Ni0-catalyzed direct animation of anisoles involving the cleavage of carbon-oxygen bonds

Article abstract of DOI:10.1246/cl.2009.710

Ni⁰-catalyzed cross-coupling of aryl methyl ethers with amines is described. The use of an N-heterocyclic carbene as a ligand and NaOt-Bu as a base promotes the amination of anisole derivatives via the cleavage of normally unreactive aryl carbo

Full text of DOI:10.1246/cl.2009.710

710
Chemistry Letters Vol.38, No.7 (2009)
Ni0-catalyzed Direct Amination of Anisoles Involving the Cleavage
of Carbon–Oxygen Bonds
Mamoru Tobisu,ꢀ1 Toshiaki Shimasaki,1 and Naoto Chataniꢀ2
1Frontier Research Base for Global Young Researchers, Graduate School of Engineering, Osaka University,
Suita, Osaka 565-0871
2Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871
(Received April 27, 2009; CL-090416; E-mail: tobisu@chem.eng.osaka-u.ac.jp, chatani@chem.eng.osaka-u.ac.jp)
Ni0-catalyzed cross-coupling of aryl methyl ethers with
Table 1. Optimization studiesa
amines is described. The use of an N-heterocyclic carbene as a
ligand and NaOt-Bu as a base promotes the amination of anisole
derivatives via the cleavage of normally unreactive aryl carbon–
oxygen bonds.
O
Ni(cod)2 / ligand
OMe
N
morpholine (2)
base
toluene, 120 °C
1
3
Entry
Ligand
Base
BuLi
KOt-Bu
Time/h
Yield/%b
In 1983, Kosugi and Migita reported on the palladium-cata-
lyzed cross-coupling of tin amides with aryl halides to form ani-
lines.1 Stimulated by this report, Buchwald and Hartwig inde-
pendently reported more practical protocols for the cross-cou-
pling of amines with aryl halides in the presence of a base
(eq 1).2 These palladium-catalyzed methods have rapidly be-
come important tools in organic synthesis, pharmaceuticals,
and materials science. Although this reaction has seen significant
advancement over the last decade, the electrophilic coupling
partner for use remains limited to organic halides and sulfonates.
We report herein a nickel-catalyzed cross-coupling of amines
with anisole derivatives, wherein a carbon–oxygen bond is
cleaved (eq 2).3
1
2
3
4
5
6
7
8
9
PCy3
PCy3
PCy3
PCy3
L1
L2
L3
L4
L5
12
12
12
48
48
48
48
48
48
48
complex
0
24
31
13
37
56
0
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
22
89
10c
L3
aReaction conditions: 1 (0.5 mmol), 2 (1.0 mmol), Ni(cod)2
(0.05 mmol), ligand (0.10 mmol), base (1.5 mmol), toluene
(1.5 mL) at 120 ꢁC in a sealed tube. Isolated yield of 3. 2
(2.5 mmol), Ni(cod)2 (0.1 mmol), L3 (0.2 mmol), and NaOt-
Bu (3.0 mmol) were used.
b
c
cat.
+
ð1Þ
Ar
X
HN
Ar
N
base
R1
R1
X = I, Br, Cl, OTf, OTs, etc
cat. Ni
base
N
N
N
N
Cl
R2
R2
Cl
+
HN
ð2Þ
Ar
OMe
Ar
N
R1
L3: R1 = i-Pr, R2 = H
L2: R1 = Et, R2 = H L4: R1 = R2 = t-Bu
L5
R1
L1: R1 = R2 = Me
Based on our studies on the nickel-catalyzed cross-coupling
of aryl methyl ethers with aryl boronic esters,4,5 we initially ex-
amined the reaction of 2-methoxynaphthalene (1) with morpho-
line (2) in the presence of a catalytic amount of Ni(cod)2 and
PCy3 (Table 1). Similar to the catalytic amination of halides,6
the choice of base proved to exert a critical impact on the reac-
tion. While the use of BuLi or KOt-Bu as a base failed to pro-
mote the desired amination reaction (Entries 1 and 2), the ex-
pected product 3 was formed in promising yield by employing
NaOt-Bu (Entries 3 and 4). With NaOt-Bu as a base, we next in-
vestigated the effect of ligands. A significant decrease in yield
was observed with other phosphine ligands, such as P(t-Bu)3,
P(i-Pr)3, (biphenyl-2-yl)dicyclohexylphosphine, and dppf, as
we have encountered a similar trend in the cross-coupling with
boronic esters.4 On the other hand, it was found that the addition
of some N-heterocyclic carbene ligands also furnished the ami-
nation product 3 (Entries 5–9). Yields were improved by increas-
ing a steric demand of the ligand (L1 < L2 < L3), whereas the
catalytic amination did not proceed when a highly bulky ligand
L4 was used. With L3 as an optimal ligand, the yield of 3 was
finally increased to 89% by increasing the catalyst loading
(20 mol %) and amount of amine (5 equiv). It is important to note
that no amination product was formed in the absence of a nickel
catalyst under otherwise identical conditions, indicating that
base-promoted nucleophilic aromatic substitution7 is not opera-
tive in this reaction. The use of NiCl2 as a nickel source also af-
forded 3, albeit in significantly lower yield.
Having optimized conditions in hand, we next explored the
scope of this reaction with respect to the amine component
(Table 2). Various cyclic amines, such as pyrrolidine (4), piper-
idines 5–7, and piperazines 8 and 9, underwent the nickel-cata-
lyzed cross-coupling with 1 to successfully construct important
structural motifs commonly found in pharmaceutical substances.
The larger the ring size, the lower the yield, indicating the sen-
sitivity of the reaction to the steric factor of the amines (compare
4, 5, and 10). Acyclic amines, as in 11 and 12, can also be ap-
plied to this catalytic amination reaction. On the other hand, pri-
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.7 (2009)
711
Table 3. Ni0-catalyzed amination of anisole derivativesa
Table 2. Ni0-catalyzed cross-coupling of
aminesa
1
with various
cat. Ni(cod)2/L3
R1
NaOt-Bu
cat. Ni(cod)2/L3
NaOt-Bu
R1
+
2
Ar OMe
Ar
N
O
toluene
120 °C, 48 h
N
R2
1
+
HN
toluene
120 °C, 48 h
R2
Entry
Anisole derivative
OMe
Yield/%b
Entry
1
Amine
Yield/%b Entry
Amine
Yield/%b
1
2
R = H (1)
89
78
R = Ph (13)
6
2
O
89
8
Ph
59
53
51
HN
HN
N
N
HN
R
OMe
7
2
3
4
5
91
HN
HN
14
3
30
N
9
8
70
HN
HN
10
4
5
6
7
R = H (15)
R = Ph (16)
R = CF3 (17)
R = CO2Me (18)
0
43
44
43c
R
OMe
Me
59c
9
11
42
51
4
5
HN
HN
Ph
6
Bu
aReaction conditions: 1 (0.5 mmol), 2 (2.5 mmol), Ni(cod)2
(0.1 mmol), L3 (0.2 mmol), and NaOt-Bu (3.0 mmol), toluene
(1.5 mL) at 120 ꢁC for 48 h in a sealed tube. bIsolated yield based
on anisole derivatives. cThe product was morpholino(4-morpho-
linophenyl)methanone.
H
Me
10
55
7
12
HN
Ph
H
aReaction conditions: 1 (0.5 mmol), amine (2.5 mmol), Ni(cod)2
(0.1 mmol), L3 (0.2 mmol), and NaOt-Bu (3.0 mmol), toluene
(1.5 mL) at 120 ꢁC for 48 h in a sealed tube. bIsolated yield based
of carbon–oxygen bonds.10 Although the reaction efficiency and
the substrate scope require further improvements, these studies
clearly indicate that anisoles can be employed as a synthetic sur-
rogate of aryl halides in transition-metal catalysis. Studies along
this line are currently underway.
c
on 1. Ni(cod)2 (0.05 mmol) and L3 (0.1 mmol) were used.
mary amines and anilines did not afford the corresponding cou-
pling products under these conditions.
Table 3 illustrates the scope of the nickel-catalyzed amina-
tion with respect to the anisole component. While 2-methoxy-
naphthalenes, as in 1 and 13, proved to be good substrates, 1-me-
thoxy isomer 14 resulted in a significant loss of yield probably
due to the steric hindrance. As is observed in the cross-coupling
with boronic esters,4 the reaction of anisole 15 with 2 did not pro-
ceed under these conditions. However, introduction of electron-
withdrawing groups, such as Ph 16, CF3 17, and CO2Me 18
groups, significantly enhanced the reactivity toward this catalyt-
ic amination to form the corresponding amines in modest yields.
The exclusive formation of the ipso substituted products in these
cases indicates that an aryne-type intermediate is not involved in
this catalysis.8 The applicability of relatively unactivated anisole
16 is in contrast to our previous results.9
This work was carried out under the Program of Promotion
of Environmental Improvement to Enhance Young Researchers’
Independence, the Special Coordination Funds for Promoting
Science and Technology, MEXT, Japan.
References and Notes
1
2
M. Kosugi, M. Kameyama, T. Migita, Chem. Lett. 1983, 927.
Recent reviews: a) D. S. Surry, S. L. Buchwald, Angew. Chem., Int. Ed. 2008, 47,
6338. b) J. F. Hartwig, Acc. Chem. Res. 2008, 41, 1534.
3
For representative reports on the nickel-catalyzed amination reactions of aryl
halides, see: a) R. Cramer, D. R. Coulson, J. Org. Chem. 1975, 40, 2267. b)
J. P. Wolfe, S. L. Buchwald, J. Am. Chem. Soc. 1997, 119, 6054. c) B. H.
Lipshutz, H. Ueda, Angew. Chem., Int. Ed. 2000, 39, 4492. d) C. Desmarets,
R. Schneider, Y. Fort, J. Org. Chem. 2002, 67, 3029. e) C. Chen, L.-M. Yang,
J. Org. Chem. 2007, 72, 6324. f) G. Manolikakes, A. Gavryushin, P. Knochel,
J. Org. Chem. 2008, 73, 1429.
Diaminonaphthalene 21 can be synthesized through the se-
quential aminations of halide and methyl ether moieties in 19
by palladium and nickel catalysts, respectively (eq 3).
4
5
M. Tobisu, T. Shimasaki, N. Chatani, Angew. Chem., Int. Ed. 2008, 47, 4866.
Nickel-catalyzed cross-coupling of anisole derivatives with Grignard reagents:
a) E. Wenkert, E. L. Michelotti, C. S. Swindell, J. Am. Chem. Soc. 1979, 101,
2246. b) E. Wenkert, E. L. Michelotti, C. S. Swindell, M. Tingoli, J. Org. Chem.
1984, 49, 4894. c) J. W. Dankwardt, Angew. Chem., Int. Ed. 2004, 43, 2428. d)
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: e) 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.
For example, see: S. L. Buchwald, C. Mauger, G. Mignani, U. Scholz, Adv.
Synth. Catal. 2006, 348, 23.
cat. Pd(OAc)2 /BINAP
5 (1.2 equiv)
OMe
OMe
NaOt-Bu, toluene
reflux, 12 h
Br
N
19
6
7
8
20 73%
ð3Þ
O
W. ten Hoeve, C. G. Kruse, J. M. Luteyn, J. R. G. Thiecke, H. Wynberg, J. Org.
Chem. 1993, 58, 5101, and references therein.
cat. Ni(cod)2 /L3
2 (5.0 equiv)
N
Reviews on arynes in organic synthesis: a) H. Pellissier, M. Santelli, Tetrahedron
2003, 59, 701. b) A. M. Dyke, A. J. Hester, G. C. Lloyd-Jones, Synthesis 2006,
4093.
NaOt-Bu, toluene
120 °C, 48 h
N
9
The cross-coupling of 16 with boronic ester using Ni0/PCy3 catalyst system did
21 64%
not proceed.
10 Supporting Information is available electronically on the CSJ-Journal Web site,
http://www.csj.jp/journals/chem-lett/index.html.
In summary, we have developed a nickel-catalyzed amina-
tion of anisole derivatives which proceeds through the cleavage
Published on the web (Advance View) June 13, 2009; doi:10.1246/cl.2009.710