Nickel-catalyzed cross-coupling of aryl methyl ethers with aryl boronic esters

Article abstract of DOI:10.1002/anie.200801447

(Chemical Equation Presented) To C-OMe and go: The title reaction, involving cleavage of a C-OMe bond, is demonstrated for the coupling of aryl methyl ethers on fused aromatic systems, such as naphthalene and phenanthrene, as well as anisoles containing electron-withdrawing groups with a wide range of boronic esters. cod=cycloocta-1,5-diene, Cy=cyclohexyl.

Full text of DOI:10.1002/anie.200801447

Communications
DOI: 10.1002/anie.200801447
Cross-Coupling Reactions
Nickel-Catalyzed Cross-Coupling of Aryl Methyl Ethers with Aryl
Boronic Esters**
Mamoru Tobisu,* Toshiaki Shimasaki, and Naoto Chatani*
Palladium- and nickel-catalyzed cross-coupling reactions
have been recognized as an indispensable tool for current
organic synthesis.[1] Among these reactions, Suzuki–Miyaura
coupling[2–7] is, arguably, of the greatest practical importance
of these methods because of the attractive features of
organoboronic acids: widespread availability, stability to air
and moisture, and low toxicity. Recently, tremendous progress
has been made in the development of more elaborate catalyst
systems that allow the couplings to be conducted at room
temperature,[3] to use unreactive chlorides,[4] and to use alkyl
electrophiles.[5,6] Despite these significant advances, the
electrophilic coupling partner for use in Suzuki–Miyaura
coupling remains limited, for the most part, to organic halides
and sulfonates; although the use of less available electro-
philes, including diazonium salts,[7a] ammonium salts,[7b] aryl-
triazene/BF3,[7c] azoles,[7d] and phosphonium salts[7e] has been
reported. Aryl methyl ethers, which are as readily available as
aryl halides, have never been used in the Suzuki–Miyaura
coupling reaction, except for the ruthenium-catalyzed
system,[8] which requires a ligating group at the ortho position
for the reaction to proceed. Herein, we describe a method for
the nickel-catalyzed cross-coupling of aryl methyl ethers with
boronic esters [Eq. (1)].
Wenkert[9a,b] and Dankwardt[9c] in the nickel-catalyzed reac-
tion with Grignard reagents (i.e., Kumada–Tamao–Corriu-
type coupling). Although functional-group compatibility and
availability of the starting Grignard reagents for these initial
methods are rather limited, these pioneering studies offer a
starting point for the development of cross-coupling reactions
between aryl methyl ethers and organoboron reagents. Thus,
we investigated the reaction of 2-methoxynaphthalene (1a)
with organoboron compounds in the presence of a catalytic
amount of [Ni(cod)2] (cod = cycloocta-1,5-diene) and PCy3
(Table 1). Whereas attempts with boronic acid (Table 1,
entry 1) and borates (Table 1, entries 2 and 3) were unsuc-
cessful, cross-coupling with boronic ester 2a furnished the
product in modest yield (Table 1, entry 4). Although the
Table 1: Optimization of reaction conditions.[a]
Entry Organoboron compd. Base
T [8C] Solvent Yield [%][b]
1[c]
2
3
PhB(OH)2
PhBF3K
NaBPh4
2a
2a
2a
NaOH 80
NaOEt 80
NaOEt 80
NaOEt 80
dioxane
dioxane
dioxane
dioxane 64
dioxane 54
dioxane 47
toluene 89
toluene 93
0
0
8
The advantages of using aryl alkyl ethers in the metal-
catalyzed cross-coupling reaction have been documented by
4
5
CsF
CsF
CsF
CsF
80
80
80
120
6[d]
7[d]
8[d]
2a
2a
[*] Dr. M. Tobisu, Dr. T. Shimasaki
[a] Reaction conditions: 1a (0.5 mmol), organoboron compound
(0.6 mmol), [Ni(cod)2] (0.05 mmol), PCy3 (0.10 mmol), NaOEt
(0.75 mmol) or CsF (2.25 mmol), toluene (1.5 mL) in a sealed tube.
[b] Yields of 2-phenylnaphthalene measured by GC. [c] Toluene/H2O=
3:1 was used as a solvent. [d] PCy3 (0.20 mmol) and 2a (0.75 mmol)
were used.
Frontier Research Base for Global Young Researchers
Graduate School of Engineering, Osaka University
Suita, Osaka 565-0871 (Japan)
Fax: (+81)6-6879-7396
E-mail: tobisu@chem.eng.osaka-u.ac.jp
Prof. Dr. N. Chatani
Department of Applied Chemistry
Faculty of Engineering, Osaka University
Suita, Osaka 565-0871 (Japan)
Fax: (+81)6-6879-7396
reaction did not proceed in the absence of base, the use of a
mild base (CsF) proved reasonably effective (Table 1,
entry 5). Ligand screening did not lead to a fruitful result
(none: 0%, PtBu3: 0%, PtBu2Me: 22%, P(cylopentyl)3: 13%,
PMe3: 0%, PPh3: 0%, dmpe: 0%, binap: 0%, IPr·HCl: 0%;
E-mail: chatani@chem.eng.osaka-u.ac.jp
[**] This work was carried out on the Program of Promotion of
Environmental Improvement to Enhance Young Researchers’
Independence, the Special Coordination Funds for Promoting
Science and Technology, Ministry of Education, Culture, Sports,
Science and Technology (MEXT) (Japan). We also thank the
Instrumental Analysis Center, Faculty of Engineering, Osaka
University, for their assistance with the MS, HRMS, and elemental
analyses.
dmpe = 1,2-bis(dimethylphosphanyl)ethane,
binap = 2,2’-
bis(diphenylphosphanyl)-1,1’-binaphthyl). However, product
yield was improved when toluene was used as the solvent:
89% at 808C (Table 1, entry 7) and 93% at 1208C (Table 1,
entry 8).
Steric bulk of the substituents at the ether oxygen atom
had a significant effect on the efficiency of the cross-coupling
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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reaction [Eq. (2)]. Primary alkyl ethers, such as methoxy and
ethoxy groups, furnished the coupling products in good yields,
whereas reactions of secondary alkyl ethers proved to be
completely inactive under the catalytic conditions employed
in this study. Examination of a series of anisole derivatives
revealed that those bearing an electron-withdrawing group
had greater reactivity in this cross-coupling reaction than
those without an electron-withdrawing group. For example,
the reaction of 4-acetylanisole with boronic ester 2a furnished
the biphenyl derivative in 55% yield (Table 2, entry 6).
Anisole derivatives containing a styryl group also afforded
the corresponding coupling products, although the yield was
less than that observed for the naphthalene derivatives
(Table 2, entry 7).
We also investigated the functional-group tolerance with
respect to the boronic ester component (Table 3). Both
electron-deficient (Table 3, entries 1–3) and -rich (Table 3,
entry 5) boronic esters afforded the coupling products in good
much less efficient. Similarly, the acetoxy group, which is, in
general, a better leaving group, was not an efficient coupling
partner in this reaction.
The scope of the nickel-catalyzed cross-coupling of aryl
Table 3: Nickel-catalyzed cross-coupling of 1a with various boronic
methyl ethers was subsequently investigated (Table 2).[10]
A
esters.[a]
methoxy group connected to a fused aromatic system, such as
naphthalene (Table 2, entries 1 and 2) and phenanthrene
Table 2: Nickel-catalyzed cross-coupling of aryl methyl ethers with 2a.[a]
Entry Boronic ester
Yield Entry Boronic ester
[%][b]
Yield
[%][b]
1
2
94
83
6
7
36
68
Entry
1
Aryl methyl ether
Product
Yield [%][b]
93
3
4
5
78[c]
92
8
74
65
89
2
3
74
92
9
79
10
4
57
[a] Reaction conditions: 1a (0.5 mmol), boronic ester (0.75 mmol),
[Ni(cod)2] (0.05 mmol), PCy3 (0.20 mmol), CsF (2.25 mmol), toluene
(1.5 mL) in a sealed tube. [b] Yields of isolated products. [c] [Ni(cod)2]
(0.10 mmol) and PCy3 (0.40 mmol) were used.
5
6
7
62
55
14
yields. The trimethylsilyl functional group also survived, even
in the presence of a fluoride base (Table 3, entry 4). 4-
Methoxyphenylboronic acid also serves as a good coupling
partner; the methoxy group on the benzene ring remained
intact (Table 3, entry 7). Sterically demanding boronic esters
were also used successfully (Table 3, entries 8 and 10). It
should be noted that the reaction proceeds cleanly in all cases,
and remaining mass balance is unconverted starting material
1a.
[a] Reaction conditions: aryl methyl ether (0.5 mmol), 2a (0.75 mmol),
[Ni(cod)2] (0.05 mmol), PCy3 (0.20 mmol), CsF (2.25 mmol), toluene
(1.5 mL) in a sealed tube. [b] Yields of isolated products.
(Table 2, entry 3), was efficiently replaced with a phenyl
group. The advantage of utilizing boronic esters as the
nucleophilic coupling partner is demonstrated by the toler-
ance of functional groups, such as ketones and esters (Table 2,
entries 4 and 5). In these cases, addition to the carbonyl
moiety did not occur. In sharp contrast to Ni-catalyzed
coupling with Grignard reagents,[9] the simple anisole was
It is plausible that the reaction proceeds through a typical
cross-coupling mechanism, as follows: 1) oxidative addition
0
[8b]
À
of a C OMe bond to Ni ; 2) transmetalation of the aryl
II
À
À
group on the fluoride-activated boronic ester to Ar Ni
OMe; and, 3) C C bond formation by reductive elimination.
The results of a competitive experiment revealed that the
À
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electronic nature of the boronic ester does not significantly
affect the yield of product [Eq. (3)], suggesting that oxidative
cleavage of unreactive bonds.[18] Although improvement of
the scope of the aryl methyl ethers requires additional studies,
the advantage of utilizing boronic esters, as in the typical
Suzuki–Miyaura reaction, is retained. Ongoing work seeks to
explore additional active catalytic systems for this and related
cross-coupling reactions.
À
addition of a C OMe bond is rate-limiting in this catalysis.
Received: March 27, 2008
Published online: May 21, 2008
Keywords: biaryls · cleavage reactions · cross-coupling · nickel ·
.
Suzuki–Miyaura reaction
[1] For general reviews of metal-catalyzed cross-coupling reactions,
see: a) Metal-Catalyzed Cross-Coupling Reactions (Eds.: A.
de Meijere, F. Diederich), Wiley-VCH, Weinheim, 2004;
b) Handbook of Organopalladium Chemistry for Organic Syn-
thesis (Ed.: E.-i. Negishi), Wiley-Interscience, New York, 2002.
[2] a) N. Miyaura, Top. Curr. Chem. 2002, 219, 11; b) A. Suzuki,
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Q. Shelby, J. P. Stambuli, J. F. Hartwig, J. Org. Chem. 2002, 67,
5553.
Thus, the reactivity of aryl methyl ethers in Ni-catalyzed
cross-coupling should reflect their relative reactivity toward
oxidative addition of the C OMe bond to Ni0.[11] Notably, the
À
range of aryl methyl ethers that can be used in Ni-catalyzed
cross-coupling with boronic esters is relatively limited com-
pared with that using Grignard reagents, even though both
À
reactions apparently proceed by oxidative addition of C
OMe bonds. This difference might be explained by the
assumption that a nickel ate complex, which is more
nucleophilic than Ni0, operates as an active catalytic species
when Grignard reagents are used in the reaction.[12,13]
The new cross-coupling reaction was successfully applied
to the synthesis of oligoarenes [Eq. (4)]. The cross-coupling of
2-bromo-6-methoxynaphthalene with phenylboronic acid
under standard Suzuki–Miyaura conditions, followed by Ni-
catalyzed cross-coupling of a methyl ether moiety, furnished
naphthalene containing two different aryl groups.
[4] A. F. Littke, G. C. Fu, Angew. Chem. 2002, 114, 4350; Angew.
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2006, 106, 4622; b) S. B. Blakey, D. W. C. MacMillan, J. Am.
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[10] Notes: a) The amount of PCy3 was not optimized for each
substrate. In the reaction of p-acetylanisole (see Table 2,
entry 6), the use of 20 mol% of PCy3 gave a inferior result
(30% yield). Thus, we routinely conducted the reaction with
40 mol% of PCy3; b) When the corresponding pinacolate was
used for the reaction in Table 2, entry 1, the yield of the product
was decreased (20% yield).
[11] Oxidative addition of aryl methyl ethers in this catalysis may
involve an intermediate in which the aromaticity of the aryl
methyl ether is lost, such as h2-arene or Meisenheimer-type
complexes. Polyaromatic compounds are expected to form such
complexes more facilely, since part of the aromaticity is retained
after complex formation.
In summary, we developed a Ni-catalyzed cross-coupling
reaction of aryl methyl ethers with boronic esters. Although it
À
has been reported that several inactive bonds, including C
F,[14] C CN, C S, and C O,[9,17] can be cleaved and used
for the cross-coupling reaction in the presence of Ni catalysts,
these reactions require strong nucleophilic coupling partners,
such as Grignard reagents. The method described herein
represents the first general catalytic protocol that utilizes
boronic acid derivatives in cross-couplings involving the
[15]
[16]
À
À
À
[12] a) W. Kaschube, K. R. Pörschke, K. Angermund, C. Krüger, G.
Wilke, Chem. Ber. 1988, 121, 1921; b) F. Mongin, L. Mojovic, B.
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Angewandte
Chemie
[13] Another possible explanation for the wider substrate scope in
Angew. Chem. Int. Ed. 2005, 44, 7216. See also references [12b]
À
the cross-couplings with Grignard reagents is activation of C O
and [13a].
bonds by Lewis acidic magnesium salts. However, the addition of
MgBr2, LiCl, and BPh3 in our system did not improve the
reactivity of aryl methyl ethers. See: a) N. Yoshikai, H. Mashima,
E. Nakamura, J. Am. Chem. Soc. 2005, 127, 17978; b) Y. Nakao,
A. Yada, S. Ebata, T. Hiyama, J. Am. Chem. Soc. 2007, 129, 2428.
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Gstöttmayr, T. Weskamp, W. A. Herrmann, Angew. Chem. 2001,
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Dankwardt, J. Organomet. Chem. 2005, 690, 932; d) T. Saeki,
Y. Takashima, K. Tamao, Synlett 2005, 1771; e) L. Ackermann,
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37, 300.
[16] For a review, see: T.-Y. Luh, Z.-J. Ni, Synthesis 1990, 89.
[17] During preparation of this manuscript, another report on
Kumada-type coupling of aryl methyl ethers with methylmagne-
sium halides was published: B.-T. Guan, S.-K. Xiang, T. Wu, Z.-P.
Sun, B.-Q. Wang, K.-Q. Zhao, Z.-J. Shi, Chem. Commun. 2008,
1437. See also: B.-T. Guan, S.-K. Xiang, B.-Q. Wang, Z.-P. Sun, Y.
Wang, K.-Q. Zhao, Z.-J. Shi, J. Am. Chem. Soc. 2008, 130, 3268.
[18] A cross-coupling reaction between activated aryl fluorides and
boronic acids has been reported: T. Schaub, M. Backes, U.
Radius, J. Am. Chem. Soc. 2006, 128, 15964.
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