Synthesis of functionalized hydroquinones via [Cp*RuCl 2]2-catalyzed cocyclization of alkynes, α,β-unsaturated carbonyl compounds, and carbon monoxide

Article abstract of DOI:10.1021/ol052291s

(Chemical Equation Presented) Catalytic [2 + 2 + 1 + 1] cocyclization reaction of an alkyne, an alkene, and two molecules of carbon monoxide, leading to functionalized hydroquinones, was studied. Using [Cp*RuCl ₂]₂ as a catalyst, we

Full text of DOI:10.1021/ol052291s

ORGANIC
LETTERS
2
005
Vol. 7, No. 26
781-5783
Synthesis of Functionalized
Hydroquinones via
5
[
Cp*RuCl ] -Catalyzed Cocyclization of
2
2
Alkynes,
r,â-Unsaturated Carbonyl
Compounds, and Carbon Monoxide
†
†
†
†
Takahide Fukuyama, Ryo Yamaura, Yuki Higashibeppu, Takahiro Okamura,
,
†
‡
,‡
Ilhyong Ryu,* Teruyuki Kondo, and Take-aki Mitsudo*
Department of Chemistry, Graduate School of Science, Osaka Prefecture UniVersity,
Sakai, Osaka 599-8531, Japan, and Department of Energy and Hydrocarbon
Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Nishikyo-ku, Kyoto 615-8510, Japan
ryu@c.s.osakafu-u.ac.jp
Received September 22, 2005
ABSTRACT
Catalytic [2
+
2
+
1
+
1] cocyclization reaction of an alkyne, an alkene, and two molecules of carbon monoxide, leading to functionalized
as a catalyst, we found that a variety of electron-deficient alkenes, such as -unsaturated
hydroquinones, was studied. Using [Cp*RuCl
2
]
2
r,â
ketones, esters, amides, and nitriles, can be employed as an alkene coupling partner to give the corresponding hydroquinones.
The Pauson-Khand reaction, which represents transition-
metal-catalyzed [2 + 2 + 1] cocyclization of an alkyne, an
alkene, and carbon monoxide, has been widely studied and
established as a useful method for the construction of
Scheme 1. Two Types of Cocyclization Reactions Using
Alkyne, Alkene, and Carbon Monoxide
1
cyclopentenones (Scheme 1, eq 1). Having one more
molecule of carbon monoxide, [2 + 2 + 1 + 1] cocyclization
reactions of an alkyne, an alkene, and two molecules of
†
Osaka Prefecture University.
Kyoto University.
‡
(1) For reviews on the Pauson-Khand reaction, see: (a) Geis, O.;
Schmalz, H.-G. Angew. Chem., Int. Ed. 1998, 37, 911. (b) Gibson, S. E.;
Stevenazzi, A. Angew. Chem., Int. Ed. 2003, 42, 1800. (c) Blanco-Urgoiti,
J.; Anorbe, L.; P e´ rez-Serrane, L.; Dominguez, G.; P e´ rez-Castells, J. Chem.
Soc. ReV. 2004, 33, 32. (d) Bo n˜ aga, L. V. R.; Krafft, M. E. Tetrahedron
2
004, 60, 9795. For Ru-catalyzed Pauson-Khand reaction, see: (e) Kondo,
T.; Suzuki, N.; Okada, T.; Mitsudo, T. J. Am. Chem. Soc. 1997, 119, 6187.
f) Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J. Org. Chem. 1997,
2, 3762.
(
6
1
0.1021/ol052291s CCC: $30.25
© 2005 American Chemical Society
Published on Web 11/19/2005

carbon monoxide would lead to substituted hydroquinones
2
(
Scheme 1, eq 2). Hydroquinone framework is widely
2 2
Table 2. [Cp*RuCl ] -Catalyzed Cocyclization of Alkynes,
Electron-Deficient Alkenes, and Carbon Monoxide
distributed in nature, and some hydroquinones are known
to possess a broad spectrum of biological activities and
unique reactivities. Hydroquinones bearing polar functional
a
3
groups are also used as a photographic developer as well as
an intermediate in the synthesis of antioxidant and polym-
3
erization inhibitor. We previously reported that strained
alkenes, such as 2-norbornene, can participate in ruthenium-
catalyzed [2 + 2 + 1 + 1] cocyclization, leading to the
4
corresponding hydroquinone derivatives. However, for the
unique cocyclization reaction to be a general scheme, the
restriction with regard to an alkene coupling partner should
be overcome. Herein, we report that the [2 + 2 + 1 + 1]
cocyclization reaction can be extended successfully to include
a wide variety of electron-deficient alkenes as a coupling
partner and [Cp*RuCl
cocyclization reaction.
2 2
] , a good catalyst for the unique
The carbonylative coupling reaction of 4-octyne (1a) with
methyl vinyl ketone (2a) was examined under a variety of
conditions (Table 1). When the reaction of 1a with 2a was
Table 1. Catalytic Activity of Several Ruthenium Complexes
for Cocyclization of 4-Octyne (1a), Methyl Vinyl Ketone (2a),
and Carbon Monoxidea
entry
catalyst
Ru3(CO)12
Ru3(CO)12
Ru3(CO)12
Ru3(CO)12
Ru3(CO)12
solvent
toluene
DMF
CH3CN
N-methylpiperidine
DMF
DMF
3a yield (%)b
1
2
3
4
53
65
60
24
51
27
39
26
48
79
c
5
6
7
8
9
[RuCl2(CO)3]2
6
[RuCl2(η -mesitylene)]2 DMF
CpRuCl(PPh3)2
RuHCl(PPh3)3
[Cp*RuCl2]2
DMF
DMF
DMF
1
0
a
Reaction conditions: 1a (0.5 mmol), 2a (1.5 mmol), catalyst (0.03 mmol
b
as Ru atom), solvent (2 mL), 140 °C, 20 h. Isolated yields by flash
chromatography on SiO2. CO (40 atm).
c
3
carried out using Ru (CO)12 as a catalyst and toluene as a
solvent under 20 atm of carbon monoxide, the desired
(
2) For [2 + 2 + 1 + 1] cocyclization using two molecules of alkynes
and two molecules of CO, see: (a) Pino, P.; Braca, G. Carbon Monoxide
Addition to Acetylenic Substrates. In Organic Synthesis Via Metal Carbo-
nyls; Wender, I., Pino, P., Eds.; Wiley: New York, 1977; Vol. 2, p 419.
(
5
b) Murayama, K.; Shio, T.; Yamamoto, Y. Bull. Chem. Soc. Jpn. 1979,
2, 1877. (c) Rameshkumar, C.; Periasamy, M. Organometallics 2000, 19,
400. (d) Mathur, P.; Bhunia, A. K.; Mobin, S. M.; Singh, V. K.; Srinivasu,
a
Reaction conditions: 1 (0.5 mmol), 2 (1.5 mmol), [Cp*RuCl2]2 (3 mol
b
%
), CO (20 atm), DMF (2 mL), 140 °C. Isolated yields by flash
2
chromatography on SiO2. 2 (2.5 mmol). d Regioisomeric ratio was deter-
mined by 1H NMR analysis of a crude reaction mixture. The absolute
regiochemistry of the products was not determined.
c
C. Organometallics 2004, 23, 3694.
3) (a) Thomson, R. H. Naturally Occurring Quinones III; Chapman and
(
Hall: New York, 1987. (b) Weissermel, K.; Arpe, H.-J. Industrial Organic
Chemistry, 4th ed.; Wiley-VCH: Weinheim, Germany, 2003; p 363.
5782
Org. Lett., Vol. 7, No. 26, 2005

hydroquinone, 5-acetyl-2,3-dipropyl-p-hydroquinone (3a),
was obtained in 53% yield (entry 1). The use of DMF as a
alkynes, such as 2-hexyne (1c) and 1-acetoxy-3-hexyne (1d),
which gave the corresponding hydroquinones as a mixture
of regioisomers in 62 and 75% yield, respectively (entries 8
and 9). Methyl crotonate failed to react with 1a and CO.
Terminal alkynes, such as 1-hexyne, gave a complex
solvent resulted in the increase of the yield up to 65% (entry
5
2
). N-Methylpiperidine, which worked well for the reaction
4
with 2-norbornenes as a solvent, gave 3a only in 24% yield
with many undefined byproducts (entry 4). The reaction
under higher CO pressure (40 atm) using DMF gave 3a in
7
mixture.
A possible mechanism for the Ru-catalyzed [2 + 2 + 1
+ 1] cocyclization reaction is summarized in Scheme 2. A
somewhat lower yield (entry 5). Ruthenium complexes, such
6
as [RuCl
and RuHCl(PPh
low to modest (entries 6-9). Consequently, we found that
Cp*RuCl can effectively catalyze the reaction to give 3a
2
(CO)
3
]
2
, [RuCl
2
(η -mesitylene)], CpRuCl(PPh
3
)
2
,
3 3
) , also gave 3a. However, the yields were
Scheme 2. Possible Mechanism of Cocyclization
[
2 2
]
6
in 79% yield (entry 10).
To explore the scope of the present reaction, several
electron-deficient alkenes were subjected to the reaction
conditions, in which [Cp*RuCl
and DMF as the solvent. The results are summarized in Table
. The reaction of 1a with acrylonitrile (2b) and ethyl acrylate
2c) gave the corresponding hydroquinones, 3b and 3c, in
2 2
] was used as the catalyst
2
(
good yield (entries 2 and 3). When acrylamide (2d) was used,
the corresponding hydroquinone 3d was obtained in 46%
yield (entry 4). The reaction of acrolein (2e) gave 39% yield
of 5-formylhydroquinone 3e along with a small amount of
decarbonylation product, 2,3-dipropyl-p-hydroquinone (4)
maleoylruthenium complex A would be formed by the
(
entry 5). We also examined unsymmetrically substituted
reaction of ruthenium with an alkyne and two molecules of
8
carbon monoxide, which would then react with an electron-
(4) Suzuki, N.; Kondo, T.; Mitsudo, T. Organometallics 1998, 17, 766.
(
5) It should be noted that the present conditions are not suitable for the
deficient alkene to give seven-membered ruthenacycles B
and/or C. Reductive elimination to give D, followed by the
enolization, would give the substituted hydroquinones 3.
In summary, we have developed a [2 + 2 + 1 + 1]-type
cocyclization method for the synthesis of functionalized
reaction of 2-norbornene (35% yield).
6) Typical procedure of [Cp*RuCl2]2-catalyzed cocyclization reactions
leading to functionalized hydroquinones. A magnetic stirring bar, 4-octyne
9
(
(
[
3
1a, 58.3 mg, 0.53 mmol), methyl vinyl ketone (2a, 110 mg, 1.6 mmol),
Cp*RuCl2]2 (10.5 mg, 0.017 mmol), and DMF (2 mL) were placed in a
0 mL stainless steel autoclave. The autoclave was closed, purged three
times with carbon monoxide, pressurized with CO (20 atm), and then heated
at 140 °C for 20 h. After the reaction mixture was cooled to room
temperature, gaseous materials were discharged. The reaction mixture was
diluted with ether (50 mL) and washed with water. The aqueous layer was
extracted with ether (2 × 30 mL). The combined organic layer was washed
with water and dried over MgSO4. After filtration, the solvent was removed
under reduced pressure. The residue was purified by flash chromatography
on silica gel (hexane/EtOAc ) 5/1) to give the corresponding hydroquinone
hydroquinones by [Cp*RuCl
alkynes, electron-deficient alkenes, and two molecules of
carbon monoxide, in which [Cp*RuCl was used as an
effective catalyst. Detailed mechanistic studies as well as
further extension of the present cocyclization reaction are
now ongoing in these laboratories.
2 2
] -catalyzed cocyclization of
2 2
]
(3a, 99.3 mg, 79%) as a white solid.
(
7) We also examined phenyl-substituted alkynes, such as diphenylacetyl-
Acknowledgment. T.F. thanks a Grant-in-Aid for Young
Scientists (B) from the MEXT, Japan, for financial support
No. 17750095). Financial support from Grants-in-Aid for
Scientific Research (A) (No. 16205014 to T.M.), (B) (No.
5350055 to T.K.), and Scientific Research on Priority Areas
A) (No. 14078217 to T.M.) from the JSPS and the MEXT,
ene and 1-phenyl-1-octyne. The former only gave a small amount of reduced
product cis-stilbene, whereas the latter gave a complex mixture of the
carbonylation products, which requires optimization of the reaction condi-
tions.
(
(
8) For recent examples of maleoylmetal complexes formed from an
alkyne, two molecules of carbon monoxide, and a transition metal complex,
see: (a) Cheng, M.-H.; Lee, G.-H.; Peng, S.-M.; Liu, R.-S. Organometallics
991, 10, 3600. (b) Cheng, M.-H.; Syu, H.-G.; Lee, G.-H, Peng, S.-M.;
1
(
1
Liu, R.-S. Organometallics 1993, 12, 108. (c) Mao, T.; Zhang, Z.;
Washington, J.; Takats, J.; Jordan, R. B. Organometallics 1999, 18, 2331.
Japan, is gratefully acknowledged. T.K. acknowledges
financial support from Sumitomo Foundation.
(d) Barrow, M.; Cromhout, N. L.; Cunningham, D.; Manning, A. R.;
McArdle, P. J. Organomet. Chem. 2000, 612, 61. (e) Barrow, M.; Cromhout,
N. L.; Manning, A. R.; Gallagher, J. F. J. Chem. Soc., Dalton Trans. 2001,
Supporting Information Available: General experimen-
tal procedure and spectral data for all products. This mater-
ial is available free of charge via Internet at http://pubs.acs.org.
1
352. (f) Elarraoui, A.; Ros. J.; Y a´ n˜ ez, R.; Solans, X.; Font-Bardia, M. J.
Organomet. Chem. 2002, 642, 107.
9) Reaction of maleoylmetal complexes with alkynes to form quinones
(
has been extensively studied. Liebeskind, L. S.; Baysdon, S. L.; South, M.
S.; Iyer, S.; Leeds, J. Tetrahedron 1985, 41, 5839 and references therein.
OL052291S
Org. Lett., Vol. 7, No. 26, 2005
5783