The effect of crown-ether on the palladium-catalyzed Ullmann-type coupling mediated by zinc in air and water

Article abstract of DOI:10.1016/S0040-4039(00)00658-4

In the presence of a catalytic amount of 18-crown-6, palladium-catalyzed reductive coupling of aryl halides mediated by zinc was found effective in water alone, at ambient temperature, and under an atmosphere of air to give improved isolated yield of the Ullmann-type reaction products. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00658-4

Tetrahedron Letters 41 (2000) 4831±4834
The e€ect of crown-ether on the palladium-catalyzed
Ullmann-type coupling mediated by zinc in air and water
Sripathy Venkatraman and Chao-Jun Li*
Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, USA
Received 16 March 2000; revised 18 April 2000; accepted 20 April 2000
Abstract
In the presence of a catalytic amount of 18-crown-6, palladium-catalyzed reductive coupling of aryl
halides mediated by zinc was found e€ective in water alone, at ambient temperature, and under an atmo-
sphere of air to give improved isolated yield of the Ullmann-type reaction products. # 2000 Elsevier
Science Ltd. All rights reserved.
The Ullmann reaction is one of the fundamental reactions in organic chemistry. The reaction
has been widely used in synthesizing various aromatic compounds. Under the classical conditions,
the reaction1,2 is mediated by copper.3 Generally, the Ullmann coupling is also carried out at a
high temperature. Recently, it has been shown that these reactions can be carried out under mild
conditions, in the presence of copper(I) thiophene-2-carboxylate.4 Palladium-catalyzed reductive
couplings are among the most important carbon±carbon bond forming reactions in modern
synthetic organic chemistry.5 These reactions are generally air sensitive. It was known that palladium
can catalyze aryl halide homo-couplings under elevated reaction temperatures in the presence of a
reducing reagent.6
Recently, we reported a palladium-catalyzed Ullmann-type reductive coupling of aryl halides
in aqueous conditions7 and under an air atmosphere.8 During the reaction, compounds formed
due to the reductive dehalogenation of the halides are potential by-products (which are volatile).
In order to determine the ratio of the desired product and by-product formed during the reaction,
we capped the reaction vessel and, after the reaction, extracted the reaction mixture fully with an
organic solvent. Then the mixture was directly subjected to GC±MS analysis, which provided the
conversion of the starting materials and the ratios of product/by-product. On careful examining
the reaction further, we noticed relatively low isolated yield of the desired product for coupling of
iodobenzene, which falls in the range of 20±30% after column chromatography on silica gel
* Corresponding author. E-mail: cjli@mailhost.tcs.tulane.edu
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00658-4

4832
(while no other product can be isolated). Initially, we attributed the low mass-balance to isolation
loss during the column chromatography. Our further investigations of the reaction under
improved conditions provided much higher isolated yields of the product, which inferred that
although the reaction has a high conversion, under the conditions reported earlier, a fair amount
of the volatile dehalogenation product was probably formed and was lost during the reaction.
Here we present that, in the presence of a catalytic amount of 18-crown-6, the zinc mediated
reductive coupling of aryl halides catalyzed by Pd/C provided improved isolated yields of the
products at ambient temperature, in water alone, and under an atmosphere of air (Eq. (1)).9
ꢀ1†
As shown in Table 1, various aromatic iodides and bromides were coupled by zinc in water
with the presence of catalytic amounts of Pd/C and 18-crown-6. In the absence of the crown ether,
the yield of the desired product diminished considerably (compare entries 1 and 2, 7 and 8). The
improvement of product yield in the presence of crown ether could be due to either a stabilization
of the arylpalladium intermediate or a surfactant e€ect, which is under further investigation. Aryl
chloride and ¯uoride were inert under the reaction conditions. An increase in steric hindrance
resulted in a decrease of the yield of the coupled product (compare entries 6, 7, and 13).
Regarding the mechanism of the reaction, subsequent to our report Sasson and co-workers
described a palladium-catalyzed reductive coupling of aryl halides under a hydrogen gas atmo-
sphere.10 Very recently, the researchers proposed that the reaction in our earlier report proceeded
via a mechanism involving the reduction of palladium intermediate by hydrogen gas generated by
the reaction of zinc with water.11 While we do not exclude such a possibility of hydrogen gas
participation, we believe that the reaction in our case most likely proceeded via a direct electron
transfer from zinc to palladium(II) (or via the reaction medium) which completed the catalytic
cycle (Scheme 1). As likely experimental evidence to support such a direct metal-to-metal electron
transfer, entry 12 provided a 70% isolated yield of dehalogenation product while maintaining the
benzylic functionality, which is known to undergo hydrogenolysis eciently.12 In conclusion, the
use of a catalytic amount of a crown ether allows us to obtain good isolated yields of the zinc-
mediated, palladium-catalyzed Ullmann-type reductive coupling in water and under an air
atmosphere.
Scheme 1. Proposed mechanism for the zinc mediated Ullmann-type coupling catalyzed by palladium in air and water

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Table 1
Zinc mediated reductive coupling of aryl halides catalyzed by Pd/C under air atmosphere

4834
Acknowledgements
We are grateful to the NSF-EPA joint program and the NSF (CAREER) for partial support of
this research.
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suspension of 4-iodotoluene (300 mg, 1.3 mmol) in 10 mL of de-ionized water in a 50 mL test-tube was added Pd/C
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was capped and stirred overnight, diluted with 4 mL 1N aqueous HCl, ®ltered through Celite and washed with
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