Conjugated enynes as a new type of substrates for olefin metathesis

Article abstract of DOI:10.1021/ol035014z

(Matrix presented) It has been demonstrated for the first time that conjugated enynes can be employed as a facile substrate in olefin metathesis with the use of a bispyridine-substituted ruthenium benzylidene catalyst. Cross-metathesis of the enynes with

Full text of DOI:10.1021/ol035014z

ORGANIC
LETTERS
2
003
Vol. 5, No. 17
041-3043
Conjugated Enynes as a New Type of
Substrates for Olefin Metathesis
3
Byungman Kang, Do-hyeon Kim, Youngkyu Do, and Sukbok Chang*
Center for Molecular Design and Synthesis (CMDS), Department of Chemistry and
School of Molecular Science (BK21), Korea AdVanced Institute of Science and
Technology (KAIST), Daejeon 305-701, Korea
sbchang@mail.kaist.ac.kr
Received June 6, 2003
ABSTRACT
It has been demonstrated for the first time that conjugated enynes can be employed as a facile substrate in olefin metathesis with the use of
a bispyridine-substituted ruthenium benzylidene catalyst. Cross-metathesis of the enynes with alkenes turns out to proceed with preferential
formation of (Z)-isomers over (E)-isomers up to >25:1 in moderate to good yields. The intramolecular version of conjugated enynes affords
novel butadienyl cycloalkenes, which are a highly useful synthetic building blocks, in acceptable yields.
Olefin metathesis is one of the most useful tools for the C-C
bond formation in a diverse area of chemistry, including
natural product synthesis, polymerization, peptide chemistry,
of conjugated enynes has not been reported yet. Due to the
fact that conjugated enynes have been extensively used for
1
and material science. Mainly due to the advent of new
Scheme 1. Substrate Types in Ru-Benzylidene-Catalyzed
carbene catalysts with advanced properties, the scope of the
metathesis has been gradually expanded. Various substrates
Metathesis
2
3
4
such as alkenes, conjugated dienes, and alkynes are readily
reacted with olefins (Scheme 1, eq 1). However, metathesis
(1) For recent reviews of olefin metathesis, see: (a) Schuster, M.;
Blechert, S. Angew. Chem., Int. Ed. 1997, 36, 2037. (b) Grubbs, R. H.;
Chang, S. Tetrahedron 1998, 54, 4413. (c) F u¨ rstner, A. Angew. Chem., Int.
Ed. 2000, 39, 3012. (d) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001,
3
4, 18. (e) Connon, S. J.; Blechert, S. Angew. Chem., Int. Ed. 2003, 42,
1
900.
(
2) For selected examples, see: (a) Ashe, A. J., III; Fang, X. Org. Lett.
2
000, 2, 2089. (b) Williams, D. R.; Cortez, G. S.; Bogen, S. L.; Rojas, C.
M. Angew. Chem., Int. Ed. 2000, 39, 4612. (c) Garbaccio, R. M.; Stachel,
S. J.; Baeschlin, D. K.; Danishefsky, S. J. J. Am. Chem. Soc. 2001, 123,
1
0903.
3) Cabrejas, L. M. M.; Rohrbach, S.; Wagner, D.; Kallen, J.; Zenke,
G.; Wagner, J. Angew. Chem., Int. Ed. 1999, 38, 2443.
4) (a) Kim, S.-H.; Bowden, N.; Grubbs, R. H. J. Am. Chem. Soc. 1994,
(
(
1
16, 10801. (b) Kinoshita, A.; Sakakibara, N.; Mori, M. J. Am. Chem. Soc.
997, 119, 12388.
1
1
0.1021/ol035014z CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/19/2003

5
6
molecular assembly, synthesis of bioactive compounds, and
Grubbs et al. recently reported the preparation and the use
of bispyridine ruthenium benzylidene catalyst 3, which
exhibited much faster initiation rates of metathesis than the
7
preparation of novel macrocycles, the facile synthesis of
conjugated enynes would be highly desirable. Herein, we
wish to report our recent results that conjugate enynes readily
participate in metathesis to react with alkenes under both
inter- and intramolecular conditions (Scheme 1, eq 2).
At the outset of our studies, a conjugated enyne, 4-phenyl-
1
0
parent complexes 1 and 2. Surprisingly, when the catalyst
3 was employed in the reaction of conjugated enynes with
alkenes, we observed that the metathesis did proceed to
1
1
afford substituted enynes (Table 1). Acceptable yields of
1-buten-3-yne (4), was subjected to metathesis conditions
with ruthenium catalysts 1 and 2. No change was observed
even after long reaction times (72 h) at temperatures above
Table 1. Cross-Metathesis of Conjugated Enynes with Olefins
Using Catalyst 3a
7
0 °C in various solvents, and enyne 4 was quantitatively
recovered intact. In addition, the ruthenium carbenes 1 and
did not show any activity for the metathesis of alkenes in
2
the presence of enynes. For example, when allyltrimethyl-
silane (5) was added to a solution of catalyst 1 or 2 (0.2
equiv) containing enyne 4 (1.0 equiv), no cross-metathesis
compounds from the added olefin were detected under a
variety of conditions examined. The significantly reduced
activity of 1 and 2 could be explained by a strong prior
binding of the triple bond to the ruthemium center. Our
assumption was confirmed by tracing IR peaks of enyne 4
in the presence of complex 2 (Figure 1). The stretching
a
Enyne (1.0 equiv), alkene (3.0 equiv), and 3 (10 mol %) in benzene
b
(
0.2 M) at 70 °C for 18 h (except entries 6, 10, and 11). Isolated yields
1
and ratios of Z/E determined by H NMR of the crude reaction mixture.
Figure 1. Change in a triple-bond stretching frequency of 4-phenyl-
c
Performed with 2.0 equiv of olefin. d Yield of desilylated alcohol.
1
-buten-3-yne (4) upon addition of Ru-benzylidene complex 2 in
e
Reaction was carried out with 5 mol % catalyst for 10 h under otherwise
CH Cl at 25 °C: (a) 4 only (0.5 M); (b) 4 (1.0 equiv, 0.5 M) and
2
2
identical conditions.
2
4
(0.05 equiv, 7.5 h); (c) 4 (1.0 equiv) and 2 (0.2 equiv, 7.5 h); (d)
(1.0 equiv) and 2 (0.5 equiv, 7.5 h).
new enynes could be obtained with the use of 5-10 mol %
catalyst 3 in benzene at 70 °C (10-18 h). It was found that
the new double bond was generated with (Z)-selectivity and
that the extent of that selectivity varied depending on the
substrate type used. It should be noted that the (Z)-selectivity
observed in this study is highly unusual considering the fact
that, in general, (E)-alkenes are favorably formed from the
frequency of the triple bond in 4 was gradually shifted from
-
1
2217 to 2151 cm upon the addition of complex 2, which
is consistent with weakening of a triple-bond character upon
8
1
binding to a metal. In addition, H NMR spectra showed
that a new and stable carbene peak appeared by the addition
of enyne 4 to a solution of 2.9
1
2
cross-metathesis between alkenes.
(
5) (a) Dosa, P. I.; Erben, C.; Iyer, V. S.; Wasser, I. M.; Vollhardt, K.
Steric hindrance around the triple bond of the alkynyl
moiety did not affect the efficiency of the reaction (entries
P. C. J. Am. Chem. Soc. 1999, 121, 10430. (b) Moonen, N. N. P.; Boudon,
C.; Gisselbrecht, J. P.; Seiler, P.; Gross, M.; Diederich, F. Angew. Chem.,
Int. Ed. 2002, 41, 3044.
(
6) (a) Schaus, S. E.; Cavalieri, D.; Myers. A. G. Proc. Natl. Acad. Sci.
U.S.A. 2001, 98, 11075. (b) Dziegielewski, J.; Beerman, T. A. J. Biol. Chem.
002, 277, 20549.
7) Campbell, K.; Kuehl, C. J.; Ferguson, M. J.; Stang, P. J.; Tykwinski,
R. R. J. Am. Chem. Soc. 2002, 124, 7266.
8) Observation that the original triple-bond stretching frequency of 4
(9) Upon addition of enyne 4 (1.0 equiv) to a solution of catalyst 2 in
CD2Cl2, the original carbene peak (18.99 ppm) disappeared gradually on
NMR and only a new peak (18.29 ppm, singlet) was observed after 2 h at
40 °C.
(10) Love, J. A.; Morgan, J. P.; Trnka, T. M.; Grubbs, R. H. Angew.
Chem., Int. Ed. 2002, 41, 4035.
2
(
(
disappeared almost completely upon addition of 0.5 equiv of 2 might indicate
that two alkynes coordinate to the ruthenium center.
(11) Bispyridine-substituted ruthenium carbene complex 3 was prepared
according to a literature procedure (ref 10) with 80-85% yields.
3042
Org. Lett., Vol. 5, No. 17, 2003

(entry 2). The efficiency of the cyclization was improved to
some extent when the reaction was carried out in the presence
Table 2. Ring-Closing Metathesis of Alkenyl Enynes Using
Catalyst 3a
1
6
of 1 atm of ethylene gas (entries 3 and 4).
The synthetic utility of the conjugated triene products is
1
7
evident. For example, triene 14 smoothly reacted with the
dienophile, tetracyanoethylene, within a few minutes at 25
°
C to afford Diels-Alder adducts with good selectivity
1
8
(Scheme 2). The structure of the major bicyclic product
Scheme 2. Diels-Alder Reaction of 14 with
Tetracyanoethylene and the Crystal Structure of Major
Cycloadduct 15
a
b
Catalyst (15 mol %) at 70 °C for 46 h under N2. Yield of isolated
c
d
product. Catalyst (10 mol %) at 70 °C for 18 h under N2. Catalyst (10
mol %) at 70 °C for 18 h under an ethylene atmosphere (1 atm).
3
-5). Internal alkenes were also reacted with conjugated
1
5 was confirmed by a single-crystal X-ray diffraction
enynes under the same conditions to afford the corresponding
enynyl adducts (entries 5, 6, and 11). When internal
conjugated enynes bearing an alkyl substituent either in (Z)-
or (E)-form were subjected to the reaction conditions, almost
no difference was observed between the isomers judged from
yields, selectivity, and reaction rates (entries 7 and 8). It
is especially noteworthy that significantly high (Z)-selectivity
was observed from the reaction of an amido enyne (8) with
olefins (entries 10 and 11).14
1
9
analysis.
In conclusion, the first example of cross-metathesis of
conjugated enynes with alkenes has been presented with the
use of a bispyridine-substituted ruthenium catalyst, in which
preferential formation of (Z)-isomers (with selectivities
ranging from 1.1:1 to >25:1) was observed. The intra-
molecular version of the conjugated enynes gave a novel
butadiene-substituted cycloalkene system that is otherwise
difficult to attain with known synthetic procedures. Although
the chemical yields obtained were moderate with the use of
the present catalytic system, it is believed that useful and
more efficient applications should soon arise as a result of
our findings.
1
3
With the results of cross-metathesis of conjugated enynes
with alkenes, we turned our attention to an intramolecular
version with the expectation of obtaining cyclic conjugated
1
5
enynes. A malonate derivative 9 bearing both alkenyl and
enynyl groups was cyclized upon treatment with 3 to afford
a cycloheptene adduct 10 as a single product in a moderate
yield (entry 1). It turned out that catalyst 2 was also effective
for the ring closure, albeit with lower efficiency (35% yield
of 10 under otherwise identical conditions) compared to 3.
It should be noted that the generated trienyl ring system is
not easily assessed using conventional organic synthetic
procedures. Substrate 11, having a longer linker to the alkene,
was also closed to provide the corresponding macroring as
a mixture of two stereoisomers, favoring the (Z)-isomers
Acknowledgment. This work was supported by a grant
of the Korea Health 21 R&D Project, Ministry of Health
and Welfare, Republic of Korea (01-PJ1-PG1-01CH12-
0
002).
Supporting Information Available: Detailed experi-
mental procedures and spectroscopic data for all new
compounds obtained in this study. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL035014Z
(
12) Recently, kinetically controlled cross-metathesis of alkenes with high
E)-selectivity has been reported, see: Engelhardt, F. C.; Schmitt, M. J.;
Taylor, R. E. Org. Lett. 2001, 3, 2209.
13) Lee and Grubbs have described the effects of positioning an auxiliary
(
(16) For previous studies of ethylene effects on enyne metathesis, see:
(a) Mori, M.; Sakakibara, N.; Kinoshita, A. J. Org. Chem. 1998, 63, 6082.
(b) Smulik, J. A.; Diver, S. T. J. Org. Chem. 2000, 65, 1788.
(17) (a) Couturier, M.; Brassard, P. Synthesis 1994, 703. (b) Jenneskens,
L. W.; de Wolf, W. H.; Bickelhaupt, F. Chem. Ber. 1986, 119, 754.
(18) Cycloaddition reactions proceeded smoothly and quantitatively also
for other cyclic trienes prepared in this study.
(
group onto the terminal olefinic site on the stereochemistry of ring formation;
see: Lee, C. W.; Grubbs, R. H. Org. Lett. 2000, 2, 2145.
(14) Previously, acrylonitrile was found to undergo cross-metathesis with
high cis-selectivity; see: Crowe, W. E.; Goldberg, D. R. J. Am. Chem.
Soc. 1995, 117, 5162.
(
15) Conjugated enynes were prepared in high yields from alkynes with
(19) Detailed X-ray analysis data of compound 15 are described in
Supporting Information.
vinyl bromides using Sonogashira conditions. See Supporting Information.
Org. Lett., Vol. 5, No. 17, 2003
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