Palladium-catalyzed silylation of electron-deficient aryl iodides using triorganosilane in the presence of pyridine and LiCl

Article abstract of DOI:10.1002/ejoc.200701141

Palladium-catalysed silylation of aryl iodides with electron-withdrawing groups was efficiently achieved using pyridine and lithium chloride as additives and conducting the reaction at room temperature. Functionalized aryl[2-(hydroxymethyl)-phenyl]dimethylsilanes were also prepared by palladium-catalysed reaction using THP-protected [2-(hydroxymethyl)-phenyl] dimethylsilane as a silylating agent followed by deprotection. Rhodium-catalysed 1,4-addition of the arylsilane was carried out using cyclohexenone as an enone in excellent yield. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200701141

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200701141
Palladium-Catalyzed Silylation of Electron-Deficient Aryl Iodides Using
Triorganosilane in the Presence of Pyridine and LiCl
Muneaki Iizuka[a] and Yoshinori Kondo*[a]
Keywords: Silylation / Palladium / Aryl iodides / Pyridine / Lithium chloride
Palladium-catalysed silylation of aryl iodides with electron-
withdrawing groups was efficiently achieved using pyridine
and lithium chloride as additives and conducting the reaction
at room temperature. Functionalized aryl[2-(hydroxymethyl)-
phenyl]dimethylsilanes were also prepared by palladium-
catalysed reaction using THP-protected [2-(hydroxymethyl)-
phenyl]dimethylsilane as a silylating agent followed by de-
protection. Rhodium-catalysed 1,4-addition of the arylsilane
was carried out using cyclohexenone as an enone in excel-
lent yield.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
In connection with our recent study on the selective
transformation of arylsilanes,[3] we investigated the selective
silylation of aryl halides with various functional groups cat-
alysed by palladium.
Introduction
The silicon-based cross coupling has become an impor-
tant method for carbon–carbon bond formation, and the
reaction is now widely used (Hiyama coupling).[1] Various
arylsilanes have been employed for the coupling partners
and the transition-metal-catalysed silylation of aryl halides
should be one of the most versatile and chemoselective
methods to prepare arylsilanes.[2] Recently, Yamanoi re-
ported the palladium-catalysed silylation of aryl halides
using tBu3P as a ligand (Figure 1).[2h] Trialkylsilyl groups
can be successfully transferred by the reaction; however, the
reaction is not applicable to aryl halides with an electron-
withdrawing group. Murata et al. also reported a palla-
dium-catalysed silylation of aryl halides with electron-do-
nating groups using triorganosilanes.[2e] Alami et al. re-
ported a platinum oxide catalysed trialkylsilylation of vari-
ous aryl halides,[2f] but there has been no successful report
of palladium-catalysed silylations of aryl halides with elec-
tron-withdrawing groups.
Results and Discussion
We first investigated the palladium-catalysed silylation of
4-iodonitrobenzene (1), which was considered to be the
most challenging substrate for the selective silylation as
shown in Figure 1. In order to avoid the formation of re-
duced product 3, various reaction conditions were screened,
and conditions free of phosphane ligands were suggested to
be favorable. After the screening of various reaction condi-
tions, we found that the use of pyridine and lithium chloride
as additives is effective for selective silylation.
When 1-iodo-4-nitrobenzene (1) was treated with Et3SiH
in the presence of Pd(OAc)2 (4 mol-%), pyridine (2.5 equiv.)
and LiCl (4 equiv.) in DMI (N,N-dimethylimidazolin-2-
one), silylated nitrobenzene 2 was obtained in 51% yield,
1
and the H NMR analysis of the crude material indicated
a ratio of 2/3 = 8:2 (Table 1, Entry 1). The use of other
solvents such as NMP or DMF gave poorer 2/3 ratios
(Table 1, Entries 2, 3). When Et3N was employed instead of
pyridine, no formation of 2 was observed, and only 3 was
produced (Table 1, Entry 4). The absence of base also re-
sulted in no formation of 2 (Table 1, Entry 5). The use of
NaOAc, LiBr, or LiI as an additive was not effective for the
formation of 2, and only 3 was formed (Table 1, Entries 6–
8). On the other hand, the use of Et4NCl was effective like
LiCl, and 2 was obtained in 56% yield (Table 1, Entry 9).
When the amount of LiCl was reduced to 1 equiv., the ratio
of 2/3 decreased (Table 1, Entry 10). Thus, pyridine was
found to be essential for selective formation of 2, and also
chloride anions play an important role for the selective
transfer of a silyl group.
Figure 1. Side reaction in the silylation of iodoarenes.[2h]
[a] Graduate School of Pharmaceutical Sciences, Tohoku Univer-
sity,
Aramaki Aza Aoba 6-3, Sendai 980-8578, Japan
Fax: +81-22-795-6804
E-mail: ykondo@mail.pharm.tohoku.ac.jp
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2008, 1161–1163
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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M. Iizuka, Y. Kondo
Table 2. Palladium-catalyzed silylation of iodoarenes.
SHORT COMMUNICATION
Table 1. Palladium-catalyzed silylation of 1-iodo-4-nitrobenzene.
1
[a] Estimated by H NMR spectroscopy. [b] Isolated yields.
[a] Estimated by 1H NMR spectroscopy. [b] Isolated yields. [c]
DMF was used as a solvent.
Further investigations were carried out for the silylation
of various aryl iodides using several silanes. On 1-iodo-4-
nitrobenzene (1), the use of PhMe2SiH gave almost similar
results with Et3SiH, and A (2b) was isolated in 45% yield
(Table 2, Entry 1). When Ph3SiH was used, the yield of A
(2c) was improved to 70% (Table 2, Entry 2). The reaction
of 4-iodobenzonitrile (5a) with Et3SiH gave A (6a) in 46%
yield (Table 2, Entry 3). The use of PhMe2SiH improved
the yield of A (6b) up to 94%, and no formation of B was
observed (Table 2, Entry 4). The reaction using Ph3SiH gave
A (6c) in 64% yield with no formation of B (Table 2, Entry
5). The reaction of 4-iodoacetophenone (5b) with Et3SiH
gave a 1:1 mixture of A/B, and the desired A (7a) was iso-
lated in 38% yield (Table 2, Entry 6). When PhMe2SiH was
used, the ratio of A/B was improved to 8:2, and A (7b) was
obtained in 73% yield (Table 2, Entry 7). The use of Ph3SiH
gave the best result, and A (7c) was obtained in 85% yield
with no formation of B (Table 2, Entry 8). The reaction of
methyl 4-iodobenzoate (5c) with Et3SiH gave a 6:4 mixture
of A/B, and A (8a) was isolated in 35% yiled (Table 2, Entry
9). The use of PhMe2SiH gave a 9:1 mixture of A/B, and A
(8b) was isolated in 82% yield (Table 2, Entry 10). The use
of Ph3SiH showed an excellent selectivity, and A (8c) was
obtained in 91% yield with no formation of B (Table 2, En-
try 11). 3-Iodopyridine (5d) was also treated with PhMe2-
SiH, and the corresponding silylated pyiridine 9 was ob-
tained in 87% yield (Table 2, Entry 12). The use of phenyl-
substituted silanes showed better selectivities, and this ten-
dency was also suggested by Murata’s report.[2e] At this mo-
ment, the silylation of an electron-rich aryl halide such as 4-
iodoanisole was unsuccessful under our reaction conditions,
and only a trace amount of silylated product was isolated.
With respect to the mechanism of the silylation reaction,
Our next interest was focused on the formation of aryl[2-
(hydroxymethyl)phenyl]dimethylsilanes, which recently were
reported to be excellent aryl donors for various transition-
metal-catalysed reactions.[4] The THP-protected [2-(hy-
droxymethyl)phenyl]dimethylsilane was treated with 4-iodo-
benzonitrile (5a) and 4-iodoacetophenone (5b) followed by
the treatment with p-TsOH to remove THP protective
group, and the silylated arenes 10 and 11 were obtained in
59% and 58% yields, respectively. The [2-(hydroxymethyl)-
phenyl]silylated acetophenone 11 was then treated with cy-
clohexenone in the presence of a rhodium catalyst which
gave the 1,4-adduct 12 in 96% yield (Scheme 1).
Scheme 1. Selective transformation of arylsilanes.
Conclusions
Palladium-catalysed silylation of aryl iodides with elec-
two types of pathways have been suggested: (i) σ-bond me- tron-withdrawing groups was efficiently achieved using pyr-
tathesis, (ii) PdIV intermediate involvement.[2a,2g] At this idine and lithium chloride as additives and conducting the
moment, it is not clear how pyridine and LiCl effectively reaction at room temperature. Aryl[2-(hydroxymethyl)-
form the silylated products; however, the combination is phenyl]dimethylsilanes were also prepared by palladium-
suggested to be favorable for the transition state of the me- catalysed reaction using protected [2-(hydroxymethyl)-
tathesis or the formation of PdIV species.
phenyl]dimethylsilane as a silylating agent followed by de-
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Eur. J. Org. Chem. 2008, 1161–1163

Palladium-Catalyzed Silylation of Electron-Deficient Aryl Iodides
219, p. 61; c) K. A. Horn, Chem. Rev. 1995, 95, 1317; d) Y.
Hatanaka, T. Hiyama, Synlett 1991, 845.
protection. Rhodium-catalysed 1,4-addition of the arylsil-
ane was carried out using cyclohexenone in excellent yield.
Further investigations on the scope and limitations of the
palladium-catalysed silylation and mechanistic studies are
underway.
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Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedure and spectroscopic data of synthesized
compounds.
Acknowledgments
This work was partly supported by the Grant-in-Aid for Scientific
Research on Priority Areas “Advanced Molecular Transformations
of Carbon Resources” (No. 19020005) and “Synergistic Effects for
Creation of Functional Molecules” (No. 19027008) and other Re-
search Grants (No. 19390002 and No. 18659001) from the Ministry
of Education, Science, Sports and Culture, Japan and a grant from
Yamada Science Foundation. We thank Professor Miki Murata for
his kind suggestions and discussions on this work.
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Commun. 2006, 4850.
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Received: December 2, 2007
Published Online: January 29, 2008
Eur. J. Org. Chem. 2008, 1161–1163
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