ficient approaches to benzofused heterocycles such as
benzothiophenes,4a,b benzo[b]furans,4c,d isoquinolines,4e
quinolines,4f isochromenes,4g,h furopyridines,4i indoles,4j,k
isoindolin-1-ones,4l and so on.4 Enynes bearing nucleo-
philic substituents such as -OH, -NHR, and SR groups
would represent an important class of suitable substrates
for this strategy due to the structural analogy with
arylalkynes; however, only limited reports concerning
electrophilic cyclization have been presented in the
literature by employing enyne derivatives.5 It is known
that (Z)-enynols undergo transition-metal-catalyzed trans-
formations to form substituted furans.6 The preparation
of (Z)-enynols are usually achieved through multistep
transformations involving Pd/Cu-catalyzed coupling of
the terminal alkynes with vinylic halides, addition of alk-
1-ynes to vinyl ketones followed by acid-catalyzed allylic
isomerization, reduction of methyl (Z)-2-en-4-ynoates
etc.6a,c Nevertheless, enhancing the efficiency of the
synthesis of these compounds is still highly attractive.
In our ongoing efforts7 to maximize the molecular com-
plexity from simple building blocks using zirconium,8 we
found that (Z)-2-en-4-yn-1-ols were readily constructed
by a one-pot, three-component reaction. This strategy
offered the advantage of the efficient route for substituted
A Facile Zr-Mediated Approach to
(Z)-Enynols and Its Application to Regio-
and Stereoselective Synthesis of Fully
Substituted Dihydrofurans
Yuanhong Liu,* Feijie Song, and Liqing Cong
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
Received May 14, 2005
Efficient synthetic approaches to stereodefined (Z)-enynols
have been developed through zirconium-mediated cross-
coupling reactions of three different components involving
alkyne, ketone, and alkynyl bromide in a one-pot procedure.
The subsequent electrophilic cyclization of a wide variety of
(Z)-enynols affords fully substituted (Z)-5-(1-iodoylidene)-
2,5-dihydrofurans with high regio- and stereoselectivity
under mild reaction conditions.
(3) (a) Balme, G.; Bouyssi, D.; Lomberget, T.; Monteiro, N. Synthesis
2003, 2115-2134. (b) Zeni, G.; Larock, R. C. Chem. Rev. 2004, 104,
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Oxygen-containing heterocycles and their analogues
widely occur as structural subunits in numerous natural
products, which have displayed interesting biological
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they are useful and versatile synthetic intermediates for
further structural elaboration. Electrophile-promoted
cycloaddition of unsaturated compounds has proven to
be a powerful synthetic route to the wide variety of
halogenated heterocyclic compounds.2 However, the elec-
trophilic cyclization performed on acetylenic compounds
has been far less studied, although alkynes have been
frequently employed in transition-metal-catalyzed inter-
or intramolecular annulations to produce fruitful results
for the synthesis of carbo- and heterocycles.3 Most of the
recent reports focused on arylalkynes bearing ortho-
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10.1021/jo050966z CCC: $30.25 © 2005 American Chemical Society
Published on Web 07/28/2005
J. Org. Chem. 2005, 70, 6999-7002
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