Nickel-catalyzed amination of aryl tosylates

Article abstract of DOI:10.1021/jo7022558

(Chemical Equation Presented) The cross-coupling of aryl tosylates with amines and anilines was accomplished by using a Ni-based catalyst system from the combination of Ni(II)-(σ-aryl) complexes/N-heterocyclic carbenes (NHCs). The feature, scope, and limitation of this reaction are disclosed.

Full text of DOI:10.1021/jo7022558

have also found applications in Ni-catalyzed C-C coupling
reactions;9,10 they, however, have not yet been well established
as synthetically useful substrates for the coupling reaction with
amines and anilines.11 We felt that this transformation should
be feasible through the proper choice of Ni-based catalyst
systems.
We very recently developed a facile, efficient protocol for
the Ni-catalyzed cross-couplings based on a type of Ni(II)-
(σ-aryl) complexes, trans-arylbis(triphenylphosphine)nickel(II)
halides, which has successfully been applied to the Suzuki
reaction12 and the amination4b of aryl chlorides. As part of our
continuing work, we wished to explore the possibility for the
amination of aryl tosylates by utilizing such Ni(II)-based
catalysts. Herein, we report our findings in this study.
Nickel-Catalyzed Amination of Aryl Tosylates
Cai-Yan Gao†,‡ and Lian-Ming Yang*,†
Beijing National Laboratory for Molecular Sciences (BNLMS),
Laboratory of New Materials, Institute of Chemistry, Chinese
Academy of Sciences, Beijing 100080, China, and Graduate
School of Chinese Academy of Sciences, Beijing 100049, China
yanglm@iccas.ac.cn
ReceiVed October 18, 2007
As shown in Table 1, our experiments for the optimal
conditions began with the coupling of phenyl tosylate with
morpholine catalyzed by a catalytic system consisting of Ni-
(II)-(σ-aryl) complexes13 and NHC ligands that are easily
derived in situ from the corresponding imidazolium salts.14 To
our pleasure, a very rapid reaction occurred with 77% yield of
the desired product when the reaction was performed under the
identical reaction conditions as for the amination of aryl
chlorides4b (run 1), but the reaction at room temperature gave
only a modest 29% yield (run 2). By replacing solvent THF
with dioxane (run 3) or toluene (run 4), elevating reaction
temperature to 110 °C led to higher isolated yield of 85% or
83%. A 1:1 ratio of IPr‚HCl (L-1) to Ni(PPh3)2(1-naphthyl)Cl
(1) seemed to be appropriate because doubling of the IPr‚HCl
amount did not contribute to the reaction very much (run 5 vs
3). The use of more σ-donating SIPr‚HCl (L-2), a saturated
counterpart of IPr‚HCl, as ligand gave a substantially low yield
The cross-coupling of aryl tosylates with amines and anilines
was accomplished by using a Ni-based catalyst system from
the combination of Ni(II)-(σ-aryl) complexes/N-heterocyclic
carbenes (NHCs). The feature, scope, and limitation of this
reaction are disclosed.
Despite remarkable advances in nickel-catalyzed aromatic
aminations in recent years, these reactions still have largely been
limited to aryl halides as electrophilic substrates.1-6 On the other
hand, aryl sulfonates, a class of synthetic equivalents of aryl
halides, are very attractive as coupling partners for the transition
metal-catalyzed processes because they are easily accessible
from the corresponding phenols.7 Among them, aryl tosylates
are of particular interest due to their ease of preparation and
handling, pronounced stability to hydrolysis, and lower cost; at
the same time they are also a challenging class of coupling
substrates because of their very low activity toward oxidative
addition that is a critical initial step in the metal-catalyzed
coupling reaction. In contrast, the palladium-catalyzed amination
of aryl sulfonates (including aryl tosylates) has been achieved,8
although Pd catalysts are oftentimes less nucleophilic than Ni
species. Furthermore, aryl sulfonates (including aryl tosylates)
(8) (a) Louie, J.; Driver, M. S.; Hamann, B. C.; Hartwig, J. F. J. Org.
Chem. 1997, 62, 1268-1273. (b) Wolfe, J. P.; Buchwald, S. L. J. Org.
Chem. 1997, 62, 1264-1267. (c) Hamann, B. C.; Hartwig, J. F. J. Am.
Chem. Soc. 1998, 120, 7369-7370. (d) Hartwig, J. F.; Hamann, B. C. U.S.
Patent 6,235,938, 2001. (e) Huang, X.-H.; Anderson, K. W.; Zim, D.; Jiang,
L.; Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 6653-
6655.
(9) For the Suzuki reaction with aryl sulfonates, see: (a) Percec, V.;
Bae, J.-Y.; Hill, D. H. J. Org. Chem. 1995, 60, 1060-1065. (b) Ueda, M.;
Saitoh, A.; Saori, O.-T.; Norio, M. Tetrahedron 1998, 54, 13079-13086.
(c) Tang, Z.-Y.; Hu, Q.-S. J. Am. Chem. Soc. 2004, 126, 3058-3059. (d)
Percec, V.; Golding, G. M.; Smidrkal, J.; Weichold, O. J. Org. Chem. 2004,
69, 3447-3452. (e) Zim, D.; Lando, V. R.; Dupont, J.; Monterio, A. L.
Org. Lett. 2001, 3, 3049-3051. (f) Tang, Z. Y.; Spinella, S.; Hu, Q. S.
Tetrahedron Lett. 2006, 47, 2427-2430.
(10) For the Kumada-Corriu reaction with aryl sulfonates, see: Cho,
C.-H.; Yun, H.-S.; Park, K. J. Org. Chem. 2003, 68, 3017-3025.
(11) For only one example on the Ni(0)-catalyzed amination of tosylates
with sulfoximine, see: Bolm, C.; Hildebrand, J. P.; Rudolph, J. Synthesis
2000, 7, 911-913.
(12) Chen, C.; Yang, L.-M. Tetrahedron Lett. 2007, 48, 2427-2430.
(13) For the preparation of the Ni(II)-(σ-aryl) complexes used, see: (a)
Cassar, L.; Ferrara, S.; Foa´, M. AdVances in Chemistry Series; American
Chemical Society: Washington, DC, 1974; Vol. 132, p 252. (b) Van
Soolingen, J.; Verkruijsse, H. D.; Keegstra, M. A.; Brandsma, L. Synth.
Commun. 1990, 20, 3153-3156. (c) Brandsma, L.; Vasilevsky, S. F.;
Verkruijsse, H. D. Application of Transition Metal Catalysts in Organic
Synthesis; Springer: New York, 1998; pp 3 and 4.
† Institute of Chemistry, Chinese Academy of Sciences.
‡ Graduate School of Chinese Academy of Sciences.
(1) Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 6054-
6058.
(2) Lipshutz, B. H.; Ueda, H. Angew. Chem., Int. Ed. 2000, 39, 4492-
4494.
(3) (a) Brenner, E.; Fort, Y. Tetrahedron Lett. 1998, 39, 5359-5362.
(b) Brenner, E.; Schneider, R.; Fort, Y. Tetrahedron 1999, 55, 12829-
12842. (c) Desmarets, C.; Schneider, R.; Fort, Y. Tetrahedron Lett. 2000,
41, 2875-2879. (d) Gradel, B.; Brenner, E.; Schneider, R.; Fort, Y.
Tetrahedron Lett. 2001, 42, 5689-5692. (e) Desmarets, C.; Schneider, R.;
Fort, Y. J. Org. Chem. 2002, 67, 3029-3036. (f) Omar-Amrani, R.; Thomas,
A.; Brenner, E.; Schneider, R.; Fort, Y. Org. Lett. 2003, 5, 2311-2314.
(4) (a) Chen, C.; Yang, L.-M. Org. Lett. 2005, 7, 2209-2211. (b) Chen,
C.; Yang, L.-M. J. Org. Chem. 2007, 72, 6324-6327.
(5) Kuhl, S.; Fort, Y.; Schneider, R. J. Organomet. Chem. 2005, 690,
6169-6177.
(6) Matsubara, K.; Ueno, K.; Koga, Y.; Hara, K. J. Org. Chem. 2007,
72, 5069-5076.
(7) For a leading reference, see: Metal-catalyzed Cross-coupling Reac-
tions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim , Germany,
1997.
(14) Two imidazolium salts used: 1,3-bis(2,6-diisopropylphenyl)imida-
zolium chloride (IPr‚HCl) and 1,3-bis(2,6-diisopropylphenyl)dihydroimi-
dazolium chloride (SIPr‚HCl). For their preparation, see: (a) Arduengo,
A. J., III; Krafczyk, R.; Schmutzler, R.; Craig, H. A.; Goerlich, J. R.;
Marshall, W. J.; Unverzagt, M. Tetrahedron 1999, 55, 14523-14534. (b)
Grasa, G. A.; Viciu, M. S.; Huang, J.; Nolan, S. P. J. Org. Chem. 2001,
66, 7729-7737.
10.1021/jo7022558 CCC: $40.75 © 2008 American Chemical Society
Published on Web 01/17/2008
1624
J. Org. Chem. 2008, 73, 1624-1627

TABLE 1. Screening of Conditions for Ni(II)-Catalyzed Amination
of Phenyl Tosylatea
TABLE 2. Ni(II)-Catalyzed Amination of Aryl Tosylates with
Secondary Cyclic Aminesa
[Ni]b
(mol %)
ligandc
(mol %)
T
(°C)
yield
(%)d
run
base
solvent
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
2 (5)
3 (5)
4 (5)
5 (5)
1 (5)
1 (3)
L-1 (5)
L-1 (5)
L-1 (5)
L-1 (5)
L-1 (10)
L-2 (5)
L-1 (5)
L-1 (5)
L-1 (5)
L-1 (5)
L-1 (5)
L-1 (5)
L-1 (5)
PPh3 (10)
L-1 (3)
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
KOtBu
NaOCH3
Cs2CO3
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
THF
THF
70
rt
77
29
85
83
80
10
e
dioxane
toluene
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
110
110
110
110
110
110
110
110
110
110
110
110
110
NRf
NRf
84
76
76
80
NRf
25
a Reaction conditions: aryl tosylate (1.0 equiv), morpholine (1.5 equiv),
base (1.6 equiv), 15 min. b 1: Ni(PPh3)2(1-naphthyl)Cl. 2: Ni(PPh3)2(1-
naphthyl)Br. 3: Ni(PPh3)2(phenyl)Cl. 4: Ni(PPh3)2(phenyl)Br. 5: Ni(PPh3)2[1-
(4-acetylnaphthyl)]Cl. c L-1: IPr‚HCl. L-2: SIPr‚HCl. d Isolated yield.
e Phenol was predominant with a trace of the coupled product. f NR: no
reaction.
(run 6); the catalyst system was ineffective for the reaction
without the use of NHC as ligand (run 14). For the bases used,
strongly basic KOtBu promoted decomposition of phenyl
tosylate into phenol (i.e., the cleavage of the O-S bonds of
tosylates) rather than the desired coupling reaction (run 7);
weaker bases NaOCH3 (run 8) and Cs2CO3 (run 9) were
ineffective for this transformation. Several other Ni(II)-(σ-aryl)
complexes, including Ni(PPh3)2(1-naphthyl)Br (2) (run 10), Ni-
(PPh3)2(phenyl)Cl (3) (run 11), Ni(PPh3)2(phenyl)Br (4) (run
12), and Ni(PPh3)2[1-(4-acetylnaphthyl)]Cl (5) (run 13), did not
seem to be superior to Ni(PPh3)2(1-naphthyl)Cl (1) under the
same conditions. An attempt to reduce catalyst loadings led to
a significantly decreased yield (run 15). Finally, the optimal
reaction conditions were set as run 3 in Table 1.
Some representative aryl tosylates and secondary cyclic
amines were examined under the standard conditions (Table 2).
As we can see, the nature of substituents on the aryl fragment
of aryl tosylates was closely responsible for this reaction.
Electron-neutral tosylates (entries 1-3, and 12-17) appeared
to be suitable substrates and could be aminated in moderate to
excellent yields, while aryl tosylates with electron-donating
groups, such as p-methoxy (entry 4) and p-tert-butyl (entry 5),
afforded mainly the recovered starting tosylates. Likewise, for
the reason of the electron-donating effect bis-tosylate was doubly
aminated only with a low yield (entry 11). Different from
haloarenes, electron-drawing groups displayed variable effects
on the amination of arenetosylates. The weakly electron-drawing
m-methoxy group was favorable for the reaction (entry 6-8),
and strongly electron-withdrawing groups could promote both
the C-O cleavage (the desired reaction) and the O-S cleavage
(side reaction). For example, in the case of the p-benzoyl group
a good yield of the desired product was afforded with small
amounts of the phenol byproduct (entry 9), while p-fluorophenyl
tosylate gave the dominant byproduct p-fluorophenol with a
trace of the coupled product (entry 10). It was found that the
a Reaction conditions: aryl tosylate (1.0 equiv), amine (1.5 equiv), base
(1.6 equiv), 1 (5 mol %), L-1 (5 mol %), dioxane, 110 °C, 15 min. b 1 (15
mol %), L-1 (15 mol %). c 4-Fluorophenol was obtained predominantly.
carbonyl group, somehow, might negatively affect the activity
of the Ni catalyst and therefore much higher catalyst loadings
were required to ensure a complete conversion of the starting
tosylate (entry 9). Additionally, the reaction was slightly
sensitive to the steric effects of the starting tosylates. For
instance, the reaction of 1-naphthyl tosylate furnished lower
yields than the corresponding reaction of 2-naphthyl tosylate
(entries 12-14 vs 15-17, respectively). Noticeably, we found
that this catalytic amination required a very short period of time,
and generally went to the end within 15 min. Control experi-
ments suggested that prolonged reaction times were helpless
for the enhancement of yields and hence unnecessary.
J. Org. Chem, Vol. 73, No. 4, 2008 1625

TABLE 3. Ni(II)-Catalyzed Amination of Aryl Tosylates with
Anilinesa
Under the above-mentioned standard conditions, aniline
reacted with phenyl tosylate to give 55% yield of the desired
product. When the molar ratio of Ni(II) to IPr‚HCl was adjusted
to 1:2, an improved yield of 68% was obtained (Table 3, entry
1). Then, the cross-couplings of various anilines and aryl
tosylates were carried out under the modified reaction conditions
(Table 3). As in the reaction with amines, the amination
reactions were strongly influenced by the electronic properties
of the starting aryl tosylates. Phenyl tosylate could be aminated
with acceptable to good yields (entries 1-5); electron-rich aryl
tosylates, such as p-methoxy and p-tert-butyl tosylates, did not
undergo the amination reaction (unlisted in Table 3); and
electron-deficient 4-tosylbenzophenone was consumed rapidly,
although yields were not very high due to partial decomposition
of the tosylate into phenol (entries 17-19). Particularly,
electron-neutral naphthyl tosylates performed very well and
good-to-excellent yields were generally afforded regardless of
both the steric and electronic natures of anilines (entries 6-10
and 12-16) except in the case of N-methylaniline (entry 11),
which is a more bulky secondary aromatic amine. Likewise, a
rapid reaction with anilines was observed (completed within
30 min), albeit a bit longer than that with secondary cyclic
amines.
Under the current conditions, byproduct biaryls from the self-
coupling of aryl tosylates were not detected in this amination
reaction, but another side reaction, decomposition of the starting
tosylate into phenoxide arising from the O-S cleavage of the
tosylate by attack of NaOtBu or/and amines on electrophilic
sulfur atom,8b,15 occurred to less or more extent in all cases
examined. Apparently, strongly electron-withdrawing groups
would promote the side reaction. The electron-rich aryl tosylates
cannot be aminated under the present conditions due presumably
to their extremely poor activity toward oxidative addition.
The catalytically active species may be the Ni(0) species that
could be formed in situ from the reaction of Ni(II)-(σ-aryl)
complex with the amine (i.e., by transmetalation of the nucleo-
philic reactant and subsequent reductive elimination prior to the
normal reaction). Indirect evidence is that a small amount of
1-naphthyl amination byproduct was usually observed,16 and a
previous stoichiometric reaction of Ni(II)-(σ-aryl) complexes
and morpholine4b supported the activation mode of the Ni(II)
pre-catalyst as well. Combining previous studies17 with our
experimental results, we presumed that the mechanism might
follow a catalytic cycle of the Ni(0)-Ni(II) shuttle involving
sequential oxidative addition, transmetalation, and reductive
elimination (Scheme 1). The rate-determining step of the
amination reaction is unclear at present.
It is noteworthy that this reaction was unusually fast compared
to the other reported Ni-1-5 and Pd-catalyzed8 amination
processes. We speculated that two major factors might be
responsible for the acceleration phenomenon. First, in our
protocol the formed Ni(0) specie might be coligated with IPr
and PPh3. The existence of the strong σ-donating IPr ligand
(15) Ahman, J.; Buchwald, S. L. Tetrahedron Lett. 1997, 38, 6363-
6366.
a Reaction conditions: aryl tosylate (1.0 equiv), aryl amine (1.5 equiv),
base (1.6 equiv), 1 (5 mol %), L-1 (10 mol %), dioxane, 110 °C, 30 min.
b 1 (15 mol %), L-1 (30 mol %).
(16) The small amount of 1-naphthyl amination byproduct generated from
Ni(PPh3)2(1-naphthyl)Cl is proportional to the amount of the complex used
and usually does not interfere with the separation of the desired amination
product. In the case of 1-naphthyl tosylate as substrate, the reported yields
have subtracted the contribution from the catalyst used according to an
estimation that Ni(PPh3)2(1-naphthyl)Cl would be completely converted.
(17) (a) Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972,
94, 4374-4376. (b) See refs 9a and 3e.
would substantially enhance the electron density of the Ni metal
center to facilitate the oxidative addition step; the hemilabile
ligand PPh3 might dissociate readily from the metal center to
1626 J. Org. Chem., Vol. 73, No. 4, 2008

SCHEME 1. Plausible Mechanism for the Amination of
Aryl Tosylates Catalyzed by Ni(II)-(σ-Aryl) Complex/NHC
Systems
overcome the limitation of aryl tosylate substrates as well as to
detail information about the mechanism of this reaction.
Experimental Section
General Procedure for the Amination of Aryl Tosylate. An
oven-dried 100-mL three-necked flask was charged with NaOtBu
(1.6 mmol), Ni(PPh3)2(1-naphthyl)Cl (5 mol %), and IPr‚HCl (5
mol % for amine or 10 mol % for aniline). The aryl tosylate (1.0
mmol) and the amine (1.5 mmol, if solid) were added at this time.
The flask was evacuated and backfilled with nitrogen, with the
operation being repeated twice. The amine (1.5 mmol, if liquid)
was added via syringe at this time, followed by dried dioxane (5
mL). The reaction mixture was heated at 110 °C for 15-30 min
and then allowed to cool to room temperature, and filtered through
a silica gel pad that was washed with ethyl acetate (3 × 20 mL).
The combined organic phases were evaporated under reduced
pressure and the residue purified by silica gel column chromatog-
raphy to give the desired product.
N-Phenylmorpholine21 (Table 2, entry 1). According to the
general procedure, phenyl tosylate (248 mg, 1.0 mmol) and
morpholine (131 mg, 1.5 mmol) were coupled and the product
purified by column chromatography with petroleum/ethyl acetate
(6:1, v/v) to give a colorless solid (138 mg, 85%): mp 49-51 °C
supply the vacant coordination site required for oxidative
addition and might re-ligate to the metal center, associated with
the steric effect of bulky IPr, to accelerate the reductive
elimination step. The analogous effects of mixed ligands have
been observed in Pd-18 and Ni-catalyzed19 couplings. Second,
the tosylate anion, like other sulfonates, is weakly coordinating
and so its metal complexes may have an ionic structure.9a,20
That implies that the leaving group might not be bound very
closely to the Ni(II) center in the oxidative adduct intermediate.
Thus such a Ni(II) complex would readily undergo the trans-
metalation step.
In conclusion, we have for the first time demonstrated the
Ni-catalyzed amination of aryl tosylates with amines and
anilines. This protocol further enhances the utility of the
methodology employing Ni(II)-(σ-aryl) complexes as the Ni-
based catalyst. Studies are underway in our laboratory to
1
(lit.21 mp 52-53 °C). H NMR (CDCl3, 400 MHz) δ 3.13-3.25
(m, 4H), 3.80-4.00 (m, 4H), 6.86-7.05 (m, 3H), 7.28-7.37 (m,
2H); MS (EI) m/z 163 (M+).
Diphenylamine22 (Table 3, entry 1). According to the general
procedure, phenyl tosylate (248 mg, 1.0 mmol) and aniline (140
mg, 1.5 mmol) were coupled and the product purified by column
chromatography with petroleum/ethyl acetate (12/1, v/v) to give a
pale yellow solid (115 mg, 68%): mp 48-50 °C (lit.22 mp 50-
1
52 °C). H NMR (CDCl3, 400 MHz) δ 6.97 (t, J ) 7.2 Hz, 2H),
7.13 (d, J ) 7.9 Hz, 4H), 7.27 (t, J ) 7.9 Hz, 4H); MS (EI) m/z
169 (M+).
Acknowledgment. The authors thank the National Natural
Science Foundation of China (Project No. 20672116) for
financial support of this work.
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Supporting Information Available: Experimental procedures,
characterization data, and references to the known compounds. This
material is available free of charge via the Internet at http://pubs.
acs.org.
JO7022558
(21) Kang, S. K.; Lee, H. W.; Choi, W. K.; Hong, R. K.; Kim, J. S.
Synth. Commun. 1996, 26, 4219-4224.
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