pubs.acs.org/joc
molecular oxygen as oxidant. However, it still remains a
Highly Chemoselective Palladium-Catalyzed
Cross-Trimerization between Alkyne and Alkenes
Leading to 1,3,5-Trienes or 1,2,4,5-Tetrasubstituted
Benzenes with Dioxygen
challenge to combine various factors of green chemistry with
Pd-catalyzed coupling reactions.
Chloropalladation of alkynes is well-recognized to be one
of the most efficient and atom economic methods for the
construction of both the carbon-carbon and carbon-halide
bonds.6 Among its application, a majority of research was
concerned about the capture of σ-vinylpalladium intermedi-
ate with alkynes, alkenes, allyl halides, and carbon monoxide
in which taking alkenes to carry out a tandem Heck cross-
coupling has been proven to be an extremely important
and convenient method for the synthesis of 1-chloro-1,3-
tetradiene.7 However, in all these systems, the activation of
the C-Cl σ-bond in vinyl chloride received little attention,
which were inert in the presence of the oxidant like cupric
salts, BQ, and etc., probably due to the efficient oxidation of
Pd(0) to Pd(II). However, a weaker oxidant may allow a
smaller TON of Pd(0) oxidation, thus sustaining Pd(0) for
another Heck catalytic cycle (Scheme 1). In this context, oxygen
was found to be a perfect candidate for its medium oxidation
ability toward Pd(0).8 Moreover, the use of oxygen may elim-
inate the byproducts from traditional oxidants in a Pd catalytic
system such as superfluous Cu(II) salts, Ag(I) salts, and
phenyliodine(III) diacetate. On the basis of our interest in oxygen
and chloropalladation chemistry on triple bonds,9 we herein
disclose a highly chemoselective palladium-catalyzed oxidative
cross-trimerization of one alkyne with two alkenes to 1,3,5-
trienes or 1,2,4,5-tetrasubstituted benzenes which both are very
useful in the field of pharmaceutical and materials chemistry.10
In an initial attempt, ethyl phenylpropiolate (1a) was used
as a model compound for the reaction with methyl acrylate
(2a) to screen the reaction conditions (see the Supporting
Information). Under the optimal conditions (10 mol %
PdCl2, 120 mol % LiCl, 150 mol % K2CO3 in acetonitrile
at 75 °C for 18 h under 1 atm O2) the cross-trimerization of 1a
Peng Zhou, Liangbin Huang, Huanfeng Jiang,*
Azhong Wang, and Xianwei Li
School of Chemistry and Chemical Engineering, South China
University of Technology, Guangzhou 510640,
People’s Republic of China
Received August 8, 2010
A palladium-catalyzed 1:2 linear/cyclic cross-trimerization
of alkyne with alkenes using molecular oxygen as the
sole oxidant has been reported for the first time. A series
of 1,3,5-trienes and 1,2,4,5-tetrasubstituted benzenes are
obtained with high chemoselectivity respectively and
mechanisms of these reactions are proposed based on
some controlled examination.
Palladium-catalyzed processes for carbon-carbon bond
formation have proven to be a powerful and useful tool for
the construction of natural products and complicated com-
pounds.1 Although classic reactions such as Sonogashira,2
Suzuki,3 Stille,4 and Heck cross-coupling5 have been devel-
oped and widely used in organic synthesis, from the view-
point of green chemistry, it is necessary to develop more
atom economic and environmental benign methodologies to
construct C-C bonds. To address this issue, a lot of effort
has been made to achieve the sequential reaction system with
(6) For a review on chloropalladation, see: Lu, X. Handbook of
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Interscience: New York, 2002; Vol. 2, pp 2267-2288.
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F.; Liang, Y.; Li, J. H. Org. Lett. 2009, 11, 1139–1142. (e) Li, Y.; Jardine, K.;
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J. L.; Muzart, J. Org. Lett. 2009, 11, 4096–4099. (e) Stahl, S. S. Science 2005,
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Chem. Rev. 2004, 104, 2285–2310.
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DOI: 10.1021/jo101554r
r
Published on Web 11/03/2010
J. Org. Chem. 2010, 75, 8279–8282 8279
2010 American Chemical Society