Tetrahedron Letters
An efficient zinc-catalyzed cross-coupling reaction of aryl iodides
with terminal aromatic alkynes
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Amrutha P. Thankachan, K. S. Sindhu, K. Keerthi Krishnan, Gopinathan Anilkumar
School of Chemical Sciences, Mahatma Gandhi University, PD Hills PO, Kottayam 686 560, India
a r t i c l e i n f o
a b s t r a c t
The first Zn-catalyzed protocol for C(sp2)–C(sp) cross-coupling reactions for the synthesis of disubstituted
alkynes is described. A broad spectrum of functional groups is tolerated during the catalysis and success-
fully afforded a variety of diaryl substituted acetylenes.
Article history:
Received 15 July 2015
Revised 10 August 2015
Accepted 11 August 2015
Available online xxxx
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Zinc-catalyst
Cross-coupling reactions
Terminal acetylenes
Transition metal catalysts
C–C bond formations
Sonogashira type coupling
Transition metal catalyzed cross coupling reactions 1 are one of
the predominant strategies for the formation of conjugated sys-
tems which possess wide applications in the synthesis of natural
products, heterocycles, pharmaceuticals, polymers, dyes, sensors,
catalyzed zinc chloride promoted coupling of terminal alkynes
with aryl bromides in 2009.14 However, to the best of our
knowledge, C(sp2)–C(sp) cross-coupling reactions of terminal
alkynes with aryl halides catalyzed by Zn(II) systems have not
yet been reported. Herein, we disclose the first efficient zinc-
catalyzed Sonogashira type cross-coupling reaction of alkynes with
aryl iodides in the absence of added Pd and Cu sources.
On the basis of our recent study on zinc-proline catalytic system
for carbon–sulfur bond-formation reactions.15 we anticipated that
the same catalytic system would be successful for C(sp2)–C(sp)
cross-coupling reaction. In this context, we tried diethyl zinc in
the presence of proline La and other commonly available ligands
Lb–Lg for screening. We initiated our studies on zinc-catalyzed
C(sp2)–C(sp) cross-coupling reaction using phenylacetylene and
4-iodoacetophenone as reactants under various catalytic condi-
tions. The reactions were carried out in a previously dried sealed
tube in the presence of K3PO4 in 1,4-dioxane at 125 °C under
nitrogen atmosphere (Table 1).
Thus the reaction of 4-iodoacetophenone 1a with pheny-
lacetylene 2a in the presence of proline La, 1,10-bi-2-naphthol Lb,
or ethylenediamine Lc and K3PO4 in 1,4-dioxane at 125 °C afforded
very small quantity of the product 3a (Table 1, entries 1–3).
However, to our delight, when the reaction of 1a with 2a was
conducted in the presence of N,N0-dimethylethylenediamine Ld
(DMEDA) and K3PO4 in 1,4-dioxane at 125 °C, the coupled product
3a was formed in promising yield of 75% along with the dimerized
product of phenylacetylene (Table 1, entry 4). The structure of the
product 3a was confirmed by NMR and mass spectrometric
2
guest-host systems, electronics, and electroopticals. Due to the
vast importance of acetylenic moieties, numerous methodologies
have been introduced for their synthesis. Among these methods,
Sonogashira coupling reactions of terminal acetylenes with aryl
halides are the most popular ones. The Sonogashira cross-coupling
reactions have been initiated independently by the seminal works
of Castro,3 Cassar,4 Heck,5 and Sonogashira.6
The typical Sonogashira reactions are performed with palla-
dium(0) catalyst and copper(I) co-catalyst in organic solvents using
a suitable base.7 Development of competent catalysts and reduc-
tion during the homocoupling of alkynes are the challenges faced
by Sonogashira (C(sp2)–C(sp)) cross-coupling reactions. Despite
all the challenges, significant modifications have been introduced
in Sonogashira coupling reactions over the last few years. Among
these, the Sonogashira type cross-coupling reaction under
copper-free conditions8 and the same under palladium-free
conditions9 serve the two promising protocols. Of great importance
are the recent modifications such as using aqueous solvents,10
aerobic atmosphere,11 room temperature,12 and solvent free
conditions8h as well as the use of certain other transition metals
for catalysis.13 Moore and co-workers reported a palladium-
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