A new route to cyclopentenones via ruthenium-catalyzed carbonylative cyclization of allylic carbonates with alkenes

Article abstract of DOI:10.1021/ol0000206

(equation presented) [RuCl₂(CO)₃]₂/Et₃N and (η³-C₃H₅)RuBr(CO)₃/Et ₃N are highly effective catalyst systems for carbonylative cyclization of allylic carbonates with alkenes to give the corresponding cyclopentenones in high yields. For example, treatment of allyl methyl carbonate (1a) with 2-norbornene (2a) in the presence of a catalytic amount of [RuCl₂(CO)₃]₂ (2.5 mol %) and Et₃N (10 mol %) at 120 °C for 5 h under 3 atm of carbon monoxide gave the corresponding cyclopentenone, exo-4-methyltricyclo[5.2.1.0^2,6]dec.4.en-3-one (3a), in 80% yield with high stereoselectivity (exo 100%).

Full text of DOI:10.1021/ol0000206

ORGANIC
LETTERS
2
000
Vol. 2, No. 7
49-952
A New Route to Cyclopentenones via
Ruthenium-Catalyzed Carbonylative
Cyclization of Allylic Carbonates with
Alkenes
9
Yasuhiro Morisaki, Teruyuki Kondo,* and Take-aki Mitsudo*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering,
Kyoto UniVersity, Sakyo-ku, Kyoto 606-8501, Japan
mitsudo@scl.kyoto-u.ac.jp
Received February 1, 2000
ABSTRACT
3
[
RuCl
2
(CO)
3
]
2
/Et
3
N and (η -C
3
H
5
)RuBr(CO)
3
/Et
3
N are highly effective catalyst systems for carbonylative cyclization of allylic carbonates with
alkenes to give the corresponding cyclopentenones in high yields. For example, treatment of allyl methyl carbonate (1a) with 2-norbornene
2a) in the presence of a catalytic amount of [RuCl (CO) (2.5 mol %) and Et N (10 mol %) at 120 °C for 5 h under 3 atm of carbon monoxide
(
2
3
]
2
3
2,6
gave the corresponding cyclopentenone, exo-4-methyltricyclo[5.2.1.0 ]dec-4-en-3-one (3a), in 80% yield with high stereoselectivity (exo 100%).
3
The development of simple and general methods for the
synthesis of cyclopentenones from readily available sub-
strates continues to be one of the most active and challenging
areas of synthetic research, due to the wide abundance of
this structural unit in a large number of natural products.
Cocyclization of alkynes, alkenes, and carbon monoxide by
natural products. Many advances relating to this method
have been reported recently, including the development of
4
catalytic versions of this reaction. Another formally related
process, the carbonylative cyclization of allylic halides with
alkynes promoted by nickel and palladium complexes via
η -allyl intermediates, has recently been reported. However,
1
5
6
3
transition metal complexes leading to cyclopentenones
the use of alkyne substrates is essential for both the Pauson-
2
(known as the Pauson-Khand reaction ) has been accepted
(3) Donkervoort, J. G.; Gordon, A. R.; Johnstone, C.; Kerr, W. J.; Lange,
as one of the most powerful and convergent methods for
the construction of cyclopentenones and has been used
successfully as the key step in the synthesis of a variety of
U. Tetrahedron 1996, 52, 7391 and references therein.
(4) For cobalt catalysts, see: (a) Rautenstrauch, V.; Megard, P.; Conesa,
J.; Kuster, W. Angew. Chem., Int. Ed. Engl. 1990, 29, 1413. (b) Jeong, N.;
Hwang, S. H.; Lee, Y.; Chung, Y. K. J. Am. Chem. Soc. 1994, 116, 3159.
(
c) Lee, B. Y.; Chung, Y. K.; Jeong, N.; Lee, Y.; Hwang, S. H. J. Am.
(
(
1) Ellison, R. A. Synthesis 1973, 397 and pertinent references therein.
2) For recent review on the Pauson-Khand reaction, see: (a) Khand,
Chem. Soc. 1994, 116, 8793. (d) Lee, N. Y.; Chung, Y. K. Tetrahedron
Lett. 1996, 37, 3145. (e) Pagenkopf, B. L.; Livinghouse, T. J. Am. Chem.
Soc. 1996, 118, 2285. (f) Jeong, N.; Hwang, S. H.; Lee, Y. W.; Lim, L. S.
J. Am. Chem. Soc. 1997, 119, 10549. (g) Sugihara, T.; Yamaguchi, M. J.
Am. Chem. Soc. 1998, 120, 10782 and references therein. For titanocene
catalysts, see: (h) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L. J. Am.
Chem. Soc. 1996, 118, 9450. (i) Hicks, F. A.; Buchwald, S. L. J. Am. Chem.
Soc. 1996, 118, 11688. (j) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L.
J. Am. Chem. Soc. 1999, 121, 5881 and references therein. For ruthenium
catalyst, see: (k) Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T. J. Am.
Chem. Soc. 1997, 119, 6187. (l) Morimoto, T.; Chatani, N.; Fukumoto, Y.;
Murai, S. J. Org. Chem. 1997, 62, 3762. For rhodium catalysts, see: (m)
Koga, Y.; Kobayashi, T.; Narasaka, K. Chem. Lett. 1998, 249. (n) Jeong,
N.; Lee, S.; Sung, B. K. Organometallics 1998, 17, 3642.
I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.; Foreman, M. I. J. Chem.
Soc., Perkin Trans. 1 1973, 977. (b) Pauson, P. L.; Khand, I. U. Ann. N.Y.
Acad. Sci. 1977, 295, 2. (c) Pauson, P. L. Tetrahedron 1985, 41, 5855. (d)
Schore, N. E. Chem. ReV. 1988, 88, 1081. (e) Schore, N. E. Org. React.
991, 40, 1. (f) Geis, O.; Schmalz, H.-G. Angew. Chem., Int. Ed. 1998, 37,
11 and references therein. (g) Schore, N. E. In ComprehensiVe Organic
Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, U.K., 1991; Vol. 5, pp
1
9
1
037-1064. (h) Schore, N. E. In ComprehensiVe Organometallic Chemistry
II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford,
U.K., 1995; Vol. 12, pp 703-739. (I) Jeong, N. In Transition Metals for
Organic Synthesis; Beller, M., Bolm, C., Eds.; Wiley-VCH: New York,
1
998; Vol. 1, pp 560-577.
1
0.1021/ol0000206 CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/09/2000

7
8
k
Khand reaction and the carbonylative cyclization reactions.
catalytic activity (yield of 3a, 60%). However, other ruthe-
nium complexes, such as Cp*RuCl(cod) [Cp* ) penta-
3
During our investigation of the η -allylruthenium chemistry
4
as well as the ruthenium-catalyzed Pauson-Khand reaction,
methylcyclopentadienyl; cod ) 1,5-cyclooctadiene], RuCl
PPh , Ru (CO)12, and Ru(CO) (PPh , were almost
ineffective even in the presence of Et N. Since the catalytic
activity of [RuCl (CO) was highly affected by the amine
2
-
(
3
)
3
3
3
3 2
)
we found the first example of the ruthenium-catalyzed
carbonylative cyclization of allylic carbonates with alkenes,
which offers a new route to cyclopentenones. We report here
the development of this new catalyst system for the synthesis
of cyclopentenones via an η -allylruthenium intermediate.
Treatment of allyl methyl carbonate (1a) with 2-nor-
3
2
3 2
]
ligand, the effect of the several amine ligands was also
examined. Tertiary alkylamines, such as quinuclidine and
N-methylpiperidine, generally enhanced the catalytic activity
3
3
(yields of 3a, 68% and 50%, respectively), and Et N gave
bornene (2a) in the presence of 2.5 mol % of [RuCl
and 10 mol % of Et N in THF at 120 °C for 5 h under 3 atm
of carbon monoxide gave the corresponding cyclopentenone,
2 3 2
(CO) ]
the best result. Almost no promoting effect was observed
with aromatic amines, such as N,N-dimethylaniline and
pyridine, or bidentate amines, such as N,N,N′,N′-tetramethyl-
ethylenediamine (TMEDA), and 1,10-phenanthroline.
3
2,6
exo-4-methyltricyclo[5.2.1.0 ]dec-4-en-3-one (3a), in 80%
yield with high stereoselectivity (exo 100%) (eq 1).
The carbon monoxide pressure also had a dramatic effect
on the carbonylative cyclization of 1a with 2a (Figure 1).
The effects of the catalysts and the amine ligands were
examined in the reaction of 1a with 2a, and the results are
summarized in Table 1. An appropriate catalyst combined
Table 1. Effects of the Catalysts and Amine Ligands on the
Carbonylative Cyclization of 1a with 2aa
yield of
3a (%)c 4a (%)c,,d
yield of
catalyst
amine ligandb
[
[
[
RuCl2(CO)3]2
RuCl2(CO)3]2
(p-cymene)RuCl2]2 Et3N
0
80
60
0
13
0
0
0
0
68
50
17
0
0
0
0
8
6
0
0
0
0
0
0
3
4
4
0
0
0
Et3N
Figure 1. Effect of CO pressure on the formation of 3a by the
carbonylative cyclization of 1a with 2a. Reaction conditions: 1a
Cp*RuCl(cod)
Cp*RuCl(cod)
RuCl2(PPh3)3
Ru3(CO)12
Ru3(CO)12
Ru(CO)3(PPh3)2
(
(
1.0 mmol), 2a (2.0 mmol), [RuCl
0.10 mmol) at 120 °C for 5 h.
2 3 2 3
(CO) ] (0.025 mmol), Et N
Et3N
Et3N
Et3N
The best result was obtained under 3 atm of carbon
monoxide, and either an increase or decrease in the carbon
monoxide pressure caused the rapid decrease in the yield of
[RuCl2(CO)3]2
[RuCl2(CO)3]2
[RuCl2(CO)3]2
[RuCl2(CO)3]2
[RuCl2(CO)3]2
[RuCl2(CO)3]2
quinuclidine
N-methylpiperidine
N,N-dimethylaniline
pyridine
TMEDA
1,10-phenanthrolinef
3
a.
3
e,f
To clarify the intermediacy of an η -allylruthenium
3
complex, the stoichiometric reaction of (η -C
3 5 3
H )RuBr(CO)
(5) with an equimolar amount of 2a was examined, and the
a
1a (1.0 mmol), 2a (2.0 mmol), catalyst (0.050 mmol as Ru atom), and
b
THF (8.0 mL) at 120 °C for 5 h under 3 atm of carbon monoxide. 0.10
mmol. Determined by GLC. 4a: exo-4-methyltricyclo[5.2.1.0 ]decan-
c
d
2,6
(
5) (a) Chiusoli, G. P. Acc. Chem. Res. 1973, 6, 422 and references
therein. (b) Camps, F.; Coll, J.; Moret o´ , J. M.; Torras, J. J. Org. Chem.
989, 54, 1969. (c) Pag e` s, L.; Llebaria, A.; Camps, F.; Molins, E.;
e
f
3
-one. N,N,N′,N′-Tetramethylethylenediamine. 0.050 mmol.
1
Miravitlles, C.; Moret o´ , J. M. J. Am. Chem. Soc. 1992, 114, 10449. (d)
Champs, F.; Llebaria, A.; Moret o´ , J. M.; Pag e` s, L. Tetrahedron Lett. 1992,
33, 109. (e) Camps, F.; Moret o´ , J. M.; Pag e` s, L. Tetrahedron 1992, 48,
with an amine ligand was critically important for a successful
reaction. For example, no catalytic activity of [RuCl (CO)
was observed in the absence of Et N, but the concomitant
use of [RuCl (CO) with Et N dramatically increased the
3
1
147. (f) Llebaria, A.; Camps, F.; Moret o´ , J. M. Tetrahedron 1993, 49,
283. (g) Villar, J. M.; Delgado, A.; Llebaria, A.; Moret o´ , J. M. Tetrahedron;
2
3 2
]
3
Asymmetry 1995, 6, 665. (h) Villar, J. M.; Delgado, A.; Llebaria, A.; Moret o´ ,
J. M. Tetrahedron 1996, 52, 10525. (i) Garc ´ı a-G o´ mez, G.; Moret o´ , J. M.
J. Am. Chem. Soc. 1999, 121, 878 and references therein.
2
3
]
2
3
catalytic activity to give 3a in the best yield of 80%. A small
amount of the hydrogenated cyclopentanone, exo-4-methyl-
(6) (a) Negishi, E.; Wu, G.; Tour, J. M. Tetrahedron Lett. 1988, 29,
6745. (b) Oppolzer, W. Angew. Chem., Int. Ed. Engl. 1989, 28, 38. (c)
Oppolzer, W. Pure Appl. Chem. 1990, 62, 1941. (d) Oppolzer, W.; Xu,
J.-Z.; Stone, C. HelV. Chim. Acta 1991, 74, 465. (e) Ihle, N. C.; Heathcock,
C. H. J. Org. Chem. 1993, 58, 560. (f) Oppolzer, W.; Robyr, C. Tetrahedron
1994, 50, 415.
2,6
tricyclo[5.2.1.0 ]decan-3-one (4a), was obtained as a byprod-
uct. [(p-Cymene)RuCl /Et N, which would give the same
active species as [RuCl (CO) /Et N, also showed good
]
2 2
3
2
]
3 2
3
950
Org. Lett., Vol. 2, No. 7, 2000

corresponding cyclopentenone (3a) was obtained in an
isolated yield of 47% (eq 2). Complex 5 also showed the
completely consumed, and the corresponding cyclopenten-
ones were obtained in high yields. The regioisomeric allylic
carbonates, e.g., 1-hexene-3-yl methyl carbonate (1d) and
(E)-2-hexenyl methyl carbonate ((E)-1e), gave the same
product (3f) in high yields, respectively, which suggests that
3
the present reaction proceeds via an η -allylruthenium
intermediate. In addition, the result that cyclopentenone (3f)
was also obtained from carbonylative cyclization of either
(
Z)-1e and (E)-1e with 2a indicates the rapid isomerization
3
high catalytic activity in the presence of Et N for the
3
between anti- and syn-η -allylruthenium intermediates.
On the other hand, aryl-substituted allylic carbonates, such
as cinnamyl methyl carbonate (1f) and 1-phenylallyl methyl
carbonate (1g), gave 2-benzylidenecyclopentanone (6a) even
by the use of (η -C H )RuBr(CO) /Et N catalyst, probably
3 5 3 3
due to the π-conjugation of an olefinic moiety with the
phenyl group (eq 5). The structure of 6a was confirmed by
carbonylative cyclization of 1a with 2a to give 3a in a 65%
3
yield. Consequently, the η -allylruthenium complex, an
analogue of complex 5, appears to be the key intermediate
9
as well as an active catalyst precursor in the present reaction.
3
9
The carbonylative cyclization of 1a with norbornene
derivatives 2b and 2c also gave the corresponding cyclo-
pentenones, 3b and 3c, in isolated yields of 65% and 73%,
respectively (eqs 3 and 4). Efforts to obtain cyclopentenones
with other alkenes are now in progress.10
X-ray crystallography (Figure 2).12
A synthetic application of the present reaction is demon-
strated in the following intramolecular carbonylative cy-
The results obtained from the reactions of several substi-
tuted allylic carbonates with 2-norbornene (2a) are sum-
marized in Table 2. In all cases, allylic carbonates were
3
Table 2. (η -C
3 5
H
)RuBr(CO)
3
/Et
3
N-Catalyzed Carbonylative
a
Cyclization of Several Allylic Carbonates with 2a
Figure 2. ORTEP drawing of 6a with 30% thermal ellipsoids.
Selected bond length [Å]: C2-C3 ) 1.53(2), C3-O1 ) 1.22(1),
C3-C4 ) 1.50(2), C4-C5 ) 1.50(2), C4-C11 ) 1.34(2), C5-
C6 ) 1.58(2). Selected bond angles [deg]: C1-C2-C3 ) 109-
(1), C3-C4-C11 ) 118(1), C4-C11-C12 ) 129(1), C5-C4-
C11 ) 130(1), C5-C6-C7 ) 114(1).
a
3
Allylic carbonate 1 (1.0 mmol), 2a (1.1 mmol), (η -C3H5)RuBr(CO)3
0.50 mmol), Et3N (0.10 mmol), and THF (2.0 mL) at 120 °C for 3 h under
3
(
b
atm of carbon monoxide. Determined by GLC based on the amount of
charged.
1
Org. Lett., Vol. 2, No. 7, 2000
951

Scheme 1
clization of 1h (eq 6). Treatment of 1h under the present
In conclusion, we have found the first practically useful
ruthenium catalyst for the rapid construction of cyclopen-
tenones without the use of an alkyne substrate. This catalytic
process, which is an alternative to the Pauson-Khand
reaction, could become a valuable tool in the field of organic
and natural product synthesis.
reaction conditions gave the bicyclic cyclopentanone 6b in
b,c,13
6
0% yield.6
Acknowledgment. This work was supported in part by
a Grant-in-Aid for Scientific Research from the Ministry of
Education, Science, Sports and Culture, Japan. Y.M. ap-
preciates Research Fellowships from the Japan Society for
the Promotion of Science for Young Scientists.
The most plausible mechanism is illustrated in Scheme 1.
Invariable exo-coordination of 2-norbornene derivatives to
3
an active η -allylruthenium intermediate, stereoselective cis-
Supporting Information Available: Complete experi-
mental procedures and compound characterization data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
carbo-ruthenation, and successive insertion of CO would give
an (acyl)ruthenium intermediate. Subsequent intramolecular
insertion of a CdC bond into an acyl-ruthenium bond,
followed by â-hydride elimination/isomerization, would give
the corresponding cyclopentenones exclusively in an exo
form. Higher carbon monoxide pressure (over 3 atm) would
suppress coordination of 2-norbornene, and lower carbon
monoxide pressure (below 3 atm) would prevent insertion
of CO.
OL0000206
(10) For example, the reaction of cinnamyl methyl carbonate with
ethylene gave the co-dimerization product, 1-phenyl-1,3-pentadiene ((1E,3E):
11
(1E,4Z) ) 79:21), in 67% yield, which would be obtained by â-hydride
elimination prior to CO insertion.
(
11) For a similar co-dimerization reaction of allylic carbonate with
3
electron-deficient alkenes via an η -allylruthenium intermediate, see:
Mitsudo, T.; Zhang, S.-W.; Kondo, T.; Watanabe, Y. Tetrahedron Lett.
1992, 33, 341.
(7) (a) Palladium-catalyzed cyclocarbonylation of allylic halides with
2
-norbornene and/or 2,5-norbornadiene to 2-alkylidenecyclopentanones, not
cyclopentenones, has been reported, see: Amari, E.; Catellani, M.; Chiusoli,
(12) Crystal data for 6a: C17H18O; FW ) 238.33, orthorhombic, space
G. P. J. Organomet. Chem. 1985, 285, 383. (b) For the stoichiometric
group P212121 [No. 19], colorless prismatic, a ) 11.51(1) Å, b ) 11.42(2)
3
3
3
reaction of [(η -C3H5)PdX]2 with 2-norbornene and CO to cyclopentenones,
Å, c ) 9.90(1) Å, V ) 1300(2) Å , Z ) 4, Dcalc ) 1.217 g/cm , µ(Mo KR)
-1
see: Larock, R. C.; Takagi, K.; Burkhart, J. P.; Hershberger, S. S.
) 0.74 cm , Rigaku AFC-7R diffractometer, λ ) 0.71069 Å, ω-2θ scan
(16.0°/min), 2θmax ) 55.1°, 1489 reflections (unique), R ) 0.068, Rw )
0.070, GOF ) 1.12.
Tetrahedron 1986, 42, 3759.
(8) (a) Kondo, T.; Kodoi, K.; Nishinaga, E.; Okada, T.; Morisaki, Y.;
Watanabe, Y.; Mitsudo, T. J. Am. Chem. Soc. 1998, 120, 5587. (b) Kondo,
T.; Ono, H.; Satake, N.; Mitsudo, T.; Watanabe, Y. Organometallics 1995,
(13) Palladium- and nickel-catalyzed intramolecular carbonylative cy-
clization of 2,7-octadienyl iodide or acetate to bicyclic cyclopentenone
derivatives has been reported. (a) Yamamoto, K.; Terakado, M.; Murai,
K.; Miyazawa, M.; Tsuji, J.; Takahashi, K.; Mikami, K. Chem. Lett. 1989,
955. (b) Oppolzer, W.; Keller, T. H.; Bedoya-Zurita, M.; Stone, C.
Tetrahedron Lett. 1989, 30, 5883. (c) Keese, R.; Guidetti-Grept, R.; Herzog,
B. Tetrahedron Lett. 1992, 33, 1207. (d) Terakado, M.; Murai, K.;
Miyazawa, M.; Yamamoto, K. Tetrahedron 1994, 50, 5705.
1
4, 1945 and references therein.
9) Since [RuCl2(CO)3]2/Et3N-catalyzed carbonylative cyclization of
(
substituted allylic carbonates often gave 2-alkylidenecyclopentanones in
3
place of the desired cyclopentenones, the catalyst system of (η -C3H5)-
RuBr(CO)3/Et3N in place of [RuCl2(CO)3]2/Et3N was used in the following
reactions.
952
Org. Lett., Vol. 2, No. 7, 2000