Ru-catalyzed intermolecular [3+2+1] cycloaddition of α,β- unsaturated ketones with silylacetylenes and carbon monoxide leading to α-pyrones

Article abstract of DOI:10.1021/ol062807n

Ruthenium catalyzes a carbonylative [3+2+1] cycloaddition, using silylacetylenes, α,β-unsaturated ketones, and CO as the starting materials, providing the new method for the synthesis of tetrasubstituted α-pyrones. In this reaction, the carbonyl group and

Full text of DOI:10.1021/ol062807n

ORGANIC
LETTERS
2007
Vol. 9, No. 4
587-589
Ru-Catalyzed Intermolecular [3
Cycloaddition of -Unsaturated
Ketones with Silylacetylenes and
Carbon Monoxide Leading to -Pyrones
+2+1]
r,â
r
Takahide Fukuyama,* Yuki Higashibeppu, Ryo Yamaura, and Ilhyong Ryu*
Department of Chemistry, Graduate School of Science, Osaka Prefecture UniVersity,
Sakai, Osaka 599-8531, Japan
ryu@c.s.osakafu-u.ac.jp
Received November 18, 2006
ABSTRACT
Ruthenium catalyzes a carbonylative [3
+
2+
1] cycloaddition, using silylacetylenes,
r,
â
-unsaturated ketones, and CO as the starting materials,
providing the new method for the synthesis of tetrasubstituted
r
-pyrones. In this reaction, the carbonyl group and -carbon of vinyl ketones
r
are incorporated as a three-atom assembling unit.
R-Pyrones are useful as intermediates in the synthesis of a
variety of important hetero- and carbocyclic molecules and
can be found in numerous biologically active natural products
as substructures.1 Transition-metal-catalyzed cycloaddition,
using carbon monoxide as a one-carbon unit, is one of the
most powerful tools available for the construction of various
carbonyl-containing cyclic and heterocyclic compounds,2
however, analogous approaches leading to R-pyrones are
scarce.3,4 A few catalytic systems for the synthesis of
R-pyrones based on the carbonylation have been developed.
These include the carbonylation of cyclopropenyl esters or
ketones,3a 2-iodoallyl-1,3-dicarbonyl compounds,3b and pro-
pargyl halides or propargyl alcohol.3c In these methods,
however, only a limited range of substrates can be tolerated.
We recently reported on the ruthenium-catalyzed [2+2+1+1]-
type cycloaddition of alkynes, electron-deficient alkenes, and
two molecules of CO, to give hydroquinones in good yields
(Scheme 1, first equation).5 During the course of our
investigation, when silylacetylenes were used as an alkyne,
we found that no such cycloaddition took place but R-pyrones
were formed as the major products. Herein, we report on
(1) (a) Kvita, V.; Fischer, W. Chimia 1993, 47, 3. (b) West, F. G.; Chase,
C. E.; Anif, A. M. J. Org. Chem. 1993, 58, 3794. (c) Posner, G. H.; Lee,
J. K.; White, M. C.; Hutchings, R. H.; Dai, H.; Kachinski, J. L.; Dolan, P.;
Kensler, T. W. J. Org. Chem. 1997, 62, 3299. (d) Schlingmann, G.; Milne,
L.; Carter, G. T. Tetrahedron 1998, 54, 13013. (e) Barrero, A. F.; Oltra, J.
E.; Herrador, M. M.; Sanchez, J. F.; Quilez, J. F.; Rojas, F. J.; Reyes, J. F.
Tetrahedron 1993, 49, 141.
(2) (a) Schore, N. E. Chem. ReV. 1988, 88, 1081. (b) Lautens, M.; Klute,
W.; Tam, W. Chem. ReV. 1996, 96, 49. (c) Ojima, I.; Tzamarioudaki, M.;
Li, Z.; Donovan, R. D. Chem. ReV. 1996, 96, 635. (d) Fru¨hauf, H.-W. Chem.
ReV. 1997, 97, 523.
(3) (a) Cho, S. H.; Liebeskind, L. S. J. Org. Chem. 1987, 52, 2631. (b)
Shimoyama, I.; Zhang, Y.; Wu, G.; Negishi, E. Tetrahedron Lett. 1990,
31, 2841. (c) Rosas, N.; Salmon, M.; Sharma, P.; Alvarez, C.; Ramirez,
R.; Garcia, J.-L.; Arzoumanian, H. J. Chem. Soc., Perkin Trans. 1 2000,
1493.
(4) (a) Larock, R. C.; Han, X.; Doty, M. J. Tetrahedron Lett. 1998, 39,
5713. (b) Larock, R. C.; Doty, M. J.; Han, X. J. Org. Chem. 1999, 64,
8770. (c) Kotora, M.; Ishikawa, M.; Tsai, F.-Y. Takahashi, T. Tetrahedron
1999, 55, 4969. (d) Rousset, S.; Abarbri, M.; Thibonnet, J.; Ducheˆne, A.;
Parrain, J.-L. Chem. Commun. 2000, 1987. (e) Yao, T.; Larock, R. C. J.
Org. Chem. 2003, 68, 5936. (f) Cherry, K.; Parrain, J.-K.; Thibonnet, J.;
Ducheˆne, A.; Abarbri, M. J. Org. Chem. 2005, 70, 6669. For [2+2+2]
cycloaddition using carbon dioxide, see: (g) Tsuda, T.; Morikawa, S.;
Saegusa, T. J. Org. Chem. 1988, 53, 3140. (h) Tsuda, T.; Morikawa, S.;
Hasegawa, N.; Saegusa, T. J. Org. Chem. 1990, 55, 2978. (i) Louie, J.;
Gibby, J. E.; Farnworth, M. V.; Tekavec, T. N. J. Am. Chem. Soc. 2002,
124, 15188.
(5) (a) Fukuyama, T.; Yamaura, R.; Higashibeppu, Y.; Okamura, T.; Ryu,
I.; Kondo, T.; Mitsudo, T. Org. Lett. 2005, 7, 5781. For earlier work, see:
(b) Suzuki, N.; Kondo, T.; Mitsudo, T. Organometallics 1998, 17, 766.
10.1021/ol062807n CCC: $37.00
© 2007 American Chemical Society
Published on Web 01/23/2007

Scheme 1. Cycloaddition Reactions Leading to
Hydroquinones and R-Pyrones Using Alkynes, Alkenes, and CO
Table 2. Ru3(CO)12-Catalyzed [3+2+1] Cycloaddition of
Vinyl Ketones, Silylacetylenes, and Carbon Monoxidea
the novel synthesis of R-pyrones by the Ru3(CO)12-catalyzed
carbonylative [3+2+1] cycloaddition of vinyl ketones,
silylacetylenes, and CO, in which vinyl ketones were
incorporated as a three-atom assembling unit (Scheme 1,
second equation).6
When the reaction of 1-(trimethylsilyl)-2-phenylacetylene
(1a) with methyl vinyl ketone (2a, 3 equiv) under pressurized
CO (20 atm) was carried out in the presence of a catalytic
amount of Ru3(CO)12 at 140 °C for 20 h, a [3+2+1]
cycloaddition reaction took place to give the R-pyrone 3a
in 20% yield (Table 1, entry 1). A significant amount of
Table 1. Optimization of the Ru3(CO)12-Catalyzed [3+2+1]
Cycloaddition of Methyl Vinyl Ketone, Trimethylsilyl
Phenylacetylene, and CO
yieldb
entry
conditionsa
additive
3a
4a
a
Reaction conditions: 1 (0.5 mmol), 2 (1.0 mmol), Ru3(CO)12 (6 mol
1
2
3
4
5
6
140 °C, 20 h
140 °C, 20 h
140 °C, 20 h
140 °C, 20 h
140 °C, 20 h
160 °C, 8 h
none
20%
24%d
30%
trace
40%
52%
-
-
-
-
15%
7%
b
%), Et2MeN‚HI (20 mol %), toluene (2 mL), 160 °C, 8 h. Isolated yield
H2Oc
c
by flash chromatography on SiO2. 20 h.
NEt3
TsOH
Et2MeN·HI
Et2MeN·HI
the desilylation product.4b,7 When the reaction was carried
out in the presence of H2O, the yield of 3a was slighty
improved (entry 2). In this case, 2-phenylvinylsilane, a
reduced product, was also formed. The addition of NEt3 led
a
Reaction conditions: 1a (0.5 mmol), Ru3(CO)12 (6 mol %), additive
(20 mol %), toluene (2 mL), 2a (1.5 mmol (1.0 mmol for entry 6)). b Isolated
yield by flash chromatography on SiO2. c 1.8 equiv. d 2-Phenylvinylsilane
was formed.
(6) Ru3(CO)12-catalyzed carbonylative [2+2+1] cycloaddition using
ketones or aldehydes as two-assembling units, see: (a) Chatani, N.;
Morimoto, T.; Fukumoto, Y.; Murai, S. J. Am. Chem. Soc. 1998, 120, 5335.
(b) Chatani, N.; Tobisu, M.; Asaumi, T.; Fukumoto, Y.; Murai, S. J. Am.
Chem. Soc. 1999, 121, 7160. (c) Tobisu, M.; Chatani, N.; Asaumi, T.;
Amako, K.; Ie, Y.; Fukumoto, Y.; Murai, S. J. Am. Chem. Soc. 2000, 122,
12663.
unreacted 1a remained, and 1H NMR and GC-MS analyses
showed that neither the other regioisomers of 3a nor
hydroquinone was formed. Regiochemistry of the cycload-
dition product 3a was confirmed by an NMR analysis of
(7) Hua, R.; Tanaka, M. New J. Chem. 2001, 25, 179.
588
Org. Lett., Vol. 9, No. 4, 2007

to a slight improvement in the yield of 3a (entry 3). The
addition of Et2MeN‚HI gave an increased yield of 3a (40%
yield). In this reaction, a four-component coupling product
4a, in which two molecules of methyl vinyl ketone had been
incorporated, was also formed as a byproduct in 15% yield
(entry 5). The slight modification of the reaction conditions
(higher temperature, smaller amounts of 2a, and shorter
reaction time) gave a better yield of 3a (52%) and a reduced
yield of 4a (7%) (entry 6). Although [RuCl2(CO)3]2 also
exhibited catalytic activity, other ruthenium complexes and
other metal carbonyl complexes, such as RuHCl(PPh3)3,
[Cp*RuCl2]2, CpRuCl(PPh3)2, [RuCl2(η6-mesitylene)]2,
Rh6(CO)16, and Ir4(CO)12, were not effective for the present
pyrone formation.
Scheme 2. Possible Reaction Mechanism
Using Ru3(CO)12 as a catalyst and Et2MeN‚HI as an
additive, the cycloaddition of several silylacetylenes and
alkenes was carried out, and the results are shown in Table
2. The reaction of ethyl vinyl ketone 2b and octyl vinyl
ketone 2c with 1a and CO gave the corresponding R-pyrones
3b and 3c in 57 and 55% yields, respectively (entries 2 and
3). The reaction of cyclohexenone (2d) also proceeded,
giving the bicyclic R-pyrone 3d in 37% yield (entry 4).8
Aliphatic silylacetylene such as 1-(trimethylsilyl)-1-octyne
(1b) gave the corresponding R-pyrone 3e in low yield (entry
5). A variety of aryl-substituted silylacetylenes 1c-g were
examined, all of which gave the corresponding R-pyrones
3f-j in good to moderate yields (entries 6-10). Triethylsilyl-
and tigermyl-substituted acetylene 1h and 1i gave the
corresponding R-pyrones 3k and 3l in low yields (entries
11 and 12).
enolate to silylacetylene gives a vinyl ruthenium complex,
which then undergoes CO insertion to give an acyl ruthenium
complex. Cyclization, followed by â-hydride elimination
would give the R-pyrone and regenerate the ruthenium
hydride species. In our previous work on hydroquinone
synthesis by ruthenium-catalyzed [2+2+1+1] cycloaddition,
we proposed that the maleoylruthenium complex, which
arises from the reaction of ruthenium with one molecule of
alkyne and two molecules of carbon monoxide, could serve
as key intermediate.5 In the present case, the formation of
maleoylruthenium would be suppressed by the trimethylsilyl
substituent of the alkyne, but the precise reason for this is
not clear at the present stage.
In summary, we report a novel ruthenium-catalyzed
[3+2+1] cycloaddition reaction leading to tetrasubstituted
R-pyrones, which uses silylacetylenes, R,â-unsaturated ke-
tones, and CO as the starting materials. A further extension
of the present cycloaddition reaction as well as detailed
mechanistic studies are currently ongoing in our laboratory.
A possible mechanism for the present cycloaddition
reaction is shown in Scheme 2. A ruthenium hydride species,
generated from the ruthenium carbonyl complex with an
amine‚HI salt or water,9 would react with methyl vinyl ketone
(2a) to give a ruthenium enolate.10 Carboruthenation of the
Acknowledgment. I.R. acknowledges a Grant-in-Aid for
Scientific Research on Priority Areas “Advanced Molecular
Transformations of Carbon Resources” from MEXT Japan.
T.F. acknowledges a Grant-in-Aid for Young Scientists (B)
from MEXT Japan for their support of this research.
(8) Acrolein can participate in the cycloaddition leading to R-pyrone in
low yield (9%), whereas ethyl acrylate failed to react with 1a and CO.
(9) Torii, S.; Okumoto, H.; Sadakane, M.; Xu, L. H. Chem. Lett. 1991,
1673.
(10) For examples of catalytic transformations containing ruthenium
enolates: (a) Murahashi, S.-I.; Naota, T.; Taki, H.; Mizuno, M.; Takaya,
H.; Komiya, S.; Mizuho, Y.; Oyasato, N.; Hiraoka, M.; Hirano, M.; Fukuoka,
A. J. Am. Chem. Soc. 1995, 117, 12436. (b) Uma, R.; Davies, M.; Cre´visy,
C.; Gre´e, R. Tetrahedron Lett. 2001, 42, 3069. (c) Trost, B. M.; Pinkerton,
A. B. J. Am. Chem. Soc. 2000, 122, 8081. (d) Chang, S.; Na, Y.; Choi, E.;
Kim, S. Org. Lett. 2001, 3, 2089. (e) Wang, H.; Watanabe, M.; Ikariya, T.
Tetrahedron Lett. 2005, 46, 963. (f) Doi, T.; Fukuyama, T.; Minamino, S.;
Husson, G.; Ryu, I. Chem. Commun. 2006, 1875. (g) Doi, T.; Fukuyama,
T.; Horiguchi, J.; Okamura, T.; Ryu, I. Synlett 2006, 721.
Supporting Information Available: Experimental pro-
cedure and compound characterization. This material is
available free of charge via the Internet at http://pubs.acs.org.
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