,
SiMe2i-Pr, and SiMe2Ph, probably because of steric effects. The
reaction of 4e (SiEt3), which afforded 5e in a much lower yield,
also suggested the role of steric effects.
he cleavage of carbonꢀsilicon bonds is an important process
T
in synthetic chemistry because it allows the construction of
new CꢀC or CꢀX bonds, thus leading to new functional
molecules.1 Most of the transition-metal-catalyzed reactions
involving cleavage of CꢀSi bonds have focused on C(sp2)ꢀSi
and C(sp)ꢀSi bonds.2,3 Trialkylsilyl groups such R1R2MeSi are
in fact among the most frequently encountered CꢀSi bonds.
However, for the cleavage of C(sp3)ꢀSi bonds, classic methods
usually apply a stoichiometric amount of either an organo-
magnesium4 or organolithium reagent5 under extremely vigorous
conditions that do not tolerate many functional groups, thus
limiting the synthetic application of these approaches. Although
transition-metal-catalyzed cleavage of C(sp3)ꢀSi bonds would
be ideal for overcoming the limitation, only a few special cases
involving either small silacycles1c,6 or activated silyl groups (e.g.,
Me3SiCF3,7 allyl- or benzylsilanes8) have been reported. As for
transition-metal-catalyzed cleavage of normal alkyl C(sp3)ꢀSi
bonds, only two reports are present in the literature. Rauf and
Brown9 reported cleavage of a methyl C(sp3)ꢀSi bond in a
SiMe3 group by palladium-catalyzed oxidative methylation of
olefins using the SiMe3 group as a methyl source. In this reaction,
the presence of an amide group at an appropriate position was
essential. Chatani and co-workers10 developed a rhodium-cata-
lyzed coupling of 2-trimethylsilylphenylboronic acids with al-
kynes via cleavage of the methyl C(sp3)ꢀSi bond. Benzosilole
derivatives were obtained in high yields. Since trialkyl C(sp3)ꢀSi
bonds are frequently encountered, their efficient selective clea-
vage and further synthetic applications would be very attractive
for both mechanistic study and synthetic chemistry. Herein we
report a novel process involving Pd-catalyzed selective cleavage
of the C(sp3)ꢀSi bond in a trialkyl group and consequent
intramolecular C(sp2)ꢀSi bond formation (Scheme 1), which
Encouraged by the above selective cleavage of the C(sp3)ꢀSi
bond and the consequent intramolecular C(sp2)ꢀSi coupl-
ing process, we then turned our attention to the synthesis of
Received: March 19, 2011
Published: April 25, 2011
r
2011 American Chemical Society
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Scheme 1
Table 1. Formation of Various Benzosilolo[2,3-b]indolesa,b
Scheme 2
Figure 1. ORTEP drawing of 3a with 30% thermal ellipsoids. Hydrogen
atoms have been omitted for clarity.
a Conditions: 2 (0.3 mmol), [PdCl(π-allyl)]2 (2.5 mol %), Pt-Bu3
(10 mol %), LiOt-Bu (0.9 mmol), 4-nitrobenzaldehyde (0.3 mmol),
Scheme 3
c
toluene (2 mL), 120 °C, 12 h. b Isolated yields are shown. The yield
in parentheses was obtained without 4-nitrobenzaldehyde. d From
SiMe2Et, 3a was also formed as the minor product (3q:3a = 2.7:1).
e From SiMe2(i-Pr).
product could be increased by 10ꢀ40%. These results again
showed that the addition of an aldehyde could obviously
promote the efficiency of this synthetic method. Similarly,
N-benzylbenzosilolo[2,3-b] indoles 3gꢀi (type II) could be
obtained in good to high isolated yields. For type III (R1 =
alkyl), N-alkylindoles with linear-chain (3j), branched-chain
(3k), and cycloalkyl (3l) groups could all be obtained in excellent
yields. For type IV (R1 = Ph), the indole derivatives 3m (R2 = F),
3n (R2 = Cl), and 3o (R2 = Me) were obtained in isolated yields
of 98, 92, and 90%, respectively. This result showed that the R2
substituent did not remarkably affect the reaction. Finally, we
investigated the selective cleavage of the substituents on the
silicon moiety. The products are shown as type V. The results
again showed that the C(Me)ꢀSi bond was more easily cleaved
than the C(Et)ꢀSi and C(i-Pr)ꢀSi bonds.5,10 All of these
benzosilolo[2,3-b]indole derivatives 3 showed fluorescence with
blue emission under excitation using UV light. Detailed studies of
their optoelectronic properties will be published in due course.
Several experiments were carried out to investigate the reac-
tion mechanism. (1) In the absence of 4-nitrobenzaldehyde,
MeBr was obviously observed by using GC analysis (see the SI
benzosilolo[2,3-b] indoles 3, which represent a new type of
silicon-bridged polyheteroarene.11,12 As shown in Table 1, a
variety of benzosilolo[2,3-b]indoles (types IꢀV) could be ob-
tained from the corresponding 3-(2-bromoaryl)-2-(trialkylsilyl)-
1H-indoles 2 under the optimal reaction conditions. The sub-
stituent of the indole moiety (R1) could be aryl (types I, IV, and
V), benzyl (type II), or alkyl (type III). For type I (R1 = Ar), the
phenyl ring could be substituted with either electron-donating
groups such as OMe or Me (3aꢀd) or electron-withdrawing
groups such as NO2 and CN (3e and 3f). In the absence of
4-nitrobenzaldehyde as the promoting reagent, the isolated yield
of 3a decreased to 62% (from 97% with 4-nitrobenzaldehyde).
In most cases, in the presence of an aldehyde, the yield of the
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Scheme 4
This material is available free of charge via the Internet at http://
pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
zfxi@pku.edu.cn
’ ACKNOWLEDGMENT
This work was supported by the Natural Science Foundation
of China and the Major State Basic Research Development
Program (2011CB808705). Y.L. is thankful for financial support
from the Postdoctorate Research Fund of China (20090460144).
We thank Prof. Zhangjie Shi and Prof. Ning Jiao for valuable
discussions on reaction mechanism. We also thank Hua Huang
and Prof. Haichao Liu for GC analyses of the gas composition of
the reactions.
for details). (2) When 4-nitrobenzaldehyde was added, the
reaction did not generate any MeBr. Instead, GC analysis clearly
showed the formation of CH4 (see the SI for details). In addition,
tert-butyl 4-nitrobenzoate (8) was obtained in 55% isolated yield.
(3) Formation of MeOt-Bu was not observed either with or
without the aldehyde.
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given in Scheme 4. First, oxidative addition of Pd(0) to the CꢀBr
bond of substrates 4 (or 2) would generate intermediate 6. Next,
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In summary, a novel process involving Pd-catalyzed selective
cleavage of the C(sp3)ꢀSi bond in a trialkyl group and conse-
quent intramolecular C(sp2)ꢀSi bond forming process has been
developed. This reaction provides the first efficient synthesis of
benzosilolo[2,3-b] indoles, which represent a new type of silicon-
bridged polyheteroarene. In addition, for the first time, aldehyde
has been found to be able to promote the efficiency of the
catalytic process remarkably. This finding opens a new method
for selective cleavage of the C(sp3)ꢀSi bond in a trialkyl group
and its synthetic applications.
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