Biaryl construction via Ni-catalyzed C-O activation of phenolic carboxylates

Article abstract of DOI:10.1021/ja8056503

Biaryl scaffolds were constructed via Ni-catalyzed aryl C-O activation by avoiding cleavage of the more reactive acyl C-O bond of aryl carboxylates. Now aryl esters, in general, can be successfully employed in cross-coupling reactions for the first time.

Full text of DOI:10.1021/ja8056503

Published on Web 10/11/2008
Biaryl Construction via Ni-Catalyzed C-O Activation of Phenolic Carboxylates
Bing-Tao Guan,† Yang Wang,† Bi-Jie Li,† Da-Gang Yu,† and Zhang-Jie Shi*,†,‡
Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and
Molecular Engineering of Ministry of Education, Peking UniVersity, Beijing 100871, China and State Key
Laboratory of Oganometallic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
Received July 20, 2008; E-mail: zshi@pku.edu.cn
Scheme 1. New Design on Activation of Aryl Carboxylate
The industrially important cross-coupling of aromatic compounds
meets the requirement of the scientific and commercial valuable biaryl
compounds, which are as ubiquitous in molecules as biaryl scaffolds
and structural units and broadly used in agrochemicals, pharmaceu-
ticals, and materials fields.1 In the past, the Suzuki-Miyaura coupling
of aryl halides with nucleophilic arylboronic reagents has become a
common and reliable method for both laboratorial and industrial
applications and has almost completely replaced classical methods for
constructing such biaryl units.2 This is evidenced by numerous
publications and patents on the development, improvement and
application of this transformation.3
Table 1. Cross-Coupling between 2-Naphthyl Acetate and
Phenylboroxine under Different Conditionsa
Extensive efforts have been made toward the use of less expensive
aryl chlorides in cross-coupling reactions, and successes have been
achieved.4 However, several important improvements are still chal-
lenging and are yet to be realized. Aryl chlorides are not necessarily
ideal starting materials for certain transformations, with some not
readily available. In many cases, direct use of ubiquitous ester moieties
in cross-coupling could be a synthetically ideal route that is more
environmentally friendly (Scheme 1). In addition, the replacement of
Pd catalysts with first row transition metal ions would significantly
lower cost.5 Here we present an efficient method to utilize phenolic
carboxylates for the Suzuki coupling reaction. For the first time, a broad
range of aryl ester substrates can be employed for the formation of
C-C bonds in cross-coupling reactions mediated by a Ni-based
catalyst.
Direct transformation of simple aryl esters to aryl-aryl products is
a very useful synthetic method. In many cases, aryl esters are desired
starting materials to replace aryl halides. Some aryl acetates are also
much less expensive than aryl halides or aryl sulfonates in large scale
productions.6 Aryl esters may also offer orthogonal groups to aryl
halides on a molecule that can be functionalized, which facilitates
synthesis of natural or synthetic compounds.1 However, due to the
intrinsic properties of carboxylates, they have only been employed as
leaving groups in Tsuji-Trost alkylation of allyl acetates.7 Use of
simple aryl esters such as aryl acetate presents several challenges. The
most significant one is to selectively activate the C-OAc bond in the
presence of a much more reactive carbonyl C-O bond (Scheme 1).8,9
If this problem can be solved, starting from simple phenol or its
derivatives, the acetate or other types of carboxylate moieties can be
readily produced and employed in cross-coupling reactions. Potentially
different carboxylic groups with varying steric/electronic properties
may be installed to facilitate the coupling selectivity in the future.
Many studies have revealed the unique and efficient catalytic
potential of Ni-based compounds to activate aryl and benzyl C-O
bonds of the ethers.10 Compared to aryl methyl ethers, aryl carboxylates
are much more affordable. Our ongoing work in Ni-catalyzed C-O
activation led us to believe that the crucial inversion of the reactivity
of related chemical bonds for cross-coupling of aryl carboxylates is
cat.
(10 mol%)
L
(20 mol%)
base
(2.0 equiv)
H2O
(mg)
yieldb
(%)
entry
solvent
1
2
3
4
5
6
7
8
Co(PCy3)2Cl2 PCy3
Cu(PCy3)2Cl2 PCy3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
KOH
4
4
4
4
4
4
4
4
4
0
2
6
0
0
0
0
0
0
4
4
4
4
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
toluene
DCE
<5
<5
<5
<5
73c
9
<5
29
20
23
58
46
51
<5
<5
6
Pd(PCy3)2Cl2
Fe(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
NiCl2 ·6H2O
NiCl2 ·6H2O
NiCl2 ·6H2O
NiCl2 ·6H2O
NiCl2 ·6H2O
NiCl2 ·6H2O
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
PCy3
PCy3
-
-
-
KOtBu
K2CO3
Na2CO3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
-
9
-
10
11
12
13
14
15
16
17
18
19
20d
21
22e
-
-
-
PCy3
PPh3
dppf
PBun
PBu5
3
3
27
17
45
<5
<5
51
P(OMe)3
-
-
-
-
DMF
dioxane
a Run using with 0.25 mmol of ester 1a and 0.30 mmol of
phenylboroxine 2a at 110 °C for 12 h. b GC yields using n-dodecane as
an internal standard. c Isolated yield. d Reaction carried out under reflux.
e PhB(OH)2 (1.5 equiv) was used.
an achievable goal. Our evaluation of the reaction system was initiated
from 2-naphthyl acetate (Table 1). Ni(PCy3)2Cl2 was the first choice
as a catalyst on the basis of our preliminary studies. Ni(PCy3)2Cl2 was
indeed found to be the best catalyst among the tested Ni and Pd
complexes. Different bases were further screened, and K3PO4, a
common inorganic base in Suzuki coupling, showed the best efficiency
for this transformation.2 Importantly the amount of water played a
vital role in promoting this transformation. With the use of completely
dried K3PO4, the relationship between the amount of water and the
efficiency of the C-C bond formation reaction was carefully studied.
We found that 0.88 equiv of water (based on the acetate) is the optimal
amount for this coupling (73% isolated yield was obtained in a test
reaction of 2-phenylnaphthalene). With 0.44 equiv of water the reaction
only gave 58% yield with an incomplete conversion, and 1.76 equiv
† Peking University.
‡ Chinese Academy of Sciences.
9
14468 J. AM. CHEM. SOC. 2008, 130, 14468–14470
10.1021/ja8056503 CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Cross-Coupling between Various Substituted Naphthyl
Carboxylates 1 and Different Arylboroxines 2a
Table 3. C-C Bond Formation via Ni-catalyzed Coupling between
Various Pivalates 1 and Arylboroxines 2a
product yieldb
entry
R′
R
Ar
3
(%)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Et
i-Pr
t-Bu
CF3
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3a
3a
3a
3a
3a <5
3a 69
3a <5
73
60
51
38
pyridin-2-yl
2,4,6-Me3C6H2 Ph
2,6-Cl2C6H3
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
3a
3a
3b
3c
3d
3e
3f
58
36
77
81
75
61
75
70
64
57
76
83
70
73
67
42
61
73
72
56
68
9
Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
p-tolyl
m-tolyl
o-tolyl
4-BuC6H4
4-MeOC6H4
4-FC6H4
3,5-(MeO)2C6H3 3h
3,5-Me2C6H3
Ph
Ph
Ph
Ph
Ph
Ph
3g
H
3i
3j
3k
3l
a Conditions: 0.25 mmol of ester 1, 0.33 mmol of boroxine 2, 0.025
mmol of Ni(PCy3)2Cl2, 0.05 mmol of PCy3, 1.0 mmol of K3PO4, 0.22
mmol of water, and 3 mL of dioxane, 110 °C, 12 h. b Isolated yield.
c GC yields using n-dodecane as an internal standard.
6-COMe
6-CH2OMe
6-COOMe
6-OMOM
6-OMe
3m
3n
3o
3p
3q
3r
3s
6-OH
high reactivity under the coupling conditions. Moreover, polysubstituted
arylboroxines also exhibited excellent reactivities to facilitate this
transformation.
5-CH2OMe-6-OMe Me
Ph
25c 6-Ph
Me
Me
Me
acetate
4-BuC6H4
4-BuC6H4
4-BuC6H4
Ph
26c 6-4-MeOC6H4
27c,d 6-OAc
The group compatibility on naphthyl acetate was systematically
studied (entries 18-27, Table 2). Generally, functional groups such
as alkyl and aryl survived well under the reaction conditions. Carbonyl
groups, such as esters, were compatible with this transformation. It is
noteworthy that the protected hydroxyl groups with methyl and MOM
survived well, which could be further functionalized based on our
developed method to perform the subsequent selective coupling in the
synthesis of complex molecules. Diphenylation of 2,6-naphthyl diac-
etate also occurred in good yield. The substrate with a free hydroxyl
group was also applied to the reaction to find that the desired
phenylated product was obtained in a moderate isolated yield (41%).
Polysubstituted naphthyl acetates with methoxyl groups both at the
benzyl position and on the phenyl ring were tested and the desired
products were isolated in good efficiency, leaving both methoxyl
groups untouched.
28
naphthalen-1-yl
3t
a Conditions: 0.25 mmol of ester 1, 0.30 mmol of boroxine 2, 0.025
mmol of Ni(PCy3)2Cl2, 0.22 mmol H2O, 0.50 mmol of K3PO4, and 2
mL of dioxine, 110 °C, 12 h. b Yields of entries 2-9 determined by GC
using n-dodecane as an internal standard, and isolated yields of entries
10-29 were reported here. c Reactions carried out with (4-nBuPhBO)3 to
increase the solubility of the products. d 2,6-Naphth-diol diacetate was
used as starting material, and diarylated product was obtained.
of water led to 46% yield with the hydrolyzed 2-naphthol as a
byproduct. Furthermore, different ligands were examined, and PCy3
was the most efficient. Other than dioxane, toluene is also a proper
solvent for this transformation.
During this catalytic transformation, a trace amount of 2-naphthol
as a hydrolyzed byproduct was observed, which may arise from the
stability of the acetate under the reaction conditions. Many different
esters were tested (entries 1-9, Table 2). As predicted, the more labile
trifluoroacetate is not suitable for this transformation and only the
hydrolyzed 2-naphthol was isolated. The more stable and sterically
hindered aliphatic carboxylates showed lower efficiencies, but the
hydrolysis side reaction was completely inhibited. Benzoate is also a
suitable substrate, and the desired product was isolated in a comparable
yield. Starting from 2-pyridinyl carboxylic ester, which could form a
five-membered chelated Ni complex,11 the coupling was completely
inhibited as expected. Similar to the pivalyl group, sterically hindered
2,4,6-trimethylbenzoate and 2,6-dichlorobenzoate are beneficial for this
transformation with slightly lower isolated yields.
Different boroxines were also explored (entries 10-17, Table 2).
The steric hindrance did not affect the efficiency, and all the para-,
meta-, and ortho-substituted aryl boroxines showed comparable
reactivities. Importantly 4-methoxylphenyl boroxine showed very good
reactivity, giving a good opportunity to further functionalize the
obtained product with the developed methods.10 Electron-deficient
C-F was also compatible with this transformation. However, low
efficiency indicated that C-Cl did not survive well, arising from its
This transformation was further applied to the direct arylation of
phenol derivatives (Table 3). Importantly substituted phenyl acetates
were not efficient substrates and hydrolyzed phenols were observed
as major products. However, the replacement of the acetate by the
pivalate made this transformation applicable. The optimal reaction was
achieved with an additional PCy3 ligand, and the desired product was
isolated in good yields (Table S1). The installation of an electron-
withdrawing group on aryl pivalates is highly beneficial for this
transformation. In contrast, electron-donating substituents slightly
lowered the reaction efficiency, but the reaction still furnished the
corresponding arylated products in moderate to good yields. Similarly,
different substituents on aryl boroxines survived well under this
condition. The electron-donating groups, such as a methoxyl group,
obviously enhanced the efficiency of this transformation. It is
noteworthy that the natural flavor derivative12 could easily be func-
tionalized in a good efficiency (entry 16, Table 3).
The mechanism of this reaction is proposed as shown in Scheme
2. First, Ni(PCy3)2Cl2 was reduced in the presence of arylboroxines
and K3PO4 to produce the active catalytic species Ni(0) (Supporting
9
J. AM. CHEM. SOC. VOL. 130, NO. 44, 2008 14469

C O M M U N I C A T I O N S
Scheme 2. Proposed Mechanism for Biaryl Synthesis Starting from
compound 14, the cross-coupling was repeated to give linear terphenyl
15, which could be further functionalized to yield longer linear
polyphenyls.10
Aryl Carboxylatesa
In summary, we developed a new class of homogeneous Ni-based
catalysis to construct biaryl scaffolds by activation of aryl carboxylates
with aryl boroxines. Our observation not only offers a new synthetic
tool for constructing C-C bonds from simple aryl esters for the
synthesis of industrially and medicinally important biaryl molecules
but also shows the power of transition metal mediated catalysis to
manipulate traditionally “inert” bonds. Aryl esters may be applied to
other cross-couplings based on the results shown here.
Acknowledgment. Support of this work by a starter grant from
Peking University, the grant from National Sciences of Foundation of
China (No. 20542001, 20521202) and National Basic Research
Program of China (973 Program 2009CB825300). We also thank Profs.
Hisashi Yamamoto and Chuan He at the University of Chicago for
constructive discussions.
a L can be phosphine.
Supporting Information Available: Experimental details, spectral
data. This material is available free of charge via the Internet at http://
pubs.acs.org.
Scheme 3. Application of Cross Coupling via Ni-Catalyzation
between Aryl Carboxylates and Arylboroxines
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Information, Figure S1), which further underwent oxidative addition
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