An Efficient Method for Cyclopentene Annulation onto α,β-Unsaturated Ketones: W(CO)5(L)-Catalyzed 5-Endo-Dig Cyclization of 6-Siloxy-5-en-1-ynes

Article abstract of DOI:10.1021/ol026993i

(Matrix Presented) A highly efficient method for the cyclopentene annulation onto α,β-unsaturated ketones is described. Indium-mediated 1,4-propargylation onto α,β-unsaturated ketones in the presence of tert-butyldimethylsilyl triflate and dimethyl sulfid

Full text of DOI:10.1021/ol026993i

ORGANIC
LETTERS
2002
Vol. 4, No. 25
4463-4466
An Efficient Method for Cyclopentene
Annulation onto r,â-Unsaturated
Ketones: W(CO)5(L)-Catalyzed
5-Endo-Dig Cyclization of
6-Siloxy-5-en-1-ynes
,†
Nobuharu Iwasawa,* Tomoya Miura,† Koichi Kiyota,† Hiroyuki Kusama,†
,‡
Kooyeon Lee,‡ and Phil Ho Lee*
Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku,
Tokyo 152-8551, Japan, and Department of Chemistry, Kangwon National UniVersity,
Chunchon 200-701, Republic of Korea
niwasawa@chem.titech.ac.jp
Received September 30, 2002
ABSTRACT
A highly efficient method for the cyclopentene annulation onto r,â-unsaturated ketones is described. Indium-mediated 1,4-propargylation
onto r,â-unsaturated ketones in the presence of tert-butyldimethylsilyl triflate and dimethyl sulfide gives the 6-siloxy-5-en-1-yne derivatives,
which undergo W(CO)5(L)-catalyzed 5-endo-dig cyclization to give the corresponding cyclopentene derivatives in good yield.
Development of concise methods for the annulation of a five-
membered ring onto alkenes is highly valuable in the field
of synthetic organic chemistry because such methods enable
a facile construction of useful carbon frameworks found in
various biologically active natural products.1,2 Although a
variety of methods have been developed for this purpose, it
is not necessarily easy to realize annulation of a simple three-
carbon unit onto R,â-unsaturated ketones by a concise
procedure.
trimethylsilylallenes and R,â-unsaturated ketones in the
presence of a stoichiometric amount of TiCl4 to afford
substituted cyclopentene derivatives.3 However, it is difficult
to obtain the parent, nonsubstituted cyclopentene derivative
because trimethylsilylpropa-1,2-diene itself failed to partici-
pate in this reaction.
We recently reported a novel, W(CO)5(L)-catalyzed cy-
clization of ω-acetylenic silyl enol ethers,4 where 5-siloxy-
5-en-1-ynes undergo 6-endo cyclization,4a while 7-siloxy-
6-en-1-ynes undergo either 5-exo or 6-endo cyclization by
For instance, Danheiser et al. have developed a highly
useful method for a one-step [3 + 2] annulation of substituted
(3) (a) Danheiser, R. L.; Carini, D. J.; Basak, A. J. Am. Chem. Soc. 1981,
103, 1604. (b) Danheiser, R. L.; Carini, D. J.; Fink, D. M.; Basak, A.
Tetrahedron 1983, 39, 935. (c) Danheiser, R. L.; Fink, D. M.; Tsai, Y.-M.
Org. Synth. 1988, 66, 8. See also: Panek, S. J. In ComprehensiVe Organic
Synthesis; Trost, B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 1, pp
596-607.
(4) (a) Maeyama, K.; Iwasawa, N. J. Am. Chem. Soc. 1998, 120, 1928.
(b) Iwasawa, N.; Maeyama, K.; Kusama, H. Org. Lett. 2001, 3, 3871. (c)
Miura, T.; Iwasawa, N. J. Am. Chem. Soc. 2002, 124, 518. (d) Kusama,
H.; Yamabe, H.; Iwasawa, N. Org. Lett. 2002, 4, 2569 and references for
W(CO)5(L)-promoted reactions cited therein. See also: (e) Imamura, K.;
Yoshikawa, E.; Gevorgyan, V.; Yamamoto, Y. Tetrahderon Lett. 1999, 40,
4081. (f) Imamura, K.; Yoshikawa, E.; Gevorgyan, V.; Sudo, T.; Asao, N.;
Yamamoto, Y. Can. J. Chem. 2001, 79, 1624.
* Corresponding authors. E-mail (P.H.L.): phlee@kangwon.ac.kr.
† Tokyo Institute of Technology.
‡ Kangwon National University.
(1) For a review on the cyclopentene annulation, see: (a) Ramaiah, M.
Synthesis 1984, 529. (b) Trost. B. M. Angew. Chem., Int. Ed. Engl. 1986,
25, 1.
(2) For recent examples of cyclopentannulation, see: (a) Crimmins, M.
T.; Tabet, E. A. J. Org. Chem. 2001, 66, 4012. (b) England, D. B.; Kuss,
T. D. O.; Keddy, R. G.; Kerr, M. A. J. Org. Chem. 2001, 66, 4704. (c)
Barluenga, J.; Mart´ınez, S.; Sua´rez-Sobrino, A. L.; Toma´s, M. J. Am. Chem.
Soc. 2002, 124, 5948. (d) Ding, P.; Ghosez, L. Tetrahedron 2002, 58, 1565.
(e) Mahuteau-Betzer, F.; Ghosez, L. Tetrahedron 2002, 58, 6991 and
references therein.
10.1021/ol026993i CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/16/2002

the appropriate choice of the reaction conditions.4b On the
other hand, only one specific example was disclosed for the
5-endo cyclization of the 6-siloxy-5-en-1-yne derivative.4a
One reason for this scarcity is the lack of a good and simple
method for the preparation of the requisite substrates.
Therefore development of a concise method for the direct
1,4-propargylation onto R,â-unsaturated ketones with si-
multaneous silylation of the produced enolates is highly
desirable.5,6 Recently, we reported that 3-tert-butyldimeth-
ylsiloxyalk-2-enylsulfonium salts generated in situ by the
reaction of R,â-unsaturated ketones with tert-butyldimeth-
ylsilyl triflate and dimethyl sulfide undergo 1,4-allylation
with allylindium reagents to afford the corresponding 1,4-
allylated silyl enol ethers (formal 1,4-addition onto R,â-
unsaturated ketones) in good yields.7 We thought of applying
this protocol for the preparation of 6-siloxy-5-en-1-yne
derivatives using propargyl bromide instead of allyl bromide.8
We then decided to examine the indium-mediated 1,4-
propargylation onto R,â-unsaturated ketones in the presence
of tert-butyldimethylsilyl triflate and dimethyl sulfide.
To a THF solution of cyclohex-2-en-1-one 1a were added
t-butyldimethylsilyl triflate and dimethyl sulfide successively
to afford in situ 3-tert-butyldimethylsiloxycyclohex-2-enyl-
sulfonium salt, which was treated at -78 °C with organoin-
dium reagent generated in situ from indium-metal and
propargyl bromide in THF at room temperature.7 Gratify-
ingly, usual workup of the reaction mixture gave the desired
silyl enol ether 2a in 76% yield. Trace amounts of the 1,2-
Table 1. Indium-Mediated 1,4-Propargylation of
R,â-Unsaturated Ketones
1
adduct and allenylated products were detected by H NMR
spectra of the crude product. As summarized in Table 1, the
present preparative method was found to be generally
applicable to the conjugate propargylation onto cyclic
alkenones. On the other hand, the reaction onto acyclic
alkenones did not proceed as expected, and a rather low yield
of the desired product was obtained when chalcone 2g was
employed.
Since various requisite substrates were obtained by this
method, we next examined the W(CO)5(thf)-catalyzed 5-endo
cyclization of these substrates. When the 6-siloxy-5-en-1-
yne derivative 2a was treated with 10% molar amounts of
preformed W(CO)5(thf) in the presence of 1 equiv of H2O,
it was completely consumed at room temperature within 5
days to give the endo-cyclized bicyclo[4.3.0]non-7-en-5-one
3a in 72% yield. The reaction is thought to proceed as
follows: treatment of 2a with W(CO)5(thf) would give an
alkyne-W(CO)5 π-complex A, which is in equilibrium with
the 1,2-hydrogen-migrated vinylidene complex B; nucleo-
philic attack of the silyl enol ether to the π-complex A and/
or the vinylidene complex B occurs to give the vinylmetallic
species C or D, which is protonated by H2O to give 3a
(Scheme 1).9,10
(5) Generally, 1,4-propargylation onto R,â-unsaturated ketones is not an
easy process because 1,2-addition of propargyl (or allenyl) metallic reagents
usually occurs preferentially. Some exceptions were reported using allenyltin
and several other reagents; see: (a) Shibata, I.; Kano, T.; Kanazawa, N.;
Fukuoka, S.; Baba, A. Angew. Chem., Int. Ed. 2002, 41, 1389. (b) Haruta,
J.; Nishi, K.; Matsuda, S.; Akai, S.; Tamura, Y.; Kita, Y. J. Org. Chem.
1990, 55, 4853. (c) Corey, E. J.; Ru¨cker, C. Tetrahedron Lett. 1982, 23,
719. (d) Paquette, L. A.; Han. Y.-K. J. Am. Chem. Soc. 1981, 103, 1831.
(6) Reaction with allyltri-n-butyltin with chalcone in the presence of
TaCl5 and TMSCl was reported to give the conjugate adduct as a silyl enol
ether.5a When we carried out the conjugate addition of allenyltri-n-butyltin
with chalcone in the presence of TaCl5 and a silyl chloride such as TMSCl
or TBSCl, only hydrolyzed conjugate adduct was obtained and none of the
desired silyl enol ether was detected in the crude mixtures.
As summarized in Table 2, the 5-endo cyclization mostly
proceeded smoothly to give the corresponding cyclopentene
derivatives 3 in good yields using 5-10% molar amounts
of W(CO)5(thf).11 Only in the case of the acyclic substrate
2g was it necessary to employ 30% molar amounts of
(9) To obtain information on the mechanism of this reaction, we have
carried out D2O experiments. The reaction of 2d in the presence of 3.0
equiv of D2O instead of H2O revealed that both olefinic protons were
partially deuterated and that the degree of deuterium incorporation at the
two olefinic protons was a total of about one proton. On the basis of these
results, we propose that the cyclization takes place both through the alkyne-
W(CO)5 π-complex and the vinylidene complex: the ratio of two reaction
pathways is about 7:3 (π-complex vs vinylidene complex) for 2d.
(10) Stereochemistry of the ring junction is assigned as cis by a NOE
experiment; for details, see Supporting Information.
(7) Lee, P. H.; Lee, K.; Kim, S. Org. Lett. 2001, 3, 3205.
(8) For examples of In-mediated propargylation or allenylation, see: (a)
Nair, V.; Jayan, C. N.; Ros, S. Tetrahedron 2001, 57, 9453. (b) Yi, X.-H.;
Meng, Y.; Hua, X.-G.; Li, C.-J. J. Org. Chem. 1998, 63, 7472. (c) Isaac,
M. B.; Chan, T.-H. J. Chem. Soc., Chem. Commun. 1995, 1003.
4464
Org. Lett., Vol. 4, No. 25, 2002

Scheme 1
Table 3. 5-Endo Cyclization of ω-Acetylenic Silyl Enol Ethers
Using a Catalytic Amount of W(CO)5(dabco) in Toluenea
W(CO)5(thf) to give the desired product 3g in good yield.
Although 5-endo-dig cyclization is a favored process ac-
cording to the Baldwin’s rule,12 there are very few reports
Table 2. 5-Endo Cyclization of ω-Acetylenic Silyl Enol Ethers
Using a Catalytic Amount of W(CO)5(thf) in THFa
a Stereochemistry of the ring junction was assigned by a NOE experiment.
For details, see Supporting Information. Conditions: A toluene solution of
the substrate, a 10% molar amount of W(CO)6, and 2 molar amounts of
DABCO was irradiated at ambient temperature for 8-10 h.
on this type of cyclization, in particular, for the nucleophilic
carbocycle formations.13
We next carried out this cyclization in the presence of
DABCO instead of H2O.4d When the reaction was performed
with 10% molar amounts of W(CO)6 in toluene under
photoirradiation conditions14 for 10 h in the presence of 2
molar amounts of DABCO, all the reactions proceeded
(11) Products 3a-f were accompanied by a small amount (about 3% of
the product) of an olefinic regioisomer such as 3a′. The reason for the
formation of this compound is not yet obvious.
(12) (a) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734. (b)
Baldwin, J. E.; Cutting, J.; Dupont, W.; Kruse, L.; Silberman, L.; Thomas,
R. C. J. Chem. Soc., Chem. Commun. 1976, 736.
(13) To our knowledge, only two methods have been reported for the
transition metal-promoted nucleophilic 5-endo-dig carbocyclization besides
our original contribution;4a see: (a) McDonald, F. E.; Olson, T. C.
Tetrahedron Lett. 1997, 38, 7691. (b) Imamura, K.; Yoshikawa, E.;
Gevorgyan, V.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 5339. (c)
Asao, N.; Yamamoto, Y. Bull. Chem. Soc. Jpn. 2000, 73, 1071. See also:
(d) Amrein, S.; Studer, A. Chem. Commun. 2002, 1592. (e) Tanaka, K.;
Fu, G. C. J. Am. Chem. Soc. 2001, 123, 11492.
(14) Reaction in the presence of DABCO needs photoirradiation for
smooth conversion.4d It is known that photoirradiation enhances dissociation
of an amine from the W(CO)5(amine) complex; see: Kirtley, S. W. In
ComprehensiVe Organometallics Chemistry; Wilkinson, G., Stone, F. G.
A., Abel, E. W., Eds; Pergamon Press: Oxford, UK, 1982; Vol. 3, p 1079.
a Stereochemistry of the ring junction was assigned by a NOE experiment
except for 3g. For details, see Supporting Information. b Conditions: A
preformed 10% molar amount of W(CO)5(thf) and 1 equiv of H2O were
added to the substrate. The mixture was stirred at room temperature for
4-5 days. c W(CO)5(thf) (5% molar amount) was used. d W(CO)5(thf) (30%
molar amount) was used.
Org. Lett., Vol. 4, No. 25, 2002
4465

reaction proceeded smoothly at room temperature to give
the iodo-substituted cyclopentene derivative 6a in 66% yield.
Although this cyclization required a stoichiometric amount
of W(CO)5(thf), the iodo-substituted cyclopentene derivatives
were obtained in good yields without formation of the
alternative iodine positional isomer.
Scheme 2
In conclusion, we have developed an efficient method for
the annulation of a simple three carbon unit onto R,â-
unsaturated ketones by the indium-mediated propargylation
followed by the W(CO)5(thf)-catalyzed cyclization to give
cyclopentene derivatives in good yield. Very rare 5-endo-
dig carbocyclization was found to proceed smoothly in all
cases. This reaction should be of practical use due to its
simple procedure and the high utility of the products.
Acknowledgment. This research was partly supported by
a Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science, and Technology of
Japan. T. M. has been granted a Research Fellowship of the
Japan Society for the Promotion of Science for Young
Scientists. We thank Central Glass Co., Ltd., for a generous
gift of TfOH and Nippon Zeon Co., Ltd., for a generous
gift of 2-methylcyclopent-2-en-1-one.
without any problem to afford the desired bicyclic silyl enol
ethers 4 in good yields as summarized in Table 3.15 The
produced silyl enol ethers would be employable for further
carbon-carbon bond-forming reaction.
Finally, this 5-endo cyclization was applied to another
useful reaction, that is, the reaction of the iodinated vi-
nylidene complexes generated from 1-iodo-1-alkynes and
W(CO)5(thf).4c Thus, when the ω-iodoacetylenic silyl enol
ether 5a was treated with an equimolar amount of W(CO)5-
(thf) in the presence of 15 molar amounts of H2O, the
Supporting Information Available: Preparative methods
and spectral and analytical data of compounds 2-6. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(15) Isolated products 4a, 4e, and 4f were gradually isomerized to the
bicyclo[4.3.0]nona-1,8-diene derivatives.
OL026993I
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