Nickel-catalyzed cross-coupling of phenols and arylboronic acids through an in situ phenol activation mediated by PyBroP

Article abstract of DOI:10.1002/chem.201003403

A new method for the Suzuki-Miyaura cross-coupling of phenols and arylboronic acids through in situ phenol activation mediated by PyBroP is presented. The reaction proceeds efficiently by using cost-effective, markedly stable [NiCl₂(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 applicability and high efficiency towards a wide range of both phenols and boronic acids, including activated, nonactivated, deactivated, and heteroaromatic coupling 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-heterocyclic boronic acids, which are generally 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 structural diversity from readily available phenol compounds.

Full text of DOI:10.1002/chem.201003403

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)
E-mail: fshan@ciac.jl.cn
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201003403.
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

FULL PAPER
Table 1. Optimization of cross-coupling conditions.[a]
Catalyst [mol%]
[PdCl2A(dppf)] (5)
[PdCl2A(dppf)] (5)
[PdCl2A(cod)] (5)
[PdCl2A(cod)] (5)
[PdCl2A(cod)] (5)
[PdCl2A(cod)] (5)
[NiCl2A(PCy3)2] (5)
[NiCl2A(PCy3)2] (5)
[NiCl2A(PCy3)2] (5)
[NiCl2A(PCy3)2] (5)
[NiCl2A(PCy3)2] (5)
NiCl2 (5)
[NiCl2A(dppp)] (5)
[NiCl2A(dppp)] (5)
[NiCl2A(dppp)] (5)
[NiCl2A(dppp)] (5)
[NiCl2A(dppp)] (5)
[NiCl2A(dppp)] (2)
[NiCl2A(dppp)] (3)
Ligand
PyBroP [equiv]
Yield [%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
N
N
PCy3
PCy3
PCy3
dppe
dppb
dppp
PCy3
PCy3
dppe
dppb
dppp
dppp
–
–
–
–
–
–
–
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.0
1.2
1.5
1.5
4
7[c]
n.r.[d]
16
15
13
Scheme 1. Reported versus newly developed methods for in situ activa-
tion and cross-coupling of Ar-OHs.
G
39
E
22[e]
4
CHTUNGTRENNUNG
R
2
27
46
is a highly active, inexpensive, and markedly stable catalyst
that allows effective cross-coupling of common phenols
through the in situ activation approach.
R
E
70[f]
81[f,g]
66[f,g,h]
41[f,g]
43[f,g]
52[f,g]
59[f,g]
N
G
N
Results and Discussion
E
G
At the outset of this study, we investigated the cross-cou-
pling of phenols with arylboronic acids (Suzuki–Miyaura
coupling) since this transformation has been recognized as
the most important method[12] for the diverse construction
of biaryls owing to the numerous advantages that pertain to
the use of boronic acids, such as wide availability, low toxici-
ty, and stability to heat, air, and moisture, as well as the ease
of removal of boron-containing by-products.[6a,13] According-
ly, optimization of the reaction conditions was carried out
by employing the reaction of 1-naphthol (1) with 4-methoxy-
phenylboronic acid (2a) as a model system (Table 1). In
comparison with the traditional stepwise processes, the
screening of suitable conditions for the one-pot transforma-
tion is far more challenging since it requires an appropriate
combination of an activating agent and a catalyst that can
not only activate phenols efficiently, but also holds high cat-
alytic activity in the following catalytic cycle.
C
[a] Reaction conditions: 1-naphthol (1; 0.5 mmol), PyBroP, Et3N
(3.0 equiv), K3PO4 (3.0 equiv) in dioxane (3 mL) at 1008C for 3 h; then
catalyst, ligand (10 mol%), and 4-methoxyphenylboronic acid 2a
(1.0 mmol) at 1008C; dppf=1,1’-bis(diphenylphosphino)ferrocene; Cy=
cyclohexyl; cod=1,5-cyclooctadiene; dppe=1,2-bis(diphenylphosphino)-
ethane; dppb=1,4-bis(diphenylphosphino)butane. [b] Isolated yield.
[c] 5% (v/v) water was added to the solvent. [d] No reaction. [e] K2CO3
was used as the base. [f] No extra ligand was added. [g] K3PO4 (4.0 equiv)
was used. [h] The reaction was performed by adding all the reagents and
the catalyst simultaneously.
is possibly due to the poor solubility of inorganic bases in
the dioxane solvent, and the volatile nature of organic Et3N
at the reaction temperature employed (vide supra). Ulti-
mately, separate use of either an inorganic or organic base
decreases the efficiency of the reaction between phenols
and PyBroP.
Thus, various activating systems were examined first, in-
cluding PPh3/I2, PPh3/NCS, PPh3/NBS, PPh3/NIS, P
(OMe)3/
By using PyBroP as the in situ activation agent, the
screening of a catalyst system for the subsequent cross-cou-
pling showed that the use of several Pd-based catalysts, such
NBS, and P(OMe)3/I2 (NCS=N-chlorosuccinimide; NBS=
ACHTUNGTRENNUNG
N-bromosuccinimide; NIS=N-iodosuccinimide). The results
showed that although these systems could react with phenols
to form phenolic phosphonium salts [(ArOPR3)+XÀ], the
subsequent metal-catalyzed cross-coupling with boronic acid
was unsuccessful in the presence of various Pd or Ni cata-
lysts. Further exploration eventually revealed that bromotri-
pyrrolidinophosphonium hexafluorophosphate (PyBroP),
which has been shown to be a mild and effective agent for
the in situ activation of a-N-activated heterocyclic are-
nols,[10,11] was also a suitable agent for the activation of
common phenols. However, here, a combination of Et3N
and K3PO4 (or K2CO3) as the base coupled with an elevated
reaction temperature (80–1008C) is crucial for effective acti-
vation of phenols. The absence of either the organic or the
inorganic base resulted in an incomplete or slow conversion
of phenols to the corresponding phosphonium salts.[14] This
as [PdCl2ACHTUNTRGENNUG(dppf)] and [PdCl2AHCUTNGTREN(NNGU cod)], led to inefficient coupling
either in the absence or presence of phosphine ligands, such
as PCy3, dppe, dppp, dppb, and dppf (Table 1, entries 1–6).
In contrast, the Ni-based catalysts were shown to be far
more active than the Pd catalysts, as shown by a comparison
of the results in Table 1, entry 7 with those in Table 1, en-
tries 1 and 3. Thus, after careful evaluation of various reac-
tion parameters, including the effect of Ni-based catalysts, li-
gands, bases, the molar equivalent of PyBroP, and tempera-
ture (Table 1, entries 8–19), we were pleased to find that the
[NiCl2ACHTUNGTRNEUNG
(dppp)] complex[15] was a competent catalyst that
could affect the cross-coupling of 1-naphthol with 4-methox-
yphenylboronic acid in 81% yield, even in the absence of
extra supporting ligands (Table 1, entry 14). However, if the
reaction was carried out under otherwise identical parame-
Chem. Eur. J. 2011, 17, 4038 – 4042
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4039

F.-S. Han et al.
ters to those in Table 1, entry 14, but by adding the reagents
and catalyst simultaneously, a somewhat decreased yield
(66%) was observed (Table 1, entry 15). In addition, reduc-
ing the molar ratio of PyBroP or the catalyst loading led to
a significantly decreased yield (Table 1, entries 16–19). Thus,
the optimized reaction conditions for the one-pot Suzuki–
Miyaura coupling of common phenols are PyBroP
(1.5 equiv), K3PO4 (4.0 equiv), Et3N (3.0 equiv), 1008C, 3 h
in dioxane (3 mL)[16] followed by addition of boronic acid
(2-thienylboronic acid) also serves as a viable substrate, pro-
viding the heterobiaryl compound in 60% yield (Table 2,
entry 7). Finally, the transformation was shown to be some-
what less efficient for a sterically hindered boronic acid
(Table 2, entry 8).
Here, two transformations are particularly worth noting.
First, the coupling of a boronic acid containing a free NH2
group (Table 2, entry 2) occurred exclusively at the boronic
acid position, with the unprotected NH2 functional group re-
maining intact. In contrast, conventional coupling with pal-
ladium catalysts generally requires prior protection of
amino groups.[17] Thus, the in situ activation of phenol, along
with the direct use of unprotected amino boronic acids, pro-
vides a much more straightforward pathway for the con-
struction of polyaromatic-ring-containing amines. Com-
pounds of this class are core motifs in or important building
blocks for the construction of a broad range of useful tar-
gets, such as pharmaceuticals, functional materials, coordina-
tion compounds, and ligands through, for instance, the well-
established Buchwald-Hartwig coupling reactions[18] (i.e.,
(2.0 equiv) and [NiCl2ACTHNUGTRNEUNG(dppp)] (5 mol%).
With the optimized reaction conditions available, we then
examined the generality of this protocol. First, the feasibility
of the method was evaluated by performing the coupling of
1-naphthol with a wide range of arylboronic acids (Table 2).
The results show that 1-naphthol couples smoothly with var-
ious boronic acids that are substituted by electron-donating
(Table 2, entries 1 and 2), -neutral (Table 2, entries 3 and 4),
or -withdrawing groups (Table 2, entries 5 and 6) on the ring
periphery of the boronic acid. Good to excellent yields were
observed for all of the boronic acids with different electron-
ic natures. In addition, a heteroaromatic boronic acid
À
C N bond formation reactions). Second, the ability to
couple with unstable 2-thienylboronic acid by use of the
nickel catalyst (Table 2, entry 7) is also attractive as effective
coupling of 2-heterocyclic boronic acids is usually problem-
atic and suffers from rapid deboronation under typical con-
ditions,[19] although a generally applicable and highly effi-
cient catalyst system based on palladium has been devel-
oped very recently by Buchwald and co-workers.[19]
Table 2. Cross-coupling of 1-naphthol (1) and various arylboronic acids
(2a–h) under the optimized reaction conditions.[a]
Next, the reaction efficiency of the synthetic process was
further inspected by varying the phenol components. As
shown in Table 3, 2-naphthol underwent smooth coupling
with electron-rich, -neutral, and -deficient boronic acids
(Table 3, entries 1–3). Moreover, naphthol analogues con-
taining either a strongly electron-withdrawing CN or a
strongly electron-donating OMe group could be converted
to the desired biaryls in good to excellent yields (Table 3,
entries 4–8). Most interestingly, we have also observed that
this transformation is tolerant of various non-fused (i.e., less
electron-deficient) phenol compounds. For instance, several
phenol compounds substituted by an electron-withdrawing
CN, CO2Me, or C(O)Me functional group could be trans-
formed smoothly into the corresponding cross-coupled prod-
ucts in high yields (Table 3, entries 9–13). In addition, effec-
tive coupling was observed for a phenol containing a strong-
ly electron-donating NMe2 substituent (Table 3, entry 14).
Finally, heteroaromatic phenols, such as 3- and 4-hydroxyl-
pyridines, are superb substrates, delivering heterobiaryls in
excellent yields (Table 3, entries 15–21). It should be men-
tioned that the cross-coupling of the ortho-substituted
phenol was somewhat challenging, providing the desired
products in 39% yield (Table 3, entry 22).
À
ArB(OH)2
Ar Ar’
Yield [%][b]
81
1
2
3
4
5
6
7
8
2a, R=4-OMe
2b, R=3-NH2
2c, R=4-Me
74
84[c]
70[c]
92
2d, R=H
2e, R=4-CO2Me
2 f, R=4-C(O)Me
2g, R=2-thienyl
2h, R=2-Me
71
60
50[c]
For a plausible mechanism for this transformation, we
have confirmed through the experiments that in the first
stage, the phenol and PyBroP form a phosphonium salt
(A;[14] Scheme 2). This species may act as an activated phe-
nolic intermediate for the subsequent cross-coupling reac-
tion. Concerning the Ni0-catalyzed coupling reaction, al-
[a] Reaction conditions: 1-Naphthol (1; 0.5 mmol), PyBroP (1.5 equiv),
Et3N (3.0 equiv), K3PO4 (4.0 equiv) in dioxane (3 mL) at 1008C for 3 h;
then [NiCl2ACHTUNGTRENNUNG(dppp)] (5 mol%) and arylboronic acid 2 (1.0 mmol) at 100–
1108C, 4–24 h. [b] Isolated yield. [c] Yield was determined by 1H NMR
analysis due to contamination by a small amount of an inseparable by-
product derived from homocoupling of boronic acid.
4040
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 4038 – 4042

Cross-Coupling of Phenols
FULL PAPER
Table 3. Cross-coupling of various phenols and arylboronic acids under the optimized reaction conditions.[a]
À
À
Ar OH
ArB(OH)2 Product
Yield
[%][b]
Ar OH
ArB(OH)2 Product
Yield
[%][b]
1
2
2a
2c
78
12
13
2a
2a
70
75
80[c]
3
2e
72
14
2a
62, 73[d]
4
5
6
7
2a
2c
2d
2e
81
97
77
95
15
16
17
18
2a
2c
2e
2 f
80
94
74
82
8
2a
78
19
2a
85[e]
9
2a
2d
82
79
20
21
2c
2e
90[e]
93[e]
10
11
2e
89
22
2e
39
[a] Reaction conditions: phenol (0.5 mmol), PyBroP (1.5 equiv), Et3N (3.0 equiv), K3PO4 (4.0 equiv) in dioxane (3 mL) at 1008C for 3 h; then [NiCl2-
1
ACHTUNGTRENNUNG(dppp)] (5 mol%) and arylboronic acid 2 (1.0 mmol) at 100–1108C, 4–24 h. [b] Isolated yield. [c] Yield was determined by H NMR analysis due to con-
tamination by a small amount of inseparable by-product derived from homocoupling of boronic acid. [d] catalyst (10 mol%) was used. [e] DMF (10%
(v/v)) was used as a co-solvent.
though the detailed catalytic cycle is not clear at present,
the mechanism may be similar to that proposed for the pal-
ladium-catalyzed cross-coupling of a-N-activated heterocy-
cles mediated by PyBroP, involving sequential oxidative ad-
dition of Ni0 to A, transmetalation, and reductive elimina-
tion.[10,11] Such a cycle is essentially similar to the general
Pd- or Ni-catalyzed cross-coupling mechanism for aryl hal-
ides (pseudo-halides) and boronic acids, as originally sug-
gested by Suzuki[20] and Percec.[21]
Conclusion
We have achieved successfully the Suzuki–Miyaura cross-
coupling of phenols through in situ phenol activation medi-
ated by PyBroP. More significantly, the reaction proceeds
smoothly by using the cost-effective, highly stable [NiCl2-
AHCTUNGTREG(NNUN dppp)] catalyst in only 5 mol% loading, as well as in the
absence of extra supporting ligands. In addition, the method
not only exhibits broad applicability and high efficiency to-
wards both a wide variety of phenols and boronic acids, in-
cluding activated, non-activated, deactivated, and heteroaro-
matic substrates, but also is tolerant of various functional
groups on the aromatic rings, such as OMe, NH2, CN,
CO2Me, and C(O)Me groups. Thus, this method offers sev-
eral advantages over the available in situ activation strat-
egies in terms of the cost and efficiency of the catalyst, as
Scheme 2. A proposed mechanism for the [NiCl
cross-coupling of phenols with arylboronic acid mediated by PyBroP.
2ACHTUNGERTN(NUNG dppp)]-catalyzed in situ
Chem. Eur. J. 2011, 17, 4038 – 4042
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4041

F.-S. Han et al.
[4] For examples of tosylates, benzenesulfonates, and mesylates, see:
a) D. Zim, V. R. Lando, J. Dupont, A. L. Monteiro, Org. Lett. 2001,
3, 3049; b) X. Huang, K. W. Anderson, D. Zim, L. Jiang, A. Klapars,
S. L. Buchwald, J. Am. Chem. Soc. 2003, 125, 6653; c) H. N. Nguyen,
X. Huang, S. L. Buchwald, J. Am. Chem. Soc. 2003, 125, 11818;
d) Z.-Y. Tang, Q.-S. Hu, J. Am. Chem. Soc. 2004, 126, 3058; e) R. H.
Munday, J. R. Martinelli, S. L. Buchwald, J. Am. Chem. Soc. 2008,
130, 2754; f) J. Kuroda, K. Inamoto, K. Hiroya, T. Doi, Eur. J. Org.
Chem. 2009, 2251; g) G. A. Molander, F. Beaumard, Org. Lett. 2010,
12, 4022; h) H. Gao, Y. Li, Y.-G. Zhou, F.-S. Han, Y.-J. Lin, Adv.
Synth. Catal. 2011, 353, 309.
well as the scope of the substrates. As a result, the method
provides a rapid and efficient pathway for the diverse con-
struction of biaryls and heterobiaryls from readily available
and cheap phenols. Finally, to best use this discovery, we are
À
currently carrying out other metal-catalyzed C X (X=C, N,
etc.) bond formation reactions through the in situ activation
of phenols.
[5] a) J. W. Dankwardt, Angew. Chem. 2004, 116, 2482; Angew. Chem.
Int. Ed. 2004, 43, 2428; b) S. Ueno, E. Mizushima, N. Chatani, F. Ka-
kiuchi, J. Am. Chem. Soc. 2006, 128, 16516; c) M. Tobisu, T. Shima-
saki, N. Chatani, Angew. Chem. 2008, 120, 4944; Angew. Chem. Int.
Ed. 2008, 47, 4866.
[6] a) K. W. Quasdorf, X. Tian, N. K. Garg, J. Am. Chem. Soc. 2008,
130, 14422; b) B.-T. Guan, Y. Wang, B.-J. Li, D.-G. Yu, Z.-J. Shi, J.
Am. Chem. Soc. 2008, 130, 14468; c) L. J. Goossen, K. Goossen, C.
Stanciu, Angew. Chem. 2009, 121, 3621; Angew. Chem. Int. Ed. 2009,
48, 3569.
[7] a) K. W. Quasdorf, M. Riener, K. V. Petrova, N. K. Garg, J. Am.
Chem. Soc. 2009, 131, 17748; b) A. Antoft-Finch, T. Blackburn, V.
Snieckus, J. Am. Chem. Soc. 2009, 131, 17750; c) L. Xu, B.-J. Li,
Z. H. Wu, X.-Y. Lu, B.-T. Guan, B.-Q. Wang, K.-Q. Zhao, Z.-J. Shi,
Org. Lett. 2010, 12, 884.
[8] Y.-L. Zhao, Y. Li, Y. Li, L.-X. Gao, F.-S. Han, Chem. Eur. J. 2010,
16, 4991.
[9] D.-G. Yu, B.-J. Li, S.-F. Zheng, B.-T. Guan, B.-Q. Wang, Z.-J. Shi,
Angew. Chem. 2010, 122, 4670; Angew. Chem. Int. Ed. 2010, 49,
4566.
[10] a) C. Shi, C. C. Aldrich, Org. Lett. 2010, 12, 2286; b) F.-A. Kang,
J. C. Lanter, C. Cai, Z. Sui, W. V. Murray, Chem. Commun. 2010, 46,
1347; c) V. P. Mehta, S. G. Modha, E. V. Van der Eycken, J. Org.
Chem. 2010, 75, 976; d) F.-A. Kang, Z. Sui, W. V. Murray, J. Am.
Chem. Soc. 2008, 130, 11300.
[11] For a review concerning the one-pot Suzuki–Miyaura coupling of
phenols mediated by phosphonium salts, see: F.-A. Kang, Z. Sui,
W. V. Murray, Eur. J. Org. Chem. 2009, 461.
Experimental Section
General methods: All reactions were carried out under a N2 atmosphere.
The dioxane solvent was dried over molecular sieves (4 ꢁ). Anhydrous
NiCl2 and dppp, dppe, and dppb ligands were purchased from J&K
Chemical Ltd and Alfa Aesar, respectively. Unless otherwise noted, the
1H and 13C NMR spectra were recorded at 400 and 100 MHz, respective-
ly, in CDCl3 with TMS as the internal standard. All chemical shifts are
given in ppm. All coupling constants (J values) are reported in Hertz
(Hz). High resolution mass spectrometry was measured by using an Ion-
Spec 7.0 T MALDI-FTICRMs spectrometer. Column chromatography
was performed on silica gel (100 mesh). Melting points were obtained on
a Laboratory Devices Mel-Temp II instrument and are uncorrected.
General procedure for the Suzuki–Miyaura coupling through in situ
phenol activation: A Schlenck tube containing a magnetic stirring bar
and charged with 1-naphthol (0.5 mmol, 72 mg), PyBroP (0.75 mmol,
349.6 mg), and K3PO4 (2.0 mmol, 424.0 mg) was evacuated three times
for 10 min under high vacuum and backfilled with N2. Triethylamine
(1.5 mmol, 0.21 mL), and dried dioxane (3 mL) were injected into the
mixture under N2 via syringe and the reaction mixture was stirred at
1008C for about 3 h, until the 1-naphthol had disappeared, as shown by
TLC. The reaction vessel was then charged with 4-methoxyphenylboronic
acid 2a (1.0 mmol, 152.0 mg) and anhydrous [NiCl2ACTHNUTRGNEUNG(dppp)] (0.025 mmol,
13.5 mg). The heterogeneous mixture was stirred at 1008C until the acti-
vated naphthyl phosphonium salt intermediate had disappeared, as
shown by TLC. The reaction mixture was poured into water (30 mL) and
extracted with CH2Cl2 (20 mLꢂ3). The combined organic extracts were
dried over anhydrous Na2SO4, filtered, concentrated, and purified by
chromatography on silica gel (hexane/CH2Cl2 =10:1, v/v) to give 1-(4-me-
thoxyphenyl)naphthalene as a white solid (94.8 mg; 81%). See the Sup-
porting Information for characterization data and copies of the 1H and
13C NMR spectra of the coupled products.
[12] X. F. Wu, P. Anbarasan, H. Neumann, M. Beller, Angew. Chem.
2010, 122, 9231; Angew. Chem. Int. Ed. 2010, 49, 9047.
[13] For a review, see: A. F. Littke, G. C. Fu, Angew. Chem. 2002, 114,
4350; Angew. Chem. Int. Ed. 2002, 41, 4176.
[14] In our experiments, the phenolic phosphonium salts formed from a
phenol and PyBroP were isolated and confirmed by NMR spectros-
copy.
[15] The [NiCl2ACTHNUGTRNEUNG(dppp)] used in our experiments was prepared by follow-
Acknowledgements
ing a known method, see: G. R. Van Hecke, W. D. Horrocks, Jr.,
Inorg. Chem. 1966, 5, 1968.
F.-S. Han is grateful to CIAC for financial support.
[16] Dioxane was the optimal solvent for this reaction, see: F.-A. Kang,
J. Kodah, Q. Guan, X. Li, W. M. Murray, J. Org. Chem. 2005, 70,
1957.
[1] For reviews, see: a) L.-M. Xu, B.-J. Li, Z. Yang, Z.-J. Shi, Chem.
Soc. Rev. 2010, 39, 712; b) A. Brennfꢃhrer, H. Neumann, M. Beller,
Angew. Chem. 2009, 121, 4176; Angew. Chem. Int. Ed. 2009, 48,
4114; c) J. S. Blakeney, R. C. Reid, G. T. Le, D. P. Fairlie, Chem. Rev.
2007, 107, 2960; d) L. Yin, J. Liebscher, Chem. Rev. 2007, 107, 133;
e) J. Corbet, G. Mignani, Chem. Rev. 2006, 106, 2651; f) M. Kertesz,
C. H. Chio, S. Yang, Chem. Rev. 2005, 105, 3448; g) J. Hassan, M.
Sevignon, C. Gozzi, E. Schulz, M. Lemaire, Chem. Rev. 2002, 102,
1359.
[17] S. Caron, S. S. Massett, D. E. Bogle, M. J. Castaldi, T. F. Braish, Org.
Process Res. Dev. 2001, 5, 254.
[18] For examples, see: a) G. Mann, J. F. Hartwig, M. S. Driver, C.
Fernꢄndez-Rivas, J. Am. Chem. Soc. 1998, 120, 827; b) B. P. Fors,
D. A. Watson, M. R. Biscoe, S. L. Buchwald, J. Am. Chem. Soc.
2008, 130, 13552; c) C. M. So, Z. Zhou, C. P. Lau, F. Y. Kwong,
Angew. Chem. 2008, 120, 6502; Angew. Chem. Int. Ed. 2008, 47,
6402.
[19] T. Kinzel, Y. Zhang, S. L. Buchwald, J. Am. Chem. Soc. 2010, 132,
14073, and references therein.
[20] N. Miyaura, K. Yamada, H. Suginome, A. Suzuki, J. Am. Chem. Soc.
1985, 107, 972.
[2] J. L. Bolliger, C. M. Frech, Chem. Eur. J. 2010, 16, 4075, and referen-
ces therein.
[3] For recent examples of the use of triflates as substrates, see: a) P.
Nilsson, M. Larhed, A. Hallberg, J. Am. Chem. Soc. 2001, 123, 8217;
b) D.-Y. Lee, J. F. Hartwig, Org. Lett. 2005, 7, 1169; c) J. P. Wolfe, H.
Tomori, J. P. Sadighi, J. Yin, S. L. Buchwald, J. Org. Chem. 2000, 65,
1158.
[21] V. Percec, J.-Y. Bae, D. H. Hill, J. Org. Chem. 1995, 60, 1060.
Received: November 25, 2010
Published online: February 24, 2011
4042
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 4038 – 4042