DOI: 10.1002/chem.201304120
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Arylation
Direct Arylation of N-Heteroarenes with Aryldiazonium Salts by
Photoredox Catalysis in Water
Dong Xue,*[a] Zhi-Hui Jia,[a] Cong-Jun Zhao,[a] Yan-Yan Zhang,[a] Chao Wang,[a] and
Jianliang Xiao[a, b]
Abstract: A highly effective visible light-promoted “radical-
type” coupling of N-heteroarenes with aryldiazonium salts in
water has been developed. The reaction proceeds at room
temperature with [Ru(bpy)3]Cl2·6H2O as a photosensitizer
and a commercial household light bulb as a light source.
Pyridine and a variety of substituted pyridines are effective
substrates under these reaction conditions, and only mono-
substituted products are formed with different regioselectivi-
ties. Using aqueous formic acid as solvent, an array of xan-
thenes, thiazole, pyrazine, and pyridazine are compatible
with this new arylation approach. The broad substrate
scope, mild reaction conditions, and use of water as reaction
solvent make this procedure a practical and environmentally
friendly method for the synthesis of compounds containing
aryl-heteroaryl motifs.
Introduction
using arylboronic acids as an aryl radical source. However, the
Gomberg–Bachmann reaction[10] is the classic “radical-type”
coupling between arene compounds and diazonium salts in
the presence of a base, leading to biaryls through an inter-
mediate aryl radical. The reaction offers wide scope in terms of
both diazonium salts and arenes, but yields are generally low
due to many side-reactions. Attempts have been made to
make the reaction applicable in organic synthesis by using cat-
alytic or stoichiometric amounts of transition metal salts[11] or
by employing phase-transfer catalysis.[12]
Aryl-heteroaryl motifs are ubiquitous in natural products, phar-
maceuticals, agrochemicals, and organic materials.[1] Transition
metal-catalyzed cross-coupling reactions between an organo-
metallic aryl reagent and an aryl halide or pseudohalide under
thermal conditions are now well-established for aryl-heteroaryl
formation.[2]
Direct functionalization of heteroarenes through CÀH bond
activation provides a highly attractive strategy.[3] However, elec-
tron-deficient N-heteroarenes, such as pyridines, pyrazines, pyr-
idazines, and pyrimidines, are often difficult to derivatize di-
rectly.[4] Although several metal catalysts have proven to be
highly effective in such direct coupling,[5–8] the synthesis of
aryl-heteroaryl compounds remains very challenging owing to
the high temperatures and harsh conditions required for these
processes. As a result, the development of more efficient and
milder direct arylations of complex electron-deficient heteroar-
omatic bases is still a major challenge for chemists.
Visible light-promoted photoredox catalysis provides
a green, sustainable, and catalytic process for generating aryl
radicals.[13–17] Recently, Sanford,[18a] Kçnig,[18b] Li,[18c] and our
group[19] reported the “radical-type” construction of aryl-aryl
bonds by visible light-driven catalysis. Since the reported
methodologies are most efficient with electron-rich arenes, the
direct addition of an aryl radical to an electron-deficient heter-
oarene under visible light-promoted photoredox catalysis is
rare. In continuation of our work on aryl-aryl coupling driven
by visible light photoredox catalysis,[15] we report herein a “radi-
cal-type” arylation of electron-deficient heteroarenes, such as
pyridines, xanthenes, thiazole, pyrazine, and pyridazine, with
aryldiazonium salts in water. This provides a general and valua-
ble method for the direct functionalization of electron-deficient
arenes.
Direct functionalization of electron-deficient heteroarenes
through radical addition[9] is one of the most straightforward
methods for constructing aryl-heteroaryl motifs. Recently,
Baran[9b] reported a “radical-type” arylation of N-heterocycles
[a] Prof. Dr. D. Xue, Z.-H. Jia, C.-J. Zhao, Y.-Y. Zhang, Prof. Dr. C. Wang,
Prof. Dr. J. Xiao
Key Laboratory of Applied Surface and Colloid Chemistry
Ministry of Education, School of Chemistry and Chemical Engineering
Shaanxi Normal University
Results and Discussion
Xi’an 710062 (China)
Initial investigations focused on the direct arylation of 4-(tri-
fluoromethyl)pyridine hydrochloride 1a with the aryldiazonium
salt 2a. [Ru(bpy)3]Cl2·6H2O was employed as the photocatalyst,
and a 3 W blue LED was utilized as the source of visible light.
The cross-coupling product 2-(4-methoxyphenyl)-4-(trifluoro-
methyl)pyridine hydrochloride was obtained in low yield in the
[b] Prof. Dr. J. Xiao
Liverpool Centre for Materials and Catalysis, University of Liverpool
Liverpool, L69 7ZD (UK)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201304120.
Chem. Eur. J. 2014, 20, 2960 – 2965
2960
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