DOI: 10.1002/chem.201003403
Nickel-Catalyzed Cross-Coupling of Phenols and Arylboronic Acids Through
an In Situ Phenol Activation Mediated by PyBroP
Guo-Jun Chen, Jie Huang, Lian-Xun Gao, and Fu-She Han*[a]
Abstract:
A
new method for the
acids, including activated, nonactivated,
deactivated, and heteroaromatic cou-
pling partners. In addition, various
functional groups, such as ether, amino,
cyano, ester, and ketone groups, are
compatible with this transformation.
Notably, arylboronic acids containing
an unprotected NH2 group and 2-heter-
ocyclic boronic acids, which are gener-
ally problematic for coupling under
conventional conditions, are also viable
substrates, although moderate yields
were obtained for sterically hindered
substrates. Consequently, the in situ
cross-coupling methodology coupled
with the use of an inexpensive and
stable nickel catalyst provides a rapid
and efficient pathway for the assembly
of biaryls and heterobiaryls with struc-
tural diversity from readily available
phenol compounds.
Suzuki–Miyaura cross-coupling of phe-
nols and arylboronic acids through
in situ phenol activation mediated by
PyBroP is presented. The reaction pro-
ceeds efficiently by using cost-effective,
markedly stable [NiCl2ACTHUNTGRNEUNG(dppp)] (dppp=
1,3-bis(diphenylphosphino)propane) as
the catalyst in only 5 mol% loading, as
well as in the absence of extra ligands.
The method exhibits broad applicabili-
ty and high efficiency towards a wide
range of both phenols and boronic
Keywords: biaryls · cross-coupling ·
homogeneous catalysis · nickel ·
phenols · phosphonium salts
Introduction
Very recently, the in situ activation of phenols through the
formation of inorganic salts (e.g., ArOMgX)[9] and organic
phenolic phosphonium salts,[10,11] or pivalate esters[6a] has
The construction of biaryl and heterobiaryl compounds has
attracted considerable interest because these structural
motifs are core scaffolds that are found in a myriad of poly-
mers, bioactive compounds, supramolecular structures, and
so forth.[1] Numerous reports have demonstrated that in re-
cently developed approaches, the transition-metal-catalyzed
cross-coupling is an exceedingly powerful transformation in
which phenol compounds are the most widely available and
inexpensive starting material for biaryl assembly. However,
several limitations of the catalyst systems, such as poor ther-
mal stability, high cost, and sensitivity towards both air and
moisture, strongly restrict their general applicability in in-
dustrial processes.[2] Moreover, most of the traditional meth-
ods require prior activation of inert phenols to a more reac-
tive, but less stable, precursor. These activation strategies in-
clude the formation of aryl triflates,[3] sulfonates,[4] ethers,[5]
esters,[6] carbamates,[7] carbonates,[7a] sulfamates,[7a] and phos-
phoramides.[8] Undoubtedly, such a stepwise process is not
only time-consuming and economically less effective, but
also generates more waste.
À
emerged as an attractive approach for C C bond formation.
These novel strategies provide an important advantage over
the traditional ones; they merge the phenol activation and
subsequent cross-coupling into a single operation and, there-
fore, make the transformation more practical in terms of ef-
ficiency, economy, and environmental impact.[10b,d] However,
the generality of inorganic salt protocols remains to be de-
termined because the use of strongly basic, as well as nucle-
ophilic, MeMgBr as the activating agent would be problem-
atic for substrates containing labile functional groups, such
as ester and ketone groups. Although the phosphonium salts
have been extensively studied by Kang et al. and other
groups,[10,11] the pathways have limited scope and utility be-
cause they usually necessitate the use of a-N-activated tau-
tomerizable N-heterocycles (cyclic amides, Scheme 1, top)
as substrates. Moreover, successful coupling requires a high
loading of expensive Pd catalysts (typically 5 mol%). Conse-
quently, a practical solution for the effective coupling of
common phenols (Scheme 1, bottom) through in situ activa-
tion has been less developed, although such transformation
is expected to be feasible.[11]
We have paid particular attention to this issue and initiat-
ed a study towards the development of a highly active and
practical catalyst system. Our efforts have been focused on
inexpensive and readily available Ni-based catalysts because
we have demonstrated previously that an appropriate com-
bination of NiCl2 and 1,3-bis(diphenylphosphino)propane
(dppp) is a highly active precatalyst for the coupling of aryl
[a] Dr. G.-J. Chen,+ J. Huang,+ Prof. L.-X. Gao, Prof. Dr. F.-S. Han
Changchun Institute of Applied Chemistry
Chinese Academy of Sciences
5625 Renmin Street, Changchun, Jilin 130022 (P.R. China)
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW
phosphoramides.[4h,8] Herein, we disclose that [NiCl
2ACHTUNGTRENNUNG(dppp)]
4038
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 4038 – 4042