New zirconium-mediated approach toward regio- and stereocontrolled synthesis of trans-enediynes

Article abstract of DOI:10.1021/ol052706+

The coupling reactions of α-alkynylated zirconacyclopentene based on 1,4-bis(trimethylsilyl)-1,3-butadiyne with unsaturated compounds are described, which provide an efficient, regio- and stereocontrollable synthesis of trans-enediynes in a one-pot procedure. An interesting alkynyl group shift from α- to β-position of the zirconium center during the reaction was observed, which was accountable for the novel transformations to trans-enediynes.

Full text of DOI:10.1021/ol052706+

ORGANIC
LETTERS
2006
Vol. 8, No. 2
309-311
New Zirconium-Mediated Approach
Toward Regio- and Stereocontrolled
Synthesis of trans-Enediynes
Yuanhong Liu* and Hongjun Gao
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, People’s Republic of China
yhliu@mail.sioc.ac.cn
Received November 8, 2005
ABSTRACT
The coupling reactions of
described, which provide an efficient, regio- and stereocontrollable synthesis of trans-enediynes in a one-pot procedure. An interesting alkynyl
group shift from - to -position of the zirconium center during the reaction was observed, which was accountable for the novel transformations
to trans-enediynes.
r-alkynylated zirconacyclopentene based on 1,4-bis(trimethylsilyl)-1,3-butadiyne with unsaturated compounds are
r
â
Enediynes (hex-3-ene-1,5-diynes, DEEs) represent important
building blocks for the construction of π-conjugated poly-
mers and designed nanoarchitectures, which have attracted
much interest due to their wide applications as advanced
materials with unique electronic and photonic properties such
as in molecular wires, switches, organic conductors, poly-
electrochromic materials, and light-emitting diodes, etc.1
Especially, oligomers having an enyne or enediyne scaffold
with an olefin substituent would greatly enhance the solubil-
ity of the materials, which permits investigation and modi-
fication of their structural and electronic properties.2 As a
consequence, much attention has been paid to the synthesis
of enediyne derivatives. Metal-catalyzed cross coupling
between alkenyl halides and terminal acetylenes or metal
acetylides provides one of the most versatile routes for
enediynes.3 The stereochemical outcome of the reaction is
highly dependent on the experimental conditions and the
substituents on the alkene groups. The preparation of (Z)
and/or (E)-DEEs could also be achieved by elimination of a
silanol from R-silyl alcohols,4 a carbenoid coupling elimina-
tion strategy,5 acid- or base-induced elimination of alcohols,6
alkyne metathesis,7 or Pd-catalyzed dimerization,8 etc.9
(3) (a) Walker, J. A.; Bitler, S. P.; Wudl, F. J. Org. Chem. 1984, 49,
4733. (b) Uenishi, J.; Kawahama, R.; Yonemitsu, O. J. Org. Chem. 1996,
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G. W., II; Hynd, G.; Huber, R. S.; Mathews, J. E. J. Am. Chem. Soc. 2000,
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(1) For reviews, see: (a) Nielsen, M. B.; Diederich, F. Chem. ReV. 2005,
105, 1837. (b) Martin, R. E.; Diederich, F. Angew. Chem., Int. Ed. 1999,
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Bosshard, C.; Gisselbrecht, J.; Diederich, F.; Gu¨nter, P.; Gross, M.; Bre´das,
J. Chem.-Eur. J. 2000, 6, 3622. (b) Takayama, Y.; Delas, C.; Muraoka,
K.; Uemura, M.; Sato, F. J. Am. Chem. Soc. 2003, 125, 14163. (c) Nakano,
Y.; Ishizuka, K.; Muraoka, K.; Ohtani, H.; Takayama, Y.; Sato, F. Org.
Lett. 2004, 6, 2373.
10.1021/ol052706+ CCC: $33.50
© 2006 American Chemical Society
Published on Web 12/30/2005

Nevertheless, the development of new protocols that allow
stereoselective and one-pot synthesis of enediynes from
readily available precursors is highly attractive. In this paper,
we report novel zirconium-mediated coupling reactions of
three different components involving 1,4-bis(trimethylsilyl)-
1,3-butadiyne, allylic ether, and alkynyl bromide in a one-
pot procedure, which provide an efficient regio- and stere-
ocontrollable synthesis of trans-enediynes (Scheme 1).
pentenes, which afforded dideuterated enyne after deuteri-
olysis and R-alkynylcyclopentenones by treatment with CO/
I2.11b In the case of diaryldiynes, a reductive elimination
proceeded upon heating or in the presence of DMAD.11c
Here, we found that treatment of zirconacycle 1 derived from
disilyldiyne with an excess amount (2 equiv) of allyloxytri-
methylsilane13b at 50 °C followed by the reaction with
alkynyl bromide14 (1.0 equiv) in the presence of a catalytic
amount of CuCl (5%) afforded trans-enediyne 2 smoothly
in good to excellent yields (Scheme 2).
Scheme 1
Scheme 2
The organometallic complexes of diynes R(CtC)2R and
polyynes R(CtC)nR with group 4 metallocenes have at-
tracted considerable attention owing to their fascinating
structural features, their unique M-C bonding, and their
unusual capacity to induce highly selective transformation
reactions.10 Takahashi et al. reported that the reaction of 1,3-
butadiynes with a zirconocene-ethylene complex gave
zirconacyclopentenes bearing an alkynyl substituent exclu-
sively at the R-position.11 Zirconacyclopentenes are known
to undergo cross-coupling reactions with unsaturated com-
pounds through a facile â,â′-carbon-carbon bond cleavage
reaction along with elimination of one ethylene molecule.12
Thus, the behavior of zirconacyclopentenes can be viewed
as a zirconocene-alkyne complex. In an attempt to achieve
coupling reactions of R-alkynylated zirconacyclopentenes
with elimination of ethylene,13 we observed the trans-
enediyne formation reaction.
The representative results are listed in Table 1. A number
of aryl-substituted (electron-deficient and electron-rich aro-
Table 1. Formation of trans-Enediynes
Reactions of conjugated diyne with Cp2Zr(CH2dCH2) in
situ prepared from Cp2ZrEt2 gave R-alkynylzirconacyclo-
(8) Camacho, D. H.; Saito, S.; Yamamoto, Y. J. Am. Chem. Soc. 2002,
124, 924.
(9) For Zr-mediated cis-enediyne formation, see: Liu, Y.; Zhong, Z.;
Nakajima, K.; Takahashi, T. J. Org. Chem. 2002, 67, 7451. For Ti-mediated
multistep (E)-enediyne formation, see refs 2b,c.
(10) For reviews, see: (a) Rosenthal, U.; Burlakov, V. V.; Arndt, P.;
Baumann, W.; Spannenberg, A. Organometallics 2005, 24, 456, and the
references therein. (b) Rosenthal, U.; Burlakov, V. V.; Arndt, P.; Baumann,
W.; Spannenberg, A. Organometallics 2003, 22, 884. (c) Rosenthal, U.;
Pellny, P.; Kirchbauer, F. G.; Burlakov, V. V. Acc. Chem. Res. 2000, 33,
119.
(11) (a) Takahashi, T.; Aoyagi, K.; Denisov, V.; Suzuki, N.; Choueiry,
D.; Negishi, E. Tetrahedron Lett. 1993, 34, 8301. (b) Takahashi, T.; Xi,
Z.; Nishihara, Y.; Huo, S.; Kasai, K.; Aoyagi, K.; Denisov, V.; Negishi E.
Tetrahedron 1997, 53, 9123. (c) Liu, Y.; Sun, W.; Nakajima, K.; Takahashi,
T. Chem. Commun. 1998, 1133.
(12) (a) Takahashi, T.; Kageyama, M.; Denisov, V.; Hara, R.; Negishi,
E. Tetrahedron Lett. 1993, 34, 687. (b) Takahashi, T.; Xi, C.; Xi, Z.;
Kageyama, M.; Fischer, R.; Nakajima, K.; Negishi, E. J. Org. Chem. 1998,
63, 6802.
(13) To the best of our knowledge, there is no report concerning the
coupling reaction of R-alkynylated zirconacyclopentenes with elimination
of ethylene. For the carbon-carbon bond formation reaction of alkyl- or
aryl-substituted zirconacyclopentenes via elimination of ethylene molecule,
see: (a) Takahashi, T.; Kondakov, D. Y.; Xi, Z.; Suzuki, N. J. Am. Chem.
Soc. 1995, 117, 5871. (b) Takahashi, T.; Kotora, M.; Kasai, K.; Suzuki, N.
Tetrahedron Lett. 1994, 35, 5685. (c) Takahashi, T.; Kondakov, D. Y.;
Suzuki, N. Tetrahedron Lett. 1993, 34, 6571. (d) Takahashi, T.; Kondakov,
D. Y.; Suzuki, N. Chem. Lett. 1994, 259.
a GC yield; isolated yields are in parentheses. b All the reactions were
carried out at 50 °C for 1 h.
matics) alkynylation agents could be incorporated success-
fully into the sequence. The corresponding enediynes were
obtained in 63-98% yield.
The functionalities of NO2, Cl, MeO, and CF3 groups in
the aromatic ring were tolerated during the reaction, affording
the corresponding products 2 in good to high yields (Table
(14) (a) Hara, R.; Liu, Y.; Sun, W.; Takahashi, T. Tetrahedron Lett. 1997,
38, 4103. (b) Liu, Y.; Shen, B.; Kotora, M.; Takahashi, T. Angew. Chem.,
Int. Ed. 1999, 38, 949-952. (c) Liu, Y.; Song, F.; Cong, L. J. Org. Chem.
2005, 70, 6999.
310
Org. Lett., Vol. 8, No. 2, 2006

1, entries 1, 3-5, and 7). The present method worked well
with butyl-, cyclohexenyl-, or ester-substituted alkynyl
bromides, furnishing the products 2g-2j in 75-93% yields
(Table 1, entries 8-10).
Scheme 4
The stereochemistry of trans-enediyne was unambiguously
established by X-ray single-crystal analysis of an enediyne
dimer 3c (Scheme 3) which was prepared by desilylation of
Scheme 3
a change of solvent from THF to toluene, which increased
the yield of 7b to 89% at 80 °C for 1 h. In both cases, no
homocoupling products of the alkynes were observed.
These results clearly demonstrate that the formation of the
zirconocene-butadiyne complex proceeded via a â,â′-C-C
bond cleavage reaction at higher temperature, which could
direct regioselective olefin or alkyne coupling by locating a
silyl group at the R-position of a zirconacycle intermediate.19
We believe that both electronic (trialkylsilyl groups are
known to stabilize R-carbanions)19 and steric factors are
responsible for the regiochemical outcome of the coupling
reactions. The mechanism for allylation of the zirconocene-
butadiyne complex to give 4 is similar to that found in allyl
zirconation reactions using zirconocene-alkyne complexes.13
Thus, the trans-enediynes 3 were formed by the coupling
reactions of alkynyl bromides with intermediate 4 in the
presence of CuCl.
In conclusion, we have developed an efficient and selective
synthesis of trans-enediynes from 1,3-butadiyne precursors.
This methodology allows for the ready synthesis of trans-
enediynes with different substituents in the central double
bond that are difficult to prepare by other available proce-
dures. Clarification of the reaction mechanism and utilizing
this and related methodologies for the synthesis of π-con-
jugated polymers will be the subject of future reports.
2d followed by an oxidative Hay coupling15 with a total yield
of 61%. It was shown that the unique enediyne framework
facilitates π-conjugation with aromatic substituents by al-
lowing coplanar orientation throughout the molecular core.
We have also developed a convenient one-flask synthesis
of conjugated diynes 3 by combination of Ag+-catalyzed
desilylation16 and Eglinton-Glaser coupling17 reactions.
Under the optimized reaction conditions, the ethynyltrim-
ethylsilanes 2f, 2c, and 2d were converted directly to
butadiynes, affording the corresponding products 3a-c in
49-55% yields.
To elucidate the reaction mechanism, we carried out the
coupling reactions of zirconacycle 1 with allylic compounds
without the addition of alkynyl bromide (Scheme 4). Surpris-
ingly, product 5 was obtained as a >98% isomerically pure
enyne derivative in which a C-C bond formation occurred
exclusively at the vinylic carbon substituted with an alkynyl18
group rather than with a TMS group. The result indicates
that an interesting alkynyl group shift from R- to â-position
with relation to the zirconium center during the reaction
occurred to afford allyl zirconation intermediate 4. In the
presence of 1 equiv of 4-octyne, zirconacyclopentadiene 6a
was formed. After hydrolysis, a 1,3-butadiene derivative 7a
was obtained in 77% yield as a single regioisomer. Diphe-
nylacetylene did not give a high yield of zirconacyclopen-
tadiene in THF; however, results improved considerably with
Acknowledgment. We thank the National Natural Sci-
ence Foundation of China (Grant No. 20402019), the Chinese
Academy of Science, and the Science and Technology
Commission of Shanghai Municipality (04QMX1446) for
financial support.
Supporting Information Available: Experimental details
and spectroscopic characterization of all isolated compounds
and CIF files giving crystallographic data of 3c. This material
is available free of charge via the Internet at http://pubs.acs.org.
(15) Martin, R. E.; Gubler, U.; Boudon, C.; Gramlich, V.; Bosshard, C.;
Gisselbrecht, J.-P.; Gu¨nter, P.; Gross, M.; Diederich, F. Chem.-Eur. J. 1997,
3, 1505.
(16) Carpita, A.; Mannocci, L.; Rossi, R. Eur. J. Org. Chem. 2005, 1859.
(17) Lee, L.; Lynch, V.; Lagow, R. J. J. Chem. Soc., Perkin Trans. 1,
2000, 16, 2805.
(18) For a regioselective dimerization of 1,4-bis(trimethylsilyl)-1,3-
butadiyne using Cp2ZrBu2, see: Hsu, D. P.; Davis, W. M.; Buchwald, S.
L. J. Am. Chem. Soc. 1993, 115, 10394.
OL052706+
(19) Buchwald, S. L.; Nielsen, R. B. J. Am. Chem. Soc. 1989, 111, 2870.
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