Ruthenium- and platinum-catalyzed sequential reactions: Selective synthesis of fused polycyclic compounds from propargylic alcohols and alkenes

Article abstract of DOI:10.1021/ja045532k

A simple method for the preparation of fused polycyclic compounds by an intramolecular cyclization of propargylic alcohols bearing an alkene moiety at a suitable position has been developed, where the presence of both Ru and Pt catalysts promotes a sequence of catalytic cycles in the same medium. This sequential system can be applied to an intermolecular reaction between a propargylic alcohol and an alkene to obtain the corresponding bicyclo[3,1,0]hex-2-ene derivative. These sequential reactions provide a conceptually new type of cycloaddition system between propargylic alcohols and alkenes.

Full text of DOI:10.1021/ja045532k

Published on Web 11/18/2004
Ruthenium- and Platinum-Catalyzed Sequential Reactions:
Selective Synthesis of Fused Polycyclic Compounds from
Propargylic Alcohols and Alkenes
Yoshiaki Nishibayashi,*,† Masato Yoshikawa,† Youichi Inada,† Masanobu Hidai,‡ and
Sakae Uemura*,†
Contribution from the Department of Energy and Hydrocarbon Chemistry, Graduate School of
Engineering, Kyoto UniVersity, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan, and
Department of Materials Science and Technology, Faculty of Industrial Science and Technology,
Tokyo UniVersity of Science, Noda, Chiba 278-8510, Japan
Received July 25, 2004; E-mail: ynishiba@scl.kyoto-u.ac.jp; uemura@scl.kyoto-u.ac.jp
Abstract: A simple method for the preparation of fused polycyclic compounds by an intramolecular
cyclization of propargylic alcohols bearing an alkene moiety at a suitable position has been developed,
where the presence of both Ru and Pt catalysts promotes a sequence of catalytic cycles in the same
medium. This sequential system can be applied to an intermolecular reaction between a propargylic alcohol
and an alkene to obtain the corresponding bicyclo[3,1,0]hex-2-ene derivative. These sequential reactions
provide a conceptually new type of cycloaddition system between propargylic alcohols and alkenes.
finding1 prompted us to develop catalytic sequential reactions
of such type to synthesize complex organic molecules from
Introduction
Quite recently, we have disclosed that the ruthenium- and
platinum-catalyzed sequential reactions of propargylic alcohols
with ketones or with both ketones and anilines afforded the
corresponding tri- and tetra-substituted furans or pyrroles,
respectively, in moderate to good yields with a high regiose-
lectivity.1 It is noteworthy that, in this catalytic reaction system,
both ruthenium and platinum catalysts sequentially promote each
catalytic cycle in the same medium. Although some interesting
results in which multiple and different transition metal catalysts
work in the same medium have already been reported,2 in most
cases, the reaction conditions such as temperature and atmo-
sphere had to be changed on the way, or successive addition of
the catalyst was necessary in each reaction step.3 Our previous
simple and readily available starting materials. Toward this end,
our attention has been focused on the platinum-catalyzed
cycloisomerization of enyne systems,4 as we have already
disclosed the preparative method of some enynes by the
ruthenium-catalyzed carbon-carbon bond forming reaction
between propargylic alcohols and alkenes.5 This combination
may provide a simple and one-pot synthetic protocol for fused
polycyclic compounds directly from propargylic alcohols and
alkenes, the first and second steps being propargylic substitution
and cycloisomerization, respectively. Although many fused poly-
cyclic compounds especially those containing cyclopropane
moiety show biological activity and are widely recognized as
potential drug leads,6 the direct approach to the synthesis of
such compounds is yet quite limited.7 In addition, this sequential
† Kyoto University.
‡ Tokyo University of Science.
(4) (a) Chatani, N.; Furukawa, N.; Sakurai, H.; Murai, S. Organometallics 1996,
15, 901. (b) Chatani, N.; Kataoka, K.; Murai, S.; Furukawa, N.; Seki, Y.
J. Am. Chem. Soc. 1998, 120, 9104. (c) Fu¨rstner, A.; Szillat, H.; Gabor,
B.; Mynott, R. J. Am. Chem. Soc. 1998, 120, 8305. (d) Fu¨rstner, A.; Szillat,
H.; Stelzaer, F. J. Am. Chem. Soc. 2000, 122, 6785. (e) Fu¨rstner, A.;
Stelzaer, F.; Szillat, H. J. Am. Chem. Soc. 2001, 123, 11863. (f) Me´ndez,
M.; Mun˜oz, M. P.; Echavarren, A. M. J. Am. Chem. Soc. 2000, 122, 11549.
(g) Me´ndez, M.; Mun˜oz, M. P.; Nevado, C.; Ca´rdenas, D. J.; Echavarren,
A. M. J. Am. Chem. Soc. 2001, 123, 10511. (h) Mart´ın-Matute, B.; Nevado,
C.; Ca´rdenas, D. J.; Echavarren, A. M. J. Am. Chem. Soc. 2003, 125, 5757.
(i) Nevado, C.; Ca´rdenas, D. J.; Echavarren, A. M. Chem.-Eur. J. 2003, 9,
2627. (j) Cadran, N.; Cariou, K.; Herve´, G.; Aubert, C.; Fensterbank, L.;
Malacria, M.; Marco-Contelles, J. J. Am. Chem. Soc. 2004, 126, 3408. (k)
Mamane, V.; Gress, T.; Krause, H.; Fu¨rstner, A. J. Am. Chem. Soc. 2004,
126, 8654. (l) Harrak, Y.; Blaszykowski, C.; Bernard, M.; Cariou, K.;
Mainetti, E.; Mourie´s, V.; Dhimane, A.-L.; Fensterbank, L.; Malacria, M.
J. Am. Chem. Soc. 2004, 126, 8656. (m) Luzung, M. R.; Markham, J. P.;
Toste, F. D. J. Am. Chem. Soc. 2004, 126, 10858. (n) Nieto-Oberhuber,
C.; Mun˜oz, M. P.; Bun˜uel, E.; Nevado, C.; Ca´rdenas, D. J.; Echavarren,
A. M. Angew. Chem., Int. Ed. 2004, 43, 2402. (o) Diver, S. T.; Giessert,
A. Chem. ReV. 2004, 104, 1317 and references therein. (p) An˜orbe, L.;
Dom´ınguez, Pe´rez-Castells, J. Chem. Eur. J., in press and references therein.
(5) Nishibayashi, Y.; Inada, Y.; Hidai, M.; Uemura, S. J. Am. Chem. Soc. 2003,
125, 6060.
(1) Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.; Milton, M. D.; Hidai, M.;
Uemura, S. Angew. Chem., Int. Ed. 2003, 42, 2681.
(2) For recent examples: examples where two catalysts activated different
functional groups in the same medium, see: (a) Sawamura, M.; Sudoh,
M.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 3309. (b) Kamijo, S.; Yamamoto,
Y. J. Org. Chem. 2003, 68, 4764 and references therein. Examples where
two different catalytic cycles proceeded in the same medium, see: (c)
Barnhart, R. W.; Bazan, G. C.; Mourey, T. J. Am. Chem. Soc. 1998, 120,
1082. (d) Jeong, N.; Seo, S. D.; Shin, J. Y. J. Am. Chem. Soc. 2000, 122,
10220. (e) Komon, Z. J. A.; Diamond, G. M.; Leclerc, M. K.; Murphy, V.;
Okazaki, M.; Bazan, G. C. J. Am. Chem. Soc. 2002, 124, 15280.
(3) For recent examples, see: (a) Evans, P. A.; Robinson, J. E. J. Am. Chem.
Soc. 2001, 123, 4609. (b) Choudary, B. M.; Chowdari, N. S.; Madhi, S.;
Kantam, M. L. Angew. Chem., Int. Ed. 2001, 40, 4620. (c) Christopher, J.
L.; Bielawski, W.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 11312. (d)
Shimada, T.; Mukaide, K.; Shinohara, A.; Han, J. W.; Hayashi, T. J. Am.
Chem. Soc. 2002, 124, 1584. (e) Tian, J.; Yamagiwa, N.; Matsunaga, S.;
Shibasaki, M. Angew. Chem., Int. Ed. 2002, 41, 3636. (f) Son, S. U.; Park,
K. H.; Chung, Y. K. J. Am. Chem. Soc. 2002, 124, 6838. (g) Trost, B. M.;
Machacek, M. R. Angew. Chem., Int. Ed. 2002, 41, 4693. (h) Sutton, A.
E.; Seigal, B. A.; Finnegan, D. F.; Snapper, M. L. J. Am. Chem. Soc. 2002,
124, 13390. (i) Klapars, A.; Parris, S.; Anderson, K. W.; Buchwald, S. L.
J. Am. Chem. Soc. 2004, 126, 3529.
9
16066
J. AM. CHEM. SOC. 2004, 126, 16066-16072
10.1021/ja045532k CCC: $27.50 © 2004 American Chemical Society

Ruthenium- and Platinum-Catalyzed Sequential Reactions
A R T I C L E S
Scheme 1
Table 1. Reaction of Propargylic Alcohol (2a) in the Presence of
Chalcogenolate-Bridged Diruthenium Complex (1) and Other
Catalysta
run
catalysts (mol %)
yield of 4a (%)b
1
2
3
4
5
6
[Cp*RuCl(µ2-SiPr)2Cp*RuCl] (1a) (5) and PtCl2 (10) 4a, 75 (83)c,d
[Cp*RuCl(µ2-SiPr)2Cp*RuCl] (1a) (5) and PtCl2 (5)
4a (74)c
[Cp*RuCl(µ2-SiPr)2Cp*RuCl] (1a) (5) and PtCl4 (10) 4a (28)c
[Cp*RuCl(µ2-SiPr)2Cp*RuCl] (1a) (5) and PdCl2 (10) 4a (22)c
[Cp*RuCl(µ2-SiPr)2Cp*RuCl] (1a) (5) and AuCl3 (10) 4a (3)c,e
Chart 1
[Cp*RuCl(µ2-SiPr)2Cp*RuCl] (1a) (5) and
4a (0)c,f
[Rh(OAc)2]2 (10)
7
8
9
[Cp*RuCl(µ2-SMe)2Cp*RuCl] (1b) (5) and PtCl2 (10) 4a (59)c
[Cp*RuCl(µ2-SeMe)2Cp*RuCl] (1c) (5) and PtCl2 (10) 4a (58)c
[Cp*RuCl(µ2-TeMe)2Cp*RuCl] (1d) and PtCl2 (10)
4a (19)c
a All of the reactions of 2a (0.30 mmol) were carried out in the presence
Scheme 2
of catalysts and NH4BF4 (10 mol %) at 60 °C for 24 h. b Isolated yield of
4a as a mixture of syn- and anti-isomers. c GLC yield of 4a as a mixture
of syn- and anti-isomers. In all cases, the ratio of stereoisomers (syn-4:
anti-4) is ca. 9:1. d The exact ratio of stereoisomers (syn-4:anti-4) is 92:8.
e An intermediate syn-3 was obtained in 14% GLC yield. f An intermediate
syn-3 was obtained in 95% GLC yield.
system is considered to provide a novel type of cycloaddition
reaction between propargylic alcohols and alkenes (Scheme 1).
We present here a unique and general method for fused poly-
cyclic compounds having bicyclo[3,1,0]hex-2-ene framework
in good to excellent yields with a high selectivity by the
ruthenium- and platinum-catalyzed sequential reactions of
propargylic alcohols with alkenes.
such as [Cp*RuCl(µ2-SMe)2RuCp*Cl] (1b) exhibited a lower
catalytic activity (Table 1, run 7). Interestingly, the methane-
selenolate-bridged diruthenium complex11 [Cp*RuCl(µ2-SeMe)2-
RuCp*Cl] (1c) worked effectively, while the methanetellurolate-
bridged diruthenium complex11 [Cp*RuCl(µ2-TeMe)2RuCp*Cl]
(1d) was not so effective (Table 1, runs 8 and 9). In all cases,
4a was obtained as a stereoisomeric mixture, syn-isomer being
rich. The use of other propargylic alcohols having various
substituents on the phenyl ring (2b-2j) under the conditions
of Table 1, run 1, resulted in the formation of a stereoisomeric
mixture (ca. 10:1) of the corresponding fused tetracyclic
compounds (4b-4j) in moderate to high yields. Typical results
are shown in Table 2. The introduction of the second halogen
atom at position 6 in the phenyl ring decreased the yield of 4
(Table 2, runs 9 and 10).
Results and Discussion
Heating of propargylic alcohols bearing an alkene moiety (2a)
in 1,2-dichloroethane (ClCH2CH2Cl) at 60 °C for 24 h in the
presence of 2-propanethiolate-bridged diruthenium complex
[Cp*RuCl(µ2-SiPr)2RuCp*Cl]8 (Cp* ) η5-C5Me5) (1a; Chart
1) (5 mol %), NH4BF4 (10 mol %), and PtCl2 (10 mol %)
afforded a stereoisomeric mixture of the fused tetracyclic
compound, syn- and anti-6b-methyl-6a,6b,7,7a-tetrahydro-6H-
5-oxacyclopropa[3,4]cyclopenta[1,2-a]naphthalene (4a), in 83%
GLC yield (75% isolated yield: syn-4a:anti-4a ) 92:8) (Scheme
2; Table 1, run 1). The reaction proceeded even in the presence
of a smaller quantity of 1a (5 mol %) and PtCl2 (5 mol %) to
give 4a in a similar yield (Table 1, run 2). Other transition metal
complexes, such as PtCl4,9 PdCl2, AuCl3,10 and [Rh(OAc)2]2,
in place of PtCl2 did not work effectively (Table 1, entries 3-6).
The complex having a less sterically demanding SMe group
Next, reactions of other propargylic alcohols bearing various
alkene moieties were similarly carried out. Typical results are
shown in Table 3. In the use of the propargylic alcohol bearing
a geranyl group (2k), the catalytic reaction proceeded to form
the corresponding fused tetracyclic compound (4k) in 86%
isolated yield (syn-4k:anti-4k ) 77:23) (Table 3, run 1).
Formation of the fused pentacyclic compound with naphthalene
moiety (4l) (syn-4l:anti-4l ) 62:38) was observed in the intra-
molecular cyclization of the propargylic alcohol (2l) (Table 3,
run 2). Moreover, the use of propargylic alcohols bearing a
cyclohexenyl or cycloheptenyl moiety (2m and 2n) resulted in
the formation of the corresponding fused pentacyclic compounds
(4m and 4n) in 90% and 89% isolated yields, respectively, syn-
isomer being almost the sole product in both cases (Table 3,
runs 3 and 4). The stereochemistry of the fused pentacyclic
(6) (a) Boger, D. L.; Boyce, C. W.; Garbaccio, R. M.; Goldberg, J. A. Chem.
ReV. 1997, 97, 787. (b) Pietruszka, J. Chem. ReV. 2003, 103, 1051. (c)
Wessjohann, L. A.; Brandt, W.; Thiemann, T. Chem. ReV. 2003, 103, 1625.
(7) For recent reviews, see: (a) Lautens, M.; Klute, W.; Tam, W. Chem. ReV.
1996, 96, 49. (b) Negishi, E.; Cope´ret, C.; Ma, S.; Liou, S.-Y.; Liu, F.
Chem. ReV. 1996, 96, 365. (c) Aubert, C.; Buisine, O.; Malacria, M. Chem.
ReV. 2002, 102, 813. (d) Skoda-Fo¨ldes, R.; Kolla´r, L. Chem. ReV. 2003,
103, 4095. (e) Zeni, G.; Larock, R. C. Chem. ReV. 2004, 104, 2285. (f)
Nakamura, I.; Yamamoto, Y. Chem. ReV. 2004, 104, 2127.
(8) (a) The thiolate-bridged diruthenium complexes have been found to provide
unique bimetallic reaction sites for activation and transformation of various
terminal alkynes, see: Nishibayashi, Y.; Yamanashi, M.; Wakiji, I.; Hidai,
M. Angew. Chem., Int. Ed. 2000, 39, 2909 and references therein. (b) The
methanethiolate-bridged diruthenium complex [Cp*RuCl(µ2-SMe)2RuCp*Cl]
(1b) is commercially available from Wako Pure Chemical Industries (Japan)
as met-DIRUX (methanethiolate-bridged diruthenium complex) (130-
14581).
(10) (a) Stephen, A.; Hashmi, K.; Schwarz, L.; Choi, J.-H.; Frost, T. M. Angew.
Chem., Int. Ed. 2000, 39, 2285. (b) Stephen, A.; Hashimi, K.; Frost, T.
M.; Bats, J. W. J. Am. Chem. Soc. 2000, 122, 11553. (c) Stephen, A.;
Hashimi, K.; Frost, T. M.; Bats, J. W. Org. Lett. 2001, 3, 3769.
(11) (a) Nishibayashi, Y.; Imajima, H.; Onodera, G.; Hidai, M.; Uemura, S.
Organometallics 2004, 23, 26. (b) Nishibayashi, Y.; Imajima, H.; Onodera,
G.; Inada, Y.; Hidai, M.; Uemura, S. Organometallics 2004, 23, 5100.
(9) (a) Blum, J.; Berr-Kraft, H.; Badrieh, Y. J. Org. Chem. 1995, 60, 5567.
(b) Pastine, S. J.; Youn, S. W.; Sames, D. Org. Lett. 2003, 5, 1055.
9
J. AM. CHEM. SOC. VOL. 126, NO. 49, 2004 16067

A R T I C L E S
Nishibayashi et al.
Table 2. Reaction of Various Propargylic Alcohols (2) in the
Scheme 3
a
Presence of [Cp*RuCl(µ2-SiPr)2RuCp*Cl] (1a) and PtCl2
run
propargylic alcohol
yield of 4 (%)b
ratio of isomersc (syn-4:anti-4)
1
2
3
4
5
6
7
8
9
2a, R ) H
4a, 75
4b, 76
4c, 66
4d, 65
4e, 69
4f, 70
4g, 83
4h, 81
4i, 38
4j, 39
92:8
91:9
92:8
94:6
93:7
95:5
92:8
92:8
98:2
93:7
Scheme 4
2b, R ) 4-Me
2c, R ) 4-OMe
2d, R ) 4-Cl
2e, R ) 4-Br
2f, R ) 4-NO2
2g, R ) 6-Me
2h, R ) 6-OMe
2i, R ) 4-Cl, 6-Cl
2j, R ) 4-Br, 6-Br
10
Scheme 5
a All of the reactions of 2 (0.30 mmol) were carried out in the presence
of 1a (5 mol %), NH4BF4 (10 mol %), and PtCl2 (10 mol %), at 60 °C for
24 h. b Isolated yield of 4 as a mixture of syn- and anti-isomers. c The ratio
1
of two stereoisomers of 4 was determined by H NMR.
the obtained mixture of syn-3a and anti-3a with the ratio of
4.6:1 was then treated with only PtCl2 (10 mol %) at 60 °C for
24 h, the intramolecular cycloisomerization of syn-3a occurred
to afford syn-4a and anti-4a, while all of anti-3a was recovered
intact; the ratio of 4a and anti-3a (4.4:1) was nearly the same
as that of the starting syn-3a and anti-3a (4.6:1) (Scheme 4).
This result clearly indicates that only syn-3a is transformed into
the corresponding tetracyclic compound (syn-4a and anti-4a)
and cycloisomerization of anti-3a does not proceed at all.
Figure 1. Crystal structure of syn-4n with 50% probability ellipsoids.
compound (syn-4n) was unambiguously confirmed by X-ray
analysis, and an ORTEP drawing of syn-4n is shown in Figure
1.
To obtain more information on the sequential reaction, the
following reactions were carried out. A mixture of syn-3a and
anti-3a with the ratio of 4.6:1 was found when 2a was heated
in the presence of only 1b at 60 °C for 1 h (Scheme 3). When
a
Table 3. Reaction of Various Propargylic Alcohols (2) in the Presence of [Cp*RuCl(µ2-SiPr)2RuCp*Cl] (1a) and PtCl2
a All of the reactions of 2 (0.30 mmol) were carried out in the presence of 1a (5 mol %), NH4BF4 (10 mol %), and PtCl2 (10 mol %), at 60 °C for
1
24 h. b Isolated yield of 4 as a mixture of syn- and anti-isomers. c The ratio of two stereoisomers of 4 was determined by H NMR.
9
16068 J. AM. CHEM. SOC. VOL. 126, NO. 49, 2004

Ruthenium- and Platinum-Catalyzed Sequential Reactions
A R T I C L E S
Scheme 6
Scheme 7
Scheme 8
Next, the catalytic transformation of propargylic alcohol
bearing the deuterium-substituted group (2a′) was investigated
(Scheme 5). Intramolecular cyclization of 2a′ in the presence
of only 1a afforded syn-3a′ in 65% yield with a high deuterium
incorporation (53% by 1H NMR) at the alkyne terminal position.
This finding supports our previous reaction pathway as shown
in Scheme 6.5 On the other hand, bimetallic sequential reaction
of 2a′ in the presence of both 1a and PtCl2 gave syn-4a′ in
82% isolated yield with the deuterium incorporation (40%) at
C-7a position. These results indicate that the deuterium incor-
poration at C-7a position of syn-4a′ surely comes from the
alkyne terminal position of syn-3a′.
On the basis of these findings, a pathway for this sequential
reaction is proposed in Scheme 7. At first, 2a was transformed
rapidly into syn-3a and anti-3a in the presence of ruthenium
catalyst 1a. In the next step, platinum-catalyzed cycloisomer-
ization proceeded only with syn-3a via the intermediates such
as I and II, to afford the product syn-4a.4 As has been pointed
out by Fu¨rstner4c-e and Echavarren,4f-i we should also consider
the scheme for this cycloisomerization involving a nonclassical
carbocation as the reactive intermediate.
improved to 30% yield. Heating of the 1,5-enyne 6, prepared
separately by the 1a-catalyzed reaction between 5 and R-meth-
ylstyrene,5 in 1,2-dichloroethane at 60 °C for 24 h in the
presence of 10 mol % of PtCl2 gave 7 in 85% isolated yield,
clearly showing that the Pt-catalyzed cycloisomerization step
is involved in this sequential reaction. It was further disclosed
that an allenylidene complex [Cp*RuCl(SMe)2Cp*Ru(dCd
CdCHPh)]BF4 (1e),12 which can be prepared by the reaction
of 1b with 1 equiv of 5 in the presence of NH4BF4 in
tetrahydrofuran (THF) at room temperature for 30 min, worked
more effectively. Thus, reaction of 5 with R-methylstyrene in
the presence of 1e (5 mol %) and PtCl2 (10 mol %) gave 7 in
57% isolated yield with a complete selectivity. This is due to
This sequential catalytic system can be applied to an
intermolecular reaction as well (Scheme 8). Treatment of
1-phenyl-2-propyn-1-ol (5) with R-methylstyrene in the presence
of 1b (5 mol %) and PtCl2 (10 mol %) in ClCH2CH2Cl at
60 °C for 24 h gave 3,5-diphenylbicyclo[3,1,0]hex-2-ene (7) in
13% yield. When 1a was used as a catalyst, the yield of 7 was
9
J. AM. CHEM. SOC. VOL. 126, NO. 49, 2004 16069

A R T I C L E S
Nishibayashi et al.
1
of 92:8. H NMR: δ 0.33 (t, 1H, J ) 4.2 Hz), 0.62 (dd, 1H, J ) 4.2
and 7.2 Hz), 1.36 (s, 3H), 1.64 (d, 1H, J ) 7.2 Hz), 3.30 (dd, 1H, J )
5.1 and 12.1 Hz), 3.74 (dd, 1H, J ) 10.2 and 12.1 Hz), 4.64 (dd, 1H,
J ) 5.1 and 10.2 Hz), 6.15 (s, 1H), 6.79-6.85 (m, 2H), 7.06 (dt, 1H,
J ) 4.8 and 15.5 Hz), 7.35 (dd, 1H, J ) 1.4 and 7.7 Hz). 13C NMR:
δ 19.0, 20.9, 21.4, 29.3, 48.3, 71.0, 116.9, 120.6, 121.0, 124.6, 126.2,
128.4, 134.0, 153.6. Anal. Calcd for C14H14O: C, 84.81; H, 7.12.
Found: C, 84.82; H, 7.32.
the fact that 1e works more effectively than others in the first
propargylic substitution step as shown in Scheme 8.
Conclusion
In summary, a novel sequential catalytic system providing a
simple and efficient one-pot synthetic method for a new type
of skeleton of fused polycyclic compounds with a potential of
biological activity is presented. In this system, thiolate-bridged
diruthenium complexes promote catalytic propargylic substitu-
tion reaction between propargylic alcohols and alkenes in the
first step, while PtCl2 catalyzes cycloisomerization of the
produced enynes in the same medium in the second step. The
reaction proceeds intermolecularly as well as intramolecularly.
These sequential reactions provide a conceptually new type
of cycloaddition system between propargylic alcohols and
alkenes.13
Spectroscopic data and isolated yields of other products are as
1
follows. The ratio of stereoisomers was determined by H NMR.
2-Methyl-6b-methyl-6a,6b,7,7a-tetrahydro-6H-5-oxacyclopropa-
[3,4]cyclopenta[1,2-a]naphthalene (4b). Yield 76%. A colorless oil.
1
Two stereoisomers with the ratio of 91:9. H NMR: δ 0.31 (t, 1H,
J ) 4.2 Hz), 0.60 (dd, 1H, J ) 4.2 Hz and J ) 7.5 Hz), 1.35 (s, 3H),
1.62 (d, 1H, J ) 7.5 Hz), 2.23 (s, 3H), 3.29 (dd, 1H, J ) 5.1 and 12.2
Hz), 3.70 (dd, 1H, J ) 10.2 and 12.2 Hz), 4.60 (dd, 1H, J ) 5.1 and
10.2 Hz), 6.12 (s, 1H), 6.70 (d, 1H, J ) 8.3 Hz), 6.87 (d, 1H, J ) 8.3
Hz), 7.15 (s, 1H). 13C NMR: δ 19.0, 20.5, 20.8, 21.4, 29.3, 48.4, 71.0,
116.6, 120.6, 124.7, 125.8, 129.2, 129.7, 134.2, 151.5. Anal. Calcd for
C15H16O: C, 84.87; H, 7.60. Found: C, 84.82; H, 7.74.
Experimental Section
General Method. 1H NMR (400, 300, and 270 MHz) and 13C NMR
(100, 75, and 67.8 MHz) spectra were recorded using CDCl3 as solvent.
Quantitative GLC analyses were performed on a Shimadzu GC-14A
instrument equipped with a flame ionization detector using a 25 m ×
0.25 mm CBP10 fused silica capillary column. GC-MS analyses were
carried out on a Shimadzu GC-MS QP-5000 spectrometer. Elemental
analyses were performed at the Microanalytical Center of Kyoto
University. Mass spectra were measured on a JEOL JMS600H mass
spectrometer. All reactions were carried out under a dry nitrogen
atmosphere. Solvents were dried by the usual methods and distilled
before use.
Materials. The chalcogenolate-bridged diruthenium complexes8,11
(1) and the allenylidene complex12 (1e) were prepared according to
our previous procedures. Propargylic alcohol (2a) was a commercial
product. Other propargylic alcohols were prepared according to literature
procedures.5,14
Selective Synthesis of Fused Polycyclic Compounds from Pro-
pargylic Alcohols Bearing an Alkene Moiety. A typical experimental
procedure for the reaction of 1-[2-(3-methyl-2-butenyloxy)phenyl]prop-
2-yn-1-ol (2a) catalyzed by [Cp*RuCl(µ2-SiPr)2RuCp*Cl] (1a) and PtCl2
is described below. In a 50 mL flask were placed 1a (10.4 mg, 0.015
mmol), NH4BF4 (3.1 mg, 0.03 mmol), and PtCl2 (8.0 mg, 0.03 mmol)
under N2. Anhydrous ClCH2CH2Cl (27 mL) was added, and then the
mixture was magnetically stirred at room temperature. After the addition
of 2a (64.9 mg, 0.30 mmol), the reaction mixture was heated at 60 °C
for 24 h. The solvent was removed under reduced pressure by an
aspirator, and then the residue was purified by TLC (SiO2) with
n-hexane as an eluent to give 6b-methyl-6a,6b,7,7a-tetrahydro-6H-5-
oxacyclopropa[3,4]cyclopenta[1,2-a]naphthalene (4a) as a colorless oil
(44.6 mg, 0.225 mmol, 75% yield). Two stereoisomers with the ratio
2-Methoxy-6b-methyl-6a,6b,7,7a-tetrahydro-6H-5-oxacyclopropa-
[3,4]cyclopenta[1,2-a]naphthalene (4c). Yield 66%. A pale yellow
oil. Two stereoisomers with the ratio of 92:8. 1H NMR: δ 0.32 (t, 1H,
J ) 4.2 Hz), 0.62 (dd, 1H, J ) 4.2 and 7.3 Hz), 1.36 (s, 3H), 1.64 (d,
1H, J ) 7.3 Hz), 3.29 (dd, 1H, J ) 5.0 and 12.1 Hz), 3.69 (dd, 1H,
J ) 10.1 and 12.1 Hz), 3.74 (s, 3H), 4.59 (dd, 1H, J ) 5.0 and 10.1
Hz), 6.14 (s, 1H), 6.64-6.78 (m, 2H), 6.86 (s, 1H). 13C NMR: δ 19.0,
20.8, 21.4, 29.3, 48.4, 55.7, 71.0, 108.4, 115.2, 117.6, 121.2, 126.5,
134.3, 147.9, 153.5. HRMS (FAB) calcd for C15H16O2 [M], 228.1150;
found, 228.1146.
2-Chloro-6b-methyl-6a,6b,7,7a-tetrahydro-6H-5-oxacyclopropa-
[3,4]cyclopenta[1,2-a]naphthalene (4d). Yield 65%. A pale yellow
oil. Two stereoisomers with the ratio of 94:6. 1H NMR: δ 0.31 (t, 1H,
J ) 4.0 Hz), 0.63 (dd, 1H, J ) 4.0 and 7.2 Hz), 1.35 (s, 3H), 1.65 (d,
1H, J ) 7.2 Hz), 3.26 (dd, 1H, J ) 4.9 and 12.7 Hz), 3.69 (dd, 1H,
J ) 10.3 and 12.7 Hz), 4.62 (dd, 1H, J ) 4.9 and 10.3 Hz), 6.16 (s,
1H), 6.73 (d, 1H, J ) 8.8 Hz), 6.99 (d, 1H, J ) 8.8 Hz), 7.29 (s, 1H).
13C NMR: δ 19.0, 20.8, 21.5, 29.4, 48.0, 71.1, 118.2, 122.3, 124.1,
125.4, 127.6, 128.0, 132.9, 152.0. Anal. Calcd for C14H13ClO: C, 72.26;
H, 5.63. Found: C, 72.24; H, 5.68.
2-Bromo-6b-methyl-6a,6b,7,7a-tetrahydro-6H-5-oxacyclopropa-
[3,4]cyclopenta[1,2-a]naphthalene (4e). Yield 69%. A pale yellow
oil. Two stereoisomers with the ratio of 93:7. 1H NMR: δ 0.31 (t, 1H,
J ) 4.4 Hz), 0.63 (dd, 1H, J ) 4.4 and 7.4 Hz), 1.35 (s, 3H), 1.65 (d,
1H, J ) 7.2 Hz), 3.25 (dd, 1H, J ) 5.1 and 12.1 Hz), 3.69 (dd, 1H,
J ) 10.2 and 12.1 Hz), 4.63 (dd, 1H, J ) 5.1 and 10.2 Hz), 6.16 (s,
1H), 6.68 (d, 1H, J ) 8.9 Hz), 7.13 (d, 1H, J ) 8.9 Hz), 7.44 (s, 1H).
13C NMR: δ 19.0, 20.8, 21.5, 29.4, 47.9, 71.1, 112.9, 118.7, 122.9,
127.1, 127.4, 131.0, 132.8, 152.6. Anal. Calcd for C14H13BrO: C, 60.67;
H, 4.73. Found: C, 60.57; H, 4.75.
6b-Methyl-2-nitro-6a,6b,7,7a-tetrahydro-6H-5-oxacyclopropa-
[3,4]cyclopenta[1,2-a]naphthalene (4f). Yield 70%. Yellow crystals.
Mp. 97.5-98.4 °C. Two stereoisomers with the ratio of 95:5. 1H
NMR: δ 0.35 (t, 1H, J ) 4.3 Hz), 0.70 (dd, 1H, J ) 4.3 and 7.4 Hz),
1.38 (s, 3H), 1.73 (m, 1H), 3.29 (dd, 1H, J ) 5.3 and 12.1 Hz), 3.79
(dd, 1H, J ) 10.3 and 12.1 Hz), 4.76 (dd, 1H, J ) 5.3 and 10.3 Hz),
6.35 (s, 1H), 6.86 (d, 1H, J ) 9.1 Hz), 7.93 (dd, 1H, J ) 2.7 and 9.1
Hz), 8.22 (d, 1H, J ) 2.7 Hz). 13C NMR: δ 19.0, 20.8, 21.8, 29.6,
47.5, 71.7, 117.3, 120.7, 121.2, 123.7, 129.6, 131.7, 141.3, 158.4. Anal.
Calcd for C14H13NO3: C, 69.12; H, 5.39; N, 5.76. Found: C, 69.13;
H, 5.44; N, 5.65.
(12) (a) Nishibayashi, Y.; Wakiji, I.; Hidai, M. J. Am. Chem. Soc. 2000, 122,
11019. (b) Nishibayashi, Y.; Wakiji, I.; Ishii, Y.; Uemura, S.; Hidai, M. J.
Am. Chem. Soc. 2001, 123, 3393. (c) Nishibayashi, Y.; Inada, Y.; Hidai,
M.; Uemura, S. J. Am. Chem. Soc. 2002, 124, 7900. (d) Nishibayashi, Y.;
Yoshikawa, M.; Inada, Y.; Hidai, M.; Uemura, S. J. Am. Chem. Soc. 2002,
124, 11846. (e) Nishibayashi, Y.; Onodera, G.; Inada, Y.; Hidai, M.;
Uemura, S. Organometallics 2003, 22, 873. (f) Nishibayashi, Y.; Yoshika-
wa, M.; Inada, Y.; Hidai, M.; Uemura, S. J. Org. Chem. 2004, 69, 3408.
(g) Nishibayashi, Y.; Milton, M. D.; Inada, Y.; Yoshikawa, M.; Wakiji, I.;
Hidai, M.; Uemura, S. Chem. Eur. J., in press.
(13) After the submission of our manuscript, a similar example of the reaction
of propargylic alcohol with alkene catalyzed by rhenium and gold
complexes was reported by Toste and co-workers.4m In this sequential
reaction, however, the reaction conditions have to be changed on the way,
and the successive addition of gold complex is necessary after the reaction
of propargylic alcohol with allylsilane in the presence of rhenium complex.
In contrast, it is noteworthy that, in our catalytic reaction system, both
ruthenium and platinum catalysts sequentially promote each catalytic cycle
in the same medium without changing the reaction conditions.
(14) Mann, A.; Muller, C.; Tyrrell, E. J. Chem. Soc., Perkin Trans. 1 1998,
1427.
4-Methyl-6b-methyl-6a,6b,7,7a-tetrahydro-6H-5-oxacyclopropa-
[3,4]cyclopenta[1,2-a]naphthalene (4g). Yield 83%. A colorless oil.
1
Two stereoisomers with the ratio of 92:8. H NMR: δ 0.32 (t, 1H,
J ) 4.1 Hz), 0.60 (dd, 1H, J ) 4.1 and 7.2 Hz), 1.35 (s, 3H), 1.62 (d,
1H, J ) 7.2 Hz), 2.16 (s, 3H), 3.28 (dd, 1H, J ) 5.1 and 12.1 Hz),
9
16070 J. AM. CHEM. SOC. VOL. 126, NO. 49, 2004

Ruthenium- and Platinum-Catalyzed Sequential Reactions
A R T I C L E S
Table 4. Crystallographic Data for syn-4n
3.72 (dd, 1H, J ) 10.1 and 12.1 Hz), 4.68 (dd, 1H, J ) 5.1 and 10.1
Hz), 6.11 (s, 1H), 6.67-6.75 (m, 1H), 6.93 (d, 1H, J ) 7.8 Hz), 7.20
(d, 1H, J ) 7.8 Hz). 13C NMR: δ 16.2, 18.9, 20.9, 21.4, 29.4, 48.3,
70.9, 120.0, 120.4, 122.2, 125.9, 126.1, 129.6, 134.5, 151.9. Anal. Calcd
for C15H16O: C, 84.87; H, 7.60. Found: C, 85.17; H, 7.80.
formula
C18H20O
252.36
formula weight
cryst size (mm3)
cryst system
space group
cryst color
a (Å)
0.80 × 0.60 × 0.10
monoclinic
P21/n (No. 14)
colorless
12.576(7)
13.2311(6)
17.2462(8)
101.968(1)
2807.5(2)
8
1.194
1088.00
0.72
6415
4933
4-Methoxy-6b-methyl-6a,6b,7,7a-tetrahydro-6H-5-oxacyclopropa-
[3,4]cyclopenta[1,2-a]naphthalene (4h). Yield 81%. A colorless oil.
1
Two stereoisomers with the ratio of 92:8. H NMR: δ 0.34 (t, 1H,
b (Å)
J ) 4.1 Hz), 0.62 (dd, 1H, J ) 4.1 and 7.2 Hz), 1.36 (s, 3H), 1.64 (d,
1H, J ) 7.2 Hz), 3.31 (dd, 1H, J ) 5.2 and 12.2 Hz), 3.77 (dd, 1H,
J ) 10.1 and 12.2 Hz), 3.84 (s, 3H), 4.78 (dd, 1H, J ) 5.2 and 10.1
Hz), 6.15 (s, 1H), 6.68 (dd, 1H, J ) 1.5 and 8.1 Hz), 6.77 (t, 1H, J )
7.8 Hz), 6.98 (dd, 1H, J ) 1.5 and 7.8 Hz). 13C NMR: δ 18.9, 20.8,
21.4, 29.3, 48.0, 55.8, 71.5, 110.0, 116.6, 120.1, 121.6, 126.8, 133.7,
142.9, 148.6. Anal. Calcd for C15H16O2: C, 78.92; H, 7.06. Found: C,
78.82; H, 7.18.
c (Å)
â (deg)
V (Å3)
Z
d
calc (g cm-3
)
F (000)
µ
calc (cm-1
)
no. of unique data
no. of observations
no. of params refined
R1
383
0.046
0.100
1.019
2,4-Dichloro-6b-methyl-6a,6b,7,7a-tetrahydro-6H-5-oxacyclopropa-
[3,4]cyclopenta[1,2-a]naphthalene (4i). Yield 38%. A colorless oil.
wR2
1
Two stereoisomers with the ratio of 98:2. H NMR: δ 0.32 (t, 1H,
goodness of fit indicator
maximum residuals (e Å-3
)
0.38
J ) 4.3 Hz), 0.67 (dd, 1H, J ) 4.3 and 7.4 Hz), 1.36 (s, 3H), 1.68 (d,
1H, J ) 7.4 Hz), 3.28 (dd, 1H, J ) 5.0 and 12.0 Hz), 3.75 (dd, 1H,
J ) 10.2 and 12.0 Hz), 4.78 (dd, 1H, J ) 5.0 and 10.2 Hz), 6.21 (s,
1H), 7.12 (d, 1H, J ) 2.3 Hz), 7.21 (d, 1H, J ) 2.3 Hz). 13C NMR:
δ 19.0, 20.7, 21.6, 29.5, 47.7, 71.7, 122.4, 122.5, 123.3, 125.0, 128.0,
129.2, 132.0, 147.8. Anal. Calcd for C14H12Cl2O: C, 62.94; H, 4.53.
Found: C, 62.79; H, 4.57.
6.84 (m, 2H), 7.02-7.09 (m, 1H), 7.34-7.37 (m, 1H). 13C NMR: δ
22.2, 22.5, 24.2, 24.6, 25.9, 27.8, 33.8, 49.7, 70.7, 116.8, 120.5, 121.1,
124.6, 125.9, 128.2, 132.6, 153.5. Anal. Calcd for C17H18O: C, 85.67;
H, 7.61. Found: C, 85.43; H, 7.62.
2,4-Dibromo-6b-methyl-6a,6b,7,7a-tetrahydro-6H-5-oxacyclopropa-
[3,4]cyclopenta[1,2-a]naphthalene (4j). Yield 39%. A colorless oil.
Two stereoisomers with the ratio of 93:7. H NMR: δ 0.32 (t, 1H,
6a,7,8,9,10,11,11a,11b-Octahydro-6H-5-oxacyclohepta[2′,3′]cyclo-
propa[1′,2′:3,4]cyclopenta[1,2-a]naphthalene (4n). Yield 89%. Color-
less crystals. Mp 54.0-55.0 °C. Only one isomer was observed. H
1
1
J ) 4.3 Hz), 0.67 (dd, 1H, J ) 4.3 and 7.4 Hz), 1.36 (s, 3H), 1.64-
1.71 (m, 1H), 3.28 (dd, 1H, J ) 5.2 and 12.2 Hz), 3.76 (dd, 1H, J )
10.2 and 12.2 Hz), 4.78 (dd, 1H, J ) 5.2 and 10.2 Hz), 6.21 (s, 1H),
7.40 (d, 1H, J ) 2.4 Hz), 7.42 (d, 1H, J ) 2.4 Hz). 13C NMR: δ 19.0,
20.9, 21.4, 29.3, 48.3, 71.0, 111.8, 112.5, 123.7, 126.2, 129.2, 131.9,
133.4, 149.2. Anal. Calcd for C14H12Br2O: C, 47.23; H, 3.40. Found:
C, 47.23; H, 3.39.
NMR: δ 0.69 (ddd, 1H, J ) 2.6, 5.8, and 10.4 Hz), 0.96 (m, 1H),
1.16-1.44 (m, 3H), 1.58-1.85 (m, 5H), 2.13-2.23 (m, 2H), 3.33 (dd,
1H, J ) 5.1 and 12.1 Hz), 3.85 (dd, 1H, J ) 10.0 and 12.1 Hz), 4.74
(dd, 1H, J ) 5.1 and 10.0 Hz), 6.12 (s, 1H), 6.77-6.83 (m, 2H), 7.04
(m, 1H), 7.33 (dd, 1H, J ) 1.7 and 8.0 Hz). 13C NMR: δ 14.1, 28.9,
29.4, 29.7, 31.2, 32.2, 35.2, 38.7, 51.1, 71.3, 116.6, 120.4, 120.9, 124.4,
125.3, 128.1, 133.3, 153.1. HRMS (FAB) calcd for C18H20O [M],
252.1514; found, 252.1515.
6b-(4-Methylpent-3-enyl)-6a,6b,7,7a-tetrahydro-6H-5-oxacyclo-
propa[3,4]cyclopenta[1,2-a]naphthalene (4k). Yield 86%. A colorless
Selective Synthesis of Fused Polycyclic Compounds from 1-Phen-
yl-2-propyn-1-ol with r-Methylstyrene. A typical experimental
procedure for the reaction of 1-phenyl-2-propyn-1-ol (5) with R-meth-
ylstyrene catalyzed by [Cp*RuCl(SMe)2Cp*Ru(dCdCdCHPh)]BF4
(1e) and PtCl2 is described below. In a 50 mL flask were placed 1e
(12.0 mg, 0.015 mmol) and PtCl2 (8.0 mg, 0.03 mmol) under N2.
Anhydrous ClCH2CH2Cl (27 mL) was added, and then the mixture
was magnetically stirred at room temperature. After the addition of 5
(39.7 mg, 0.30 mmol) and R-methylstyrene (709.1 mg, 6.00 mmol),
the reaction mixture was heated at 60 °C for 24 h. The solvent was
removed under reduced pressure by an aspirator, and then the residue
was purified by TLC (SiO2) with n-hexane as an eluent to give 3,5-
diphenylbicyclo[3,1,0]hex-2-ene (7) as a white solid (39.7 mg, 0.171
1
oil. Two stereoisomers with the ratio of 77:23. H NMR: δ 0.38 (t,
1H, J ) 4.2 Hz), 0.67 (dd, 1H, J ) 4.3 and J ) 7.3 Hz), 1.62 (s, 3H),
1.69 (s, 3H), 1.80 (m, 1H), 2.01-2.13 (m, 2H), 3.40 (dd, 1H, J ) 5.0
and 11.9 Hz), 3.76 (dd, 1H, J ) 10.3 and 11.9 Hz), 4.67 (dd, 1H, J )
5.0 and 10.3 Hz), 5.10-5.15 (m, 1H), 6.13 (s, 1H), 6.79-6.84 (m,
2H), 7.03-7.09 (m, 1H), 7.34 (d, 1H, J ) 7.7 Hz). 13C NMR: δ 17.7,
18.3, 25.7, 26.2, 26.3, 28.3, 35.9, 46.5, 71.6, 116.6, 120.5, 120.9, 123.9,
124.5, 125.7, 128.2, 131.6, 134.1, 153.3. Anal. Calcd for C18H20O: C,
85.67; H, 7.99. Found: C, 85.45; H, 8.41.
8b-Methyl-8a,8b,9,9a-tetrahydro-8H-7-oxacyclopropa[3,4]cyclo-
penta[1,2-c]phenanthrene (4l). Yield 68%. A pale yellow oil. Two
stereoisomers with the ratio of 62:38. 1H NMR: δ 0.38 (t, 1H, J ) 3.9
Hz, anti isomer), 0.50 (t, 1H, J ) 3.6 Hz, syn isomer), 0.64 (dd, 1H,
J ) 3.6 and 7.5 Hz, syn isomer), 0.84 (dd, 1H, J ) 3.9 and 7.8 Hz,
anti isomer), 1.40 (s, 3H, anti isomer), 1.35 (s, 3H, syn isomer), 1.58-
1.64 (m, 1H, anti isomer), 1.84 (dt, 1H, J ) 2.4 and 7.5 Hz, syn isomer),
3.11 (d, 1H, J ) 16.2 Hz, anti isomer), 3.40-3.45 (m, 1H, syn isomer),
3.93 (dd, 1H, J ) 10.2 and 12.0 Hz, syn isomer), 4.76 (dd, 1H, J )
5.6 and 10.2 Hz, syn isomer), 4.90-5.07 (m, 2H, anti isomer), 6.52 (s,
1H, syn isomer), 6.99-7.73 (m, 13H), 8.12 (d, 1H, J ) 8.4 Hz, anti
isomer), 8.28 (d, 1H, J ) 8.7 Hz). HRMS (FAB) calcd for C18H16O
[M], 248.1201; found, 248.1203.
1
mmol, 57% yield). H NMR: δ 0.72 (t, 1H, J ) 3.8 Hz), 1.42 (dd,
1H, J ) 3.8 and 7.6 Hz), 2.28 (m, 1H), 3.14 (d, 1H, J ) 16.9 Hz),
3.32 (d, 1H, J ) 16.9 Hz), 6.50 (d, 1H, J ) 2.0 Hz), 7.17-7.41 (m,
10H). 13C NMR: δ 27.1, 31.5, 32.8, 42.0, 124.9, 125.5, 126.7, 126.8,
128.2, 129.1, 136.1, 140.1, 144.6. Anal. Calcd for C18H16: C, 93.06;
H, 6.94. Found: C, 93.25; H, 6.93.
X-ray Crystallographic Studies of 4n. Colorless crystals of syn-
4n suitable for X-ray analysis were obtained by recrystallization from
CH2Cl2-n-hexane. A single crystal was sealed in a Pyrex glass capillary
under N2 atm and was used for data collection. All measurements were
made on a Rigaku RAXIS imaging plate area detector with graphite
monochromated Mo KR radiation. Details of crystal and data collection
parameters are summarized in Table 4. The positions of non-hydrogen
atoms were determined by direct methods (SIR88) and subsequent
Fourier syntheses (DIRDIF99).
6a,7,8,9,10,10a,10b-Heptahydro-6H-5-oxacyclohexa[2′,3′]cyclo-
propa[1′,2′:3,4]cyclopenta[1,2-a]naphthalene (4m). Yield 90%. A
1
pale yellow oil. Only one isomer was observed. H NMR: δ 0.73 (d,
1H, J ) 3.6 Hz), 1.22-1.44 (m, 3H), 1.50-1.65 (m, 2H), 1.78-2.06
(m, 4H), 3.28 (dd, 1H, J ) 5.1 and 12.0 Hz), 3.77 (dd, 1H, J ) 10.0
and 12.0 Hz), 4.61 (dd, 1H, J ) 5.1 and 10.0 Hz), 6.15 (s, 1H), 6.79-
9
J. AM. CHEM. SOC. VOL. 126, NO. 49, 2004 16071

A R T I C L E S
Nishibayashi et al.
Acknowledgment. This work was supported by a Grant-in-
Aid for Scientific Research for Young Scientists (A) (No.
15685006) from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan. Y.I. is a recipient of the JSPS
Predoctoral Fellowships for Young Scientists.
Supporting Information Available: Crystallographic data of
syn-4n as a CIF file. This material is available free of charge
via the Internet at http://pubs.acs.org.
JA045532K
9
16072 J. AM. CHEM. SOC. VOL. 126, NO. 49, 2004