Palladium-catalyzed cross-coupling reaction of alkenyldimethyl(2-pyridyl)silanes with organic halides: Complete switch from the carbometalation pathway to the transmetalation pathway [13]

Full text of DOI:10.1021/ja015655u

5600
J. Am. Chem. Soc. 2001, 123, 5600-5601
integrated into the one-pot sequential reactions which have never
been accomplished to date.
Palladium-Catalyzed Cross-Coupling Reaction of
Alkenyldimethyl(2-pyridyl)silanes with Organic
Halides: Complete Switch from the Carbometalation
Pathway to the Transmetalation Pathway
As we already established,3 the Mizoroki-Heck-type reaction6
occurs with dimethylhexenyl(2-pyridyl)silane (1) and iodobenzene
in the presence of palladium catalyst [Pd2(dba)3‚CHCl3 + tri-2-
furylphosphine (TFP)] (Table 1, entry 1). Although various Pd
catalysts were examined, the only product detected was the
carbometalation product 4. This may be due to the strong directing
effect of the pyridyl group and the poor transmetalation ability
of silicon. Thus we followed the lead of Hiyama,4 who has
established that the transmetalation from silicon to palladium can
be accelerated by adding a fluoride ion.7 We subjected 1 and
iodobenzene to the action of palladium catalyst and fluoride source
at 60 °C in THF. By adding tetrabutylammonium fluoride (TBAF)
to the Pd/TFP catalyst, the course of the reaction changed to the
transmetalation pathway and the carbometalation pathway was
completely suppressed (entry 2). Moreover, we found that
phosphine-free Pd complexes were more active catalysts giving
the transmetalation product 2 in extremely high yields (entries
3-6). The observed excellent 2/3 ratio (99/1) is noteworthy since
the production of cine substitution product (3) is the plague in
this chemistry for some instances.4
Kenichiro Itami, Toshiki Nokami, and Jun-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry
Kyoto UniVersity, Yoshida, Kyoto 606-8501, Japan
ReceiVed February 9, 2001
ReVised Manuscript ReceiVed May 1, 2001
The transition metal-catalyzed cross-coupling reactions con-
stitute one of the most versatile and efficacious carbon-carbon
bond formations, and the development of improved catalysts and
reagents continues to evolve at a rapid pace.1 Although there are
a number of reaction types known to date, integration of these
reaction types by utilizing a multifunctional substrate lags far
behind presumably due to the difficulty in controlling those
individual reaction pathways. It would be of great importance in
organic synthesis if such plural reaction pathways were perfectly
controlled, ideally with slight changes of additive or reaction
conditions, and integrated into sequential and/or one-pot reactions.
During the course of our investigations in this area, we became
interested in the multiform reactivities of vinylsilanes, which can
potentially react with organic halides and palladium catalyst in
two mechanistically different modes, namely carbometalation
pathway (path a, eq 1)2,3 and transmetalation pathway (path b,
eq 1).4 Although both of these reaction pathways have been
extensively utilized in organic synthesis, their integration has not
been examined to date.
Table 1. Effect of Catalyst and Additive in the
Palladium-Catalyzed Cross-Coupling Reaction of 1 and
Iodobenzenea
entry
Pd catalyst
additive
yield (%)
2/3/4c
1a
2b
3b
4b
5b
6b
Pd2(dba)3/TFP
Pd2(dba)3/TFP
Pd(OAc)2
[allylPdCl]2
PdCl2(CH3CN)2
PdCl2(PhCN)2
Et3N
94
59
93
95
96
99
0/0/100
97/3/0
98/2/0
98/2/0
99/1/0
99/1/0
TBAF
TBAF
TBAF
TBAF
TBAF
a Reaction was performed at 50 °C for 2 h using 1 (0.5 mmol), PhI
(0.55 mmol), Pd2(dba)3‚CHCl3 (0.5 mol %), tri-2-furylphosphine (TFP)
(2 mol %), and Et3N (0.6 mmol) in THF. b Reactions were performed
at 60 °C for 1.5 h using 1 (0.3 mmol), PhI (0.2 mmol), Pd catalyst (5
mol %), and TBAF (0.3 mmol) in THF. c Determined by GC and NMR
analysis.
Recently we reported that the palladium-catalyzed cross-
coupling reaction of vinyl(2-pyridyl)silanes with organic halides
occurs in the carbometalation pathway (path a) to give the
substituted vinyl(2-pyridyl)silanes in extremely high yields.3,5 The
realization of the previously difficult Heck-type reaction of
vinylsilane may be due to the strong coordination effect of the
pyridyl group on silicon. In this communication, we establish that
(1) this carbometalation pathway (path a) can be completely
switched to the transmetalation pathway (path b) by the Pd/TBAF
system and (2) these two distinct reaction pathways can be
We were pleased to find that the potentially transferable pyridyl
group is not transferred into the product and ends up in the
quantitative formation of pyridine.8 These facts led us to inves-
tigate the reaction mechanism in more detail. First, styryldimethyl-
(2-pyridyl)silane (5) was allowed to react with 1.0 equiv of
PdCl2(CH3CN)2 in the presence of TBAF (1.2 equiv) and (E,E)-
1,4-diphenylbutadiene was isolated in 72% yield. This result
unambiguously supports the occurrence of the transmetalation
pathway. Again, the pyridyl group transferred products (2,2′-
bipyridyl and styrylpyridine) were not observed at all.
(1) Diederich, F.; Stang, P. J., Eds. Metal-Catalyzed Cross-Coupling
Reactions; Wiley-VCH: Weinheim, 1998.
(2) (a) Karabelas, K.; Westerlund, C.; Hallberg, A. J. Org. Chem. 1985,
50, 3896. (b) Karabelas, K.; Hallberg, A. Tetrahedron Lett. 1985, 26, 3131.
(c) Karabelas, K.; Hallberg, A. J. Org. Chem. 1986, 51, 5286. (d) Karabelas,
K.; Hallberg, A. J. Org. Chem. 1988, 53, 4909. (e) Daves, G. D., Jr.; Hallberg,
A. Chem. ReV. 1989, 89, 1433. (f) Yamashita, H.; Roan, B. L.; Tanaka, M.
Chem. Lett. 1990, 2175. (g) Voigt, K.; von Zezschwitz, P.; Rosauer, K.;
Lansky, A.; Adams, A.; Reiser, O.; de Meijere, A. Eur. J. Org. Chem. 1998,
1521. (h) Jeffery, T. Tetrahedron Lett. 1999, 40, 1673.
(3) Itami, K.; Mitsudo, K.; Kamei, T.; Koike, T.; Nokami, T.; Yoshida, J.
J. Am. Chem. Soc. 2000, 122, 12013.
(4) (a) Hatanaka, Y.; Hiyama, T. Synlett 1991, 845. (b) Hiyama, T. In ref
1, Chapter 10.
(5) For other related chemistry of 2-pyridylsilanes, see: (a) Yoshida, J.;
Itami, K.; Mitsudo, K.; Suga, S. Tetrahedron Lett. 1999, 40, 3403. (b) Itami,
K.; Mitsudo, K.; Yoshida, J. Tetrahedron Lett. 1999, 40, 5533. (c) Itami, K.;
Mitsudo, K.; Yoshida, J. Tetrahedron Lett. 1999, 40, 5537. (d) Itami, K.;
Nokami, T.; Yoshida, J. Angew. Chem., Int. Ed. 2001, 40, 1074.
(6) (a) Bra¨se, S.; de Meijere, A. In ref 1, Chapter 3. (b) Heck, R. F. In
ComprehensiVe Organic Synthesis; Trost, B. M., Ed.; Pergamon: New York,
1991; Vol. 4, Chapter 4.3.
(7) Pd-catalyzed cross-coupling reaction utilizing fluorosilicates; see: (a)
Yoshida, J.; Tamao, K.; Takahashi, M.; Kumada, M. Tetrahedron Lett. 1978,
2161. (b) Yoshida, J.; Tamao, K.; Yamamoto, H.; Kakui, T.; Uchida, T.;
Kumada, M. Organometallics 1982, 1, 542.
10.1021/ja015655u CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/18/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 23, 2001 5601
Table 2. Palladium-Catalyzed Cross-Coupling Reaction of
vinylsilanes in good to excellent yields. The advantage of using
2-pyridyl-substituted vinylsilanes as coupling components is
apparent, as they are readily available in stereoisomerically pure
form by the Peterson-type reaction of carbonyl compounds with
(2-PyMe2Si)2CHLi.14 Thus, the overall process can be regarded
as a novel carbonyl olefination reaction.
Alkenyldimethyl(2-pyridyl)silanes and Various Organic Halidesa
In light of the ability of 2-pyridyl-substituted vinylsilane to
cross-couple with organic halide in two mechanistically different
modes (Table 1), we next embarked on the one-pot sequential
cross coupling, in which the carbometalation-oriented cross
coupling (path a, eq 1) occurs first and the transmetalation-oriented
cross coupling (path b, eq 1) takes place thereafter. The â-sub-
stituted vinylsilane 1 was initially cross-coupled with 4-iodoben-
zoic acid ethyl ester in the presence of Pd/TFP catalyst. After
the initial reaction was completed, 4-iodoacetophenone and TBAF
were added to the mixture. The sequential cross-coupling product
10 was obtained in 71% yield (eq 3).15 Interestingly, the
regioisomer 11 can be obtained in 79% yield by simply changing
the order of addition (eq 3). In both cases, the reaction proceeded
in virtually complete regio- and stereoselective fashion. This
procedure provides an extremely facile entry into a diverse range
of stereodefined polysubstituted olefins, the synthesis of which
has been a central issue in organic synthesis.16
a All reactions were performed at 60 °C for 2-5 h using alkenyldi-
methylpyridylsilane (0.3 mmol), organic halide (0.2 mmol), TBAF (0.3
mmol), and PdCl2(PhCN)2 (5 mol %) in THF.
Next, we monitored the reaction of 5 and TBAF in THF-d8 by
1H NMR and found that 5 is converted into styryldimethylsilanol
and pyridine within 30 min at 30 °C (eq 2).9 The small amount
of water (ca. 5%) present in the commercially available THF
solution of TBAF seemed to be the reactant in this case. Indeed,
silanol was not formed with anhydrous TASF instead. This 2-Py-
Si bond cleavage is reminiscent to that attained by the KF-
promoted methanolysis of 2-pyridylsilanes.10 Very recently, Mori11
and Denmark12 have reported that silanols can be cross-coupled
with organic halides in the presence of Pd catalyst and we assume
that our cross coupling using 2-pyridylsilanes is mechanistically
similar to theirs.13 After all, it seems plausible to deduce that the
perfect switch of the reaction pathway stems from the selectiVe
remoVal of the carbometalation-directing pyridyl group and the
introduction of an electronegatiVe group that actiVates silicon
as a leaVing group.
In summary, a highly efficient palladium-catalyzed cross-
coupling reaction of alkenyldimethyl(2-pyridyl)silanes with or-
ganic halides has been developed. The potentially occurring two
reaction pathways (carbometalation and transmetalation pathways)
were perfectly controlled by simply changing the additives, and
integrated into the one-pot sequential cross-coupling reaction.
Although both of these reaction pathways are the types that are
already known, the integration of two mechanistically distinct
reactions clearly opens up new possibilities in the catalytic cross-
coupling chemistry.
Acknowledgment. This research was supported by a Grant-in-Aid
for Scientific Research from the Ministry of Education, Science, Sports,
and Culture, Japan. This paper is dedicated to our mentor Professor
Yoshihiko Ito.
With the feasibility of the selective transmetalation pathway
established, a survey of the substrate scope was undertaken (Table
2). Various electronically and structurally diverse aryl and alkenyl
halides were found to cross-couple with 2-pyridyl-substituted
Supporting Information Available: Experimental procedures and
analytical and spectroscopic data (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
(8) The transfer of the substituted pyridyl group from Si to Pd in the
presence of KF has been reported. Hagiwara, E.; Kusumoto, T.; Hiyama, T.
76th National Meeting of the Chemical Society of Japan, Yokohama, 1999.
(9) Protodesilylation of styryldimethylsilanol was found to take place upon
letting the mixture stand for several hours to afford styrene quantitatively.
(10) Itami, K.; Mitsudo, K.; Yoshida, J. J. Org. Chem. 1999, 64, 8709.
(11) (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.
(12) Denmark, S. E.; Wehrli, D. Org. Lett. 2000, 2, 565.
JA015655U
(14) Itami, K.; Nokami, T.; Yoshida, J. Org. Lett. 2000, 2, 1299.
(15) Substituted stilbenes are known to display interesting pharmacological
and physical properties. For examples, see: (a) Young, W. R.; Aviram, A.;
Cox, R. J. J. Am. Chem. Soc. 1972, 94, 3976. (b) Kagechika, H.; Himi, T.;
Namikawa, K.; Kawachi, E.; Hashimoto, Y.; Shudo, K. J. Med. Chem. 1989,
32, 1098. (c) Meier, H. Angew. Chem., Int. Ed. Engl. 1992, 31, 1399.
(16) Organ, M. G.; Cooper, J. T.; Rogers, L. R.; Soleymanzadeh, F.; Paul,
T. J. Org. Chem. 2000, 65, 7959 and references therein.
(13) Indeed, the cross coupling of styryldimethylsilanol with iodobenzene
did occur under our reaction conditions (Table 1, entry 6) giving stilbene in
98% yield.