Copper-Catalyzed Electrophilic Amination of Organoaluminum Nucleophiles with O -Benzoyl Hydroxylamines

Article abstract of DOI:10.1021/acs.joc.5b00767

A copper-catalyzed electrophilic amination of aryl and heteroaryl aluminums with N,N-dialkyl-O-benzoyl hydroxylamines that affords the corresponding anilines in good yields has been developed. The catalytic reaction proceeds very smoothly under mild conditions and exhibits good substrate scope. Moreover, the developed catalytic system is also well suited for heteroaryl aluminum nucleophiles, providing facile access to heteroaryl amines.

Full text of DOI:10.1021/acs.joc.5b00767

Article
pubs.acs.org/joc
Copper-Catalyzed Electrophilic Amination of Organoaluminum
Nucleophiles with O‑Benzoyl Hydroxylamines
,†
†
†
†
†
†
†
Shuangliu Zhou,* Zhiyong Yang, Xu Chen, Yimei Li, Lijun Zhang, Hong Fang, Wei Wang,
†
,†,‡
Xiancui Zhu, and Shaowu Wang*
†Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Laboratory of Molecule-Based Materials, College of
Chemistry and Materials Science, Anhui Normal University, Wuhu, Anhui 241000, P. R. China
‡
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, P. R. China
*
S Supporting Information
ABSTRACT: A copper-catalyzed electrophilic amination of aryl
and heteroaryl aluminums with N,N-dialkyl-O-benzoyl hydroxyl-
amines that affords the corresponding anilines in good yields has
been developed. The catalytic reaction proceeds very smoothly
under mild conditions and exhibits good substrate scope.
Moreover, the developed catalytic system is also well suited for
heteroaryl aluminum nucleophiles, providing facile access to
heteroaryl amines.
INTRODUCTION
Organoaluminum compounds are excellent nucleophiles for
organic reactions because of their high reactivities, the high
Lewis acidity of the aluminum center, and their low toxicities.
Therefore, organoalanes are widely applied in addition to
■
Aromatic amines are important structural motifs in many
bioactive compounds, pharmaceutical and agrochemical targets,
and functional materials. Transition metal-catalyzed aromatic
1
17
18
carbonyl compounds and cross-coupling reactions. More-
over, arylalanes have been demonstrated to be highly efficient
coupling reagents with aryl bromides and chlorides without the
C−N cross-coupling reactions are one of the most powerful
2
methods for synthesizing arylamines. After Buchwald−
Hartwig’s pioneering work on the Pd- or Cu-catalyzed cross-
19
use of a base. As an extension of our research on arylalanes,
3
coupling of aryl halides with various amines, Chan and Lam
reported the copper-mediated oxidative coupling of nucleo-
philic arylboronic acids with amines. Although there have been
we herein describe an umpolung strategy for synthesizing
tertiary amines via the copper-catalyzed electrophilic amination
of (hetero)arylalanes with O-benzoyl hydroxylamines.
4
recent improvements to transition metal-catalyzed nucleophilic
5
amination strategies, this approach still suffers from several
RESULTS AND DISCUSSION
■
limitations, including harsh reaction conditions and low
functional group tolerance.
The reaction of 4-benzoyloxymorpholine (1a) with 4-
methoxyphenyl aluminum (2a) was first tested as the template
for optimizing the reaction conditions, and the results are
summarized in Table 1. Notably, we found that 5 mol % CuI
was effective as a catalyst, even at room temperature, to provide
a good yield without ligand and base. Similar to the previously
Catalytic electrophilic amination using umpolung strategies
would provide a complementary method for constructing C−N
6
bonds under mild conditions. An umpolung electrophilic
+
amination using a R N -type reagent, such as chloroamines and
2
hydroxylamines, has recently received significant attention. In
004, Johnson and co-workers reported their pioneering
research on the Cu-catalyzed amination of organozinc reagents
with N,N-dialkyl-O-acyl hydroxylamine derivatives. Barker and
reported coupling of mixed organoalanes, such as RAlEt and
2
i
2
RAl Bu (R = Ar, alkenyl, alkynyl), the unsaturated R group was
2
1
9e,f,20
always selectively transferred.
Further screening of
7
different solvents revealed that performing the reaction in
THF afforded the best yield of 87% (entries 1−5, Table 1). It
was also found that the reactions provided the product 3aa in
the highest yield at room temperature (entries 2, 6−7, Table 1).
The product yields remained almost constant when the
equivalent of aryl aluminum was reduced to 1.7 or 1.5 (entries
Jarvo also developed an analogous Ni-catalyzed reaction with
8
organozinc reagents and N,N-dialkyl-N-chloramines. Subse-
+
quently, R N synthons were used as an effective nitrogen
2
source not only for the electrophilic amination of organo-
metallic reagents based on B, Mg, Sn, Ti, Zr, and Si
but also for direct (hetero)aromatic C−H amination via a
similar catalytic process. More recently, a copper-catalyzed
electrophilic amination of organolithiums mediated by siloxane
transfer agents with O-benzoylhydroxylamines was developed
9
10
11
12
13
14
8
and 9, Table 1). The product yield decreased to 71% when
15
the equivalent of aryl aluminum was decreased to 1.3 (entry 10,
Received: April 7, 2015
16
to access various aryl and heteroaryl amines.
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00767
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Table 1. Optimization of Copper-Catalyzed Electrophilic
Table 1). A further increase in the copper catalyst (10 mol %)
afforded the product 3aa in slightly high yield (entry 11, Table
1). However, the product was obtained in the low yield of 62%
when the catalyst loading was increased to 1 mol % (entry 12,
Table 1). When the reaction was conducted in the absence of
catalyst, no electrophilic amination product 3aa was isolated
under the same conditions (entry 13, Table 1). Nonoxygenated
Cu(I) sources, such as CuBr and CuCl, afforded similar yields
(entries 14 and 15, Table 1), whereas the Cu(II) source
Cu(OAc) ·H O afforded the lowest yield of 51% (entry 16,
Amination of 4-Methoxyphenyl Diethylaluminum (2a) with
a
4
-Benzoyloxymorpholine (1a)
copper salt
(mol %)
ArAlEt (OEt )
temp
(°C)
yield
(%)
2
2
b
entry
solvent
(equiv)
2
2
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
CuI (5)
toluene
THF
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.7
1.5
1.3
1.5
1.5
1.5
1.5
1.5
1.5
rt
rt
rt
rt
rt
0
78
87
42
58
65
63
73
86
88
71
90
62
NR
80
78
51
Table 1).
CuI (5)
CuI (5)
CuI (5)
CuI (5)
CuI (5)
CuI (5)
CuI (5)
CuI (5)
CuI (5)
CuI (10)
CuI (1)
CuI (0)
CuBr (5)
CuCl (5)
With the optimized conditions established, the scope of this
transformation was explored using various arylalanes and O-
benzoyl hydroxylamines (Table 2). The treatment of
morpholino benzoate (1a) with a series of arylalanes indicated
that the reaction is significantly affected by the electronic effect
of the substituents on the aromatic ring of arylalanes. The
electron-rich aryl-substituted alanes were effective, affording the
corresponding products 3aa−ad in high yields. In contrast, no
reaction was observed in the case of the electron-deficient aryl-
substituted alanes such as 4-nitrophenyl, 4-cyanophenyl, and 4-
trifluomethylphenyl aluminum reagents. Notably, the reaction
also performed well with heteroarylalanes such as pyridyl
aluminums and thienyl aluminums to afford the corresponding
products 3ag−aj in good yields. In particular, 3-thienyl amines
have potential use in the synthesis of polythiophene derivatives,
which have been the focus of many studies because of their
hexane
Et O
2
CH Cl
2
2
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
50
rt
rt
rt
rt
rt
rt
rt
rt
0
1
2
3
4
5
6
Cu(OAc) (5)
rt
2
a
b
Reaction conditions: 1a (1.0 mmol), solvent (3 mL). Equivalent of
c
ArAlEt (OEt ) relative to 1a. NR: no reaction.
2
2
21
promising applications in polymer solar cells, light-emitting
22
23
diodes, and field-effect transistors.
a
Table 2. Substrate Scope for the Copper-Catalyzed Electrophilic Amination of (Hetero)arylalanes.
a
b
Reaction conditions: CuI (0.05 mmol), 1 (1.0 mmol), 2 (1.5 mmol), THF (3 mL). Reaction time: 2 h.
B
DOI: 10.1021/acs.joc.5b00767
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Considering the convenience of the subsequent derivatiza-
tion of the corresponding products, O-benzoyl-N,N-dibenzyl-
hydroxylamine (1b) was employed as another electrophilic
nitrogen source for this reaction (Table 2). Similarly, various
arylalanes exhibited high reactivities in this transformation,
affording the corresponding products in high yields of 82−90%,
except for the electron-deficient aryl-substituted alanes such as
CONCLUSION
■
In summary, an umpolung strategy for preparing various
tertiary amines via the copper-catalyzed electrophilic amination
of arylalanes with O-benzoyl hydroxylamines has been
developed. The reaction afforded the corresponding arylamines
in moderate to good yields in the presence of 5 mol % CuI
without the need for ligand and base. The developed catalytic
system exhibited good substrate scope in terms of both the
functional groups tolerated on the nucleophilic component and
the steric hindrance of the coupling partners. Moreover, the
catalytic system could also be applied to heteroaryl aluminum
nucleophiles to provide facile access to heteroaryl amines. This
reaction provides an alternative method for accessing various
aromatic amines.
4-cyanophenyl and 4-trifluomethylphenyl aluminum reagents.
For heteroarylalanes such as pyridyl aluminums and thienyl
aluminums, the corresponding heteroaryl amines 3bg, 3bh, and
3
1
bj were also obtained in good yields. Notably, the reactions of
b with halogenated arylalanes, such as 4-bromophenyl
aluminum and 4-chlorophenyl aluminum, afforded the
corresponding halogenated arylamines 3bk and 3bl, which
may allow further useful transformations via halogen-exchange
reactions.
EXPERIMENTAL SECTION
Next, the reactions of a series of O-benzoyl hydroxylamines
c−i with arylalanes were examined under the optimized
■
1
General Methods. All syntheses and manipulations of air- and
moisture-sensitive materials were performed under a dry argon
atmosphere using standard Schlenk techniques or in a glovebox.
Solvents were refluxed and distilled over sodium/benzophenone
reaction conditions (Table 2). In general, the amination
reactions with 1 derived from secondary amines proceeded
smoothly to provide the desired products in moderate to good
yields. It is worth mentioning that the reactions of sterically
hindered amines such as O-benzoyl-N,N-isopropylbenzylhy-
droxylamine (1e), O-benzoyl-N,N-diisopropylhydroxylamine
(
THF, Et O, n-hexane, and toluene) and P O (CH Cl ) under argon
2 2 5 2 2
7a,b
prior to use. N,N-Dialkyl-O-benzoyl hydroxylamines and (hetero)-
1
7j,19f
ArAlEt (OEt )
were prepared according to previously reported
2
2
1
13
procedures. H and C NMR spectra in CDCl were recorded at 300
MHz/75 MHz ( H NMR/ C NMR) or 500 MHz/125 MHz ( H
NMR/ C NMR) with chemical shifts given in ppm from the internal
3
(
1f), and O-benzoyl-N,N-dicyclohexylhydroxylamine (1g)
1
13
1
with the corresponding arylalanes afforded the corresponding
products 3ee−ge in moderate yields (58−70%). However, this
reaction was ineffective for O-benzoyl-N-alkylhydroxylamine 1h
and 1i, which are derived from primary amines, probably due to
the protonation of arylalanes by the corresponding amines.
In view of the mechanism previously proposed for the
13
TMS. High resolution mass spectral (HRMS) data were obtained with
an ionization mode of ESI and a TOF analyzer.
General Procedures for Copper-Catalyzed Electrophilic
Amination of Organoaluminum Nucleophiles with O-Benzoyl
Hydroxylamines. Under a dry argon atmosphere, an oven-dried 25
mL Schlenk tube was charged with CuI (9.5 mg, 0.05 mmol), O-
benzoyl hydroxylamine (1.0 mmol), and anhydrous THF (3 mL) at
room temperature. The solution was stirred for 10 min, followed by
the addition of (hetero)arylaluminum reagent (1.5 mmol). After being
stirred at ambient temperature for 1−2 h, the resulting mixture was
quenched with water. The mixture was diluted with ethyl acetate (40
mL) and then passed through a filter and concentrated. The crude
product was purified by column chromatography (silica gel), eluting
with petroleum ether and ethyl acetate to give the product 3.
7c,9c
electrophilic amination of aryl zincs and boronic esters,
we
proposed that this reaction involved transmetalation from
aluminum to copper, affording aryl copper [ArCu] species as
intermediate (I) and subsequent electrophilic amination of the
aryl copper intermediate (I) to afford the final products
(
Scheme 1, part A). To obtain a preliminary understanding of
Scheme 1. Proposed Mechanism for the Copper-Catalyzed
Coupling of O-Benzoyl Hydroxylamines with Organoalanes
7
b
4
-(4-Methoxyphenyl)morpholine (3aa). White solid (171
1
mg, 88% yield). H NMR (300 MHz, CDCl ): δ 6.91−6.83 (m, 4H),
3
3
.86 (t, J = 4.5 Hz, 4H), 3.77 (s, 3H), 3.06 (t, J = 4.8 Hz, 4H).
13
1
C{ H} NMR (75 MHz, CDCl ): δ 154.0, 145.6, 117.8, 114.5, 67.0,
3
+
5
5.5, 50.8. HRMS (ESI) calcd for C H NO [M + H ] 194.1176,
11
16
2
found 194.1177.
5
h
4-(3-Methoxyphenyl)morpholine (3ab). Colorless oil (168
1
mg, 87% yield). H NMR (300 MHz, CDCl ): δ 7.25−7.15 (m, 1H),
3
6
4
1
.55−6.42 (m, 3H), 3.84 (t, J = 4.8 Hz, 4H), 3.79 (s, 3H), 3.14 (t, J =
.8 Hz, 4H). 13C{ H} NMR (75 MHz, CDCl ): δ 160.6, 152.7, 129.8,
1
3
08.5, 104.7, 102.2, 66.9, 55.2, 49.3. HRMS (ESI) calcd for
+
C H NO [M + H ] 194.1176, found 194.1177.
11
16
2
2
4
4
-(4-Methylphenyl)morpholine (3ac). White solid (151 mg,
1
the mechanism, the reaction of 1b with [PhCu], generated in
situ from PhMgCl and CuI, afforded the amination product 3be
in a comparable yield of 87%. It should be noted that the result
was different from the reaction of [PhCu] with N-chloroamides
to afford biphenyl as the homocoupling products in electro-
philic amination of arylboronic acids with N-chloroamides
catalyzed by CuCl, indicating that the transmetalation of aryl
aluminum to aryl copper was a favorable route in our current
reaction system. However, an alternative catalytic mechanism,
which proceeds by the further oxidative addition of [PhCu] (I)
to afford the intermediate (II) and next reductive elimination of
the intermediate (II) to afford the final product, cannot be
ruled out (Scheme 1, part B).
8
5% yield). H NMR (300 MHz, CDCl ): δ 7.09 (d, J = 8.1 Hz, 2H),
3
6.83 (d, J = 8.4 Hz, 2H), 3.86 (t, J = 4.5 Hz, 4H), 3.11 (t, J = 4.5 Hz,
4H), 2.28 (s, 3H). 13C{ H} NMR (75 MHz, CDCl ): δ 149.2, 129.7,
1
3
129.6, 116.0, 67.0, 49.9, 20.4. HRMS (ESI) calcd for C11
H
16NO [M +
+
H ] 178.1226, found 178.1229.
7
b
4
-(2-Methylphenyl)morpholine (3ad). Pale yellow oil (147
1
9b
mg, 83% yield). H NMR (300 MHz, CDCl ): δ 7.19−7.15 (m, 2H),
3
7
2
1
.02−6.98 (m, 2H), 3.84 (t, J = 4.5 Hz, 4H), 2.90 (t, J = 4.5 Hz, 4H),
13
1
.31 (s, 3H). C{ H} NMR (75 MHz, CDCl ): δ 151.2, 132.6, 131.1,
3
26.6, 123.4, 118.9, 67.4, 52.2, 17.8. HRMS (ESI) calcd for C H NO
M + H ] 178.1226, found 194.1228.
1
1
16
+
[
7b
4-Phenylmorpholine (3ae). White solid (140 mg, 86% yield).
1
H NMR (300 MHz, CDCl ): δ 7.16−7.23 (m, 2H), 6.85−6.80 (m,
3
13
1
3H), 3.78−3.75 (m, 4H), 3.08−3.04 (m, 4H). C{ H} NMR (75
C
DOI: 10.1021/acs.joc.5b00767
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
+
MHz, CDCl ): δ 151.2, 129.1, 120.0, 115.7, 66.9, 49.3. HRMS (ESI)
121.5, 113.7, 54.5. HRMS (ESI) calcd for C H ClN [M + H ]
3
20 19
+
calcd for C H NO [M + H ] 164.1070, found 164.1072.
308.1201, found 308.1202.
1
0
14
7
b
7b
4
-Pyridin-2-ylmorpholine (3ag). Yellow oil (138 mg, 84%
N,N-Diethylaniline (3ce). Pale yellow oil (106 mg, 71% yield).
H NMR (300 MHz, CDCl ) δ 7.27−7.19 (m, 2H), 6.71−6.64 (m,
3H), 3.35 (q, J = 6.9 Hz, 4H), 1.16 (t, J = 7.2 Hz, 6H). C{ H} NMR
1
1
yield). H NMR (300 MHz, CDCl ): δ 8.21−8.19 (m, 1H), 7.53−7.47
3
3
1
3
1
(
m, 1H), 6.68−6.62 (m, 2H), 3.83 (t, J = 4.8 Hz, 4H), 3.49 (d, J = 4.8
1
3
1
Hz, 4H). C{ H} NMR (75 MHz, CDCl ): δ 159.5, 147.9, 137.5,
(75 MHz, CDCl ) δ 148.2, 129.6, 115.8, 112.3, 44.7, 12.9. HRMS
3
3
+
+
1
13.8, 106.9, 66.7, 45.6. HRMS (ESI) calcd for C H N O [M + H ]
(ESI) calcd for C H N [M + H ] 150.1277, found 150.1281.
9
13
2
10 15
2
6
1
65.1022, found 165.1024.
-Pyridin-3-ylmorpholine (3ah). Yellow oil (146 mg, 89% yield).
H NMR (300 MHz, CDCl ): δ 8.31 (s, 1H), 8.14−8.11 (m, 1H),
N,N-Diethylthiophen-2-amine (3ci). Pale yellow oil (107 mg,
1
4
69% yield). H NMR (300 MHz, CDCl ) δ 7.21−7.18 (m, 1H), 6.78−
3
1
3
6.75 (m, 1H), 5.90−5.88 (m, 1H), 3.25 (q, J = 7.2 Hz, 4H), 1.13 (t, J =
7.2 Hz, 6H). 13C{ H} NMR (75 MHz, CDCl ) δ 150.4, 125.2, 119.6,
1
7
.19−7.17 (m, 2H), 3.88 (t, J = 4.8 Hz, 4H), 3.18 (t, J = 4.8 Hz, 4H).
3
1
3
1
+
C{ H} NMR (75 MHz, CDCl ): δ 146.8, 141.0, 138.2, 123.5, 122.0,
96.2, 45.9, 12.7. HRMS (ESI) calcd for C H NS [M + H ] 156.0841,
found 156.0844.
N-Benzyl-4-methoxy-N-methylaniline (3da). Red oil (166 mg,
3
8
14
+
6
6.6, 48.5. HRMS (ESI) calcd for C H N O [M + H ] 165.1022,
9
12
2
found 165.1028.
1
4
-Thien-2-ylmorpholine (3ai). Yellow oil (146 mg, 86% yield).
73% yield). H NMR (300 MHz, CDCl ): δ 7.22−7.14 (m, 5H),
3
13 1
1
H NMR (300 MHz, CDCl ): δ 6.81−6.77 (m, 1H), 6.64−6.61 (m,
6.76−6.64 (m, 4H), 4.34 (s, 2H), 3.66 (s, 3H), 2.83 (s, 3H). C{ H}
3
NMR (75 MHz, CDCl ): δ 152.2, 145.2, 139.6, 128.9, 127.6, 127.3,
1
H), 6.16−6.13 (m, 1H), 3.85−3.80 (m, 4H), 3.13−3.09 (m, 4H).
3
1
3
1
115.2, 115.0, 58.5, 56.2, 39.5. HRMS (ESI) calcd for C H NO [M +
C{ H} NMR (75 MHz, CDCl ): δ 159.3, 126.1, 112.7, 105.6, 66.4,
15 17
3
+
+
H ] 228.1383, found 228.1388.
5
1.9. HRMS (ESI) calcd for C H NOS [M + H ] 170.0634, found
8
11
N-Benzyl-N-methylaniline (3de). Yellow oil (124 mg, 63%
yield). H NMR (300 MHz, CDCl ): δ 7.34−7.19 (m, 7H), 6.76−6.68
(m, 3H), 4.54 (s, 2H), 3.02 (s, 3H). C{ H} NMR (75 MHz,
1
70.0638.
-Thien-3-ylmorpholine (3aj). White solid (149 mg, 88% yield).
H NMR (300 MHz, CDCl ): δ 7.26−7.24 (m, 1H), 6.87−6.84 (m,
1
4
3
13
1
1
3
CDCl ): δ 150.2, 139. 5, 129.6, 129.0, 127.3, 127,2, 116.9, 112.8, 57.0,
3
1
4
H), 6.21−6.19 (m, 1H), 3.84 (d, J = 4.8 Hz, 4H), 3.08 (d, J = 4.8 Hz,
+
H). 1 C{ H} NMR (75 MHz, CDCl ): δ 152.4, 125.6, 119.6, 100.4,
3
1
39.0. HRMS (ESI) calcd for C14
H
15N [M + H ] 198. 1277, found
3
+
198.1283.
66.7, 50.7. HRMS (ESI) calcd for C H NOS [M + H ] 170.0634,
8
11
N-Benzyl-N-methylpyridin-2-amine (3dg). Yellow oil (123 mg,
found 170.0639.
1
6
2% yield). H NMR (300 MHz, CDCl ): δ 8.20−8.17 (m, 1H),
3
N-(3-Methoxyphenyl)dibenzylamine (3bb). Yellow oil (267
1
7.45−7.39 (m, 1H), 7.33−7.20 (m, 5H), 6.58−6.48 (m, 2H), 4.80 (s,
mg, 88% yield). H NMR (300 MHz, CDCl ): δ 7.37−7.21 (m, 10H),
3
13 1
2
H), 3.07 (s, 3H). C{ H} NMR (75 MHz, CDCl ): δ 159.3, 148.4,
3
7
4
1
.08−7.05 (m, 1H), 6.38−6.34 (m, 1H), 6.30−6.26 (m, 2H), 4.63 (s,
H), 3.69 (s, 3H). C{ H} NMR (75 MHz, CDCl ): δ 160.7, 150.6,
38.5, 129.9, 128.6, 126.8, 126.6, 105.6, 101.4, 98.9, 55.0, 54.2. HRMS
ESI) calcd for C H NO [M + H ] 304.1696, found 304.1701.
1
3
1
139.1, 137.7, 128.9, 127.4, 127.3, 112.2, 106.1, 53.6, 36.6. HRMS (ESI)
3
+
calcd for C H N [M + H ] 199.1230, found 199.1235.
13
14
2
2
7
+
N-Benzyl-N-isopropylbenzenamine (3ee). Pale yellow oil
(
21
21
1
(
129 mg, 61% yield). H NMR (300 MHz, CDCl ): δ 7.33−7.13 (m,
3
N-(4-Methylphenyl)dibenzylamine (3bc). Colorless oil (236
1
7H), 6.72−6.66 (m, 3H), 4.41 (s, 2H), 4.34−4.20 (dt, 1H), 1.20 (d, J
mg, 82% yield). H NMR (300 MHz, CDCl ): δ 7.33−7.16 (m, 10H),
3
13 1
=
6.6 Hz, 6H). C{ H} NMR (75 MHz, CDCl ): δ 149.4, 140.9,
3
6
.96 (d, J = 8.4 Hz, 2H), 6.64 (d, J = 8.4 Hz, 2H), 4.60 (s, 4H), 2.21
s, 3H). 1 C{ H} NMR (75 MHz, CDCl ): δ 147.0, 138.8, 129.7,
3
1
129.2, 128.5, 126.5, 126.3, 116.5, 113.2, 48.5, 48.3, 20.0. HRMS (ESI)
(
3
+
calcd for C H N [M + H ] 226.1596, found 260.1593.
16
20
1
28.6, 126.8, 126.7, 125.8, 112.6, 54.3, 20.2. HRMS (ESI) calcd for
+
N-Benzyl-4-chloro-N-isopropylbenzenamine (3el). Pale yel-
low oil (200 mg, 67% yield). H NMR (300 MHz, CDCl ): δ 7.31−
7.21 (m, 5H), 7.09 (d, J = 8.7 Hz, 2H), 6.60 (d, J = 8.7 Hz, 2H), 4.38
C H N [M + H ] 288.1747, found 288.1752.
2
1
21
1
7
b
3
N,N-Dibenzylaniline (3be). White solid (246 mg, 90% yield).
1
H NMR (300 MHz, CDCl ): δ 7.24−7.03 (m, 10H), 6.65−6.57 (m,
3
13
1
1
3
1
(s, 2H), 4.26−4.16 (m, 1H), 1.20 (d, J = 6.6 Hz, 6H). C{ H} NMR
4
H), 4.56 (s, 4H). C{ H} NMR (75 MHz, CDCl ): δ 149.1, 138.5,
3
(
75 MHz, CDCl ): δ 147.8, 140.1, 128.8, 128.5, 126.6, 126.1, 121.1,
3
1
29.2, 128.6, 126.8, 126.6, 116.7, 112.3, 54.1. HRMS (ESI) calcd for
+
+
114.4, 48.6, 48.3, 19.8. HRMS (ESI) calcd for C16H19NCl [M + H ]
C H N [M + H ] 274.1590, found 274.1597.
20
20
2
60.1206, found 260.1202.
N-(2-Pyridyl)dibenzylamine (3bg). Yellow oil (228 mg, 83%
9c
1
N,N-Diisopropylbenzenamine (3fe). Colorless oil (105 mg,
yield). H NMR (300 MHz, CDCl ): δ 8.14−8.10 (m, 1H), 7.24−7.13
3
1
5
6
=
9% yield). H NMR (300 MHz, CDCl ): δ 7.22−7.16 (m, 2H),
3
(
m, 11H), 6.51−6.46 (m, 1H), 6.38−6.35 (m, 1H), 4.71 (s, 4H).
C{ H} NMR (75 MHz, CDCl ): δ 158.6, 148.0, 138.4, 137.4, 128.5,
.91−6.88 (m, 2H), 6.79−6.74 (m, 1H), 3.81−3.72 (m, 2H), 1.20 (d, J
1
3
1
3
13
1
6.6 Hz, 12H). C{ H} NMR (75 MHz, CDCl ): δ 148.0, 128.4,
3
1
+
27.0, 126.9, 112.2, 105.8, 50.8. HRMS (ESI) calcd for C H N [M
+
19
18
2
1
19.4, 118.2, 47.5, 21.3. HRMS (ESI) calcd for C H N [M + H ]
+
12 20
H ] 275.1543, found 275.1548.
N-(3-Pyridyl)dibenzylamine (3bh). Yellow oil (241 mg, 88%
1
78.1590, found 178.1593.
2
5
9c
4
-Bromo-N,N-diisopropylbenzenamine (3fk). Colorless oil
91 mg, 58% yield). H NMR (300 MHz, CDCl ): δ 7.25 (d, J = 6.0
1
yield). H NMR (500 MHz, CDCl ) δ 8.06 (d, J = 3.5 Hz, 1H), 7.94
1
3
(
3
(
4
1
d, J = 4.0 Hz, 1H), 7.35−7.28 (m, 8H), 7.18−7.16 (m, 4H), 4.72 (s,
Hz, 2H), 6.74 (d, J = 6.0 Hz, 2H), 3.78−3.69 (m, 2H), 1.20 (d, J = 6.6
H). 13C{ H} NMR (CDCl , 125 MHz) δ 147.1, 134.3, 129.5, 128.6,
1
3
13
1
Hz, 12H). C{ H} NMR (75 MHz, CDCl ): δ 147.1, 137.2, 120.3,
3
28.3, 127.9, 126.7, 126.2, 124.5, 54.9. HRMS (ESI) calcd for
+
1
2
09.9, 47.6, 21.2. HRMS (ESI) calcd for C H BrN [M + H ]
+
12 19
C H N [M + H ] 275.1543, found 274.1548.
19
19
2
56.0695, found 256.0697.
N-(3-Thienyl)dibenzylamine (3bj). Yellow oil (237 mg, 85%
9d
N,N-Dicyclohexylbenzenamine (3ge). Pale yellow oil (180
1
yield). H NMR (300 MHz, CDCl ): δ 7.27−7.17 (m, 10H), 7.10−
1
3
mg, 70% yield). H NMR (300 MHz, CDCl ): δ 7.25−7.15 (m, 2H),
13
1
3
7
.08 (m, 1H), 6.74−6.72 (m, 1H), 5.92 (s, 1H), 4.48 (s, 4H). C{ H}
NMR (75 MHz, CDCl ): δ 150.6, 138.6, 128.4, 127.2, 126.9, 124.9,
19.1, 96.9, 56.0. HRMS (ESI) calcd for C H NS [M + H ]
80.1154, found 280.1160.
N-(4-Bromophenyl)dibenzylamine (3bk). White solid (250
6
1
1
.95−6.92 (m, 2H), 6.82−6.77 (m, 1H), 3.27−3.20 (m, 2H), 1.78−
3
13
1
.08 (m, 20H). C{ H} NMR (75 MHz, CDCl ): δ 148.7, 128.2,
+
3
1
2
18 17
21.0, 119.0, 57.5, 32.0, 26.3, 26.0. HRMS (ESI) calcd for C H N
1
8
28
+
[
M + H ] 258.2216, found 258.2218.
9
g
1
mg, 71% yield). H NMR (300 MHz, CDCl ): δ 7.36−7.20 (m, 12H),
3
13
1
6
.50−6.57 (m, 2H), 4.63 (s, 4H). C{ H} NMR (75 MHz, CDCl ): δ
ASSOCIATED CONTENT
3
■
1
48.1, 140.0, 131.9, 128.7, 127.1, 126.5, 111.4, 108.6, 54.4.
6
* Supporting Information
S
N-(4-Chlorophenyl)dibenzylamine (3bl). White solid (212 mg,
9% yield). H NMR (300 MHz, CDCl ): δ 7.36−7.20 (m, 10H), 7.08
d, J = 8.7 Hz, 2H), 6.63 (d, J = 8.7 Hz, 2H), 4.63 (s, 4H). C{ H}
Copies of H and 13C NMR spectra of the compounds 3. The
Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.joc.5b00767.
1
1
6
3
13
1
(
NMR (75 MHz, CDCl ): δ 147.7, 138.1, 128.9, 128.7, 127.0, 126.5,
3
D
DOI: 10.1021/acs.joc.5b00767
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(
(
8) Barker, T. J.; Jarvo, E. R. J. Am. Chem. Soc. 2009, 131, 15598.
9) (a) Liu, S.; Liebeskind, L. S. J. Am. Chem. Soc. 2008, 130, 6918.
AUTHOR INFORMATION
Corresponding Authors
E-mail: slzhou@mail.ahnu.edu.cn.
E-mail: swwang@mail.ahnu.edu.cn.
■
(
b) He, C.; Chen, C.; Cheng, J.; Liu, C.; Liu, W. W.; Li, Q.; Lei, A.
*
Angew. Chem., Int. Ed. 2008, 47, 6414. (c) Rucker, R. P.; Whittaker, A.
M.; Dang, H.; Lalic, G. Angew. Chem., Int. Ed. 2012, 51, 3953. (d) Xiao,
Q.; Tian, L.; Tan, R.; Xia, Y.; Qiu, D.; Zhang, Y.; Wang, J. Org. Lett.
2012, 14, 4230. (e) Mlynarski, S. N.; Karns, A. S.; Morken, J. P. J. Am.
Chem. Soc. 2012, 134, 16449. (f) Zhu, C.; Li, G.; Ess, D. H.; Falck, J.
R.; Kurti, L. J. Am. Chem. Soc. 2012, 134, 18253. (g) Matsuda, N.;
Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int. Ed. 2012, 51,
*
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank the National Natural Science Foundation of
China (21172003, 21172004, 21372009, 21432001) for the
financial support for this work.
3
(
3
642−3645.
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DOI: 10.1021/acs.joc.5b00767
J. Org. Chem. XXXX, XXX, XXX−XXX