Highly efficient carbopalladation across vinylsilane: Dual role of the 2-PyMe2Si group as a directing group and as a phase tag [10]

Full text of DOI:10.1021/ja002582q

J. Am. Chem. Soc. 2000, 122, 12013-12014
12013
Scheme 1
Highly Efficient Carbopalladation Across
Vinylsilane: Dual Role of the 2-PyMe2Si Group as a
Directing Group and as a Phase Tag
Kenichiro Itami, Koichi Mitsudo, Toshiyuki Kamei,
Tooru Koike, Toshiki Nokami, and Jun-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry
Kyoto UniVersity, Yoshida, Kyoto 606-8501, Japan
Table 1. Effect of the Ligand on the Rate of the
ReceiVed July 18, 2000
Palladium-Catalyzed Heck Coupling of 1 and Iodobenzenea
Carbopalladation, the insertion of unsaturated molecules into
carbon-palladium bonds, is a critically important step in many
palladium-catalyzed carbon-carbon bond-forming processes1 such
as the Mizoroki-Heck reaction,2 cyclic cascade reaction,1d
cyclooligomerization, and polymerization. We have recently been
engaged in the development of removable directing groups,3 which
control the metal-mediated and -catalyzed processes by complex
induced proximity effect (CIPE).4 For example, expeditious
hydrosilylation was achieved by utilizing a 2-pyridyldimethylsilyl
(2-PyMe2Si) group as a directing group.3a The removal of the
2-PyMe2Si group was achieved by H2O2 oxidation.3a,d Moreover,
the phase tag property of this group enables easy product
purification (acid-base extraction).3 In ongoing efforts to exploit
the utility of this removable directing group, investigation of
carbopalladation across the vinylsilane bearing 2-PyMe2Si group
was undertaken (Scheme 1).5
It already has been known that there are several difficulties
upon carbopalladation across vinylsilane. For example, the
treatment of vinylsilane with aryl iodide under the typical Heck
reaction conditions affords exclusively styrene derivative as a
result of carbon-silicon bond cleavage.6,7 The only procedure
realizing the vinylsilane carbopalladation (Heck-type reaction) to
some extent is the use of an equimolar amount of silver nitrate,
which is not very useful from the practical point of view.8 By
taking advantage of efficacious CIPE through the coordination
of the pyridyl group to the catalyst palladium, we expected the
occurrence of the Heck-type reaction without the need of silver
salt. In this communication, we describe the “proof-of-principle”
of our strategy and the dual role of the 2-PyMe2Si group as a
directing group and as a phase tag.
entry
ligand
conversion (%)b
yield (%)b
58
5c
1
2
3
4
5
6
7
8
PPh3
63
6
24
100
91
100
100
100
Ph2PCH2CH2PPh2
P(C6H4OCH3-4)3
P(C6H4CF3-4)3
AsPh3
15
90
80
P(OPh)3
85
TFP
TFP
97d
78e
a Unless otherwise noted, all reactions were performed at 50 °C
for 6 h using 1 (0.5 mmol), PhI (1.1 equiv), Et3N (1.2 equiv),
Pd2(dba)3‚CHCl3 (2.5 mol %), and ligand (10 mol %) in THF (1.5 mL).
b Determined by GC analysis. c 5 mol % of ligand was employed. d The
reaction completed within 2 h. e The mixture was stirred for 38 h using
0.1 mol % of catalyst.
absence of silver salt. On the basis of this auspicious preliminary
result, we have set out to investigate the effect of added ligand
(Table 1). Chelating diphosphine enormously shut down the
reaction presumably due to the occupation of the coordination
site for 1 (entry 2).2b Electronic tuning of PPh3 was found to be
very informative. Whereas the use of electron-donating P(C6H4-
OCH3-4)3 gave rise to the detrimental effect on rate, electron-
withdrawing P(C6H4CF3-4)3 greatly accelerated the reaction
(entries 3 and 4). Substantial rate enhancements over PPh3 were
also observed with AsPh3, P(OPh)3, and tri-2-furylphosphine
(TFP). Particularly, the use of TFP gave rise to an extremely high
yield of 2a (97%, entry 7). Remarkably, this Pd/TFP catalyst
system permits the coupling at low catalyst loading (0.1 mol %)
without significant loss of catalytic activity (entry 8).
To evaluate the carbopalladation aptitude of vinylsilane 1,
competitive reaction was carried out with methyl acrylate and
styrene, the most commonly used reactive substrates in the Heck
chemistry (eq 1).2 To our surprise, the only product detected in
the reaction mixture was 2a (89% yield), which clearly signi-
fies the high reactivity of 1 toward the Heck reaction.8e It is
reasonable to assume that the coordination of the pyridyl group
to palladium might render the carbopalladation event kinetically
In early experiments we established that iodobenzene and
2-pyridyldimethyl(vinyl)silane (1) are cross-coupled in the pres-
ence of 2.5 mol % of [Pd2(dba)3‚CHCl3], 10 mol % of PPh3, and
1.2 equiv of Et3N (THF, 50 °C; 58% yield after 6 h; Table 1,
entry 1). Noteworthy is that the formation of styrene (carbon-
silicon bond cleavage) was completely suppressed even in the
(1) For excellent reviews, see: (a) Hegedus, L. S. Transition Metals in the
Synthesis of Complex Organic Molecules, 2nd ed.; University Science
Books: Sausalito, CA, 1999. (b) Diederich, F.; Stang, P. J., Eds. Metal-
Catalyzed Cross-Coupling Reactions; Wiley-VCH: Weinheim, 1998. (c) Tsuji,
J. Palladium Reagents and Catalysts; John Wiley: Chiester, 1995. (d) Negishi,
E.; Cope´ret, C.; Ma, S.; Liou, S.-Y.; Liu, F. Chem. ReV. 1996, 96, 365.
(2) (a) Bra¨se, S.; de Meijere, A. In ref 1b, Chapter 3. (b) Cabri, W.;
Candiani, I. Acc. Chem. Res. 1995, 28, 2. (c) de Meijere, A.; Meyer, F. E.
Angew. Chem., Int. Ed. Engl. 1994, 33, 2379. (d) Heck, R. F. In ComprehensiVe
Organic Synthesis; Trost, B. M., Ed.; Pergamon: New York, 1991; Vol. 4,
Chapter 4.3.
(3) (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.; Mitsudo, K.; Yoshida, J. J. Org. Chem. 1999, 64, 8709. (e)
Itami, K.; Nokami, T.; Yoshida, J. Org. Lett. 2000, 2, 1299.
(4) (a) Beak, P.; Meyers, A. I. Acc. Chem. Res. 1986, 19, 356. (b) Snieckus,
V. Chem. ReV. 1990, 90, 879. (c) Beak, P.; Basu, A.; Gallagher, D. J.; Park,
Y. S.; Thayumanavan, S. Acc. Chem. Res. 1996, 29, 552. See also: (d)
Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. ReV. 1993, 93, 1307.
(5) For chelation-controlled Heck arylation, see: (a) Andersson, C.-M.;
Larsson, J.; Hallberg, A. J. Org. Chem. 1990, 55, 5757. (b) Nilsson, K.;
Hallberg, A. J. Org. Chem. 1992, 57, 4015. (c) Buezo, N. D.; Alonso, I.;
Carretero, J. C. J. Am. Chem. Soc. 1998, 120, 7129 and references therein.
See also ref 2b.
(6) (a) Hallberg, A.; Westerlund, C. Chem. Lett. 1982, 1993. (b) Karabelas,
K.; Hallberg, A. J. Org. Chem. 1989, 54, 1773.
(7) (a) Akhrem, I. S.; Chistovalova, N. M.; Mysov, E. I.; Vol’pin, M. E. J.
Organomet. Chem. 1974, 72, 163. (b) Yoshida, J.; Tamao, K.; Yamamoto,
H.; Kakui, T.; Uchida, T.; Kumada, M. Organometallics 1982, 1, 542. (c)
Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 920. For a review on the
Pd-catalyzed C-C coupling reactions involving C-Si bond cleavage (Hiyama
coupling), see: (d) Hiyama, T. In ref 1b, Chapter 10.
(8) (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) Voigt, K.; von Zezschwitz,
P.; Rosauer, K.; Lansky, A.; Adams, A.; Reiser, O.; de Meijere, A. Eur. J.
Org. Chem. 1998, 1521. See also: (f) Yamashita, H.; Roan, B. L.; Tanaka,
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10.1021/ja002582q CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/17/2000

12014 J. Am. Chem. Soc., Vol. 122, No. 48, 2000
Communications to the Editor
Table 2. Palladium-Catalyzed Heck-type Coupling of Pyridyl-
Scheme 2
Substituted Vinylsilane with Aryl, Heteroaryl, and Alkenyl Iodidesa
Table 3. Reuse of Palladium Catalyst in the Heck Coupling of 1
and Iodobenzenea
entry time, h yield (2a), % purity, % stereoselectivity, % E
1a
2b
3b
4b
2
5
6
6
93
90
89
91
>95
>95
>95
>95
>99
>99
>99
>99
a Reaction was performed at 50 °C using 1 (0.5 mmol), iodobenzene
(1.1 equiv), Et3N (1.2 equiv), Pd2(dba)3‚CHCl3 (2.5 mol %), and TFP
(10 mol %) in THF (1.5 mL). b Reactions were performed at 50 °C
using 1 (0.5 mmol), iodobenzene (1.0 equiv), Et3N (1.2 equiv), and
recovered palladium catalyst in THF (1.5 mL).
generally higher (∼5%) than that using silica gel chromatography
and is slightly lower (∼3%) than that determined by GC analysis
of the reaction mixture. Importantly, the purities of the products
are over 95% in all cases as judged by NMR and GC analysis.
This easy separation/purification protocol without using any
chromatographic isolation technique is notable.13
One important corollary of these findings is that the palladium
catalyst may possibly be recovered from the initial organic phase
in the acid-base extraction purification process (Scheme 2),
leading to the consecutive use for the next run. In practice, thus
recovered palladium catalyst can be used in the second, third,
and forth runs without eroding the catalytic activity (Table 3).14
Importantly, the purities of the isolated 2a (by acid-base
extraction) were over 95% in every run as in the case in Table 2.
In summary, we have developed a new strategy for the
carbopalladation across vinylsilane by exploiting the 2-PyMe2Si
group as a directing group. In addition, easy product purification,
catalyst recovery, and catalyst reuse are now viable by taking
advantage of the phase tag property of 2-PyMe2Si group.
a Unless otherwise noted, all reactions were performed at 50 °C using
vinylsilane (0.5 mmol), organic iodide (1.1 equiv), Et3N (1.2 equiv),
Pd2(dba)3‚CHCl3 (0.5 mol %), and TFP (2 mol %) in THF (1.5 mL).
b Isolated yields. c Determined by GC and NMR analysis. d 2 mol %
of catalyst was used. e Reaction was performed at 90 °C in toluene.
and/or thermodynamically favorable.
Acknowledgment. This research was supported by a Grant-in-Aid
for Scientific Research from the Ministry of Education, Science, Sports,
and Culture, Japan, and the Mitsubishi Foundation. K.M. thanks the Japan
Society for the Promotion of Science for Young Scientists.
Under the standard set of reaction conditions (0.5 mol % of
[Pd2(dba)3‚CHCl3], 2 mol % of TFP, and 1.2 equiv of Et3N at 50
°C in THF), pyridyl-substituted vinylsilanes (1 and 3) cross-
coupled with a wide array of electronically and structurally diverse
aryl, heteroaryl, and alkenyl iodides9 in high yield (Table 2).10 In
all cases, virtually complete stereoselectivities (>99% E) were
observed. Quite interestingly, the regio- and stereoselective Heck
reaction proceeded even with â-substituted vinylsilane 3, provid-
ing compelling evidence for the enhanced reactivity of pyridyl-
substituted vinylsilane (entries 9 and 10). In light of the prevailing
dogma that the intermolecular Heck reaction is sensitive to the
substitution pattern on the alkene scaffold, the regio- and
stereocontrolled carbopalladation across the acyclic 1,2-disubsti-
tuted alkene 3 is extremely appealing.2,11
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.
JA002582Q
(9) Under the identical reaction conditions, cross coupling did not take place
when aryl bromides were used instead of aryl iodides.
(10) Pyridyl-substituted vinylsilane can be converted to other vinylsilanes
via pyridyl-silyl bond cleavage (ref 3e), or can be directly subjected to the
reactions with various electrophiles. See Supporting Information for details.
As we recently reported, the additional benefit of using the
2-PyMe2Si group is that it can also be utilized as a phase tag,3a
which enables easy purification.12 By taking advantage of this
phase tag property of the 2-PyMe2Si group, all products listed in
Table 2 were isolated only by simple acid-base extraction
(Scheme 2). Acid extraction (1 N HCl, 6 times) of the reaction
mixture transfers the product and base (Et3N) to the aqueous
phase, while the catalyst and excess aryl iodide remain in the
organic phase. Neutralization of the aqueous phase and subsequent
extraction with organic solvent re-transfer the product to the
organic phase. Finally, the evaporation of organic solvent affords
the product 2. The yield of 2 using this acid-base extraction is
(11) For the stereoselective synthesis of trisubstituted alkene by the Heck
reaction of 1,2-disubstituted alkene, see: (a) Moreno-Man˜as, M.; Pleixats,
R.; Roglans, A. Synlett 1997, 1157. (b) Blettner, C. G.; Ko¨nig, W. A.; Stenzel,
W.; Schotten, T. Tetrahedron Lett. 1999, 40, 2101. (c) Gu¨rtler, C.; Buchwald,
S. L. Chem. Eur. J. 1999, 5, 3107 and references therein.
(12) For an excellent review on the strategic separations in organic synthesis,
see: Curran, D. P. Angew. Chem., Int. Ed. Engl. 1998, 37, 1174.
(13) Green Chemistry: Frontiers in Benign Chemical Synthesis and
Processes; Anastas, P. T., Williamson, T. C., Eds.; Oxford University Press:
New York, 1998.
(14) See Supporting Information for details.