Ruthenium-catalyzed [2 + 2] cycloaddition of allenynes leading to a bicyclo[4.2.0]octa-1 (8),5-diene skeleton

Article abstract of DOI:10.1021/ol901616b

The reaction pathway of Cp*RuCl(cod)-catalyzed cyclization of allenynes was dramatically changed depending on the type of solvent employed. That Is, while a cyclodimerization of allenyne proceeded to give a pentacyclic compound In toluene, a bicyclo[4.2.0

Full text of DOI:10.1021/ol901616b

ORGANIC
LETTERS
2009
Vol. 11, No. 18
4124-4126
Ruthenium-Catalyzed [2 + 2]
Cycloaddition of Allenynes Leading to a
Bicyclo[4.2.0]octa-1(8),5-diene Skeleton
Nozomi Saito,* Yuki Tanaka, and Yoshihiro Sato*
Faculty of Pharmaceutical Sciences, Hokkaido UniVersity, Sapporo 060-0812, Japan
nozomi-s@pharm.hokudai.ac.jp; biyo@pharm.hokudai.ac.jp
Received July 15, 2009
ABSTRACT
The reaction pathway of Cp*RuCl(cod)-catalyzed cyclization of allenynes was dramatically changed depending on the type of solvent employed.
That is, while a cyclodimerization of allenyne proceeded to give a pentacyclic compound in toluene, a bicyclo[4.2.0]octa-1(8),5-diene derivative
was exclusively produced by [2 + 2] cycloaddition of allenyne in methanol. It was also demonstrated that the [2 + 2] cycloaddition was
catalyzed by a cationic ruthenium complex generated from Cp*RuCl(cod) and methanol in situ.
A cyclization of enynes via a ruthenacyclopentene generated
by oxidative cycloaddition of alkyne and alkene to a low-valent
ruthenium complex has been recognized as a powerful and
efficient methodology for the construction of various carbo- and
heterocycles in recent organic synthesis, and a variety of useful
reactions have been reported to date.1-3 In contrast to the
extensive studies on ruthenium-catalyzed reactions of enynes,
there are still only a few examples of reaction of allenyne
with a ruthenium catalyst.4 In the case of allenyne, two types
of ruthenacycles can be formed from a substrate and a
ruthenium complex, as shown in Scheme 1.
(1) For reviews, see: (a) Naota, T.; Takaya, H.; Murahashi, S.-i. Chem.
ReV. 1998, 98, 2599. (b) Trost, B. M.; Toste, F. D.; Pinkerton, A. B. Chem.
ReV. 2001, 101, 2067. (c) Trost, B. M.; Frederiksen, M. U.; Rudd, M. T.
Angew. Chem., Int. Ed. 2005, 44, 6630. (d) Ruthenium in Organic Synthesis;
Murahashi, S.-i., Ed.; Wiley-VCH, Inc.: New York, 2004. (e) Top.
Organomet. Chem. Vol. 11, Ruthenium Catalysts and Fine Chemistry;
Scheme 1
Bruneau, C., Dixneuf, P. H., Eds.; Springer-Verlag: Berlin-Heidelberg, 2004
.
(2) For representative examples of Ru-catalyzed enyne cyclizations, see:
(a) Chatani, N.; Morimoto, T.; Muto, T.; Murai, S. J. Am. Chem. Soc. 1994,
116, 6049. (b) Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J. Org.
Chem. 1997, 62, 3762. (c) Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T.
J. Am. Chem. Soc. 1997, 119, 6187. (d) Trost, B. M.; Toste, F. D. J. Am.
Chem. Soc. 1999, 121, 9728. (e) Trost, B. M.; Toste, F. D. J. Am. Chem.
Soc. 2000, 122, 714. (f) Trost, B. M.; Toste, F. D.; Shen, H. J. Am. Chem.
Soc. 2000, 122, 2379. (g) Trost, B. M.; Doherty, G. A. J. Am. Chem. Soc.
2000, 122, 3801. (h) Ackermann, L.; Bruneau, C.; Dixneuf, P. H. Synlett
2001, 397
.
(3) For our previous studies on Ru-catalyzed enyne cyclizations, see:
(a) Mori, M.; Saito, N.; Tanaka, D.; Takimoto, M.; Sato, Y. J. Am. Chem.
Soc. 2003, 125, 5606. (b) Mori, M.; Tanaka, D.; Saito, N.; Sato, Y.
Organometallics 2008, 27, 6313. (c) Tanaka, D.; Sato, Y.; Mori, M.
Organometallics 2006, 25, 799. (d) Tanaka, D.; Sato, Y.; Mori, M. J. Am.
Recently, we have reported a cyclodimerization of al-
lenynes giving unique pentacyclic compounds 2, which is
the first example for the reaction via type I of ruthenacy-
Chem. Soc. 2007, 129, 7730
.
10.1021/ol901616b CCC: $40.75
Published on Web 08/12/2009
 2009 American Chemical Society

clopentene derived from allenynes.5 For the reactions via
type II of ruthenacyclopentene, only intramolecular [2 + 2]
cycloaddition4a and intermolecular coupling using cyclonona-
1,2-diene have been reported so far.4b During the course of
further studies on the cyclodimerization via type I ruthena-
cyclopentene, we encountered an unexpected cyclization via
type II ruthenacyclopentene. That is, when an allenyne 1a
was reacted with Cp*RuCl(cod) in toluene under the previous
optimal conditions, the desired cyclodimerization product 2a
was obtained in only 28% yield, and an unidentified
compound 3a was produced in 63% yield (Scheme 2, eq 1).
ture of 3a, which has a bicyclo[4.2.0]octa-1(8),5-diene
skeleton. It was speculated that the product 3a is formed by
[2 + 2] cycloaddition via formation of type II ruthenacycle
followed by reductive elimination6-8 and that the existence
of the hydroxy group(s) in 1a affects the reaction pathway.
To examine the influence of hydroxy functional groups on
this reaction, the reaction of 1a with Cp*RuCl(cod) catalyst
was carried out in methanol instead of toluene (Scheme 2,
eq 2). We were surprised to find that the reaction was
completed within 2 h, and only the [2 + 2] cycloaddition
product 3a was exclusively produced in quantitative yield.
Furthermore, the reaction of 1b with Cp*RuCl(cod)
catalyst in methanol again produced only [2 + 2] cycload-
dition product 3b in quantitative yield, while the use of
toluene as a solvent in the same reaction exclusively
produced cyclodimerization product 2b in an excellent yield,
as was previously reported (Scheme 3).5 These results
Scheme 2
Scheme 3
Detailed analyses of various spectral data, including 2D-
NMR (COSY, NOESY, HMBC, HSQC, and INAD-
EQUATE, see Supporting Information), revealed the struc-
(4) For reaction of allenynes via ruthenacyclopentene, see: (a) Oh, C. H.;
Gupta, A. K.; Park, D. I.; Kim, N. Chem. Commun. 2005, 5670. (b) Bai,
T.; Xue, P.; Zhang, L.; Ma, S.; Jia, G. Chem. Commun. 2008, 2929. For
Ru-catalyzed reaction of allene and other multiple bonds, see: (c) Yamagu-
chi, M.; Kido, Y.; Omata, K.; Hirama, M. Synlett 1995, 1181. (d) Trost,
B. M.; Pinkerton, A. B. J. Am. Chem. Soc. 1999, 121, 4068. (e) Kang,
S.-K.; Kim, K.-J.; Hong, Y.-T. Angew. Chem., Int. Ed. 2002, 41, 1584. (f)
Bustelo, E.; Gue´rot, C.; Hercouet, A.; Carboni, B.; Toupet, L.; Dixneuf,
P. H. J. Am. Chem. Soc. 2005, 127, 11582. (g) Ngai, M.-Y.; Skucas, E.;
Krische, M. J. Org. Lett. 2008, 10, 2705. (h) Vovard-Le Bray, C.; De´rien,
S.; Dixneuf, P. H.; Murakami, M. Synlett 2008, 193.
indicate that the reaction pathway of ruthenium-catalyzed
cyclization of allenynes was dramatically changed depending
on the type of solVent employed and that the formation of
two quite different types of products from the identical
allenyne could be controlled by only changing the solVent.9
Thus, the [2 + 2] cycloaddition of various allenynes in
methanol was investigated, and the results are summarized
in Table 1. The cyclization of 1c in methanol proceeded
smoothly to afford the bicyclic compound 3c in 94% yield
(run 1). The reactions of 1d-g having an aromatic group or
a siloxymethyl group on the alkyne afforded 3d-g in high
yields (runs 2-5). When the allenyne with a cyclic acetal
part 1h was used as a substrate, the spiro compound 3h was
produced in 98% yield (run 6). Furthermore, fused-nitrogen
heterocyclic compound 3i was also synthesized by [2 + 2]
cycloaddition of 1i (run 7). It is noteworthy that the reaction
of these substrates in toluene under the previously optimized
conditions had exclusively proceeded via type I ruthenacy-
clopentene, affording the corresponding cyclodimerization
products in high yields.
(5) Saito, N.; Tanaka, Y.; Sato, Y. Organometallics 2009, 28, 669.
(6) For transition-metal-catalyzed [2 + 2] cycloaddition of allenynes,
see: (a) Shen, Q.; Hammond, G. B. J. Am. Chem. Soc. 2002, 124, 6534. (b)
Oh, C. H.; Park, D. I.; Jung, S. H.; Reddy, V. R.; Gupta, A. K.; Kim, Y. M.
Synlett 2005, 2092. See also: ref 4a.
(7) For recent examples of thermal [2 + 2] cycloaddition of allenynes,
see: (a) Cao, H.; Van Ornum, S. G.; Deschamps, J.; Flippen-Anderson, J.;
Laib, F.; Cook, J. M. J. Am. Chem. Soc. 2005, 127, 933. (b) Brummond,
K. M.; Chen, D. Org. Lett. 2005, 7, 3473. (c) Mukai, C.; Hara, Y.; Miyashita,
Y.; Inagaki, F. J. Org. Chem. 2007, 72, 4454. (d) Jiang, X.; Ma, S.
Tetrahedron 2007, 63, 7589. (e) Ohno, H.; Mizutani, T.; Kadoh, Y.; Aso,
A.; Miyamura, K.; Fujii, N.; Tanaka, T. J. Org. Chem. 2007, 72, 4378. (f)
Buisine, O.; Gandon, V.; Fensterbank, L.; Aubert, C.; Malacria, M. Synlett
2008, 751. See also: ref 4a.
(8) For examples of four-membered ring formation by ruthenium-
catalyzed [2 + 2] cycloaddition of multiple bonds, see: (a) Mitsudo, T.;
Kokuryo, K.; Takegami, Y. J. Chem. Soc., Chem. Commun. 1976, 722. (b)
Mitsudo, T.; Kokuryo, K.; Shinsugi, T.; Nakagawa, Y.; Watanabe, Y.;
Takegami, Y. J. Org. Chem. 1979, 44, 4492. (c) Mitsudo, T.; Naruse, H.;
Kondo, T.; Ozaki, Y.; Watanabe, Y. Angew. Chem., Int. Ed. Engl. 1994,
33, 580. (d) Yi, C. S.; Lee, D. W.; Chen, Y. Organometallics 1999, 18,
2043. (e) Yamamoto, Y.; Kitahara, H.; Ogawa, R.; Kawaguchi, H.; Tatsumi,
K.; Itoh, K. J. Am. Chem. Soc. 2000, 122, 4310. (f) Jordan, R. W.; Tam,
W. Org. Lett. 2000, 2, 3031. (g) Le Paih, J.; De´rien, S.; Bruneau, C.;
Demerseman, B.; Toupet, L.; Dixneuf, P. H. Angew. Chem., Int. Ed. 2001,
40, 2912. (h) Alvarez, P.; Gimeno, J.; Lastra, E.; Garc´ıa-Granda, S.; Van
der Maelen, J. F.; Bassetti, M. Organometallics 2001, 20, 3762. (i) Tenaglia,
A.; Giordano, L. Synlett 2003, 2333. (j) Le Paih, J.; De´rien, S.; Demerseman,
B.; Bruneau, C.; Dixneuf, P. H.; Toupet, L.; Dazinger, G.; Kirchner, K.
Chem.sEur. J. 2005, 11, 1312. See also: ref 4f.
It is known that a chloro ligand on the Ru(II) complex
having a Cp ligand dissociates in alcoholic solvents, giving
a cationic ruthenium species.10 Therefore, the reaction of 1b
withthecationicrutheniumcomplexpreparedfromCp*RuCl(cod)
and AgOTf in situ in THF was examined, and it was found
Org. Lett., Vol. 11, No. 18, 2009
4125

yields. The remarkable points of this study are as follows:
(1) the [2 + 2] cycloaddition via type II ruthenacyclopentene
formed from allenynes and ruthenium complex has been
established as a rare example and (2) it has been revealed
that the reaction pathway of ruthenium-catalyzed cyclization
of allenynes was dramatically changed depending on the
nature of the solvent employed. We also demonstrated that
the real active species of the [2 + 2] cyclization would be a
cationic ruthenium complex generated from Cp*RuCl(cod)
and methanol in situ. Although the reason why the [2 + 2]
cycloaddition proceeded via type II ruthenacycle by using
cationic species while the neutral ruthenium complex gave
a cyclodimerization product via type I intermediate is not
clear yet,11 it is notable that two quite different types of cyclic
compounds can be synthesized from the identical allenyne
by a simple operation, exchange of solvents. Further studies
are in progress.
Table 1. [2 + 2] Cycloaddition of Various Allenynesa
Acknowledgment. Part of this work was supported by a
Grant-in-Aid for Young Scientist (B) (No. 19790002) and a
Grant-in-Aid for Scientific Research (B) (No. 19390001)
from JSPS and by The Novartis Foundation (Japan) for the
Promotion of Science, The Uehara Memorial Foundation,
and Akiyama Foundation, which are gratefully acknowl-
edged.
a Reaction conditions: Cp*RuCl(cod) (5 mol %), MeOH, room
temperature.
that the reaction resulted in production of the bicyclic product
3b in quantitative yield (Scheme 4). This result strongly
Supporting Information Available: Experimental pro-
cedure and spectral data. This material is available free of
charge via the Internet at http://pubs.acs.org.
Scheme 4
OL901616B
(9) The [2 + 2] cycloaddition of 1b in MeOH at 50 °C is completed
within 1 h, giving 3b in 98% yield.
(10) For examples, see: (a) Albers, M. O.; Robinson, D. J.; Shaver, A.;
Singleton, E. Organometalllics 1986, 5, 2199. (b) Davies, S. G.; McNally,
J. P.; Smallridge, A. J. AdV. Organomet. Chem. 1990, 30, 1.
(11) It is known that the reaction pathways of transition-metal-catalyzed
cyclization of allenynes are significantly different depending on the type
of metal employed. For instance, when Rh(I) complex was used, oxidative
cyclization proceeded between alkyne and the distal double bond of allene
to give a type I metallacycle. On the other hand, a type II metallacycle
was produced in the case of Mo(0) complex. In this context, theoretical
studies on the metallacycle formation step from allenynes and Rh or Mo
complex were conducted, see: Bayden, A. S.; Brummond, K. M.; Jordan,
K. D. Organometallics 2006, 25, 5204.
supports our speculation that the cationic ruthenium complex
generated from Cp*RuCl(cod) in methanol is the real active
species and that it promotes the [2 + 2] cycloaddition.
In summary, we have succeeded in developing a Ru-
catalyzed [2 + 2] cycloaddition of allenynes that provides
various bicyclo[4.2.0]octa-1(8),5-diene derivatives in high
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