9158
J . Org. Chem. 1998, 63, 9158-9159
Sch em e 1
In tr a m olecu la r Cycliza tion s of En yn es Usin g
Ru ClH(CO)(P P h 3)3
Mayumi Nishida, Naoko Adachi, Kiyoko Onozuka,
Hiroshi Matsumura, and Miwako Mori*
Graduate School of Pharmaceutical Sciences,
Hokkaido University, Sapporo 060-0812, J apan
Ta ble 1. Cycliza tion of 1 Usin g Ru ClH(CO)(P P h 3)3
Received August 24, 1998
Transition metal-catalyzed coupling reaction between
alkyne and alkene is a useful synthetic protocol for synthesis
of 1,3-diene.1 Not only are 1,3-dienes themselves important
but they have also wide applicability in the Diels-Alder
reaction. Recently, Mitsudo2 and Trost3 reported ruthenium-
catalyzed intermolecular addition of alkynes to alkenes. In
both reactions, formation of ruthenacyclopentene was pro-
posed as an intermediate. We now report two types of
intramolecular cyclizations of enynes using RuClH(CO)-
(PPh3)3 as a catalyst via the following three steps: hydro-
metalation, carbometalation, and then â-hydride elimina-
tion,4 which provide cyclized compounds I5 and II, respectively
(Scheme 1). Among the many reports on hydroruthenation
of RuClH(CO)(PPh3)3 toward multiple bonds,6 this is the first
example of a stereoselective carbon-carbon bond-forming
reaction using RuClH(CO)(PPh3)3.
run
substrate
R1
R2
h
2a -e (%)
1
2
3
4
5
1a
1b
1c
1d
1e
Me
Ph
(CH2)3Ph
9
62
57
82
67
53a
Et
Et
Et
Et
18
18
18
18
4-MeO-Ph
4-Me-Ph
4-CF3-Ph
a
The recovery of 1e was 34%.
Sch em e 2
First, we examined ruthenium-catalyzed cyclizations us-
ing 1a as a substrate (n ) 3, Table 1, run 1). A solution of
1a (0. 32 mmol) and RuClH(CO)(PPh3)3 (5 mol %) in toluene
(1.5 mL) was refluxed for 9 h to afford the cyclized product
2a in 62% yield. A strong NOE between two olefinic protons
of 2a clarified the structure of the product. The cyclization
of 1b also succeeded in providing 2b in 57% yield (run 2). It
is notable that both substrates, having an aromatic group
or an alkyl group on the alkyne, can be used in this reaction.7
To examine the substituent effects on the aromatic ring,
the cyclization of 1c, having a methoxy group on the
aromatic ring, was carried out to provide 2c in 82% yield
(run 3). Similarly, the reaction of 1d , having a methyl group,
proceeded to give 2d in 67% yield (run 4). However, in the
case of 1e, having a trifluoromethyl group, the cyclized
product 2e was obtained in 53% yield along with recovered
starting material 1e (34% yield) (run 5). These results clearly
indicated that the electron-withdrawing group on the alkyne
reduced the yield of the product.
product in 81% yield (Scheme 2). However, 1H NMR and 13C
NMR spectra could not clarify the ring size of the product
(4 or 5a ). To confirm the structure of 5a , hydrogenation was
carried out to give 6 as a mixture of two isomers. The COSY
data of one isomer confirmed that a five-membered ring was
formed in this reaction.8
Surprisingly, when cyclization of 3a , having a two-carbon
tether between the alkyne and olefin, was carried out, the
reaction was accomplished within 1 h to afford the cyclized
The effects of substituents on the aromatic ring were
studied again (Table 2). Cyclization of 3b afforded 5b in 75%
yield (run 2), and cyclization of 3c provided 5c in 67% yield
(run 3). However, the reaction of 3d was not completed to
provide 5d in only 48% yield along with 3d (run 4).
Accordingly, a tendency similar to that shown in the
previous cyclization was also observed in this reaction.9
The reaction mechanism can be envisioned as shown in
Scheme 3. The reaction starts with a hydroruthenation of
the alkyne to give the vinylruthenium complex III or IV,
which is in a state of equilibrium with 1 or 3. In the reaction
of 1 and RuClH(CO)(PPh3)3, intramolecular olefin insertion
(1) Trost, B. M. Angew Chem., Int. Ed. Engl. 1995, 34, 259 and references
therein.
(2) Mitsudo, T.; Zhang, S.; Naagao, M.; Wakatuki, Y. J . Chem. Soc.,
Chem. Commun. 1991, 598.
(3) (a) Trost, B. M.; Katsuharu Imi; Indolese, A. J . Am. Chem. Soc. 1993,
115, 8831. (b) Trost, B. M.; Indolese, A. F.; Mu¨ller, T. J . J .; Treptow, B. J .
Am. Chem. Soc. 1995, 117, 615. (c) Trost, B. M.; Mu¨ller, T. J . J .; Martinez,
J . J . Am. Chem. Soc. 1995, 117, 1888.
(4) Levison J . J .; Robinson. S. D. J . Chem. Soc. A 1970, 2947.
(5) Trost reported that the same type of compound as I was obtained in
the Pd-catalyzed enyne cyclization. Trost, B. M.; Romero, D. L.; Rise, L. J .
Am. Chem. Soc. 1994, 116, 4268.
(6) (a) Bingham, D.; Webster, D. E.; Wells, P. B. J . Chem. Soc., Dalton
Trans. 1974, 1519. (b) Hirai, K.; Suzuki, H.; Kashiwagi, H.; Morooka, Y.;
Ikawa, T. Chem. Lett. 1982, 23. (c) Suzuki, H.; Yashima, H.; Hirose, T.;
Takahashi, M.; Morooka, Y.; Ikawa, T. Tetrahedron Lett. 1980, 21, 5747.
(d) Matuda, I.; Kato, T.; Sato, S.; Izumi, Y. Tetrahedron Lett. 1986, 47, 5747.
(e) Hirai, K.; Matunaga, T. Organometallics 1994, 13, 1878.
(7) Cyclizations were examined using 1f (R1 ) H, R2 ) (CH2)3Ph), 1g (R1
) TMS, R2 ) (CH2)3Ph), and 1h (R1 ) COOMe, R2 ) COOEt) as substrates.
In the case of 1f and 1g, double-bond isomerization took place to provide
deconjugated compounds. In the reaction of 1h , the starting material was
recovered. Unfortunately, a six-membered ring compound was not formed
in the reaction of (E)-9-(4-methoxyphenyl)-2-nonen-7-ynote.
(8) HMBC data of 5a indicated that the aromatic group was connected
to the tertially vinyllic carbon.
(9) Cyclizations were examined using 3e (R1 ) Me, R2 ) 4-NO2-C6H4-
CH2), 3f (R1 ) Et, R2 ) 4-NO2-C6H4CH2), and 3g (R1 ) i-Pr, R2 ) Et) as the
substrates. In the reaction of 3e, the starting material was recovered. In
the case of 3g, double-bond isomerization took place to provide deconjugated
compounds. However, in the reaction of 3f, a cyclized product was obtained
in 22% yield along with 15% of 3f.
10.1021/jo981715b CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/20/1998
Nishida, Mayumi
