Palladium-catalyzed cross-coupling reactions of (2-pyridyl) allyldimethylsilanes with aryl iodides

Article abstract of DOI:10.1021/ol052961u

(2-Pyridyl)allyldimethylsilanes were found to be novel pyridyl transfer reagents in palladium-catalyzed cross-coupling reactions of various aryl iodides in the presence of silver(I) oxide as an activator.

Full text of DOI:10.1021/ol052961u

ORGANIC
LETTERS
2
006
Vol. 8, No. 4
29-731
Palladium-Catalyzed Cross-Coupling
Reactions of
7
(2-Pyridyl)allyldimethylsilanes with Aryl
Iodides
†
Toshiki Nokami, Yutaka Tomida, Toshiyuki Kamei, Kenichiro Itami, and
Jun-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry,
Graduate School of Engineering, Kyoto UniVersity,
Nishikyo-ku, Kyoto 615-8510, Japan
yoshida@sbchem.kyoto-u.ac.jp
Received December 7, 2005
ABSTRACT
(2-Pyridyl)allyldimethylsilanes were found to be novel pyridyl transfer reagents in palladium-catalyzed cross-coupling reactions of various aryl
iodides in the presence of silver(I) oxide as an activator.
2
-Substituted pyridines constitute an important class of
examples of the use of 2-pyridylmetals, however, have been
reported in the literature, presumably because 2-pyridylmetal
reagents are often unstable.
compounds, which are ubiquitous in biologically active
molecules, π-conjugated systems, and ligands for metal-
catalyzed reactions. Although various methods for the
synthesis of 2-substituted pyridines have been developed so
3
Recently, Gros and co-workers reported a palladium-
catalyzed cross-coupling reaction using 2-pyridyltrimethyl-
1
4
far, a new method, which enables the introduction of
silanes. They revealed that copper iodide and Bu
4
NF activate
2-pyridyl groups to organic structures under milder condi-
the pyridyl carbon-silicon bond. Although some activating
substituents such as chlorine should be present on the
pyridine ring, this reaction is quite useful from a synthetic
tions, is still needed. Palladium-catalyzed cross-coupling
reactions serve as a powerful method for carbon-carbon
bond formation, and various aryl and heteroarylmetals have
5
point of view. We envisioned that pyridylsilanes having no
2
been used for such cross-coupling reactions. Only a few
activating substituents on the pyridine ring can be utilized
†
Current address: Research Center for Materials Science, Nagoya
University, Nagoya 464-8602, Japan.
(3) (Trialkylstannyl)pyridines are commercially available; see also ref
2a. In situ generation of (2-pyridyl)dichlorosilanes has been reported: (a)
Hagiwara, E.; Kusumoto, T.; Hiyama, T. 76th National Meeting of the
Chemical Society of Japan, Yokohama, 1999. 2-Pyridylboron reagents have
been reported: (b) Hodgson, P. B.; Salingue, F. H. Tetrahedron Lett. 2004,
45, 685. See also ref 1b.
(
1) Recent reviews for pyridine syntheses: (a) Henry, G. D. Tetrahedron
2
004, 60, 6043. (b) Tyrrell, E.; Brookes, P. Synthesis 2004, 469. For recent
metal-catalyzed reactions to synthesize pyridine derivatives, see: (c) Godula,
K.; Sezen, B.; Sames, D. J. Am. Chem. Soc. 2005, 127, 3648. (d) Jordan,
R. F.; Taylor, D. F. J. Am. Chem. Soc. 1989, 111, 778. (e) Moore, E. J.;
Pretzer, W. R.; O’Connell, T. J.; Harris, J.; LaBounty, L.; Chou, L.;
Grimmer, S. S. J. Am. Chem. Soc. 1992, 114, 5888. (f) Murakami, M.;
Hori, S. J. Am. Chem. Soc. 2003, 125, 4720 and references therein.
(4) Pierrat, P.; Gros, P.; Fort, Y. Org. Lett. 2005, 7, 697.
(5) Biaryl syntheses using arylsilanes and pyridyl halides have been
reported: (a) Hatanaka, Y.; Gouda, K.-i.; Okahara, Y.; Hiyama, T.
Tetrahedron 1994, 50, 8301. (b) Hagiwara, E.; Gouda, K.-i.; Hatanaka, Y.;
Hiyama, T. Tetrahedron Lett. 1997, 38, 439. (c) Mowery, M. E.; Deshong,
P. Org. Lett. 1999, 1, 2137. (d) Lee, H. M.; Nolan, S. P. Org. Lett. 2000,
2, 2053. (e) Sahoo, A. K.; Nakao, Y.; Hiyama, T. Chem. Lett. 2004, 33,
632. (f) Sahoo, A. K.; Oda, T.; Nakao, Y.; Hiyama, T. AdV. Synth. Catal.
2004, 346, 1715. (g) Wolf, C.; Lerebours, R. Org. Lett. 2004, 6, 1147.
(2) (a) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere,
A., Diederich, F., Eds.; Wiley-VCH: Weinheim, Germany, 2004. Recent
reviews for cross-coupling reactions using organosilicon compounds: (b)
Hiyama, T.; Shirakawa, E. Top. Curr. Chem. 2002, 219, 61. (c) Hiyama,
T. J. Organomet. Chem. 2002, 653, 58. (d) Denmark, S. E.; Sweis, R. F.
Chem. Pharm. Bull. 2002, 50, 1531.
1
0.1021/ol052961u CCC: $33.50
© 2006 American Chemical Society
Published on Web 01/28/2006

in the cross-coupling reactions by introducing an appropriate
substituent on silicon. Herein, we report that the cross-
coupling reaction of the 2-pyridyl group does take place
effectively using (2-pyridyl)allyldimethylsilanes as coupling
to the decomposition of 1a, (entry 2),12 the combined
activator CuI/Bu NF afforded 2a in low yield (entry 3). Silver
salts were more effective as activators (entries 4 and 5). In
the case of Ag O, a large amount of 1a remained unchanged.
6
4
13
2
reagents in the presence of Ag
2
O as an activator.
Thus, by elongation of the reaction time, the yield was
increased to 60% (entry 6). Since the homocoupling reaction
of iodobenzene also took place, the use of an excess amount
(1.5 equiv) of iodobenzene gave the best yield (78% yield)
Recently, we have developed 2-pyridylsilanes as novel
7
8
9
transfer reagents of alkenyl, alkynyl, and benzyl groups
in palladium-catalyzed cross-coupling reactions (Scheme 1).
(entry 7).
3 4 2
Using the Pd(PPh ) /Ag O system, we examined several
(
2-pyridyl)silanes having different substituents on silicon
Scheme 1. Cross-Coupling Reactions Using 2-Pyridylsilanes
1
4
(Figure 1). As mentioned previously, the reaction of 1a
In these cases, the 2-pyridylsilyl group works as an activating
group of the silicon atom, and cross-coupling products of
the 2-pyridyl group were hardly observed.
During the course of our study, we found that cross-
coupling products involving the 2-pyridyl group were
obtained when 2-pyridyl(benzyl)silanes or 2-pyridyl(allyl)-
silanes were used in the presence of silver salts. Although
the reaction of 2-pyridyl(benzyl)silanes with aryl iodides gave
both diarylmethanes and 2-pyridylbenzenes, 2-pyridyl(allyl)-
silanes gave only 2-pyridylbenzenes.
Figure 1. Effect of substituents on silicon atom.
Thus, we searched for a suitable activator for the reaction
of (2-pyridyl)allyldimethylsilane 1a with iodobenzene to
gave 2a in 78% yield and no allyl transfer product,
allylbenzene, was formed. The use of 2-pyridyl(cinnamyl)-
silane 1b, however, resulted in the formation of the homo-
coupling product of the cinnamyl group (38%) and 1,3-
diphenylpropene (21%) together with the desired 2a (83%).
Although 2-pyridyltrimethylsilane 3 did not give 2a, 2-py-
obtain 2-pyridylbenzene 2a in the presence of Pd(PPh
3 4
)
(Table 1). The reaction did not take place in the absence of
1
5
Table 1. Effect of Activators
ridyl(vinyl)silane 4 and 2-pyridyl(3-butenyl)silane 5 af-
forded 2a. 2-Pyridyl(benzyl)silane 6 also gave 2a, but benzyl
9
coupling occurred predominantly. Based on these results,
we assume that the coordination of the carbon-carbon
double bond to silver assists the attack of oxygen on silicon
(
vide infra), although isolation of silver-coordinated complex
1
6
a
was unsuccessful.
entry
activator
yield (%)
1
2
3
4
5
Bu4NF
CuI
CuI/Bu4NF
AgF
Ag2O
Ag2O
0
0
8
21
35
60
78
(
7) (a) Itami, K.; Nokami, T.; Yoshida, J. J. Am. Chem. Soc. 2001, 123,
600. (b) Itami, K.; Nokami, T.; Ishimura, Y.; Mitsudo, K.; Kamei, T.;
Yoshida, J. J. Am. Chem. Soc. 2001, 123, 11577.
5
8) Itami, K.; Kamei, T.; Yoshida, J. Unpublished results.
3
635.
b
6
7
(10) Bu4NF has been the most versatile fluoride ion source in cross-
b,c
Ag2O
coupling reactions since Hiyama revealed its efficiency: Hatanaka, Y.;
Hiyama, T. J. Org. Chem. 1988, 54, 268. See also ref 2.
a
GC yield. b 10 h. c 1.5 equiv based on 1a of PhI was used.
(11) Palladium-catalyzed cross-coupling reactions using alkenyl- or
arylsilanes in the presence of copper salts: (a) Suginome, M.; Kinugasa,
H.; Ito, Y. Tetrahedron Lett. 1994, 35, 8635. (b) Taguchi, H.; Ghoroku,
K.; Tadaki, M.; Tsubouchi, A.; Takeda, T. J. Org. Chem. 2002, 67, 8450.
(c) Denmark, S. E.; Kobayashi, T. J. Org. Chem. 2003, 68, 5153. (d)
Denmark, S. E.; Baird, J. D. Org. Lett. 2004, 6, 3649. See also ref 6b.
4
an activator. The use of Bu NF as an activator was
unsuccessful (entry 1). Although the use of CuI gave rise
10
11
(12) Under the conditions reported by Gros, 2-pyridyltrimethylsilane did
not give 2-pyridylbenzene either.
(
6) Silicates can transfer the activated pyridyl group in excellent yields:
(13) Palladium-catalyzed cross-coupling reactions using aryl- or alky-
nylsilanes in the presence of silver salts: (a) Hirabayashi, K.; Kawashima,
J.; Nishihara, Y.; Mori, A.; Hiyama, T. Org. Lett. 1999, 1, 299. (b)
Hirabayashi, K.; Mori, A.; Kawashima, J.; Suguro, M.; Nishihara, Y.;
Hiyama, T. J. Org. Chem. 2000, 65, 5342. (c) Koseki, Y.; Omino, K.; Anzai,
S.; Nagasaka, T. Tetrahedron Lett. 2000, 41, 2377.
(
a) Seganish, W. M.; Deshong, P. J. Org. Chem. 2004, 69, 1137. Recently,
the (2-hydroxymethyl)phenyl group was developed as a reusable activating
group of the silicon atom and can transfer 2-pyridyl group: (b) Nakao, Y.;
Imanaka, H.; Sahoo, A. K.; Yada, A.; Hiyama, T. J. Am. Chem. Soc. 2005,
1
27, 6952. See also ref 3a.
730
Org. Lett., Vol. 8, No. 4, 2006

The successful cross-coupling reaction of (2-pyridyl)-
allyldimethylsilane 1a prompted us to examine the reactions
of related organosilicon compounds (Figure 2). The introduc-
such as methyl and methoxy groups and electron-withdraw-
ing groups such as the trifluoromethyl group.
The following mechanistic discussion seems to be reason-
able, although there is no definite evidence (Scheme 2). The
Scheme 2. Proposed Reaction Mechanism
Figure 2. Effect of aryl group on silicon atom.
tion of a methyl group on the pyridine ring did not interfere
with the coupling reaction. On the other hand, (3-pyridyl)-
allyldimethylsilane 1d and (2-thienyl)allyldimethylsilane 1e
did not give the corresponding coupling product, and the
starting organosilicon compounds were recovered unchanged.
These results indicate that the presence of a nitrogen atom
â to the silicon atom seems to be crucial for the reaction.
Various aryl iodides can be used for the present reaction,
and the corresponding cross-coupling products were obtained
as shown in Figure 3. The nature of substituents of aryl
initial step involves the coordination of the allyl group and
the pyridyl nitrogen to silver followed by the Lewis basic
activation of the silicon by oxygen. This process leads to
9
either allyl carbon-silicon bond cleavage or pyridyl carbon-
17
silicon bond cleavage. The former mode of cleavage may
give the siloxysilver species 7, which seems to be active in
palladium-catalyzed cross-coupling reactions. The second
mode of cleavage leads to the formation of 2-pyridylsilver
intermediate 8. The transmetalation from silver to palladium
followed by the coupling gives 2a. It is difficult to distinguish
these two possibilities, and more information should be
accumulated in order to reveal the mechanistic details.
In summary, we have developed a palladium-catalyzed
cross-coupling reaction using (2-pyridyl)allyldimethylsilanes
2
as pyridyl transfer reagents. Ag O was found to be quite
effective as an activator. Further work aimed at elucidating
the detailed mechanism and the applications to the synthesis
of various 2-pyridyl group containing compounds are cur-
rently in progress.
Acknowledgment. This work was financially supported
in part by a Grant-in-Aid for Scientific Research from the
Japan Society for the Promotion of Science.
Supporting Information Available: Experimental pro-
cedures and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Figure 3. Scope and limitation of aryl halides.
OL052961U
iodides did not affect yields significantly. The reaction is
compatible with electron-donating groups on the aryl group
(
15) Styrene, which is the cross-coupling product between the vinyl group
and iodobenzene, was observed as a byproduct.
16) We reported syntheses and crystal structures of copper-(2-pyridyl)-
(
(14) Various substituents have been reported as potentially activating
vinyldimethylsilane and copper-(2-pyridyl)allyldimethylsilane com-
plexes: (a) Itami, K.; Ushiogi, Y.; Nokami, T.; Ohashi, Y.; Yoshida, J.
Org. Lett. 2004, 6, 3695. (b) Kamei, T.; Fujita, K.; Itami, K.; Yoshida, J.
Org. Lett. 2005, 7, 4725.
groups of silicon atom. (a) Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc.
1999, 121, 5821. (b) Hosoi, K.; Nozaki, K.; Hiyama, T. Chem. Lett. 2002,
138. (c) Trost, B. M.; Machacek, M. R.; Ball, Z. T. Org. Lett. 2003, 5,
1895. (d) Anderson, J. C.; Munday, R. H. J. Org. Chem. 2004, 69, 8971.
(17) Itami, K.; Kamei, T.; Mineno, M.; Yoshida, J. Chem. Lett. 2002,
1084.
See also refs 5e,f and 7.
Org. Lett., Vol. 8, No. 4, 2006
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