Nickel-catalyzed C-H direct amination of benzoxazoles with secondary amines

Article abstract of DOI:10.1039/c2ob25425e

In this article, a facile, efficient and practical method for Ni-catalyzed direct C-H amination of benzoxazole with secondary amines has been developed. This procedure requires Ni(OAc)₂·4H₂O as catalyst, TBHP as oxidant and acid as the additive. A variety of substituted benzoxazol-2-amines were synthesized in moderate to good yields.

Full text of DOI:10.1039/c2ob25425e

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PAPER
Nickel-catalyzed C–H direct amination of benzoxazoles with secondary
amines†
Yaming Li,* Jin Liu, Yusheng Xie, Rong Zhang, Kun Jin, Xiuna Wang and Chunying Duan*
Received 27th February 2012, Accepted 11th March 2012
DOI: 10.1039/c2ob25425e
In this article, a facile, efficient and practical method for Ni-catalyzed direct C–H amination of
benzoxazole with secondary amines has been developed. This procedure requires Ni(OAc)2·4H2O as
catalyst, TBHP as oxidant and acid as the additive. Avariety of substituted benzoxazol-2-amines were
synthesized in moderate to good yields.
Introduction
Results and discussion
The sp2 C–N bond reaction is of great interest in organic syn-
thesis. Traditionally, methods include nucleophilic substitution,1
the Cu-catalyzed Ullmann and Goldberg C–N couplings2 and
the Pd-catalyzed Buchwald–Hartwig reaction.3 2-Aminooxazoles
are widely employed in biological, pharmaceutical and material
sciences.4 Thus, the synthesis of 2-aminooxazoles has reached
more and more attention in recent years. While, for the above
methods, they often require pre-installation of reactive functional
groups5 (e.g., aryl iodides, bromides, chlorides, triflates and sul-
fonates) and high temperature as well as the use of expensive
ligands (for Ullmann and Buchwald–Hartwig reaction). To
further improve the efficiency, an immense effort has been made
to develop efficient strategies for the construction of C–N
bond.6–8 Transition-metal-catalyzed C–H direct amination of
azoles have been described recently, a wide range of metal cata-
lysts, including Ag,9 Mn,5 Co,5 Fe,10 Cu,11 Sc,12 have been
exploited with varying degrees of success (Scheme 1, route A).
Another route to synthesize 2-aminooxazoles is the metal-free
version of the C–H direct amination13 (Scheme 1, route B).
Nickel catalysts have recently been developed for cross coupling
of C–X (X = O, N, etc.).6,14 Often, the use of expensive Ni-
(cod)2 [cod = 1,5-cyclooctadiene] and toxic P(Cy)3 ligand limit
the scope of the Ni-catalyzed reaction. The advantage of using
other Ni sources as a catalyst is apparent, as they are often ready
available and inexpensive. Our laboratory focuses on the C–X
bond construction. Recently, we successfully developed a milder
Cu-catalytic protocol for azole amination under acid conditions.
Herein, we report a cheap and easily available Ni-catalyzed C–H
direct amination of azoles.
Our laboratory has already reported the direct copper-catalyzed
C–H amination of benzoxazoles with oxygen as oxidant,11f and
so we were eager to develop a new approach and expand the sub-
strate scope. We started our study by examining the conversion
of benzoxazole into 2-dibutylamine benzoxazole as shown in
Table 1. The use of 20 mol% Ni(OAc)2·4H2O in CH3CN at
70 °C under an oxygen atmosphere in acid conditions produced
the desired product in 7% yield after 12 h and no dimer of ben-
zoxazole was observed. A satisfactory result was obtained when
O2 was replaced by TBHP as the oxidant (82% yield, Table 1,
entries 2–3). Using propanoic acid, the yield was enhanced to
89% yield (Table 1, entry 4). We subsequently tested other oxi-
dants and acids, the results demonstrated that TBHP was the best
choice as the oxidant and p-anisic acid provided comparable
results (see ESI†). Other nickel sources, including NiCl2·6H2O,
Ni(acac)2, Ni(NO3)2·6H2O, Ni(ClO4)2 were also tested, but only
NiCl2·6H2O gave comparable yield (see ESI†). In addition, in
the absence of oxidant, catalyst or acid, the reaction proceeded
unsuccessfully. The catalyst loading could be decreased to 5 mol
% and still provided good yield without increasing the reaction
temperature. With further optimization of reaction conditions, the
best result was obtained using the Ni(OAc)2·H2O (0.05 equiv.)/
TBHP (3 equiv.) system in acid conditions at 70 °C after 12 h
(Table 1, entry 14).
Using the optimized conditions, we next explored the scope
and generality of the procedure. Various linear and cyclic sec-
ondary amines such as dibutylamine, dipropylamine, diethyl-
amine, piperidine, 4-methylpiperidine could be used efficiently
in our procedure. The desired products 3a–3h were obtained in
68–78% yields. Unsymmetrical N-methylbenzylamine gave the
desired product 3i in 67% yield. Furthermore we could syn-
thesize 3j in 67% yield starting from unsymmetrical and bulky
N-methyl-2-chlorobenzylamine. In addition to simple dialkyl-
amines, synthetically more useful diallylamines were tolerated
(65% yield, Scheme 2, 3k), which was obtained in 20% GC
State Key Laboratory of Fine Chemicals, School of Chemical
Engineering, Dalian University of Technology, Dalian 116024,
P.R. China. E-mail: ymli@dlut.edu.cn
†Electronic supplementary information (ESI) available: See DOI:
10.1039/c2ob25425e
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Scheme 1 C–H direct amination methods.
Table 1 Optimization of reaction conditionsa
Entry
[Ni] (equiv.)
Oxidant (equiv.)
Acid (equiv.)
Yieldb (%)
1
2
3
4
5
6
7
8
Ni(OAc)2·4H2O (0.2)
Ni(OAc)2·4H2O (0.2)
Ni(OAc)2·4H2O (0.2)
Ni(OAc)2·4H2O (0.2)
—
Ni(OAc)2·4H2O (0.2)
Ni(OAc)2·4H2O (0.2)
Ni(OAc)2·4H2O (0.2)
Ni(OAc)2·4H2O (0.2)
Ni(OAc)2·4H2O (0.05)
Ni(OAc)2·4H2O (0 02)
Ni(OAc)2·4H2O (0 05)
Ni(OAc)2·4H2O (0.05)
Ni(OAc)2·4H2O (0.05)
O2,
AcOH (2)
AcOH (1.2)
AcOH (1.2)
7
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
—
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.5)
TBHP (2)
TBHP (3)
82
82c
89c
25c
5c
C2H5COOH (1.2)
C2H5COOH (1.2)
C2H5COOH (1 2)
—
C2H5COOH (1.2)
C2H5COOH (1.2)
C2H5COOH (1.2)
C2 H5COOH (1.2)
C2H5COOH (1.2)
C2H5COOH (1.2)
C2H5COOH (1.2)
45c
87d
87
9
10
11
12
13
14
85
74
89
95
96 (68)e
a Reaction conditions. Benzoxazole (0.5 mmol), amine (0.6 mmol), Ni(OAc)z·4H2O, oxidant acid under air. CH3CN (2 ml), 70 °C, 12 h. b GC yield.
c Under O2. d Under Ar. e Isolated yield in parenthesis.
yield in our previous Cu(OAc)2·H2O/O2 catalytic system. In
addition, we were pleased to find that with Ni(OAc)2·4H2O/
TBHP catalytic system an aryl secondary amine N-methylaniline
could produce the desired product 3l in 35% yield.
Although the exact reaction mechanism still remains unclear,
the reaction may proceed in a similar way to Co-catalyzed ami-
nation reported by Chang: (I) protonation of benzoxazole, (II)
nucleophilic addition of amines, (III) oxidation provides the
desired product. Ongoing work seeks to uncover the detailed
mechanism and expand the reaction scope in the Ni-catalyzed
direct amination of heterocycles.
Subsequently, the scope of heterocycles was expanded to test
the generality of this synthetic protocol and the results are sum-
marized in Scheme 3. Various types of benzoxazoles were
readily employed and afforded the desired products 3a, 3d, 4a–
4f in moderate to good yields. Here a significant difference was
observed in the amounts of propanoic acid between 5-tert-butyl-
benzoxazole and other benzoxazoles. In contrast to the high
efficiency of benzoxazole or benzoxazoles bearing substituents
such as methyl and chloro at 5-position in 5 equiv. propanoic
acid condition, 5-tert-butylbenzoxazole reacted more smoothly
in 1.2 equiv. acid than in 5 equiv. acid conditions (Scheme 3, 4a,
4d–4f). It was also observed that electron-withdrawing groups
attached at the 5-position of benzoxazole resulted in lower con-
version than benzoxazoles bearing electron-donating groups, 5-
chlorobenzoxazole yielded the desired products 4b, 4c in 57%,
31% yield (5 equiv. acid conditions) and 43%, 26% yield (1.2
equiv. acid conditions) respectively. Notably, moderate yield was
obtained even in the case of bulky 5-tert-butylbenzoxazole with
bulky N-methyl-2-chlorobenzylamine. In contrast to benzoxa-
zole, benzothiazole and benzimidazole didn’t yield the desired
product.
Conclusion
In conclusion, an efficient nickel-catalyzed C–H functionaliza-
tion approach providing regioselective formation of C–N bonds
through C–H direct amination of benzoxazoles has been devel-
oped. Moderate to good results were achieved for a series of sub-
strates including arylamine. The new methods require
inexpensive reagents, such as Ni(OAc)2·4H2O or NiCl2·6H2O,
TBHP, propanoic acid or acetic acid under air, which is antici-
pated to be a useful and complementary tool for the synthesis of
2-aminobenzoxazoles.
Experimental
Typical experimental procedure
A dried Schlenk test tube containing a magnetic stirring bar was
charged under air with benzoxazole (0.5 mmol), amine
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Scheme 2 Nickel-catalyzed C–H amination of benzoxazole and 5-methylbenzoxazole with amines.a
N,N-Dipropylbenzoxazol-2-amine (3b)11d
(0.6 mmol), Ni(OAc)2·4H2O (5 mol%), C2H5CO2H (1.2 or
5 equiv.), TBHP (70% solution in water, 3 equiv.), CH3CN
(2 mL). Then the tube was sealed and the mixture was treated at
70 °C for 12 h. The resulting mixture was allowed to cool to
room temperature and washed with a saturated solution of
NaHCO3, extracted with ethyl acetate for three times. The com-
bined organic layers were dried with Na2SO4 and concentrated
under reduced pressure. The resulting residue was purified by
column chromatography on silica gel with EtOAc–petroleum
(1 : 1–1 : 30) to provide the desired product.
Light yellow liquid; Yield 73%; Prepared as shown in the
general experimental procedure. H NMR (CDCl3, 400 MHz) δ
1
(ppm): 0.96 (t, J = 7.2 Hz, 6H), 1.66–1.76 (m, 4H), 3.48 (t, J =
7.6 Hz, 4H), 6.95–6.99 (m, 1H), 7.11–7.15 (m, 1H), 7.23 (d, J =
8.0 Hz, 1H), 7.35 (d, J = 7.6 Hz, 1H); 13C NMR (CDCl3,
100 MHz) δ (ppm): 11.3, 21.4, 50.5, 108.6, 115.9, 120.0, 123.9,
143.8, 148.9, 162.8; GC-MS (EI) m/z = 218 [M]+.
N,N-Dibutylbenzoxazol-2-amine (3a)11f
N,N-Diethylbenzoxazol-2-amine (3c)11f
Light yellow liquid; Yield 68%; Prepared as shown in the
1
general experimental procedure. H NMR (CDCl3, 400 MHz) δ
(ppm): 0.96 (t, J = 7.2 Hz, 6H), 1.34–1.43 (m, 4H), 1.62–1.70
(m, 4H), 3.51 (m, 4H), 6.97 (m, 1H), 7.13 (t, J = 8.0 Hz, 1H),
7.23 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) δ (ppm): 14.1, 20.2, 30.3, 48.5, 108.6,
115.9, 120.0, 123.9, 143.8, 148.9, 162.8; GC-MS (EI) m/z = 246
[M]+.
Colorless liquid; Yield 66%; Prepared as shown in the general
experimental procedure. H NMR (CDCl3, 400 MHz) δ (ppm):
1.29 (t, J = 7.2 Hz, 6H), 3.57–3.62 (q, J = 7.2, 4H), 6.96–7.00
(m, 1H), 7.12–7.16 (m, 1H), 7.24 (d, J = 8.0 Hz, 1H), 7.36 (d,
J = 8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ (ppm): 13.6,
1
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Scheme 3 Ni-catalyzed C–H amination of benzoxazoles.a
43.1, 108.7, 115.9, 120.1, 124.0, 143.5, 148.9, 162.2; GC – MS
(EI) m/z = 190 [M]+.
2.38 (s, 3H), 3.46 (t, J = 7.2 Hz, 4H), 6.77 (d, J = 8.0 Hz, 1H),
7.10 (d, J = 8.0 Hz, 1H), 7.15 (s, 1H); 13C NMR (CDCl3,
100 MHz) δ (ppm): 11.3, 21.4, 50.5, 108.7, 115.9, 120.0, 123.9,
143.8, 148.9, 162.8; HRESI-MS (m/z): Calculated for
C14H21N2O [M + H]+ 233.1654, found [M + H]+: 233.1657.
N,N-Dibutyl-5-methylbenzoxazol-2-amine (3d)
N,N-Diethyl-5-methylbenzoxazol-2-amine (3f)11f
White solid; Yield 70%; M.p. 58–60 °C; Prepared as shown in
the general experimental procedure. 1H NMR (CDCl3,
400 MHz) δ (ppm): 0.95 (t, J = 7.2 Hz, 6H), 1.33–1.42 (m, 4H),
1.61–1.69 (m, 4H), 2.38 (s, 3H), 3.49 (t, J = 7.6 Hz, 4H), 6.77
(d, J = 8.0 Hz, 1H), 7.09 (d, J = 8.0 Hz, 1H), 7.15 (s, 1H); 13C
NMR (CDCl3, 100 MHz) δ (ppm): 14.1, 20.2, 21.7, 30.3, 48.4,
107.9, 116.4, 120.6, 133.5, 144.0, 147.0, 163.0; GC-MS (EI)
m/z = 260 [M]+.
Colorless liquid; Yield 75%; Prepared as shown in the general
experimental procedure. H NMR (CDCl3, 400 MHz) δ (ppm):
1
1.27 (t, J = 7.2 Hz, 6H), 2.38 (s, 3H), 3.57 (q, J = 7.2 Hz, 4H),
6.78 (d, J = 8.0 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 7.15 (s, 1H);
13C NMR (CDCl3, 100 MHz) δ (ppm): 13.7, 21.7, 43.1, 108.0,
116.4, 120.7, 133.6, 143.9, 147.1, 162.5; GC-MS (EI) m/z = 204
[M]+.
5-Methyl-N,N-dipropylbenzoxazol-2-amine (3e)
5-Methyl-2-(piperidin-1-yl)benzoxazole (3g)11a
White solid; Yield 78%; M.p. 38–40 °C; Prepared as shown in
the general experimental procedure. 1H NMR (CDCl3,
400 MHz) δ (ppm): 0.96 (t, J = 7.2 Hz, 6H), 1.66–1.75 (m, 4H),
White solid; Yield 77%; M.p. 97–98 °C; Prepared as shown in
the general experimental procedure. 1H NMR (CDCl3,
3718 | Org. Biomol. Chem., 2012, 10, 3715–3720
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400 MHz) δ (ppm): 1.669 (s, 6H), 2.38 (s, 3H), 3.64 (s, 4H),
6.79 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 8.0 Hz, 1H), 7.14 (s, 1H);
13C NMR (CDCl3, 100 MHz) δ (ppm): 21.7, 24.2, 25.4, 46.7,
108.0, 116.6, 121.1, 133.6, 143.6, 147.0, 162.8; GC-MS (EI)
m/z = 216 [M]+.
2.39 (s, 3H), 4.14 (d, J = 5.6 Hz, 4H), 5.21–5.26 (m, 4H),
5.83–5.92 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ (ppm):
21.7, 50.0, 108.2, 116.7, 118.0, 121.2, 132.8, 133.7, 143.6,
147.2, 162.6; GC-MS (EI) m/z = 228 [M]+.
N,5-Dimethyl-N-phenylbenzoxazol-2-amine (3l)
5-Methyl-2-(4-methylpiperidin-1-yl)benzoxazole (3h)
Yellow crystal; Yield 35%; M.p. 55–56 °C; Prepared as shown
in the general experimental procedure. 1H NMR (CDCl3,
400 MHz) δ (ppm): 2.40 (s, 3H), 3.62 (s, 3H), 6.84 (d, J = 8.0
Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 7.23–7.25 (m, 2H), 7.42 (s,
4H); 13C NMR (CDCl3, 100 MHz) δ (ppm): 21.7, 39.2, 108.5,
117.2, 122.0, 124.6, 126.1, 129.4, 133.9, 143.1, 143.2, 147.1,
161.6; HRESI-MS (m/z): Calculated for C15H15N2O [M + H]+
239.1184, found [M + H]+: 239.1189.
White solid; Yield 72%; M.p. 63–65 °C; Prepared as shown in
the general experimental procedure. 1H NMR (CDCl3,
400 MHz) δ (ppm): 0.98 (d, J = 6.4 Hz, 3H), 1.22–1.32 (m,
2H), 1.61–1.64 (m, 1H), 1.74 (d, J = 13.2 Hz, 2H), 2.38 (s, 3H),
3.01–3.08 (m, 2H), 4.25 (d, J = 12.8 Hz, 2H), 6.79 (d, J = 8.0
Hz, 1H), 7.09 (d, J = 8.0 Hz, 1H), 7.14 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ (ppm): 21.7, 22.0, 30.8, 33.6, 46.2, 108.0,
116.6, 121.1, 133.6, 143.6, 147.0, 162.8; HRESI-MS (m/z): Cal-
culated for C14H19N2O [M + H]+ 231.1497, found [M + H]+:
231.1496.
5-tert-Butyl-N,N-dibutylbenzoxazol-2-amine (4a)11f
N-Benzyl-N,5-dimethylbenzoxazol-2-amine (3i)11f
Light yellow liquid; Yield 64% (5 equiv. acid), 69% (1.2 equiv.
acid); Prepared as shown in the general experimental procedure.
1H NMR (CDCl3, 400 MHz) δ (ppm): 0.95 (t, J = 7.2 Hz, 6H),
1.34–1.40 (m, 13H), 1.61–1.69 (m, 4H), 3.49 (t, J = 7.6 Hz,
4H), 7.01 (dd, J = 8.4 Hz, 1.6 Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H),
7.43 (d, J = 1.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ (ppm):
14.0, 20.1, 30.3, 32.0, 35.0, 48.5, 107.6, 113.1, 117.1, 143.6,
146.8, 147.3, 163.0; GC-MS (EI) m/z = 302 [M]+.
White solid; Yield 67%; M.p. 50–51 °C; Prepared as shown in
the general experimental procedure. 1H NMR (CDCl3,
400 MHz) δ (ppm): 2.40 (s, 3H), 3.11 (s, 3H), 4.74 (s, 2H), 6.81
(d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.18 (s, 1H),
7.28–7.35 (m, 5H); 13C NMR (CDCl3, 100 MHz) δ (ppm):
21.7, 35.3, 54.0, 108.3, 116.7, 121.2, 127.9, 127.9, 128.9, 133.8,
136.7, 143.8, 147.3, 163.3; GC-MS (EI) m/z = 252 [M]+.
N,N-Dibutyl-5-chlorobenzoxazol-2-amine (4b)11f
N-(2-Chlorobenzyl)-N,5-dimethylbenzoxazol-2-amine (3j)
White solid; Yield 57% (5 equiv. acid), 43% (1.2 equiv. acid);
M.p. 60–61 °C; Prepared as shown in the general experimental
1
procedure. H NMR (CDCl3, 400 MHz) δ (ppm): 0.96 (t, J =
White solid; Yield 67%; M.p. 69–70 °C; Prepared as shown in
the general experimental procedure. 1H NMR (CDCl3,
400 MHz) δ (ppm): 2.40 (s, 3H), 3.19 (s, 3H), 4.88 (s, 2H), 6.82
(d, J = 8.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 7.19 (s, 1H),
7.21–7.28 (m, 3H), 7.39–7.41 (m, 1H); 13C NMR (CDCl3,
100 MHz) δ (ppm): 21.7, 35.9, 51.5, 108.3, 116.8, 121.3, 127.3,
128.5, 129.0, 130.0, 133.6, 133.8, 134.2, 143.7, 147.4, 163.2;
HRESI-MS (m/z): Calculated for C16H15N2ONaCl [M + Na]+
309.0771, found [M + Na]+: 309.0776.
7.2 Hz, 6H), 1.33–1.43 (m, 4H), 1.61–1.69 (m, 4H), 3.49 (t, J =
7.6 Hz, 4H), 6.92 (dd, J = 8.4 Hz, 2 Hz, 1H), 7.12 (d, J = 8.4
Hz, 1H), 7.29 (d, J = 2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ
(ppm): 14.0, 20.1, 30.2, 48.6, 109.0, 116.0, 119.8, 129.2, 145.3,
147.5, 163.6; GC-MS (EI) m/z = 280 [M]+.
N,N-Diallyl-5-chlorobenzoxazol-2-amine (4c)
N,N-Diallyl-5-methylbenzoxazol-2-amine (3k)5
Colorless liquid; Yield 31% (5 equiv acid), 26% (1.2 equiv
acid); Prepared as shown in the general experimental procedure.
1H NMR (CDCl3, 400 MHz) δ (ppm): 4.15 (d, J = 5.6 Hz, 4H),
5.23–5.27 (m, 4H), 5.82–5.92 (m, 2H), 6.96 (dd, J = 8.4 Hz, 2
Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H), 7.32 (d, J = 2.0 Hz, 1H);
Yellow liquid; Yield 65%; Prepared as shown in the general
experimental procedure. H NMR (CDCl3, 400 MHz) δ (ppm):
1
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13C NMR (CDCl3, 100 MHz) δ (ppm): 50.2, 109.4, 116.4,
118.4, 120.4, 129.5, 132.4, 144.8, 147.7, 163.3; HRESI-MS
(m/z): Calculated for C13H13N2ONaCl [M + Na]+ 271.0614,
found [M + Na]+: 271.0613.
Acknowledgements
This work was supported by the National Natural Science Foun-
dation of China (Project No. 21176039, 20876021 and
20923006) and the Education Department of Liaoning Province
(2009S021).
N,N-Diallyl-5-tert-butylbenzoxazol-2-amine (4d)
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Colorless liquid; Yield 46% (5 equiv acid), 64% (1.2 equiv
acid); Prepared as shown in general experimental procedure. H
1
NMR (CDCl3, 400 MHz) δ (ppm): 1.34 (s, 9H), 4.15 (d, J = 5.6
Hz, 4H), 5.21–5.26 (m, 4H), 5.83–5.91 (m, 2H), 7.05 (dd, J =
8.4 Hz, 1.6 Hz, 1H), 7.17 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 1.6
Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ (ppm): 32.0, 35.0,
50.1, 108.0, 113.5, 117.7, 118.0, 132.8, 143.3, 147.1, 147.5,
162.7; HRESI-MS (m/z): Calculated for C17H22N2ONa [M +
Na]+ 293.1630, found [M + Na]+: 293.1634.
5 J. Y. Kim, S. H. Cho, J. Joseph and S. Chang, Angew. Chem., Int. Ed.,
2010, 49, 9899.
6 Selected examples for the constrution of C–N by nickel-catalyzed C–O
cleavage: (a) S. Ueno, R. Shimizu and R. Kuwano, Angew. Chem., Int.
Ed., 2009, 48, 4543; (b) S. D. Ramgren, A. L. Silberstein, Y. Yang and
N. K. Garg, Angew. Chem., Int. Ed., 2011, 123, 2219; (c) J.-H. Huang
and L.-M. Yang, Org. Lett., 2011, 13, 3750; (d) T. Mesganaw, A.
L. Silberstein, S. D. Ramgren, N. F. F. Nathel, X. Hong, P. Liu and N.
K. Garg, Chem. Sci., 2011, 2, 1766; (e) T. Shimasaki, M. Tobisu and
N. Chatani, Angew. Chem., Int. Ed., 2010, 49, 2929.
5-tert-Butyl-N-(2-chlorobenzyl)-N-methylbenzoxazol-2-amine
(4e)
7 Selected examples for C–H amination: (a) G. Ayker, Angew. Chem., Int.
Ed., 1999, 38, 1698; (b) R. k. Thalji, K. A. Ahrendt, R. G. Bergman and
J. A. Ellman, J. Am. Chem. Soc., 2001, 123, 9692; (c) V. Ritleng,
C. Sirlin and G. Pfeffer, Chem. Rev., 2002, 102, 1731; (d) X. Chen, X.-
S. Hao, C. E. Goodhue and J.-Q. Yu, J. Am. Chem. Soc., 2006, 128,
6790; (e) P. Thansandote and M. Lautens, Chem.–Eur. J., 2009, 15,
5874; (f) J. Bouffard and K. Itami, Top. Curr. Chem., 2010, 292, 231;
(g) E. M. Beck and M. J. Gaunt, Top. Curr. Chem., 2010, 292, 85; (h) E.
J. Yoo, S. Ma, T.-S. Mei, K. S. L. Chan and J.-Q. Yu, J. Am. Chem. Soc.,
2011, 133, 7652.
8 For reviews on direct C–H amination reactions, see: (a) F. Collet, R.
H. Dodd and P. Dauban, Chem. Commun., 2009, 5061; (b) D. N. Zalatan
and J. D. Bois, Top. Curr. Chem., 2010, 292, 347; (c) A. Armstrong and
J. C. Collins, Angew. Chem., Int. Ed., 2010, 49, 2282; (d) K. Hirano and
M. Miura, Synlett, 2011, 3, 294; (e) S. H. Cho, J. Y. Kim, J. Kwak and
S. Chang, Chem. Soc. Rev., 2011, 40, 5068.
Yellow solid; Yield 37% (5 equiv. acid), 54% (1.2 equiv. acid);
M.p. 89–92 °C; Prepared as shown in the general experimental
1
procedure. H NMR (CDCl3, 400 MHz) δ (ppm): 1.35 (s, 1H),
3.20 (s, 3H), 4.88 (s, 2H), 7.07 (dd, J = 8.4 Hz, 2 Hz, 1H), 7.17
(d, J = 8.4 Hz, 1H), 7.21–7.26 (m, 3H), 7.39–7.41 (m, 1H), 7.46
(d, J = 1.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ (ppm):
32.0, 35.0, 36.0, 51.5, 108.0, 113.6, 117.8, 127.3, 128.5, 129.0,
130.0, 133.6, 134.2, 143.3, 147.2, 147.7, 163.2; HRESI-MS
(m/z): Calculated for C19H22N2OCl [M + H]+ 329.1421, found
[M + H]+: 329.1427.
9 S. H. Cho, J. Y. Kim, S. Y. Lee and S. Chang, Angew. Chem., Int. Ed.,
2009, 48, 9127.
5-tert-Butyl-2-(piperidin-1-yl)benzoxazole (4f)
10 J. Wang, J.-T. Hou, J. Wen, J. Zhang and Y. Xiao-Qi, Chem. Commun.,
2011, 47, 3652.
11 (a) D. Monguchi, T. Fujiwara, H. Furukawa and A. Mori, Org. Lett.,
2009, 11, 1607; (b) Q. Wang and S. L. Schreiber, Org. Lett., 2009, 11,
5178; (c) T. Kawano, K. Hirano, T. Satoh and M. Miura, J. Am. Chem.
Soc., 2010, 132, 6900; (d) S. Guo, B. Qian, Y. Xie, C. Xia and H. Huang,
Org. Lett., 2011, 13, 522; (e) N. Matsuda, K. Hirano, T. Satoh and
M. Miura, Org. Lett., 2011, 13, 2860; (f) Y. Li, Y. Xie, R. Zhang, K. Jin,
X. Wang and C. Duan, J. Org. Chem., 2011, 76, 5444.
12 S. Wertz, S. Kodama and A. Studer, Angew. Chem., Int. Ed., 2011, 50,
11511.
13 (a) J. Joseph, J. Y. Kim and S. Chang, Chem.–Eur. J., 2011, 17, 8294;
(b) T. Froehr, C. P. Sindlinger, U. Kloeckner, P. Finkbeiner and B.
J. Nachtsheim, Org. Lett., 2011, 13, 3754; (c) M. Lamani and K.
R. Prabhu, J. Org. Chem., 2011, 76, 7938.
White acicular crystal; Yield 60% (5 equiv. acid), 70% (1.2
equiv. acid); M.p. 84–87 °C; Prepared as shown in the general
1
experimental procedure. H NMR (CDCl3, 400 MHz) δ (ppm):
1.34 (s, 9H), 1.67 (s, 6H), 3.64 (s, 4H), 7.03 (dd, J = 8.4 Hz, 1.6
Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H), 7.42 (d, J = 1.6 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ (ppm): 24.2, 25.4, 32.0, 35.0, 46.8,
107.7, 113.3, 117.5, 143.2, 146.8, 147.4, 162.8; HRESI-MS
(m/z): Calculated for C16H23N2O [M + H]+ 259.1810, found
[M + H]+: 259.1815.
14 T. Yamamoto, K. Muto, M. Komiyama, J. Canivet, J. Yamaguchi and
K. Itami, Chem.–Eur. J., 2011, 17, 10113.
3720 | Org. Biomol. Chem., 2012, 10, 3715–3720
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