Rhodium-catalyzed three-component reaction between silylacetylene and two ketenes leading to 1,3-enynes bearing a carboxylic ester group via double insertion of ketenes

Article abstract of DOI:10.1021/ol301897h

The first cross-reaction between a terminal silylacetylene and two ketene molecules leading to 1,3-enynes bearing a carboxylic ester group via double insertion of ketenes is achieved using a cationic rhodium complex catalyst. This reaction is applicable for various symmetrical and unsymmetrical ketenes with good stereoselectivities.

Full text of DOI:10.1021/ol301897h

ORGANIC
LETTERS
2012
Vol. 14, No. 16
4214–4217
Rhodium-Catalyzed Three-Component
Reaction between Silylacetylene and Two
Ketenes Leading to 1,3-Enynes Bearing a
Carboxylic Ester Group via Double
Insertion of Ketenes
Kenichi Ogata,* Itsuki Ohashi, and Shin-ichi Fukuzawa*
Department of Applied Chemistry, Institute of Science and Enginnering,
Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan
kogata@kc.chuo-u.ac.jp; orgsynth@kc.chuo-u.ac.jp
Received July 10, 2012
ABSTRACT
The first cross-reaction between a terminal silylacetylene and two ketene molecules leading to 1,3-enynes bearing a carboxylic ester group via
double insertion of ketenes is achieved using a cationic rhodium complex catalyst. This reaction is applicable for various symmetrical and
unsymmetrical ketenes with good stereoselectivities.
Ketenes are highly reactive and important molecules in
the field of organic synthesis.1 In transition-metal complex
chemistry, many metal complexes that coordinate ketenes
by the η2-coordination mode have been reported.2 How-
ever, applications of ketenes to catalytic transformation
reactions that proceed without decarbonylation of the
ketene moiety using transition-metal catalysts have rarely
been reported,3 because transition-metal complexes of
η2-ketenes often undergo decarbonylation of the ketene
fragment, producing unreactive carbonyl complexes.4 Re-
cently, a few examples of linear coupling and cycloaddition
reactions of ketenes with alkynes have been reported.3h,i
However, examples of transition-metal catalyzed reactions
have been limited to a two-component reaction of
one molecule of ketene with a reaction partner. A three-
component cross-reaction via double insertion of two
(1) Patai, S. The Chemistry of Functional Groups: The Chemistry of
Ketenes, Allenes, and Related Compounds Part 1; John Wiley & Sons: New
York, NY, USA, 1980.
(2) For recent examples of transition-metal ketene complexes, see: (a)
Lo, H. C.; Grotjahn, D. B. J. Am. Chem. Soc. 1997, 119, 2958. (b) Bleuel,
€
E.; Laubender, M.; Weberndorfer, B.; Werner, H. Angew. Chem., Int.
Ed. 1999, 38, 156. (c) Grotjahn, D. B.; Hoerter, J. M.; Hubbard, J. L.
Organometallics 1999, 18, 5614. (d) Grotjahn, D. B.; Bikzhanova, G. A.;
Collins, L. S. B.; Concolino, T.; Lam, K.-C.; Rheingold, A. L. J. Am.
Chem. Soc. 2000, 122, 5222. (e) Grotjahn, D. B.; Collins, L. S. B.;
Wolpert, M.; Bikzhanova, G. A.; Lo, H. C.; Combs, D.; Hubbard, J. L.
J. Am. Chem. Soc. 2001, 123, 8260. (f) Werner, H.; Bleuel, E. Angew.
Chem., Int. Ed. 2001, 40, 145. (g) Grotjahn, D. B.; Hoerter, J. M.;
Hubbard, J. H. J. Am. Chem. Soc. 2004, 126, 8866. (h) Tsurugi, H.;
€
Ohno, T.; Kanayama, T.; Arteaga-Muller, R. A.; Mashima, K. Orga-
nometallics 2009, 28, 1950.
(3) (a) Hong, P.; Yamazaki, H.; Sonogashira, K.; Hagihara, N.
Chem. Lett. 1978, 535. (b) Yamazaki, H.; Hong, P. J. Mol. Catal.
1983, 21, 133. (c) Mitsudo, T.; Kadokura, M.; Watanabe, Y. Tetrahe-
dron Lett. 1985, 26, 3697. (d) Mitsudo, T.; Kadokura, M.; Watanabe, Y.
Tetrahedron Lett. 1985, 26, 5143. (e) Mitsudo, T.; Kadokura, M.;
Watanabe, Y. J. Chem. Soc., Chem. Commun. 1986, 1539. (f) Mitsudo,
T.; Kadokura, M.; Watanabe, Y. J. Org. Chem. 1987, 52, 1695. (g)
Mitsudo, T.; Kadokura, M.; Watanabe, Y. J. Org. Chem. 1987, 52, 3186.
(h) Kondo, T.; Niimi, M.; Yoshida, Y.; Wada, K.; Mitsudo, T.; Kimura,
Y.; Toshimitsu, A. Molecules 2010, 15, 4189. (i) Kumar, P.; Troast,
D. M.; Cella, R.; Louie, J. J. Am. Chem. Soc. 2011, 133, 7719.
(4) Ketene ligands of an η2-transition-metal complex have a tendency
to undergo decomposition. For recent examples, see: (a) Hoffman, P.;
Perez-Moya, L. A.; Steigelman, O.; Riede, J. Organometallics 1992,
11, 1167. (b) Grotjahn, D. B.; Bikzhanova, G. A.; Collins, L. S. B.;
Concolino, T.; Lam, K.-C.; Rheingold, A. L. J. Am. Chem. Soc. 2000,
122, 5222. (c) Urtel, H.; Bikzhanova, G. A.; Grotjahn, D. B.; Hofmann,
P. Organometallics 2001, 20, 3938. (d) Goll, J. M.; Fillion, E. Organo-
metallics 2008, 27, 3622. (e) Kondo, T.; Tokoro, Y.; Ura, Y.; Wada, K.;
Mitsudo, T. ChemCatChem 2009, 122, 5222.
r
10.1021/ol301897h
Published on Web 08/02/2012
2012 American Chemical Society

ketenes has yet to be developed. Although highly reac-
tive ketenes easily undergo homodimerization to give
β-lactones,5 a selective multicomponent reaction with other
unsaturated compounds that introduce two ketene mole-
cules via double insertion is challenging due to the need to
control the reactivity of the ketene molecules.
Table 1. Effect of Rhodium Complex Catalysts and Solventsa
We have recently reported highly selective cross-trimer-
ization of three alkynes, between two alkynes and one
alkene, using triisopropylsilylacetylene as the terminal
alkyne in the presence of a nickel catalyst.6 The sterically
hindered terminal silylacetylene plays an important role in
the selective three-component reaction. Herein, we de-
scribe a selective three-component reaction between ter-
minal silylacetylene and two ketenes using a cationic
rhodium complex catalyst leading to a 1,3-enyne bearing
a carboxylic ester group with high stereoselectivity.7 This
report is the first example of a transition-metal catalyzed
three-component reaction involving two ketenes through
double insertion of ketene molecules.
entry
rhodium catalyst
solvent
yield (%)b
1
[Rh(cod)2]BF4
[Rh(cod)2]BF4
[Rh(cod)2]BF4
[Rh(cod)2]PF6
[Rh(cod)2]OTf
[RhCl(cod)]2
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
(CH2Cl)2
CH3CN
DMF
92
2d
3e
4
92 (88)c
53
64
5
84
6d
7
4
Rh(acac)(cod)
[Rh(cod)2]BF4
[Rh(cod)2]BF4
[Rh(cod)2]BF4
[Rh(cod)2]BF4
72
8
90
9
13
10
11
trace
24
toluene
First, rhodium catalysts and solvents were screened in
the three-component reaction of triisopropylsilylacetylene
1a and diphenylketene 2a (2.2 equiv), as shown in Table 1.
Using the cationic rhodium catalyst [Rh(cod)2]BF4
(10 mol %) in dioxane solution, the selective three-component
reaction proceeded smoothly at 80 °C to afford carboxylic
ester substituted 1,3-enyne 3aa in high yield (entry 1). The
reaction also proceeded in the same yield by the use of a
5 mol % [Rh(cod)2]BF4 catalyst loading (entry 2). The yield
of 3aa was decreased with a 2 mol % catalyst loading (entry
3). Using other cationic rhodium complexes bearing PF6 or
OTf anions, the product 3aa was obtained in slightly lower
yields than that obtained using [Rh(cod)2]BF4 (entries 4
and 5). Although the chloride-bridging neutral rhodium
complex was not effective in this reaction, a neutral
rhodium complex bearing an acetylacetonate ligand parti-
cipated in this reaction to afford the product 3aa in good
yield (entries 6 and 7). When the reaction was performed
using [Rh(cod)2]BF4 in 1,2-dichloroethane solvent, pro-
duct 3aa was also obtained in high yield (entry 8). The
reaction conducted in other polar or aromatic solvents
such as acetonitrile, DMF, and toluene resulted in low
yields of 3aa (entries 9ꢀ11). On the basis of this screen of
rhodium catalysts and reaction conditions, the highest
yield for the formation of three-component product 3aa
was achieved using [Rh(cod)2]BF4 in dioxane solution. In
comparison, 3aa was not obtained using a Ni(cod)2 or
Ni(cod)2/PnPr3 catalyst, which were previously shown to
be effective for the alkyne cross-trimerization between 1a
and two molecules of internal alkynes.6
a Reaction conditions: rhodium complex (0.05 mmol), 1a (0.5 mmol),
2a (1.1 mmol), and dioxane (3 mL) were employed. b NMR yield using
1,3,5-trimethoxybenzene as internal standard. c Isolated yield. d 5 mol %
of rhodium catalyst was used. e 2 mol % of rhodium catalyst was used.
various types of terminal alkynes as shown in Table 2. When
the reaction was conducted using other bulky silylacetylene
compounds such as tert-butyldimethylsilylacetylene (1b),
triethylsilylacetylene (1c), and trimethylsilylacetylene (1d)
under these conditions, the corresponding product 3 was also
obtained, albeit the yield was lower than that using triisopro-
pylsilylacetylene (entries 2ꢀ4). The bulky propargylic silyl
ether 1e, whose masking group is readily removable as well as
the silyl group, also participated in this reaction to afford the
corresponding product 3ea in good yield (entry 5). However,
other aliphatic and aromatic alkynes such as 1-hexyne and
phenylacetylene did not participate in this reaction (entries 6
and 7). Other bulky alkylacetylenes such as 3,3,-dimethylbut-
1-yne also did not participate in this reaction.
Table 2. Rhodium-Catalyzed Three-Component Reaction
between Terminal Alkyne 1 and Diphenylketene 2aa
entry
1
R
3
yield (%)b
Using the optimized catalytic system and reaction condi-
tions, the three-component reaction was next examined using
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
SiiPr3
3aa
3ba
3ca
3da
3ea
3fa
88
72
74
50
70
0
SitBuMe2
SiEt3
(5) Tidwell, T. T. Ketenes; Wiley-Interscience: New York, 1995.
(6) (a) Ogata, K.; Murayama, H.; Sugasawa, J.; Suzuki, N.; Fukuzawa,
S.-i. J. Am. Chem. Soc. 2009, 131, 3176. (b) Ogata, K.; Sugasawa, J.;
Fukuzawa, S.-i. Angew. Chem., Int. Ed. 2009, 48, 6078. (c) Ogata, K.;
Sugasawa, J.; Atsuumi, Y.; Fukuzawa, S.-i. Org. Lett. 2010, 12, 148. (d)
Ogata, K.; Atsuumi, Y.; Fukuzawa, S.-i. Org. Lett. 2011, 13, 122.
(7) A 1,3-enyne unit bearing a carboxylic ester group was found in
marine natural products:McPhail, K. L.; France, D.; Cornell-Kennon,
S.; Gerwick, W. H. J. Nat. Prod. 2004, 67, 1010.
SiMe3
CiPr2OSiMe3
nC6H13
Ph
1g
3ga
0
a Reaction conditions: [Rh(cod)2]BF4 (0.025 mmol), 1 (0.5 mmol),
2a (1.1 mmol), and dioxane (3 mL) were employed. b Isolated yield.
Org. Lett., Vol. 14, No. 16, 2012
4215

After screening the terminal alkynes, we next examined
the scope for the ketene partner (Table 3). The unsym-
metric ketene bearing ethyl and phenyl groups participated
in this reaction to afford product 3ab in high yield
with good Z-selectivity in the double bond (entry 2).8
The use of unsymmetric ketenes bearing p-substituted
aryl groups such as electron-donating (methyl and methoxy)
or electron-withdrawing (fluoro and chloro) substituents
also afforded product 3 in good to high yields with good
stereoselectivities (entries 2ꢀ6). The reaction with a ketene
bearing a methyl group 2g also proceeded to give the
corresponding product 2ag with good stereoselectivity
(entry 7). However, upon replacement of either the ethyl
or methyl group with an isopropyl group, the correspond-
ing three-component product 3ah was formed in low yield,
and two-component product 4ah was also obtained (entry 8).
Reactions of 2i and 2j, which possess two aliphatic groups
such as n-alkyl and cyclic alkyl groups, also proceeded to
form the products 3ai and 3aj (entries 9 and 10).
Table 3. Rhodium-Catalyzed Three-Component Reaction
between Triisopropylsilylacetylene 1a and Ketenes 2a
To confirm the structure by X-ray analysis and demon-
strate the synthetic utility, products 3aa and 3af were
subjected to click chemistry, which has been widely used
as a method for the synthesis of 1,2,3-triazoles.9 The silyl
groups of 3aa and 3af were readily removed by treatment
with tetrabutylammonium fluoride (TBAF), and the re-
sulting crude products could participate in a click reaction
with ferrocenylmethyl azide to afford 4-substituted 1,2,3-
triazoles 5aa and 5af (Z/E = 85:15), respectively, in the
presence of CuSO4/Na-L-ascorbate (Scheme 1). In the case
of 5af, the two stereoisomers (Z/E) could be separated by
recrystallization.10 Products 5aa and 5af-E were subjected
to X-ray diffraction, and stereostructures for the reaction
using an unsymmetrical ketene were revealed(see Support-
ing Information).11
To examine the reaction mechanism for the three-
component reaction, we carried out the following experi-
ments. Since the reaction between triisopropylsilylacetylene
and diketene (β-lactone), which was prepared by catalytic
ketene dimerization,12 did not proceed, the possibility of
the mechanism occurring via dimerization of the ketene,
followed by ring-opening hydroalkynylation, could be
ruled out.13 In addition to this experiment, the reaction
using rhodium acetylide complex 6, which was prepared by
(8) The stereostructure of the product which was obtained by the
reaction of unsymmetric ketene was determined by X-ray analysis of
compound 5; see ref 11 and Supporting Information.
(9) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2002, 41, 2596. (b) Bock, V. D.; Hiemstra, H.;
Maarseveen, van, J. H. Eur. J. Org. Chem. 2006, 51.
(10) Stereoisomers of 5af-Z and 5af-E were separated by repeating
recrystallization in toluene/hexane solution, respectively (5af-Z: 26%
yield, 5af-E: 3% yield).
a Reaction conditions: [Rh(cod)2]BF4 (0.025 mmol), 1a (0.5 mmol), 2
(1.1 mmol), and dioxane (3 mL) were employed. b Isolated yield. c Ratio
of stereoisomer (Z/E) which was determined by 1H NMR. d Stereo-
structure of isomers were not determined.
(11) CCDC 879868 (5aa) and 879867 (5af) contain the supplemen-
tary crystallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif.
(12) Corresponding β-lactone was prepared by the dimerization
reaction of 2a in the presence of the PnBu3 catalyst:Wei, P.-H.; Ibrahim,
A. A.; Mondal, M.; Nalla, D.; Harzmann, G. D.; Tedeschi, F. A.;
Wheeler, K. A.; Kerrigan, N. J. Tetrahedron Lett. 2010, 51, 6690.
(13) The reaction of 1a and β-lactone under the same reaction
conditions of a three-component reaction resulted in recovery of
β-lactone quantitatively.
the reaction of [RhCl(cod)]2 with 2 equiv of lithium
triisopropylsilylacetylide, was carried out (Scheme 2).14
(14) Synthesis, characterization, and an ORTEP drawing of acetylide
complex 6 were described in the Supporting Information. The CCDC of 6
(883083) contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
4216
Org. Lett., Vol. 14, No. 16, 2012

Scheme 1
Scheme 3
Upon treatment of 6 with diphenylketene 2a, followed by
protonation, product 3aa was obtained. This result indi-
cated that the catalytic three-component reaction pro-
ceeded via a rhodiumꢀacetylide intermediate formed by
the cationic rhodium complex with the terminal silylace-
tylene in the first step, and protonation occurred in the
last step.
bond to afford intermediate C. Lastly, the formation of 3
was achieved by protonation of C by HBF4, which was
generated in the first step.15 When sterically hindered
ketene 2h bearing an isopropyl group was used (Table 1,
entry 8), product 4ah was also produced. The formation of
4ah was likely a result of steric hindrance; the second
ketene was difficult to insert into the rhodiumꢀoxygen
bond of intermediate B. As a result, protonation of inter-
mediate B resulted in the formation of product 4.
In summary, we have demonstrated a three-component
coupling reaction between terminal silylacetylene and two
ketenes leading to 1,3-enynes bearing a carboxylic ester
group with high stereoselectivities using a cationic rhodium
complex catalyst. This is the first example of a transition-
metal catalyzed three-component reaction through double
insertion of ketenes.
Scheme 2
A possible pathway for the three-component reaction
between terminal silylacetylene and two molecules of
ketene is shown in Scheme 3. First, neutral rhodium
acetylide complex A was formed by the reaction of the
cationic rhodium complex with terminal silylacetylene.
Next, the insertion of a ketene into the rhodiumꢀalkynyl
bond of A via π-coordination of the ketene to the rhodium
metal2b,c,f resulted in the formation of oxa-π-allyl inter-
mediate B. In the reaction using an unsymmetric ketene,
the stereoselectivity of product 3 can be explained because
it avoids the steric hindrance between the aryl group and
the alkynyl moiety of oxa-π-allyl intermediate B0, and thus
intermediate B is generated preferentially. Next, another
ketene molecule was inserted into the rhodiumꢀoxygen
Acknowledgment. This work was financially supported
by a Grant-in-Aid for Young Scientists B from the Japan
Society for the Promotion of Science (JSPS), Japan.
Supporting Information Available. Standard experi-
mental procedure, characterization data for the new
products. This material is available free of charge via
the Internet at http://pubs.acs.org.
(15) In a recent example of a [Rh(cod)2]BF4-catalyzed reaction
between triisopropylsilylacetylene and two internal alkynes, a mecha-
nism via a rhodiumꢀacetylide complex, protonation with HBF4 in the
last step was proposed: Shibata, Y.; Tanaka, K. Angew. Chem., Int. Ed.
2011, 50, 10917.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 16, 2012
4217