Catalytic intermolecular Pauson-Khand-type reaction: Strong directing effect of pyridylsilyl and pyrimidylsilyl groups and isolation of Ru complexes relevant to catalytic reaction

Article abstract of DOI:10.1021/ja047484+

Some circumstantial evidence for the directing effect of the 2-pyhdylsilyl group in the Ru-catalyzed intermolecular Pauson-Khand-type reaction (PKR) of alkenyl(2-pyridyl)silane, alkyne, and carbon monoxide has been provided. Most importantly, we have succeeded in isolating several monometallic Ru complexes relevant to the catalytic reaction: Ru(vinylsilane)(CO)₃ complexes and ruthenacyclopentene. While the stoichimetric reaction of the Ru(vinylsilane)(CO)₃ complex with an alkyne led to the formation of the corresponding cyclopentenone (PKR product) at 100 °C, the ruthenacyclopentene intermediate was quantitatively produced at 50 °C. This complex was also converted to a cyclopentenone upon heating at 100 °C. Moreover, it was also found that the Ru(vinylsilane)(CO)₃ complex and ruthenacyclopentene serve as catalysts in intermolecular PKR.

Full text of DOI:10.1021/ja047484+

Published on Web 08/11/2004
Catalytic Intermolecular Pauson-Khand-Type Reaction:
Strong Directing Effect of Pyridylsilyl and Pyrimidylsilyl
Groups and Isolation of Ru Complexes Relevant to Catalytic
Reaction
Kenichiro Itami,* Koichi Mitsudo, Kazuyoshi Fujita, Youichi Ohashi, and
Jun-ichi Yoshida*
Contribution from the Department of Synthetic Chemistry and Biological Chemistry,
Graduate School of Engineering, Kyoto UniVersity, Nishikyo-ku, Kyoto 615-8510, Japan
Received April 30, 2004; E-mail: itami@sbchem.kyoto-u.ac.jp; yoshida@sbchem.kyoto-u.ac.jp
Abstract: Some circumstantial evidence for the directing effect of the 2-pyridylsilyl group in the Ru-catalyzed
intermolecular Pauson-Khand-type reaction (PKR) of alkenyl(2-pyridyl)silane, alkyne, and carbon monoxide
has been provided. Most importantly, we have succeeded in isolating several monometallic Ru complexes
relevant to the catalytic reaction: Ru(vinylsilane)(CO)3 complexes and ruthenacyclopentene. While the
stoichimetric reaction of the Ru(vinylsilane)(CO)3 complex with an alkyne led to the formation of the
corresponding cyclopentenone (PKR product) at 100 °C, the ruthenacyclopentene intermediate was
quantitatively produced at 50 °C. This complex was also converted to a cyclopentenone upon heating at
100 °C. Moreover, it was also found that the Ru(vinylsilane)(CO)3 complex and ruthenacyclopentene serve
as catalysts in intermolecular PKR.
Scheme 1
Introduction
The Pauson-Khand-type reaction (PKR), the metal-mediated
[2 + 2 + 1] cycloaddition of alkyne, alkene, and carbon
monoxide to generate 2-cyclopentenones,1,2 has received in-
creasing attention in the synthetic community because it allows
the construction of synthetically useful and biologically interest-
ing five-membered carbocycles in a convergent and atom-
economical manner.3 Therefore, PKR has been used as the key
step in a number of natural product syntheses.4 Conventionally,
PKR requires the stoichiometric use of Co2(CO)8 (heating a Co2-
(CO)6(alkyne) complex with an alkene). However, the arena of
catalytic PKR (the use of a catalytic amount of metal complex
(1) For reviews, see: (a) Brummond, K. M.; Kent, J. L. Tetrahedron 2000,
56, 3263-3283. (b) Fletcher, A. J.; Christie, S. D. R. J. Chem. Soc., Perkin
Trans. 1 2000, 1657-1668. (c) Chung, Y. K. Coord. Chem. ReV. 1999,
188, 297-341. (d) Geis, O.; Schmalz, H. G. Angew. Chem., Int. Ed. 1998,
37, 911-914. (e) Fru¨hauf, H. W. Chem. ReV. 1997, 97, 523-596. (f)
Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49-92. (g) Schore,
N. E. Org. React. 1991, 40, 1-90. (h) Blanco-Urgoiti, J.; An˜orbe, L.; Pe´rez-
Serrano, L.; Dom´ınguez, G.; Pe´rez-Castells, J. Chem. Soc. ReV. 2004, 33,
32-42.
(2) Although the term “Pauson-Khand reaction” applies only to Co-mediated
process, we refer to any closely related metal-mediated or -catalyzed [2 +
2 + 1] cycloannulation process of alkyne, alkene, and carbon monoxide
(or its equivalent such as isocyanide) as “Pauson-Khand-type reaction”
(PKR) in this paper.
(3) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259-281.
(4) For selected examples, see: (a) Castro, J.; Moyano, A.; Perica`s, M. A.;
Riera, A.; Greene, A. E.; Alvarez-larena, A.; Piniella, J. F. J. Org. Chem.
1996, 61, 9016-9020. (b) Jamison, T. F.; Shambayati, S.; Crowe, W. E.;
Schreiber, S. L. J. Am. Chem. Soc. 1997, 119, 4353-4363. (c) Cassayre,
J.; Zard, S. Z. J. Am. Chem. Soc. 1999, 121, 6072-6073. (d) Cassayre, J.;
Gagosz, F.; Zard, S. Z. Angew. Chem., Int. Ed. 2002, 41, 1783-1785. (e)
Mukai, C.; Kobayashi, M.; Kim, I. J.; Hanaoka, M. Tetrahedron 2002, 58,
5225-5230. (f) Nomura, I.; Mukai, C. Org. Lett. 2002, 4, 4301-4304. (g)
Ishizaki, M.; Niimi, Y.; Hoshino, O. Tetrahedron Lett. 2003, 44, 6029-
6031.
to achieve this transformation) has prospered recently because
of the apparent advantages (Scheme 1).5
Catalytic Pauson-Khand-Type Reaction. The first example
of Co-catalyzed PKR was reported in 1973 by Pauson and
Khand, which utilized strained (reactive) alkenes with a continu-
ous supply of ethyne.6 Several other groups also attempted to
render this fascinating catalytic reaction in 1980s.7 In 1994,
(5) Gibson, S. E.; Stevenazzi, A. Angew. Chem., Int. Ed. 2003, 42, 1800-
1810.
(6) Khand, I.; Knox, G. R.; Pauson, P. L.; Watts, W. E.; Foreman, M. I. J.
Chem. Soc., Perkin Trans. 1 1973, 977-981.
(7) (a) Billington, D. C. Tetrahedron Lett. 1983, 24, 2905-2908. (b) Magnus,
P.; Principe, L. M.; Slater, M. J. J. Org. Chem. 1987, 52, 1483-1486. (c)
Billington, D. C.; Kerr, W. J.; Pauson, P. L.; Farnocchi, C. F. J. Organomet.
Chem. 1988, 356, 213-219. (d) Rautenstrauch, V.; Me´gard, P.; Conesa, J.;
Ku¨ster, W. Angew. Chem., Int. Ed. Engl. 1990, 29, 1413-1416.
9
11058
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10.1021/ja047484+ CCC: $27.50 © 2004 American Chemical Society

Catalytic Intermolecular Pauson−Khand-Type Reaction
A R T I C L E S
Jeong reported a catalytic intramolecular PKR of enynes using
P(OPh)3 as a supporting ligand for Co2(CO)8.8 This probably
is the first example of practical catalytic PKR.
[RhCl(CO)(dppp)]2 could serve as catalysts for intramolecular
PKR of enynes.16,17 Examples of Rh-catalyzed intermolecular
PKR were provided by Narasaka using reactive alkenes such
as norbornene and ethylene.16e However, less reactive alkenes
such as styrene and 1-phenyl-3-butene were not applicable.
Shibata disclosed that iridium-phosphine catalysts are effective
in the intramolecular PKR of enynes and allenynes.18 An
example of intermolecular reaction was also provided, but low
reactivity was the apparent bane in this system as well.
Nevertheless, the synthetically most challenging catalytic
intermolecular PKR has been essentially limited to the utilization
of highly reactive norbornene, norbornadiene, or ethylene as
an alkene component (Scheme 1). Therefore, novel catalytic
conditions and/or a synthetic strategy to alleviate such limitations
imposed on the alkene counterpart are strongly desired.
Directed Pauson-Khand Reaction. Where there is a lack
of reactivity and/or selectivity in a certain metal-catalyzed or
-mediated process, it is commonplace to tune the stereoelec-
tronics of the catalyst or metal-containing reagent by adjusting
the ligand field to enhance the reactivity or selectivity.
Alternatively, a directing group (often a heteroatom that is
suitably attached on the substrate) could provide a powerful
strategy for enhancing the efficiency of an otherwise sluggish
process and for steering the course of the reaction by taking
advantage of the attractive substrate-catalyst interaction.19
In 1988, Krafft elegantly disclosed that a coordinating
heteroatom such as sulfur or nitrogen tethered to an alkene
counterpart enormously enhanced the regioselectivity and
productivity of the stoichiometric intermolecular PKR.20,21
Since then, extensive efforts have been made toward the
modification of the original Co2(CO)8 catalyst (promoter) to
achieve more efficient and reliable catalytic PKR.9,10 However,
while tremendous progress has been seen for the Co-catalyzed
intramolecular PKR using enynes as substrates,9 the successful
examples of catalytic intermolecular PKR have been limited
to the utilization of strained (reactive) alkenes such as nor-
bornene and norbornadiene or supercritical ethylene.10
The use of transition metals other than cobalt has been another
area of active research. In 1993, Hoye reported a batch-catalytic
protocol for intramolecular PKR using W(CO)5‚THF as a
promoter.11 Buchwald reported that titanocene complexes such
as Cp2Ti(CO)2 could catalyze the intramolecular PKR of
enynes.12 In 1996, the Ni-catalyzed intermolecular PKR was
reported by the same group using isocyanide as a CO equiva-
lent.13,14 In 1997, Murai and Mitsudo independently reported
that the intramolecular PKR of enynes could be catalyzed by
Ru3(CO)12.15 In 1998, Narasaka and Jeong independently
reported that rhodium complexes such as [RhCl(CO)2]2 and
(8) Jeong, N.; Hwang, S. H.; Lee, Y.; Chung, Y. K. J. Am. Chem. Soc. 1994,
116, 3159-3160.
(9) Co-catalyzed intramolecular PKR: (a) Pagenkopf, B. L.; Livinghouse, T.
J. Am. Chem. Soc. 1996, 118, 2285-2286. (b) Belanger, D. B.; O’Mahony,
D. J. R.; Livinghouse, T. Tetrahedron Lett. 1998, 39, 7637-7640. (c)
Belanger, D. B.; Livinghouse, T. Tetrahedron Lett. 1998, 39, 7641-7644.
(d) Krafft, M. E.; Bonaga, L. V. R.; Hirosawa, C. Tetrahedron Lett. 1999,
40, 9171-9175. (e) Comely, A. C.; Gibson, S. E.; Hales, N. J. Chem.
Commun. 2000, 305-306. (f) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe,
I. Tetrahedron Lett. 2000, 41, 891-895. (g) Comely, A. C.; Gibson, S. E.;
Stevenazzi, A.; Hales, N. J. Tetrahedron Lett. 2001, 42, 1183-1185. (h)
Son, S. U.; Lee, S. I.; Chung, Y. K.; Kim, S. W.; Hyeon, T. Org. Lett.
2002, 4, 277-279. (i) Park, K. H.; Son, S. U.; Chung, Y. K. Org. Lett.
2002, 4, 4361-4363. (j) Sturla, S. J.; Buchwald, S. L. J. Org. Chem. 2002,
67, 3398-3403.
(15) (a) Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J. Org. Chem.
1997, 62, 3762-3765. (b) Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T.
J. Am. Chem. Soc. 1997, 119, 6187-6188. Related processes: (c) Chatani,
N.; Morimoto, T.; Fukumoto, Y.; Murai, S. J. Am. Chem. Soc. 1998, 120,
5335-5336. (d) Kang, S. K.; Kim, K. J.; Hong, Y. T. Angew. Chem., Int.
Ed. 2002, 41, 1584-1586.
(10) Recent examples of Co-catalyzed PKR that involve intermolecular reac-
tions: (a) Lee, B. Y.; Chung, Y. K.; Jeong, N.; Lee, Y.; Hwang, S. E. J.
Am. Chem. Soc. 1994, 116, 8793-8794. (b) Costa, M.; Mor, A. Tetrahedron
Lett. 1995, 36, 2867-2870. (c) Lee, N. Y.; Chung, Y. K. Tetrahedron
Lett. 1996, 37, 3145-3148. (d) Jeong, N.; Hwang, S. H.; Lee, Y. W.; Lim,
J. S. J. Am. Chem. Soc. 1997, 119, 10549-10550. (e) Sugihara, T.;
Yamaguchi, M. J. Am. Chem. Soc. 1998, 120, 10782-10783. (f) Kim, J.
W.; Chung, Y. K. Synthesis 1998, 142-144. (g) Sugihara, T.; Yamaguchi,
M. Synlett 1998, 1384-1386. (h) Rajesh, T.; Periasamy, M. Tetrahedron
Lett. 1999, 40, 817-818. (i) Kim, S. W.; Son, S. U.; Lee, S. I.; Hyeon, T.;
Chung, Y. K. J. Am. Chem. Soc. 2000, 122, 1550-1551. (j) Hayashi, M.;
Hashimoto, Y.; Yamamoto, Y.; Usuki, J.; Saigo, K. Angew. Chem., Int.
Ed. 2000, 39, 631-633. (k) Jeong, N.; Hwang, S. H. Angew. Chem., Int.
Ed. 2000, 39, 636-638. (l) Krafft, M. E.; Bon˜aga, L. V. R. Angew. Chem.,
Int. Ed. 2000, 39, 3676-3680. (m) Son, S. U.; Lee, S. I.; Chung, Y. K.
Angew. Chem., Int. Ed. 2000, 39, 4158-4160. (n) Sugihara, T.; Yamaguchi,
M.; Nishizawa, M. Chem. Eur. J. 2001, 7, 1589-1595. (o) Krafft, M. E.;
Bon˜aga, L. V. R.; Hirosawa, C. J. Org. Chem. 2001, 66, 3004-3020. (p)
Gibson, S. E.; Johnstone, C.; Stevenazzi, A. Tetrahedron 2002, 58, 4937-
4942. (q) Fischer, S.; Groth, U.; Jung, M.; Schneider, A. Synlett 2002,
2023-2026. (r) Son, S. U.; Park, K. H.; Chung, Y. K. Org. Lett. 2002, 4,
3983-3986. (s) Blanco-Urgoiti, J.; Casarrubios, L.; Dom´ınguez, G.; Pe´rez-
Castells, J. Tetrahedron Lett. 2002, 43, 5763-5765. (t) Kim, D. H.; Son,
S. U.; Chung, Y. K. Org. Lett. 2003, 5, 3151-3153.
(11) Hoye, T. R.; Suriano, J. A. J. Am. Chem. Soc. 1993, 115, 1154-1156.
(12) (a) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L. J. Am. Chem. Soc.
1996, 118, 9450-9451. (b) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S.
L. J. Am. Chem. Soc. 1999, 121, 5881-5898. (c) Sturla, S. J.; Buchwald,
S. L. Organometallics 2002, 21, 739-748. Enantioselective process: (d)
Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 11688-11689.
(e) Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 7026-
7033. (f) Sturla, S. J.; Buchwald, S. L. J. Org. Chem. 1999, 64, 5547-
5550. Related processes using isocyanide as a CO equivalent: (g) Berk,
S. C.; Grossman, R. B.; Buchwald, S. L. J. Am. Chem. Soc. 1993, 115,
4912-4913. (h) Berk, S. C.; Grossman, R. B.; Buchwald, S. L. J. Am.
Chem. Soc. 1994, 116, 8593-8601. (i) Hicks, F. A.; Berk, S. C.; Buchwald,
S. L. J. Org. Chem. 1996, 61, 2713-2718.
(16) (a) Koga, Y.; Kobayashi, T.; Narasaka, K. Chem. Lett. 1998, 249-250.
(b) Jeong, N.; Lee, S.; Sung, B. K. Organometallics 1998, 17, 3642-3644.
(c) Jeong, N.; Sung, B. K.; Choi, Y. K. J. Am. Chem. Soc. 2000, 122,
6771-6772. (d) Jeong, N.; Seo, S. D.; Shin, J. Y. J. Am. Chem. Soc. 2000,
122, 10220-10221. (e) Kobayashi, T.; Koga, Y.; Narasaka, K. J.
Organomet. Chem. 2001, 624, 73-87. (f) Evans, P. A.; Robinson, J. E. J.
Am. Chem. Soc. 2001, 123, 4609-4610. (g) Jeong, N.; Sung, B. K.; Kim,
J. S.; Park, S. B.; Seo, S. D.; Shin, J. Y.; In, K. Y.; Choi, Y. K. Pure Appl.
Chem. 2002, 74, 85-91. (h) Mukai, C.; Nomura, I.; Yamanishi, K.;
Hanaoka, M. Org. Lett. 2002, 4, 1755-1758. (i) Brummond, K. M.; Chen,
H.; Fisher, K. D.; Kerekes, A. D.; Rickards, B.; Sill, P. C.; Geib, S. J.
Org. Lett. 2002, 4, 1931-1934. (j) Mukai, C.; Nomura, I.; Kitagaki, S. J.
Org. Chem. 2003, 68, 1376-1385. (k) Wender, P. A.; Deschamps, N. M.;
Gamber, G. G. Angew. Chem., Int. Ed. 2003, 42, 1853-1857. (l) Park, K.
H.; Son, S. U.; Chung, Y. K. Tetrahedron Lett. 2003, 44, 2827-2830. (m)
Cao, H.; Mundla, S. R.; Cook, J. M. Tetrahedron Lett. 2003, 44, 6165-
6168.
(17) Rh-catalyzed intramolecular PKR of enynes using an aldehyde as a source
of CO has been reported independently by two groups: (a) Morimoto, T.;
Fuji, K.; Tsutsumi, K.; Kakiuchi, K. J. Am. Chem. Soc. 2002, 124, 3806-
3807. (b) Shibata, T.; Toshida, N.; Takagi, K. Org. Lett. 2002, 4, 1619-
1621. (c) Shibata, T.; Toshida, N.; Takagi, K. J. Org. Chem. 2002, 67,
7446-7450. (d) Fuji, K.; Morimoto, T.; Tsutsumi, K.; Kakiuchi, K. Angew.
Chem., Int. Ed. 2003, 42, 2409-2411.
(18) (a) Shibata, T.; Takagi, K. J. Am. Chem. Soc. 2000, 122, 9852-9853. (b)
Shibata, T.; Kadowaki, S.; Hirase, M.; Takagi, K. Synlett 2003, 573-575.
(19) For excellent reviews on directed chemical reactions, see: (a) Hoveyda,
A. H.; Evans, D. A.; Fu, G. C. Chem. ReV. 1993, 93, 1307-1370. (b) Beak,
P.; Meyers, A. I. Acc. Chem. Res. 1986, 19, 356-363. (c) Snieckus, V.
Chem. ReV. 1990, 90, 879. (d) Beak, P.; Basu, A.; Gallagher, D. J.; Park,
Y. S.; Thayumanavan, S. Acc. Chem. Res. 1996, 29, 552-560. (e) Whisler,
M. C.; MacNeil, S.; Snieckus, V.; Beak, P. Angew. Chem., Int. Ed. 2004,
43, 2206-2225.
(20) (a) Krafft, M. E. J. Am. Chem. Soc. 1988, 110, 968-970. (b) Krafft, M.
E.; Juliano, C. A.; Scott, I. L.; Wright, C.; McEachin, M. D. J. Am. Chem.
Soc. 1991, 113, 1693-1703. (c) Krafft, M. E.; Juliano, C. A. J. Org. Chem.
1992, 57, 5106-5115.
(21) Directed (stoichiometric) intramolecular PKR from the same group: (a)
Krafft, M. E.; Scott, I. L.; Romero, R. H. Tetrahedron Lett. 1992, 33, 3829-
3832. (b) Krafft, M. E.; Scott, I. L.; Romero, R. H.; Feibelmann, S.; Van
Pelt, C. E. J. Am. Chem. Soc. 1993, 115, 7199-7207.
(13) Zhang, M.; Buchwald, S. L. J. Org. Chem. 1996, 61, 4498-4499.
(14) Ni-promoted cyclization of enynes with isocyanides was originally reported
by Ito and Tamao: (a) Tamao, K.; Kobayashi, K.; Ito, Y. J. Am. Chem.
Soc. 1988, 110, 1286-1288. (b) Tamao, K.; Kobayashi, K.; Ito, Y. Synlett
1992, 539-546.
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A R T I C L E S
Itami et al.
Scheme 2
Several control experiments strongly supported that the high
level of regiocontrol is attributed to the attractive cobalt-
heteroatom interactions during the reaction. The occurrence of
such an interaction has been validated recently in the density
functional study of PKR from Nakamura’s laboratory.22,23
Moreover, these attractive cobalt-heteroatom interactions have
been successfully merged into the design of efficient chiral
controllers (chelating auxiliaries) for asymmetric PKR.24 How-
ever, no such directing group strategy has been applied to the
catalytic intermolecular PKR.25 From a synthetic point of view,
a directing group strategy is extremely promising for broadening
the scope of applicable alkenes in catalytic PKR. In addition,
the application of such a strategy to other metal-catalyzed
processes (Ti, Ru, Rh, and Ir) is also intriguing since mono-
metallic (noncluster) mechanisms are often proposed in other
systems.
(CIPE),19 yet the initial product can still be transformed into a
variety of products with removal of the directing group.
Very recently, we reported the [2 + 2 + 1] cycloaddition
reaction of alkenyl(2-pyridyl)silanes, alkynes, and carbon
monoxide under the influence of Ru3(CO)12 catalyst precursor,15
which would represent an important advance in the catalytic
intermolecular Pauson-Khand-type reaction (Scheme 2).30 The
noteworthy features are that (i) it realizes a catalytic intermo-
lecular PKR using unstrained alkenes, which was previously
difficult to achieve; (ii) the pyridylsilyl group is removed from
the product under the reaction conditions in most cases; (iii) it
realizes a complete regioselective incorporation of the alkene
counterpart (the substituent â to the silyl group always occupies
the 4-position in the final 2-cyclopentenone structure); (iv) it
does not require high CO pressure conditions (0.5-1.0 atm is
optimal); and (v) the pretreatment of Ru3(CO)12 and alkenyl-
(2-pyridyl)silane and the slow addition of alkyne are often
required.
Although the synthetic scope of this catalytic intermolecular
PKR and its application to the synthesis of jasmone precursor
were disclosed in our previous paper,30,31 the beneficial effects
of the pyridylsilyl group have not been clarified yet. In view of
the apparent significance of catalytic intermolecular PKR, we
initiated our study aimed at (i) clarifying the role of the
pyridylsilyl group, (ii) developing other promoting groups, and
(iii) isolating Ru complexes relevant to the catalytic reaction.
In this paper, we report on our investigation of this subject.
Catalytic Intermolecular Pauson-Khand-Type Reaction
Directed by Pyridylsilyl Group. During the past few years,
we have been particularly interested in the utilization of the
dimethyl(2-pyridyl)silyl group (2-PyMe2Si group) as a “remov-
able directing group” in metal-catalyzed26 and -mediated27
processes for enhancing the total efficiency of chemical reac-
tions.28,29 In such a strategy, a range of reactions can be directed
through the agency of the complex-induced proximity effect
(22) Yamanaka, M.; Nakamura, E. J. Am. Chem. Soc. 2001, 123, 1703-1708.
(23) For other theoretical studies on PKR, see: (a) Robert, F.; Milet, A.; Gimbert,
Y.; Konya, D.; Greene, A. E. J. Am. Chem. Soc. 2001, 123, 5396-5400.
(b) de Bruin, T. J. M.; Milet, A.; Robert, F.; Gimbert, Y.; Greene, A. E. J.
Am. Chem. Soc. 2001, 123, 7184-7185.
(24) (a) Verdaguer, X.; Moyano, A.; Perica`s, M. A.; Riera, A.; Bernardes, V.;
Greene, A. E.; Alvarez-Larena, A.; Piniella, J. F. J. Am. Chem. Soc. 1994,
116, 2153-2154. (b) Montenegro, E.; Poch, M.; Moyano, A.; Perica`s, M.
A.; Riera, A. Tetrahedron Lett. 1998, 39, 335-338. (c) Verdaguer, X.;
Va´zquez, J.; Fuster, G.; Bernardes-Ge´nisson, V.; Greene, A. E.; Moyano,
A.; Perica`s, M. A.; Riera, A. J. Org. Chem. 1998, 63, 7037-7052. (d)
Montenegro, E.; Moyano, A.; Perica`s, M. A.; Riera, A.; Alvarez-Larena,
A.; Piniella, J. F. Tetrahedron: Asymmetry 1999, 10, 457-471. (e) Hiroi,
K.; Watanabe, T. Tetrahedron Lett. 2000, 41, 3935-3939. (f) Marchueta,
I.; Montenegro, E.; Panov, D.; Poch, M.; Verdaguer, X.; Moyano, A.;
Perica`s, M. A.; Riera, A. J. Org. Chem. 2001, 66, 6400-6409. (g) Adrio,
J.; Carretero, J. C. J. Am. Chem. Soc. 1999, 121, 7411-7412. (h) Rivero,
M. R.; de la Rosa, J. C.; Carretero, J. C. J. Am. Chem. Soc. 2003, 125,
14992-14993.
(25) Though not PKR, Itoh and Yamamoto have found the beneficial effect of
a coordinating atom in several catalytic cycloaddition reactions: (a)
Yamamoto, Y.; Kitahara, H.; Ogawa, R.; Itoh, K. J. Org. Chem. 1998, 63,
9610-9611. (b) Yamamoto, Y.; Kitahara, H.; Ogawa, R.; Kawaguchi, H.;
Tatsumi, K.; Itoh, K. J. Am. Chem. Soc. 2000, 122, 4310-4319.
(26) (a) Itami, K.; Mitsudo, K.; Kamei, T.; Koike, T.; Nokami, T.; Yoshida, J.
J. Am. Chem. Soc. 2000, 122, 12013-12014. (b) Itami, K.; Nokami, T.;
Yoshida, J. J. Am. Chem. Soc. 2001, 123, 5600-5601. (c) Itami, K.; Koike,
T.; Yoshida, J. J. Am. Chem. Soc. 2001, 123, 6957-6958. (d) Itami, K.;
Kamei, T.; Yoshida, J. J. Am. Chem. Soc. 2001, 123, 8773-8779. (e) Itami,
K.; Nokami, T.; Ishimura, Y.; Mitsudo, K.; Kamei, T.; Yoshida, J. J. Am.
Chem. Soc. 2001, 123, 11577-11585. (f) Itami, K.; Mitsudo, K.; Nishino,
A.; Yoshida, J. J. Org. Chem. 2002, 67, 2645-2652. (g) Itami, K.; Kamei,
T.; Mineno, M.; Yoshida, J. Chem. Lett. 2002, 1084-1085. (h) Itami, K.;
Mineno, M.; Kamei, T.; Yoshida, J. Org. Lett. 2002, 4, 3635-3638. (i)
Itami, K.; Kamei, T.; Yoshida, J. J. Am. Chem. Soc. 2003, 125, 14670-
14671.
(27) (a) Itami, K.; Kamei, T.; Mitsudo, K.; Nokami, T.; Yoshida, J. J. Org.
Chem. 2001, 66, 3970-3976. (b) Itami, K.; Nokami, T.; Yoshida, J.
Tetrahedron 2001, 57, 5045-5054. (c) Itami, K.; Mitsudo, K.; Yoshida, J.
Angew. Chem., Int. Ed. 2001, 40, 2337-2339.
(28) For a review, see: Itami, K.; Mitsudo, K.; Nokami, T.; Kamei, T.; Koike,
T.; Yoshida, J. J. Organomet. Chem. 2002, 653, 105-113.
(29) For the use of removable directing groups for metal-catalyzed and -mediated
reactions, see: (a) Evans, D. A.; Fu, G. C.; Hoveyda, A. H. J. Am. Chem.
Soc. 1988, 110, 6917-6918. (b) Breit, B. Eur. J. Org. Chem. 1998, 1123-
1134. (c) Jun, C. H.; Lee, H. J. Am. Chem. Soc. 1999, 121, 880-881. (d)
Breit, B. Chem. Eur. J. 2000, 6, 1519-1524. (e) Ishiyama, T.; Hartwig, J.
J. Am. Chem. Soc. 2000, 122, 12043-12044. (f) Buezo, N. D.; de la Rosa,
J. C.; Priego, J.; Alonso, I.; Carretero, J. C. Chem. Eur. J. 2001, 7, 3890-
3900. (g) Chatani, N.; Tatamidani, H.; Ie, Y.; Kakiuchi, F.; Murai, S. J.
Am. Chem. Soc. 2001, 123, 4849-4850. (h) Krauss, I. J.; Wang, C. C. Y.;
Leighton, J. L. J. Am. Chem. Soc. 2001, 123, 11514-11515. (i) Ko, S.;
Na, Y.; Chang, S. J. Am. Chem. Soc. 2002, 124, 750-751. (j) Jun, C. H.;
Moon, C. W.; Lee, D. Y. Chem. Eur. J. 2002, 8, 2422-2428. (k) Nilsson,
P.; Larhed, M.; Hallberg, A. J. Am. Chem. Soc. 2003, 125, 3430-3431.
Results and Discussion
Effect of Directing Group. As can be easily concluded from
our synthetic study of Ru-catalyzed PKR,30,31 alkenyl(2-pyridyl)-
silanes possess unusually high reactivity toward the catalytic
intermolecular PKR. Although we have been assuming the
coordination effect as an origin of their high reactivity as
mentioned in the previous paper,30 providing direct evidence
for this is rather difficult. Thus, we conducted several control
experiments to provide circumstantial evidence for the directing
effect of the 2-pyridyl group on silicon.
Under the catalytic influence of Ru3(CO)12 (5 mol %), no
reaction occurred with dimethylphenyl(vinyl)silane (eq 1).32 The
addition of pyridine (1.0 equiv) into the reaction system did
not promote the reaction either. Thus, it is obvious that the
(directing) pyridyl group should be attached onto silicon.
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11060 J. AM. CHEM. SOC. VOL. 126, NO. 35, 2004

Catalytic Intermolecular Pauson−Khand-Type Reaction
Table 1. Effect of Directing Groupa
A R T I C L E S
Figure 1. Comparison of vinylic 13C NMR chemical shifts of 1, 2, 3, and
run
vinylsilane
alkyne
temp (°C)
solvent
5 (yield, %)
dimethylphenyl(vinyl)silane in CDCl3.
1
2
3
4
5
6
7
8
1
1
1
1
2
2
2
2
2
2
3
4a
4b
4b
4c
4a
4a
4b
4b
4c
4c
4b
100
100
120
120
100
120
100
120
120
140
100
toluene
toluene
xylenes
xylenes
toluene
xylenes
toluene
xylenes
xylenes
xylenes
toluene
5a (55)
5b (75)
5b (75)
5c (59)
5a (46)
5a (55)
5b (75)
5b (91)
5c (50)
5c (65)
5b (79)
the reactions are performed at higher temperature. However, it
should be mentioned that the reactivity of 2 seems to be slightly
lower than that of 1 in the Ru-catalyzed intermolecular PKR.
The variation of methyl groups on the silicon atom is another
interesting modification of 1. Thus, we prepared diphenyl(2-
pyridyl)vinylsilane 3 and tested it in the Ru-catalyzed PKR.
When 3 was employed in the reaction with 4b, 5b was obtained
in 79% yield at 100 °C (run 11). This implies that 3 is slightly
more reactive than 1 in PKR.
9
10
11
a
These preliminary studies indicate the reactivity order to be
3 g 1 > 2, and the stability order 2 > 1 > 3. Taking these
aspects and the ease of preparation into consideration, the
prototypical 1 is the choice of alkene at this stage. Nevertheless,
the emergence of substantial reactivity by appending the
potentially coordinating heteroaromatic groups lends credence
to our proposal.
Other than the beneficial coordination effect of the pyridyl
and pyrimidyl groups on catalyst ruthenium as we envisioned,
it is also possible to assume that those groups on silicon might
electronically activate the reacting vinyl group at a certain step
of the reaction. Therefore, we compared the vinylic 13C NMR
chemical shifts of 1, 2, 3, and dimethylphenyl(vinyl)silane in
CDCl3 as indices of electron density (Figure 1).33 Although the
13C NMR chemical shifts are influenced by several factors,
comparison within a family is thought to allow a qualitative
evaluation of electron density.34 The minor chemical shift
differences seem to support the notion that the through-bond
electronic activation is not a viable explanation for the high
reactivity of pyridyl- and pyrimidyl-substituted vinylsilanes
toward catalytic PKR.
We next examined the catalytic intermolecular PKR using
the congeners of dimethyl(2-pyridyl)(vinyl)silane 1 (vinylsilanes
with a potentially directing heteroaromatic group on silicon) to
advocate the proposed directed PKR scenario (Table 1). As for
alkynes for this study, we selected phenylacetylene (4a),
1-phenylpropyne (4b), and 4-octyne (4c). The reactions using
prototypical 1 were first examined (runs 1-4). The reaction of
1 with 4a gave cyclopentenone 5a in 55% yield at 100 °C (run
1). The reaction using 4b furnished 5b in 75% yield at 100 °C
(run 2). Raising the temperature had little effect on the chemical
yield (75% at 120 °C) for these substrates (run 3).
Next, we prepared the 2-pyrimidyl analogue 2 and tested it
in the Ru-catalyzed PKR (runs 5-10). When 4a was subjected
to reaction with 2, 5a was obtained in 46% yield at 100 °C
(run 5). The yield was lower than that obtained when 1 was
employed as an alkene (run 2). However, at higher temperature
(120 °C), 5a could be obtained in slightly higher yield (55%,
run 6). When 4b was employed in the reaction with 2, 5b was
obtained in 75% yield at 100 °C (run 7). At higher temperature
(120 °C), 5b could be obtained in 91% yield (run 8). The
reaction using 4c furnished 5c in 50% yield at 120 °C (run 9).
Similarly, 5c was obtained in higher yield (65%) at higher
temperature (140 °C, run 10). Throughout these reactions using
2, we observed obvious phenomena that cannot be seen in the
reactions using 1. In many cases, a significant amount of the
starting material (2) was recovered even after prolonged reaction
time (24 h). These results clearly implicate that 2 is more stable
than 1 under the reaction conditions, thereby allowing us to
conduct the reaction under more forcing conditions. Indeed, the
chemical yields of 5 using 2 are higher than those using 1 when
Synthesis and Structure of Mononuclear Ru(vinylsilane)
Complexes. To get further insight into the role of the pyridyl
and pyrimidyl groups, we conducted the stoichiometric reaction
of vinylsilanes (1, 2, and 3) with Ru3(CO)12. The treatment of
1 (5.0 mmol) and Ru3(CO)12 (1.0 mmol) in toluene (30 mL) at
100 °C for 24 h furnished the Ru(vinylsilane) complex 6 (eq
2). The excess 1 was recovered from the reaction mixture.
Subjection of the crude mixture to gel permeation chromatog-
raphy (CHCl3) afforded 6 in 59% yield. Similarly, the reactions
using 2 and 3 gave the corresponding Ru(vinylsilane) complexes
7 and 8 in 46% and 68% yield, respectively (eq 2). No such
complex was obtained by the treatment of Ru3(CO)12 with
dimethylphenyl(vinyl)silane under similar conditions.
(30) Itami, K.; Mitsudo, K.; Yoshida, J. Angew. Chem., Int. Ed. 2002, 41, 3481.
(31) See Supporting Information for the synthetic scope (including the previous
published materials) of the Ru-catalyzed intermolecular PKR.
(32) Under identical conditions, the reaction of dimethyl(2-pyridyl)(vinyl)silane
(1) and phenylacetylene (4a) furnished 2-phenyl-2-cyclopentenone (5a) in
55% yield.
9
J. AM. CHEM. SOC. VOL. 126, NO. 35, 2004 11061

A R T I C L E S
Itami et al.
that the σ-donor ligands occupy the apical positions and the
π-accepting ligands occupy the equatorial positions.37 The
vinylic CdC bond lies approximately in the equatorial plane.
Overall, the structure of 6 is similar (bond lengths, bond angles,
and torsion angles) to that of the PdCl2(1) complex prepared
previously from our laboratory.26e It should also be mentioned
that the complexes 6-8 are stable to air and moisture (even
stable to silica gel chromatography and gel permeation chro-
matography), which is in contrast to other Ru(0)-olefin
complexes. This may be a consequence of two factors: (i) the
presence of a nitrogen donor, which should favor metal-olefin
π back-bonding, and (ii) the presence of vinyl-N chelation,
which should reduce the tendency toward olefin dissociation.
Reactivity of Ru(vinylsilane) Complexes. The reactivity of
Ru(vinylsilane) complexes toward PKR is of great interest from
a mechanistic point of view. Upon heating a toluene solution
of 6 (1.0 equiv) and 4b (1.5 equiv) under argon at 100 °C for
24 h, cyclopentenone 5b was obtained in 62% isolated yield
(eq 3). The complete regioselectivity observed in the catalytic
reaction was also maintained. Subjection of other Ru(vinylsilane)
complexes 7 and 8 to the identical conditions afforded 5b in
52% and 70% yield, respectively. The reactivity order (8 > 6
> 7) was in a good correlation to that observed in the catalytic
reactions (Table 1, runs 1, 5, and 11). These stoichiometric
reactions are extremely interesting because they might be
relevant to our catalytic intermolecular PKR. These results
clearly indicate that the reaction pathway through a mononuclear
Ru complex is feasible though trinuclear Ru3(CO)12 is employed
as the catalyst precursor at the beginning.
Figure 2. Structure of 6. Thermal ellipsoids are drawn at the 40%
probability level. The hydrogen atoms are omitted for clarity. Selected bond
lengths (Å): Ru-N ) 2.184(6), Ru-C1 ) 2.182(9), Ru-C2 ) 2.184(8),
Ru-C10 ) 1.92(1), Ru-C11 ) 1.94(1), Ru-C12 ) 1.86(1), C1-C2 )
1.38(1), C10-O1 ) 1.12(1), C11-O2 ) 1.15(1), C12-O3 ) 1.19(1).
Selected bond angles (deg): N-Ru-C1 ) 86.5(3), N-Ru-C2 ) 85.2(3),
N-Ru-C10 ) 93.1(3), N-Ru-C11 ) 89.0(3), N-Ru-C12 ) 175.9(3),
C1-Ru-C2 ) 36.8(3), Ru-C1-C2 ) 71.7(5), Ru-C2-C1 ) 71.5(5).
Selected torsion angles (deg): N-Ru-C2-Si ) 28.9(1), Ru-C2-Si-C5
) 32.8(1), C2-Si-C5-N ) 21.4(2), Si-C5-N-Ru ) -0.5(9), C1-
Ru-N-C5 ) -55.0(1), Ru-C1-C2-Si ) -99.9(9).
1
In the H NMR spectra, the presence of an η2-complexed
CH2dCH fragment was shown by three equal intensity reso-
nances at δ 1-3 ppm (δ 1.18 dd, 1.77 dd, 2.62 dd for 6). These
resonances have chemical shifts similar to those found in other
(η2-olefin)Ru(0) complexes,35 but are quite distinct from those
of a noncomplexed vinyl group of vinylsilanes, which appear
at lower fields (δ 5.5-6.5). The additional coordination of the
pyridyl and pyrimidyl groups to Ru was also indicated by the
noticeable changes in the NMR chemical shifts. The two
nonequivalent methyl groups on silicon (for 6 and 7) in the 1H
and 13C NMR spectra were consistent with the assumed vinyl-N
chelation to Ru. Moreover, the three nonequivalent CO carbons
(δ 201.3, 203.3, 205.1 for 6) in the 13C NMR spectra were also
in line with the structure shown in eq 2. A similar structure
was assumed for the Ru(CO)2(o-CH2dCHC6H4PPh2) complex
prepared by Bennett.36
Although complex 6 is soluble in most organic solvents, it
was possible to obtain a single crystal suitable for X-ray crystal
structure analysis by leaving a concentrated CHCl3 solution of
6 to stand in refrigerator. An ORTEP diagram of 6 is shown in
Figure 2. Complex 6 has an approximately trigonal-bipyramidal
ligand arrangement, with the vinyl group and two CO groups
in equatorial positions and the pyridyl nitrogen and one CO in
apical positions. This is in line with the general observation
In addition, it should be mentioned that the reactions depicted
in eq 3 represent an unusual type of stoichiometric PKR.
Conventionally, the stoichiometric PKR has been performed
through (i) a precomplexation of an alkyne and a metal carbonyl
fragment [usually Co2(CO)6] and (ii) subsequent reaction with
an excess amount of an alkene (Scheme 3). On the other hand,
the stoichiometric reactions demonstrated in eq 3 proceed in a
reverse mode to the conventional PKR with respect to the
precomplexation component (alkyne f alkene). To our knowl-
Scheme 3
(33) Tamao, K.; Kanatani, R.; Kumada, M. Tetrahedron Lett. 1984, 25, 1905-
1908.
(34) (a) Sardella, D. J. J. Am. Chem. Soc. 1973, 95, 3809-3811. (b) Happ, B.;
Bartik, T.; Zucchi, C.; Rossi, M. C.; Ghelfi, F.; Pa´lyi, G.; Va´radi, G.;
Szalontai, G.; Horva´th, I. T.; Chiesi-Villa, A.; Guastini, C. Organometallics
1995, 14, 809-819. (c) Alami, M.; Liron, F.; Gervais, M.; Peyrat, J. F.;
Brion, J. D. Angew. Chem., Int. Ed. 2002, 41, 1578-1580.
(35) (a) Grevels, F. W.; Reuvers, J. G. A.; Takats, J. J. Am. Chem. Soc. 1981,
103, 4069-4073. (b) Helliwell, M.; Vessey, J. D.; Mawby, R. J. J. Chem.
Soc., Dalton Trans. 1994, 1193-1205.
(36) Bennett, M. A.; Johnson, R. N.; Tomkins, I. B. J. Am. Chem. Soc. 1974,
96, 61-69.
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11062 J. AM. CHEM. SOC. VOL. 126, NO. 35, 2004

Catalytic Intermolecular Pauson−Khand-Type Reaction
A R T I C L E S
Table 2. Catalytic PKR of 1 with 4 Using Ru Complex 6
run
Ru complex
alkyne
time (h)
5 (yield, %)
1a
2b
3a
4b
5a
6b
6
4a
4a
4b
4b
4b
4b
24
24
24
24
3
5a (56)
5a (55)
5b (71)
5b (75)
5b (72)
5b (17)
Ru3(CO)12
6
Ru3(CO)12
6
Ru3(CO)12
3
a 15 mol % of Ru complex was employed. b 5 mol % of Ru3(CO)12 (15
mol % Ru atom) was employed.
edge, such a stoichiometric PKR has not been reported in the
literature. This may be partly because of the low coordination
ability of usual alkenes compared with that of alkynes or carbon
monoxide. The need of an excess amount of alkene in the
conventional PKR reflects these aspects. Therefore, it may be
reasonable to assume that the strong coordinating ability of
vinyl(2-pyridyl)silane (through vinyl-N chelation) leads to the
realization of such a stoichiometric PKR.
Figure 3. NMR spectra of 9. (a) Representative proton and carbon (italics)
NMR assignments. (b) Representative correlations established by HMBC
(arrows) and NOESY (dotted arrow) experiments.
treatment with 4b (1.03 equiv) in toluene at 50 °C for 1.5 h (eq
4). Because further heating of this solution at 100 °C afforded
5b, we assume this new complex to be ruthenacyclopentene 9,
which might also be involved in the catalytic cycle.38
Moreover, we found that the Ru(vinylsilane) complex 6 serves
not only as a reagent but also as a catalyst precursor for
intermolecular PKR of 1 (Table 2). Thus, in the presence of a
catalytic amount of 6 (15 mol %), intermolecular PKR of 1
and 4a proceeded to afford 5a in 56% yield (run 1). Similarly,
the reactions using 4b afforded the corresponding cyclopen-
tenones 5b in 71% yield (run 3). In both cases, the yields of 5
were quite similar to those obtained from Ru3(CO)12 (15 mol
% Ru atom) under otherwise identical conditions (runs 2 and
4). This Ru(vinylsilane) complex 6 turned out to be the second
active catalyst (precursor) in our intermolecular PKR. Interest-
ingly, we found that the catalytic reaction using 6 proceeds much
faster than that using Ru3(CO)12 at the early stage of reaction
(runs 5 and 6), although the product yields after prolonged
reaction time (24 h) are similar (runs 3 and 4). These results
suggest the presence of an induction period in the reaction using
Ru3(CO)12, most likely to generate catalytically active Ru-
(vinylsilane) complex. Nevertheless, these results of stoichio-
metric and catalytic reactions (eq 3 and Table 2) suggest that
the mononuclear Ru complex 6 might be involved in the
catalytic cycle of PKR using vinyl(2-pyridyl)silane 1.
The representative NMR assignments of 9 (protons and
carbons) are shown in Figure 3a, and followings are some
comparisons of its NMR chemical shifts with those of Ru-
(vinylsilane) complex 6 and free vinylsilane 1: (i) All 13C
resonances of pyridine rings in 6 and 9 appear at lower field
compared to those of free vinylsilane 1, which is in line with
the pyridyl-to-Ru coordination in complexes 6 and 9. (ii) The
13C resonances of the carbon R to silicon (derived from the
R-vinyl carbon of 1) appear in the order of 9 (19.5 ppm) < 6
(27.6 ppm) < 1 (136.8 ppm), which is in parallel with a decrease
of s-character of the R-carbon. (iii) Similarly, the 13C resonance
of the carbon â to silicon in 9 appears at higher field (47.6
ppm) compared to that of 1 (133.4 ppm), again reflecting a
decrease of s-character of this carbon. The appearance of this
carbon in lower field compared with that of 6 (34.9 ppm) may
be due to the allylic nature of this carbon in 9. (iv) The 13C
carbonyl resonances of 9 appear at slightly higher field (190.6,
194.7, 199.7 ppm) compared to those of 6 (201.3, 203.3, 205.1
ppm), which is in parallel with a decrease in Ru f π*(CO)
back-donation.
Isolation of Ruthenacyclopentene 9. While investigating the
reaction of Ru(vinylsilane) complex 6 and alkyne 4b with NMR,
we found an obvious generation of a new Ru complex before
the formation of cyclopentenone 5b. After several experiments,
we found that 6 is quantitatively converted to this complex by
Though it was not possible to obtain a single crystal of 9
suitable for X-ray crystal structure analysis, extensive NMR
experiments (COSY, NOESY, HMQC, and HMBC) revealed
its structure to be in line with that shown in eq 4. Important
correlations established by HMBC and NOESY experiments
are shown in Figure 3b. These experiments unambiguously
elucidated the bond formation between the alkyne and vinyl-
silane moieties in the ruthenacyclopentene 9.
(37) Rossi, A. R.; Hoffmann, R. Inorg. Chem. 1975, 14, 365-374.
(38) Selected examples for the isolation of late-metal metallacyclopentenes
relevant to transition-metal-catalyzed reactions: (a) Wakatsuki, Y.; Aoki,
K.; Yamazaki, H. J. Am. Chem. Soc. 1979, 101, 1123-1130. (b) Scozzafava,
M.; Stolzenberg, A. M. Organometallics 1988, 7, 1073-1083. (c)
O’Connor, J. M.; Closson, A.; Gantzel, P. J. Am. Chem. Soc. 2002, 124,
2434-2435.
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A R T I C L E S
Itami et al.
This may be the rare example that succeeded in isolating
multiple metal complexes relevant to the catalytic cycle in metal-
catalyzed cycloaddition chemistry. Moreover, it should be noted
that these experiments clearly revealed that the rate-determining
step is not the formation of the metallacycle intermediate
(oxidative cyclization step; 6 f 9), which proceeds at 50 °C,
but rather the formation of the Ru(olefin) complex (such as 6)
and/or the later steps (carbonyl insertion and reductive elimina-
tion) that require higher temperature (>100 °C). As in the case
of Ru(vinylsilane) complex 6, this ruthenacyclopentene 9 was
also found to serve as a catalyst (precursor) in the intermolecular
PKR of 1 and 4b, yielding the corresponding cyclopentenone
5b in 52% yield (eq 5).
Mechanistic Considerations. A plausible mechanism of the
Ru-catalyzed [2 + 2 + 1] cycloaddition of alkenyl(2-pyridyl)-
silane, alkyne, and carbon monoxide is depicted in Figure 4.
The reaction is thought to begin with the formation of
Ru(alkenylsilane) complex A. The successive coordination of
an alkyne leads to the formation of Ru(alkyne)(alkenylsilane)
complex B, which undergoes a typical oxidative cyclization
process to produce ruthenacyclopentene intermediate C. A
migratory insertion of a carbon monoxide ligand into the
C(sp2)-Ru bond produces the six-membered ruthenacycle
intermediate D. Although an alternative mechanism that involves
a migratory insertion into the C(sp3)-Ru bond may also be
plausible, we prefer the former simply because it retains the
strong pyridyl-to-ruthenium complexation. Finally, reductive
elimination furnishes the silylated cyclopentenone F and “Ru-
(CO)n” complex E, which should be trapped by alkenyl(2-
pyridyl)silane to regenerate Ru(alkenylsilane) complex A. The
in situ desilylation of F produces G as the final product. It must
be noted that an alternative mechanism that involves the initial
coordination of an alkyne to Ru, followed by the coordination
of alkenylsilane to give Ru(alkyne)(alkenylsilane) complex B,
cannot be strictly ruled out at present.
As for the catalytically active metal species, we speculate
those to be nonclustered monometallic Ru complexes rather than
clustered multimetallic metal complexes (like the Co2(CO)8-
mediated PKR). The following observations are in line with
this assumption: (i) Significant improvement of reaction ef-
ficiency is observed by the pretreatment of clustered Ru3(CO)12
with alkenyl(2-pyridyl)silane (Scheme 2). (ii) Such a pretreat-
ment most likely produces a monometallic Ru(alkenylsilane)
complex A. (iii) The monometallic Ru(alkenylsilane) complex
A exhibits reasonable reactivity both as reagent and as catalyst
precursor (eq 3 and Table 2).
Figure 4. A plausible mechanism.
alkene counterpart, thereby making it capable of competing with
alkyne and carbon monoxide for a coordination site on the metal
(A and B). The well-balanced coordination abilities are ex-
tremely important for the realization of catalytic multicomponent
assembly.
(2) In addition to the kinetic preference mentioned above,
the stabilization of the metallacycle intermediate (C) by
complexation with the suitably positioned pyridyl (or pyrimidyl)
group might also contribute to accelerating the rate-determining
oxidative cyclization step (B f C).22 We indeed found this to
be true by the stoichiometric reaction of Ru(vinylsilane) complex
6 with alkyne 4b (eq 4).
The complete regioselective incorporation of the alkene
subunit in this catalytic intermolecular PKR is worth mentioning.
The use of R- or â-substituted vinylsilane results in the
regioselective production of substituted cyclopentenones with
the substituent at the 5- or 4-position, respectively (G in Figure
4).30,31 This is clearly implicated in the regioselective formation
of metallacyclopentene intermediate C. During these studies,
we have been assuming that the formation of metallacyclopen-
tene from alkyne, alkene, and low-valent metal (oxidative
cyclization) may be regarded as a carbometalation reaction of
an (alkyne)metal complex across an alkene (B f C). Indeed,
in accord with this assumption, there are many examples
indicating that the metallacycle formation occurs preferentially
at the most electropositive terminus of the alkene.39 Recent
studies from our laboratory clearly indicated that the carbo-
metalation (carbopalladation26a,e and carbomagnesation27c) across
alkenyl(2-pyridyl)silane is extremely facile and regioselective
The following aspects may be the reasons for the realization
of a hard-to-achieve catalytic, intermolecular, and regioselective
Pauson-Khand-type reaction when alkenyl(2-pyridyl)silanes or
alkenyl(2-pyrimidyl)silanes are used as alkene components.
(1) The suitably positioned pyridyl (or pyrimidyl) group
should help the reacting CdC bond to coordinate to metal center
through pre-coordination (complex-induced proximity effect).
This should greatly enhance the coordinating aptitude of the
(39) (a) Pauson, P. L. Tetrahedron 1985, 41, 5855-5860. (b) La Belle, B. E.;
Knudsen, M. J.; Olmstead, M. M.; Hope, H.; Yanuck, M. D.; Schore, N.
E. J. Org. Chem. 1985, 50, 5215-5222. (c) Sampath, V.; Lund, E. C.;
Knudsen, M. J.; Olmstead, M. M.; Schore, N. E. J. Org. Chem. 1987, 52,
3595-3603. (d) MacWhorter, S. E.; Sampath, V.; Olmstead, M. M.; Schore,
N. E. J. Org. Chem. 1988, 53, 203-205. (e) Ahmar, M.; Antras, F.; Cazes,
B. Tetrahedron Lett. 1999, 40, 5503-5506. (f) Reference 10b.
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11064 J. AM. CHEM. SOC. VOL. 126, NO. 35, 2004

Catalytic Intermolecular Pauson−Khand-Type Reaction
A R T I C L E S
0.9 Hz, 1H), 7.56 (td, J ) 7.8, 1.5 Hz, 1H), 8.72 (dt, J ) 5.7, 1.2 Hz,
1H). 13C NMR (75 MHz, CDCl3): δ -2.0, 0.7, 27.6, 34.9, 123.8, 131.4,
135.2, 155.4, 172.4, 201.3, 203.3, 205.1. IR (neat): 1945, 1460, 1281,
1248 cm-1. HRMS (FAB): m/z calcd for C12H13NO3SiRu, 348.9711;
found, 348.9707. X-ray data for 6: C12H13NO3SiRu, M ) 348.40,
triclinic, space group P1h (No. 2), a ) 8.9301 Å, b ) 9.493(1) Å, c )
9.7181(1) Å, R ) 71.094(8)°, â ) 82.6320(3)°, γ ) 73.3640(4)°, V )
746.20(7) Å3, Z ) 2, Dc ) 1.55 g/cm3, µ ) 11.29 cm-1. Intensity data
were measured on a Rigaku RAXIS imaging plate area detector with
graphite-monochromated Mo KR radiation. The data were collected at
23 ( 1 °C to a maximum 2θ value of 54.9°. A total of 3102 reflections
were collected. The structure was solved by heavy-atom Patterson
methods and expanded using Fourier techniques. The non-hydrogen
atoms were refined anisotropically. Hydrogen atoms were refined
isotropically. The final cycle of full-matrix least-squares refinement
on F was based on 2534 observed reflections (I > 3.00σ(I)) and 177
variable parameters and converged (largest parameter shift was 0.00
times its esd) with unweighted and weighted agreement factors of R )
0.059 (Rw ) 0.066). All calculations were performed using the
CrystalStructure crystallographic software package.
because of the strong complex-induced proximity effect of the
pyridyl group on silicon, together with the inherent silicon R
effect.
As is apparent from the regioselective incorporation of
substituents on alkenylsilane, the pyridylsilyl group should be
incorporated in the 5-position of the initially formed 2-cyclo-
pentenone (F). However, in most cases, such silylated cyclo-
pentenones F were not observed in the reaction mixture. We
assume that the desilylation occurs by hydrolysis of the silyl
enolate, which is produced by the [1,3]-silyl migration of
5-silylcyclopenten-2-one F.40 In line with these assumptions,
we detected the pyridyl-substituted disiloxane (product derived
from the corresponding silanol produced by hydrolysis) in the
mass spectrum of the reaction mixture. Moreover, we also found
that the addition of D2O (2.0 equiv) in the reaction of 1 and 4b
resulted in the regioselective incorporation of deuterium at the
5-position (eq 6). This result suggests that (i) the source of the
hydrogen atom is residual water contained in the reaction
mixture and (ii) vinylsilane 1 is incorporated in the cyclopen-
tenone skeleton in a regioselective fashion (at the 5-position).
Conclusions
In conclusion, we have succeeded in providing some cir-
cumstantial evidence for the directing effect of the 2-pyridylsilyl
group in the Ru-catalyzed intermolecular Pauson-Khand-type
reaction of alkenyl(2-pyridyl)silane, alkyne, and carbon mon-
oxide. Other than the prototypical dimethyl(2-pyridyl)silyl
group, dimethyl(2-pyrimidyl)silyl and diphenyl(2-pyridyl)silyl
groups have been developed as new removable directing groups
for catalytic intermolecular PKR. From the 13C NMR study of
several reactive and unreactive vinylsilanes, the through-bond
electronic activation seems not to be a viable explanation for
the promoting effect of pyridylsilyl and pyrimidylsilyl groups.
Most importantly, we have succeeded in isolating several
monometallic Ru complexes relevant to catalytic intermolecular
PKR: Ru(vinylsilane) complexes (6-8) and ruthenacyclopen-
tene 9. The reaction of Ru3(CO)12 with vinyl(2-pyridyl)silanes
and vinyl(2-pyrimidyl)silanes produces the nonclustered mono-
metallic Ru(vinylsilane)(CO)3 complexes 6-8. While the
stoichiometric reactions of Ru(vinylsilane)(CO)3 complexes 6-8
with alkynes 4 led to the formation of the corresponding
cyclopentenones 5 at 100 °C, the ruthenacyclopentene inter-
mediate 9 was quantitatively produced at 50 °C (from 6 and
4b). This complex was also converted to a cyclopentenone 5
upon heating at 100 °C. Moreover, it was found that Ru-
(vinylsilane)(CO)3 complex 6 and ruthenacyclopentene 9 also
serve as catalyst precursors in intermolecular PKR. Taking all
these results into account, we assume these complexes (6-9)
to be involved in the catalytic cycle of intermolecular PKR.
Experimental Section
General Method. See the Supporting Information.
Synthetic Scope of Ru-Catalyzed Intermolecular Pauson-Khand-
Type Reaction of Alkenyl(2-pyridyl)silane with Alkyne. See the
Supporting Information.
Synthesis of Starting Materials. See the Supporting Information.
Typical Procedure for Ru-Catalyzed Intermolecular Pauson-
Khand-Type Reaction of Vinyl(2-pyridyl)silane or Vinyl(2-pyrim-
idyl)silane with Alkyne. A suspension of Ru3(CO)12 (16 mg, 0.025
mmol, 5 mol %) and vinylsilane (0.50 mmol) in toluene (1.5 mL) was
stirred at 100 °C for 10 min under CO (1 atm). To this mixture was
added alkyne (0.75 mmol) over 3 h at 100 °C, and the mixture was
stirred for 24 h. After the mixture was cooled to room temperature, 1
N aqueous HCl (1 mL) was added, and the organic phase was extracted
with Et2O (3 × 2 mL). The aqueous phase was neutralized by adding
NaHCO3 and then was extracted with Et2O (3 × 2 mL). The combined
organic phase was dried over MgSO4, and removal of solvents under
reduced pressure afforded the crude product. The residue was chro-
matographed on silica gel to afford 5.
Ru(vinylsilane) Complex 6. To a suspension of Ru3(CO)12 (662.7
mg, 1.04 mmol) in dry toluene (20 mL) was added a solution of 1
(791.2 mg, 5.00 mmol) in dry toluene (10 mL). After the mixture was
stirred at 100 °C for 24 h, the solvent was removed under vacuum.
Subjection of the crude mixture to gel permeation chromatography
In view of the apparent significance of catalytic intermolecular
PKR, the present findings not only allow us to better understand
the high reactivity of alkenyl(2-pyridyl)silanes and alkenyl(2-
pyrimidyl)silanes in PKR, but also help us to design more
efficient and/or strategic PKR in organic synthesis. In particular,
the “removable directing group strategy” demonstrated herein
should find many applications, and the evolution of other
functional groups of this type would be easily accomplished
by a relatively straightforward design.
1
(CHCl3) afforded 6 (639.5 mg, 59%) as a pale yellow oil. H NMR
(300 MHz, CDCl3): δ 0.38 (s, 3H), 0.41 (s, 3H), 1.18 (dd, J ) 13.2,
1.5 Hz, 1H), 1.77 (dd, J ) 13.2, 11.1 Hz, 1H), 2.62 (dd, J ) 11.1, 1.5
Hz, 1H), 7.05 (ddd, J ) 7.8, 5.7, 1.5 Hz, 1H), 7.35 (ddd, J ) 7.8, 1.5,
(40) Similar desilylation of the 2-PyMe2Si group R to the carbonyl group was
observed during the course of our investigation of Migita-Kosugi-Stille
coupling reactions using 2-PyMe2SiCH2SnBu3.26d Namely, the Pd-catalyzed
coupling reaction of 2-PyMe2SiCH2SnBu3 with acid chloride produced the
corresponding methyl ketone exclusively (unpublished results). Moreover,
we have also discovered that the oxophilicity of the 2-PyMe2Si group is
substantially higher than that of the PhMe2Si group,27b which should render
this isomerization easier.
Acknowledgment. This work was supported by a Grant-in-
Aid for Scientific Research from the Ministry of Education,
Culture, Sports, Science, and Technology, Japan.
9
J. AM. CHEM. SOC. VOL. 126, NO. 35, 2004 11065

A R T I C L E S
Itami et al.
Supporting Information Available: Synthetic scope of the
Ru-catalyzed intermolecular PKR; experimental procedures and
analytical and spectroscopic data of compounds (PDF). X-ray
crystallographic data (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
JA047484+
9
11066 J. AM. CHEM. SOC. VOL. 126, NO. 35, 2004