Palladium-catalyzed reductive coupling of nitroarenes with phenols leading to n-cyclohexylanilines

Article abstract of DOI:10.1055/s-0037-1610231

A direct and efficient palladium-catalyzed reductive coupling reaction of nitroarenes with phenols has been developed. A series of Ncyclohexylaniline derivatives was easily and efficiently obtained in moderate to good yields via C-N bond formation by the

Full text of DOI:10.1055/s-0037-1610231

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–H
paper
A
en
K.-J. Liu et al.
Paper
Synthesis
Palladium-Catalyzed Reductive Coupling of Nitroarenes with
Phenols leading to N-Cyclohexylanilines
Kai-Jian Liua
Xiu-Ling Zenga
Yong Zhanga
Yi Wanga
Xin-Sheng Xiaoa
Huilan Yueb
Ming Wangc
Zilong Tangc
Wei-Min He*a
H
N
Pd/C (10 mol%)
R2
R1
NO2
+
HO
R1
R2
HCO2Na, TFA
toluene, 100 °C
21 examples
up to 92% yield
0
0
0
0
0-
0
0
2
9-
4
8
1
6-
6
9
7
a Hunan Provincial Engineering Research Center for Ginkgo biloba, Hunan
University of Science and Engineering, Yongzhou 425100, P. R. of China
weiminhe2016@yeah.net
b Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau
Biology, Chinese Academy of Sciences and Qinghai Provincial Key Laboratory of
Tibetan Medicine Research, Qinghai 810008, P. R. of China
c Key Laboratory of Theoretical Organic Chemistry and Functional Molecule of
Ministry of Education, Hunan University of Science and Technology, Xiangtan
411201, P. R. of China
Received: 17.05.2018
Accepted after revision: 12.07.2018
Published online: 16.08.2018
ary arylamines [Scheme 1 (a)].5 Tokunaga and co-workers
6a
utilized Au/Fe2O3 and Sreedhar and co-workers6b utilized
gum acacia stabilized palladium (GA-Pd) nanoparticles cat-
alyzed hydrogenation/reductive amination to form aniline
derivatives from nitroarenes and aldehydes under a H2 at-
mosphere [Scheme 1 (b)]. The methods for the one-pot syn-
thesis of arylamines from nitroarenes and alcohols cata-
lyzed by ruthenium, rhodium, or gold complex have also
been developed [Scheme 1 (c)].7 The Deng and Lemaire
groups independently described efficient palladium-cata-
lyzed diarylamine formation from nitroarenes and cyclo-
hexanone derivatives using borrowed hydrogen strategy
[Scheme 1 (d)].8 Although these methods are undoubtedly
useful, there is still a great demand for the development of
new, efficient, and practical methods to access arylamines
from simple and easily accessible coupling partners.
Phenols are important structural units of renewable
biomass, which can be readily obtained from naturally
abundant lignins.9 The direct use of non-preactivated phe-
nols as aromatic coupling partners and cyclic C6 feedstocks
has attracted increasingly synthetic pursuit of chemists in
terms of their easy available and renewable features.10 Re-
cently, palladium-catalyzed reductive coupling of phenols
with amines to afford cyclohexylamines10g and cross-cou-
pling of phenols with amines to access aromatic amines10h
have been successfully established by Li and co-workers.
Palladium-catalyzed reduction of nitroarenes to anilines
with formic acid has been also developed by Johnstone and
DOI: 10.1055/s-0037-1610231; Art ID: ss-2018-h0340-op
Abstract A direct and efficient palladium-catalyzed reductive coupling
reaction of nitroarenes with phenols has been developed. A series of N-
cyclohexylaniline derivatives was easily and efficiently obtained in mod-
erate to good yields via C–N bond formation by the simple use of safe
and inexpensive sodium formate as the hydrogen donor.
Key words green chemistry, palladium catalysis, reductive coupling,
nitroarene, phenol, cyclohexylamine
Nitroarenes are a stable, cheap, and readily available
starting material in synthetic chemistry and the reduction
of nitro compounds is an important step in the preparation
of biologically active compounds and fine chemicals.1 Al-
though numerous procedures have been established for the
reduction of nitro compounds,2 the selective reduction and
further transformation of nitroarenes under mild reaction
conditions is still a challenging problem.3
On the other hand, as an important class of compounds,
arylamines exhibit a wide range of applications in pharma-
ceuticals, agrochemicals, dyes, and functional materials.2b,4
In recent years, transition-metal-catalyzed or metal-free
methods for the synthesis of N-substituted arylamines via
C–N bond formation from nitroarenes have attracted great
attention of chemists.5–8 For examples, in 2009, Li and co-
workers reported the peroxide-mediated direct amination
of simple cycloalkanes with nitroarenes leading to second-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

B
K.-J. Liu et al.
Paper
Synthesis
ducted in solvent such as THF, 1,4-dioxane, EtOH, or H2O
(Table 1, entries 20–23). DMF, DMSO, and MeCN all resulted
in no transformation (Table 1, entries 24–26). The tempera-
ture has a great impact on the reaction efficiency. The tar-
get product was isolated in moderate yield when the reac-
tion was carried out at 80 °C (Table 1, entry 27). In contrast,
Previous work:
(a)
H
N
peroxide
NO2
+
(b)
(c)
(d)
H
N
O
R
Au/Fe2O3/H2 or
H
GA-Pd Nano/H2
NO2
NO2
+
+
R
R
Table 1 Optimization of Reaction Conditionsa
R
Ru, Rh, or Au
150 °C
or
N
HO
R
NH
R
H
N
catalyst
H
Me
NO2
N
HO
+
Pd(OAc)2/L or Pd/C
NMP, 150 °C
HCO2Na, acid
solvent
NO2
+ O
Me
1a
2a
3aa
This work:
(e)
Entry Catalyst (mol%)
Acid
Solvent
Yield (%)b
H
Pd/C (10 mol%)
N
NO2
HO
+
1
2
Pd/CaCO3 (10)
PdCl2 (10)
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
21
0
HCO2Na, TFA
toluene,100 °C
3
Pd(dba)2 (10)
Pd(OAc)2 (10)
0
Scheme 1 The methods for the synthesis of amines from nitroarenes
4
0
5
PdCl2(dtbpf) (10)
Pd(acac)2 (10)
Pd(NO3)2·H2O (10)
Pd(OH)2 (10)
Pd/C (10)
0
co-workers.11 Nevertheless, the direct reductive coupling of
phenols with nitroarenes is so far unreported. With our
continuing interest in green organic synthesis,12 herein we
report an efficient Pd/C-catalyzed direct reductive coupling
of readily available nitroarenes with phenols leading to var-
ious N-cyclohexylaniline derivatives assisted by trifluoro-
acetic acid, in which safe and cheap sodium formate was
used as hydrogen source [Scheme 1 (e)].
6
74
69
38
87 (83)
52
0
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Pd/C (5)
–
Pd/C nanoparticles (10) TFA
TsOH
85
78
81
55
32
0
Initially, under an argon atmosphere, the model reac-
tion of 1-methyl-4-nitrobenzene (1a) and phenol (2a) was
performed to examine the catalytic activity of various tran-
sition-metal catalysts (10 mol%) including Ru, Rh, Pd, Cu,
Au, Ag, Fe, and Ni in the presence of sodium formate (HCO2Na)
and TFA. Among those transition-metal salts examined (see
Table 1 and Table S1 in the Supporting Information), Pd/C
catalyst was found to be best one to catalyze the formation
of cyclohexylamine 3aa (Table 1, entry 9). The reaction effi-
ciency decreased dramatically when the loading of catalyst
was reduced to 5 mol% and no transformation was observed
in the absence of Pd/C catalyst (Table 1, entries 10 and 11).
The use of a Pd/C nanoparticle catalyst (10 mol%) did not
improve the reaction efficiency (Table 1, entry 12). Further
exploration found that the acid was the critical additive for
promoting this reaction (Table 1, entries 13–19). Among
various acids examined, TFA turned out to be the best
choice, while TsOH and H3PO4 also gave satisfactory yields
(Table 1, entries 13 and 14). The desired product was only
obtained in 26% yield when formic acid was used instead of
sodium formate/TFA in this reaction system (Table 1, entry
18). In addition, no product was detected in the absence of
acid (Table 1, entry 19). The solvent is essential for this re-
action. Replacing toluene with other solvents dramatically
decreased the yield of 3aa (Table 1, entries 20–26). Low to
moderate yields were obtained when the reaction was con-
Pd/C (10)
Pd/C (10)
Pd/C (10)
Pd/C (10)
Pd/C (10 )
Pd/C (10 )
Pd/C (10)
Pd/C (10)
Pd/C (10)
Pd/C (10)
Pd/C (10)
Pd/C (10)
Pd/C (10)
Pd/C (10)
Pd/C (10)
Pd/C (10)
H3PO4
HCl
PhCO2H
AcOH
HCO2H
–
26c
0
TFA
56
TFA
1,4-dioxane 57
TFA
EtOH
39
19
0
TFA
H2O
TFA
DMF
TFA
DMSO
MeCN
toluene
toluene
0
TFA
0
TFA
46d
8e
TFA
a Reaction conditions: 1a (0.24 mmol), 2a (0.2 mmol), catalyst (10 mol%),
sodium formate (1.8 mmol), acid (0.6 mmol), solvent (1 mL), Ar, 24 h.
b NMR yields based on 2a; isolated yield in bracket.
c Sodium formate was omitted and HCO2H (1.8 mmol) was used with TFA
(0.6 mmol).
d 80 °C.
e 25 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

C
K.-J. Liu et al.
Paper
Synthesis
the desired product was only obtained in 8% yield when re-
action was conducted at room temperature (Table 1, entry
28).
gave 3da, 3ea, and 3la in lower yields in comparison with at
the para-, meta-position. It is noteworthy that a series of
functionalities such as methoxy, fluoro, ester, and acetoxy
groups survived well under the present procedure leading
to the corresponding products 3ga–ma, which could be po-
tentially employed for further modifications. Furthermore,
some substituted phenols were explored under standard
conditions, and diastereomers were formed. The reactions
proceeded well in all cases, with the ratios of cis/trans iso-
mers between 2.4:1 and 4.5:1 (Scheme 2, 3ab–af). When an
ortho-substituted phenol, such as o-cresol, was used under
the standard conditions, only a trace amount of product
was detected, which might be caused by the greater steric
effect. β-Naphthol also reacted smoothly with 1-methyl-4-
nitrobenzene (1a) to give the corresponding product 3ag in
moderate yield. As expected, the corresponding dehaloge-
nated cyclohexylamines 3aa were obtained when halo-sub-
stituted phenols (Cl, Br) were employed as substrates.10g,k,13
Two control experiments were carried out to explore
the possible reaction mechanism. As demonstrated in
Scheme 3, when 1-methyl-4-nitrobenzene (1a) was added
to a palladium-catalyzed reductive system of sodium for-
mate (3 equiv) and TFA (3 equiv), p-toluidine (4a) was ob-
tained in 89% yield. Furthermore, the desired product 3aa
was isolated in 85% yield when the reaction of p-toluidine
(4a) with phenol (2a) was conducted in [Pd]/[H]-catalyzed
conditions. The above result demonstrated that aniline
should be the key intermediate in the present transforma-
tion.
After the establishment of the optimal reaction condi-
tions, the substrate scope in this palladium-catalyzed re-
ductive coupling of nitroarenes with phenols was exam-
ined. As shown in Scheme 2, in general, reactions of ni-
troarenes containing electron-donating or electron-
withdrawing groups with phenol worked well under the
standard procedure and their corresponding cyclohexyl-
amines 3aa–ma were obtained in moderate to good yields.
The steric effect has an obvious impact on the reaction effi-
ciency, and nitroarene substrates 1d,e,l bearing a methyl,
ethyl, or ester group in the ortho-position of the aryl ring
H
N
Pd/C (10 mol%)
R2
R1
NO2
+ HO
HCO2Na, TFA
toluene, 100 °C
R1
R2
1
2
3
H
N
H
N
H
Me
N
Me
3aa, 83%
3ba, 82%
3ca, 81%
H
N
H
N
H
N
Me
Me
Me
Et
3da, 73%
3ea, 71%
3fa, 92%
H
H
N
H
N
N
MeO
MeO
MeO
F
3ha, 67%a
(a)
3ga, 89%
3ia, 73%
Pd/C (10 mol%)
H
N
CO2Me
Me
NO2
Me
NH2
H
MeO2C
H
N
HCO2Na (3 equiv)
TFA (3 equiv)
toluene, 100 °C
N
1a
4a (89%)
MeO2C
AcO
3ka, 78%a
3ja, 88%a
3la, 51%a
(b)
Me
H
N
H
N
H
N
Pd/C (10 mol%)
Me
H
N
HO
+
NH2
HCO2Na (6 equiv)
toluene, 100 °C
Me
Me
Me
3ma, 50%c
4a
2a
3ac, 71%a
cis/trans 4.5:1
3aa (85%)
Me
3ab, 81%
cis/trans 3:1
H
N
Scheme 3 Preliminary mechanistic study
H
N
H
N
Me
Me
Et
Me
3ad, 60%a
cis/trans 3.3:1
OMe
On the basis of the above results and previous re-
ports,10,14,15 a possible reaction mechanism is described in
Scheme 4. Initially, nitroarene 1 is reduced to aniline 4 in
the palladium-catalyzed reductive system. Meanwhile, the
reduction of phenol 2 to cyclohexanone 5 also proceeds un-
der [Pd]/[H]-catalyzed conditions.14 Next, the condensation
of aniline 4 with cyclohexanone 5 leads to the formation of
the imine intermediate 6. Finally, the desired N-cyclohex-
ylaniline product 3 is formed through the reduction of the
imine intermediate along with the regeneration of the ac-
tive palladium catalyst.15
3bf, 62%a
cis/trans 2.4:1
Bn
3ae, 61%a
cis/trans 3:1
H
N
H
N
H
N
Me
3aa, 70%c
3ag, 42%
Me
3aa, 64%b
Scheme 2 Reaction scope. Reagents and conditions: 1 (0.24 mmol), 2
(0.2 mmol), Pd/C (10 mol%), sodium formate (1.8 mmol), TFA (0.6
mmol), toluene (1 mL), Ar, 24 h; isolated yields based on 2. a 36 h.
b 4-Chlorophenol was used. c 4-Bromophenol was used.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

D
K.-J. Liu et al.
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Synthesis
mate (40.8 mg, 0.6 mmol), and TFA (44.4 μL, 0.6 mmol) in toluene (1
mL). The mixture was then stirred at 100 °C for 24 under an argon at-
mosphere. The mixture was then diluted with EtOAc (3 mL), filtered
and eluted through a short silica gel plug with more EtOAc (2 × 3 mL).
Solvent was removed, and the residue was separated by column chro-
matography to give pure 4a (19.0 mg, 89%).
[Pd]/[H]
H
NH2
NO2
H2O
4
1
N
O
R1
5
6
N-Cyclohexyl-4-methylaniline (3aa) by Reaction of p-Toluidine
(4a) and Phenol (2a)
OH
[Pd]/[H]
To a mixture of p-toluidine (4a; 25.7 mg, 0.24 mmol), phenol (2a;
18.8 mg, 0.2 mmol), Pd/C (10 wt%, 21.2 mg, 10 mol% based on Pd con-
tent), and sodium formate (81.6 mg, 1.2 mmol) in toluene (1 mL). The
mixture was then stirred at 100 °C for 24 under an argon atmosphere.
The mixture was then diluted with EtOAc (5 mL), filtered and eluted
through a short silica gel plug with more EtOAc (2 × 5 mL). Solvent
was removed, and the residue was separated by column chromatog-
raphy to give pure 3aa (32.1 mg, 85%).
[H]
[Pd]
H
N
2
R1
3
Scheme 4 Postulated reaction pathway
N-Cyclohexyl-4-methylaniline (3aa)10g
In summary, an efficient palladium-catalyzed method
for the construction of N-cyclohexylanilines via reductive
coupling of stable and easily available nitroarenes with
phenols using cheap sodium formate as the hydrogen donor
has been successfully developed. A series of N-cyclohex-
ylaniline derivatives was obtained by this novel method in
moderate to good yields from naturally abundant and sus-
tainable phenols. The present protocol is expected to find
wide applications in synthetic chemistry, pharmaceutical
research, and the fine chemical industry. Further studies on
the scope and application of this reaction are underway in
our laboratory.
Yellow oil; yield: 31.4 mg (83%).
1H NMR (400 MHz, CDCl3): δ = 7.00 (d, J = 8.1 Hz, 2 H), 6.56 (d, J = 8.1
Hz, 2 H), 3.28–3.23 (m, 1 H), 2.27 (s, 3 H), 2.11–2.07 (m, 2 H), 1.82–
1.77 (m, 2 H), 1.71–1.66 (m, 1 H), 1.42–1.30 (m, 2 H), 1.27–1.53 (m, 3
H).
13C NMR (100 MHz, CDCl3): δ = 145.1, 129.7, 126.1, 113.5, 52.1, 33.6,
26.0, 25.1, 20.4.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19NNa: 212.1415; found:
212.1419.
N-Cyclohexylaniline (3ba)10g
Yellow oil; yield: 28.7 mg (82%).
1H NMR (400 MHz, CDCl3): δ = 7.21–7.17 (m, 2 H), 6.69 (t, J = 7.5 Hz, 1
H), 6.62 (d, J = 7.6 Hz, 2 H), 3.33–3.26 (m, 1 H), 2.12–2.08 (m, 2 H),
1.83–1.78 (m, 2 H), 1.71–1.68 (m, 1 H), 1.47–1.36 (m, 2 H), 1.32–1.14
(m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 147.4, 129.3, 116.9, 113.2, 51.7, 33.5,
26.0, 25.1.
Unless otherwise specified, all reagents and solvents were obtained
from commercial suppliers and used without further purification.
Pd/C nanoparticles were purchased from Neijiang Noble Material
Technology Co. Ltd. 1H NMR spectra were recorded at 400 MHz or 500
MHz and 13C NMR spectra were recorded at 100 MHz or 125 MHz by
using a Bruker Avance 400 or 500 spectrometer. Chemical shifts were
calibrated using residual undeuterated solvent as an internal refer-
ence (1H NMR: CDCl3 δ = 7.26, 13C NMR: CDCl3 δ = 77.0). Chromato-
graphic purifications were carried out on a Biotage Isolera Four in-
strument. Mass spectra were performed on a spectrometer operating
on ESI-TOF.
HRMS (ESI): m/z [M + Na]+ calcd for C12H17NNa: 198.1259; found:
198.1265.
N-Cyclohexyl-3-methylaniline (3ca)10g
Yellow oil; yield: 30.6 mg (81%).
1H NMR (400 MHz, CDCl3): δ = 7.08 (t, J = 7.4 Hz, 2 H), 6.53 (t, J = 7.5
Hz, 1 H), 6.45 (d, J = 6.8 Hz, 2 H), 3.32–3.25 (m, 1 H), 2.3 (s, 3 H), 2.11–
2.07 (m, 2 H), 1.83–1.77 (m, 2 H), 1.71–1.68 (m, 1 H), 1.47–1.36 (m, 2
H), 1.32–1.14 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 147.4, 139.0, 129.1, 117.8, 113.9,
110.3, 51.7, 33.6, 26.0, 25.1, 21.7.
N-Cyclohexyl-4-methylaniline (3aa); Typical Procedure
In a 10-mL microwave vial were combined nitroarene 1a (32.9 mg,
0.24 mmol), phenol (2a, 18.8 mg, 0.20 mmol), Pd/C (10 wt%, 21.2 mg,
10 mol% based on Pd content), sodium formate (122.4 mg, 1.8 mmol),
and TFA (44.4 μL, 0.6 mmol) in toluene (1 mL). The mixture was then
stirred at 100 °C for 24 h under an argon atmosphere. The mixture
was then diluted with EtOAc (5 mL), filtered, and eluted through a
short silica gel plug with more EtOAc (2 × 5 mL). Solvent was re-
moved, and the residue was separated by column chromatography to
give the pure product 3aa.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19NNa: 212.1415; found:
212.1421.
N-Cyclohexyl-2-methylaniline (3da)10g
Yellow oil; yield: 27.6 mg (73%).
1H NMR (400 MHz, CDCl3): δ = 7.14 (t, J = 7.7 Hz, 2 H), 7.08 (d, J = 7.5
Hz, 1 H), 6.68–6.64 (m, 2 H), 3.39–3.33 (m, 1 H), 2.16 (s, 3 H), 2.15–
2.09 (m, 2 H), 1.84–1.79 (m, 2 H), 1.73–1.68 (m, 1 H), 1.49–1.39 (m, 2
H), 1.34–1.20 (m, 3 H).
p-Toluidine (4a) by Reaction of 1-Methyl-4-nitrobenzene (1a) Un-
der Standard Conditions
To a mixture of 1-methyl-4-nitrobenzene (1a; 27.4 mg, 0.2 mmol),
Pd/C (10 wt%, 21.2 mg, 10 mol% based on Pd content), sodium for-
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K.-J. Liu et al.
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Synthesis
13C NMR (100 MHz, CDCl3): δ = 145.3, 130.3, 127.1, 121.6, 116.3,
110.2, 51.7, 33.7, 26.0, 25.1, 17.6.
13C NMR (100 MHz, CDCl3): δ = 155.5 (d, J = 232.9 Hz), 143.7, 115.6 (d,
J = 22.0 Hz), 114.1 (d, J = 7.3 Hz), 52.5, 33.5, 25.9, 25.0.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19NNa: 212.1415; found:
HRMS (ESI): m/z [M + Na]+ calcd for C12H16NFNa: 216.1164; found:
212.1420.
216.1167.
N-Cyclohexyl-2-ethylaniline (3ea)10g
Methyl 4-(Cyclohexylamino)benzoate (3ja)
Yellow oil; yield: 28.8 mg (71%).
Yellow oil; yield: 40.9 mg (88%).
1H NMR (500 MHz, CDCl3): δ = 7.16–7.13 (m, 1 H), 7.11 (d, J = 7.4 Hz, 1
H), 6.71 (t, J = 7.5 Hz, 2 H), 3.52 (br s, 1 H), 3.39–3.34 (m, 1 H), 2.51 (q,
J = 7.5 Hz, 2 H), 2.15–2.11 (m, 2 H), 1.84–1.79 (m, 2 H), 1.73–1.69 (m,
1 H), 1.48–1.40 (m, 2 H), 1.34–1.21 (m, 6 H).
1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 7.1 Hz, 2 H), 6.55 (d, J = 7.0
Hz, 2 H), 4.19 (br s, 1 H), 3.86 (s, 3 H), 3.37–3.31 (m, 1 H), 2.08–2.05
(m, 2 H), 1.81–1.77 (m, 2 H), 1.70–1.66 (m, 1 H), 1.44–1.37 (m, 2 H),
1.26–1.19 (m, 3 H).
13C NMR (125 MHz, CDCl3): δ = 144.7, 128.0, 127.2, 126.9, 116.4,
13C NMR (100 MHz, CDCl3): δ = 167.3, 151.0, 131.6, 117.7, 111.7, 51.5,
110.5, 51.5, 33.6, 26.1, 25.1, 23.9, 12.9.
51.3, 33.1, 25.7, 24.9.
HRMS (ESI): m/z [M + Na]+ calcd for C14H21NNa: 226.1572; found:
HRMS (ESI): m/z [M + Na]+ calcd for C14H19NO2Na: 256.1313; found:
226.1577.
256.1316.
N-Cyclohexyl-3,4-dimethylaniline (3fa)10g
Methyl 3-(Cyclohexylamino)benzoate (3ka)
Yellow oil; yield: 37.3 mg (92%).
Yellow oil; yield: 36.2 mg (78%).
1H NMR (400 MHz, CDCl3): δ = 6.95 (d, J = 8.0 Hz, 1 H), 6.46 (d, J = 2.4
Hz, 1 H), 6.42–6.39 (m, 1 H), 3.29–3.21 (m, 1 H), 2.94 (br s, 1 H), 2.22
(s, 3 H), 2.18 (s, 3 H), 2.10–2.06 (m, 2 H), 1.81–1.76 (m, 2 H), 1.70–
1.65 (m, 1 H), 1.44–1.34 (m, 2 H), 1.28–1.11 (m, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.36–7.33 (m, 1 H), 7.27 (d, J = 1.7 Hz, 1
H), 7.22 (d, J = 7.9 Hz, 1 H), 6.80–6.77 (m, 1 H), 3.91 (s, 3 H), 3.36–3.30
(m, 1 H), 2.09–2.05 (m, 2 H), 1.81–1.76 (m, 2 H), 1.71–1.65 (m, 1 H),
1.47–1.36 (m, 2 H), 1.24–1.14 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 145.5, 137.3, 130.3, 125.0, 115.3,
13C NMR (100 MHz, CDCl3): δ = 167.6, 147.3, 131.1, 129.2, 118.0,
110.8, 52.0, 33.6, 26.0, 25.1, 20.1, 18.7.
117.6, 113.8, 52.0, 51.7, 33.3, 25.9, 24.9.
HRMS (ESI): m/z [M + Na]+ calcd for C14H21NNa: 226.1572; found:
HRMS (ESI): m/z [M + Na]+ calcd for C14H19NO2Na: 256.1313; found:
226.1575.
256.1317.
N-Cyclohexyl-4-methoxyaniline (3ga)10g
Methyl 2-(Cyclohexylamino)benzoate (3la)
Yellow oil; yield: 36.5 mg (89%).
Yellow oil; yield: 24.1 mg (51%).
1H NMR (500 MHz, CDCl3): δ = 6.79 (d, J = 7.2 Hz, 2 H), 6.60 (d, J = 7.2
Hz, 2 H), 3.77 (s, 3 H), 3.21–3.06 (m, 1 H), 2.08–2.06 (m, 2 H), 1.80–
1.76 (m, 2 H), 1.69–1.65 (m, 1 H), 1.42–1.33 (m, 2 H), 1.28–1.22 (m, 1
H), 1.18–1.11 (m, 2 H).
1H NMR (400 MHz, CDCl3): δ = 7.93–7.90 (m, 1 H), 7.82 (br s, 1 H),
7.36–7.32 (m, 1 H), 6.74 (d, J = 8.5 Hz, 1 H), 6.56 (t, J = 7.9 Hz, 1 H),
3.87 (s, 3 H), 3.43 (br s, 1 H), 2.06–2.03 (m, 2 H), 1.82–1.79 (m, 2 H),
1.67–1.63 (m, 1 H), 1.45–1.31 (m, 5 H).
13C NMR (125 MHz, CDCl3): δ = 151.9, 141.6, 114.9, 114.9, 55.8, 52.8,
13C NMR (100 MHz, CDCl3): δ = 169.1, 150.2, 134.5, 131.8, 114.0,
33.6, 26.0, 25.1.
111.8, 109.6, 51.4, 50.6, 32.8, 25.9, 24.7.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19NONa: 228.1364; found:
HRMS (ESI): m/z [M + Na]+ calcd for C14H19NO2Na: 256.1313; found:
228.1369.
256.1315.
N-Cyclohexyl-3,4-dimethoxyaniline (3ha)10g
4-(Cyclohexylamino)phenyl Acetate (3ma)
Yellow oil; yield: 31.5 mg (67%).
Yellow oil; yield: 23.8 mg (50%).
1H NMR (400 MHz, CDCl3): δ = 6.74 (d, J = 8.2 Hz, 1 H), 6.25 (d, J = 2.6
Hz, 1 H), 6.18–6.15 (m, 1 H), 3.85 (s, 3 H), 3.82 (s, 3 H), 3.22–3.16 (m, 1
H), 2.09–2.05 (m, 2 H), 1.79–1.75 (m, 2 H), 1.69–1.64 (m, 1 H), 1.43–
1.33 (m, 2 H), 1.28–1.11 (m, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.88 (d, J = 8.9 Hz, 2 H), 6.56 (d, J = 8.9
Hz, 2 H), 3.25–3.19 (m, 1 H), 3.27 (s, 3 H), 2.08–2.04 (m, 2 H), 1.81–
1.75 (m, 2 H), 1.70–1.64 (m, 1 H), 1.43–1.33 (m, 2 H), 1.28–1.14 (m, 3
H).
13C NMR (100 MHz, CDCl3): δ = 150.1, 142.2, 141.3, 113.3, 104.3, 99.6,
13C NMR (100 MHz, CDCl3): δ = 170.2, 145.3, 141.5, 122.0, 113.4, 52.1,
55.8, 55.7, 52.7, 33.6, 26.0, 25.1.
33.4, 25.9, 25.0, 21.1.
HRMS (ESI): m/z [M + Na]+ calcd for C14H21NO2Na: 258.1470; found:
HRMS (ESI): m/z [M + Na]+ calcd for C14H19NO2Na: 256.1313; found:
258.1473.
256.1316.
N-Cyclohexyl-4-fluoroaniline (3ia)
4-Methyl-N-(4-methylcyclohexyl)aniline (3ab)10g
Yellow oil; yield: 27.6 mg (73%).
Yellow oil; yield: 32.1 mg (81%).
1H NMR (400 MHz, CDCl3): δ = 6.91–6.87 (m, 2 H), 6.56–6.53 (m, 2 H),
3.24–3.17 (m, 1 H), 2.09–2.05 (m, 2 H), 1.81–1.76 (m, 2 H), 1.71–1.66
(m, 1 H), 1.44–1.33 (m, 2 H), 1.30–1.22 (m, 1 H), 1.20–1.11 (m, 2 H).
cis-4-Methyl-N-(4-methylcyclohexyl)aniline
Purified by preparative TLC (hexanes/EtOAc) to give a yellow oil;
yield: 24.0 mg (60%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

F
K.-J. Liu et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.00 (d, J = 8.0 Hz, 2 H), 6.58 (d, J = 8.3
Hz, 2 H), 3.56–3.50 (m, 1 H), 2.27 (s, 3 H), 1.80–1.76 (m, 2 H), 1.70–
1.63 (m, 2 H), 1.60–1.56 (m, 3 H), 1.30–1.24 (m, 3 H), 0.95 (d, J = 6.5
Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.01 (d, J = 8.1 Hz, 2 H), 6.58 (d, J = 8.1
Hz, 2 H), 3.59–3.55 (m, 1 H), 2.27 (s, 3 H), 1.79–1.76 (m, 2 H), 1.70–
1.67 (m, 4 H), 1.35–1.27 (m, 5 H), 0.93 (t, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 145.0, 129.8, 126.1, 113.5, 48.9, 37.8,
29.8, 29.3, 27.4, 20.4, 11.7.
13C NMR (100 MHz, CDCl3): δ = 145.1, 129.8, 126.0, 113.5, 48.5, 30.9,
29.8, 29.3, 21.4, 20.4.
HRMS (ESI): m/z [M + Na]+ calcd for C14H21NNa: 226.1572; found:
HRMS (ESI): m/z [M + Na]+ calcd for C15H23NNa: 240.1728; found:
240.1731.
226.1577.
trans-N-(4-Ethylcyclohexyl)-4-methylaniline
cis-4-Methyl-N-(4-methylcyclohexyl)aniline
Purified by preparative TLC (hexanes/EtOAc) to give a yellow oil;
yield: 6.2 mg (14%).
1H NMR (400 MHz, CDCl3): δ = 7.00 (d, J = 8.2 Hz, 2 H), 6.59 (d, J = 8.2
Hz, 2 H), 3.20–3.15 (m, 1 H), 2.26 (s, 3 H), 2.16–2.11 (m, 2 H), 1.85–
1.78 (m, 2 H), 1.30–1.23 (m, 2 H), 1.17–1.00 (m, 5 H), 0.91 (d, J = 7.0
Hz, 3 H).
Purified by preparative TLC (hexanes/EtOAc) to give a yellow oil;
yield: 8.1 mg (21%).
1H NMR (400 MHz, CDCl3): δ = 6.99 (d, J = 8.5 Hz, 2 H), 6.51 (d, J = 8.5
Hz, 2 H), 3.20–3.14 (m, 1 H), 2.25 (s, 3 H), 2.14–2.11 (m, 2 H), 1.78–
1.75 (m, 2 H), 1.41–1.38 (m, 1 H), 1.14–1.05 (m, 4 H), 0.93 (d, J = 6.5
Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 144.4, 129.8, 126.9, 114.1, 53.4, 38.9,
33.4, 31.6, 29.6, 20.4, 11.6.
13C NMR (100 MHz, CDCl3): δ = 145.2, 129.7, 126.3, 113.6, 52.6, 34.2,
33.6, 32.4, 22.3, 20.3.
HRMS (ESI): m/z [M + Na]+ calcd for C14H21NNa: 226.1572; found:
HRMS (ESI): m/z [M + Na]+ calcd for C15H23NNa: 240.1728; found:
240.1733.
226.1575.
N-(4-Benzylcyclohexyl)-4-methylaniline (3ae)
4-Methyl-N-(3-methylcyclohexyl)aniline (3ac)10g
Yellow oil; yield: 26.1 mg (61%).
Yield: 28.9 mg (71%).
cis-N-(4-Benzylcyclohexyl)-4-methylaniline
cis-4-Methyl-N-(3-methylcyclohexyl)aniline
Purified by preparative TLC (hexanes/EtOAc) to give a yellow oil;
yield: 25.7 mg (46%).
Purified by preparative TLC (hexanes/EtOAc) to give a yellow oil;
yield: 23.5 mg (58%).
1H NMR (400 MHz, CDCl3): δ = 7.00 (d, J = 8.0 Hz, 2 H), 6.57 (d, J = 8.0
Hz, 2 H), 3.69–3.65 (m, 1 H), 2.26 (s, 3 H), 1.79–1.75 (m, 2 H), 1.70–
1.63 (m, 2 H), 1.62–1.55 (m, 3 H), 1.41–1.33 (m, 1 H), 1.12–1.05 (m, 1
H), 0.94 (d, J = 6.5 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.31 (t, J = 7.2 Hz, 2 H), 7.22 (t, J = 7.3
Hz, 1 H), 7.18 (d, J = 7.4 Hz, 2 H), 7.18 (d, J = 7.0 Hz, 2 H), 7.01 (d, J = 8.0
Hz, 2 H), 6.58 (d, J = 8.0 Hz, 2 H), 3.58–3.57 (m, 1 H), 2.60 (d, J = 7.3 Hz,
2 H), 2.27 (s, 3 H), 1.83–1.79 (m, 2 H), 1.67–1.58 (m, 3 H), 1.36–1.30
(m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 145.1, 129.8, 126.0, 113.4, 47.9, 38.9,
13C NMR (100 MHz, CDCl3): δ = 144.9, 141.1, 129.8, 129.1, 128.2,
34.0, 30.4, 27.2, 21.8, 20.6, 20.4.
126.2, 125.8, 113.5, 48.7, 42.4, 38.2, 29.3, 27.5, 20.4.
HRMS (ESI): m/z [M + Na]+ calcd for C14H21NNa: 226.1572; found:
HRMS (ESI): m/z [M + Na]+ calcd for C20H25NNa: 302.1885; found:
226.1576.
302.1891.
trans-4-Methyl-N-(3-methylcyclohexyl)aniline
trans-N-(4-Benzylcyclohexyl)-4-methylaniline
Purified by preparative TLC (hexanes/EtOAc) to give a yellow oil;
yield: 5.4 mg (13%).
Purified by preparative TLC (hexanes/EtOAc) to give a pale yellow oil;
yield: 8.4 mg (15%).
1H NMR (400 MHz, CDCl3): δ = 7.00 (d, J = 8.2 Hz, 2 H), 6.54 (d, J = 8.2
Hz, 2 H), 3.26–3.19 (m, 1 H), 2.26 (s, 3 H), 2.14–2.09 (m, 2 H), 1.82–
1.76 (m, 1 H), 1.71–1.68 (m, 1 H), 1.53–1.48 (m, 1 H), 1.42–1.32 (m, 1
H), 1.00–0.99 (m, 1 H), 0.93 (d, J = 6.5 Hz, 3 H), 0.89–0.82 (m, 1 H),
0.79–0.73 (m, 1 H).
1H NMR (400 MHz, CDCl3): δ = 7.31 (t, J = 7.2 Hz, 2 H), 7.21 (t, J = 7.4
Hz, 1 H), 7.17 (d, J = 7.0 Hz, 1 H), 6.99 (d, J = 8.0 Hz, 2 H), 6.57 (d, J = 8.0
Hz, 2 H), 3.22–3.16 (m, 1 H), 2.55 (d, J = 7.0 Hz, 2 H), 2.25 (s, 3 H),
2.15–2.13 (m, 2 H), 1.81–1.79 (m, 2 H), 1.60–1.55 (m, 1 H), 1.14–1.08
(m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 143.9, 129.8, 127.2, 114.7, 53.3, 42.1,
13C NMR (100 MHz, CDCl3): δ = 144.9, 141.0, 129.7, 129.1, 128.1,
34.6, 33.3, 32.0, 25.0, 22.5, 20.4.
126.3, 125.7, 113.6, 52.8, 43.6, 39.4, 33.5, 31.9, 20.3.
HRMS (ESI): m/z [M + Na]+ calcd for C14H21NNa: 226.1572; found:
HRMS (ESI): m/z [M + Na]+ calcd for C20H25NNa: 302.1885; found:
226.1577.
302.1891.
N-(4-Ethylcyclohexyl)-4-methylaniline (3ad)
N-(4-Methoxycyclohexyl)aniline (3bf)10g
Yield: 26.1 mg (60%).
Yellow oil; yield: 25.8 mg (62%).
cis-N-(4-Ethylcyclohexyl)-4-methylaniline
cis-N-(4-Methoxycyclohexyl)aniline
Purified by preparative TLC (hexanes/EtOAc) to give a colorless oil;
yield: 19.9 mg (46%).
Purified by preparative TLC (hexanes/EtOAc) to give a yellow oil;
yield: 17.6 mg (43%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

G
K.-J. Liu et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.21–7.16 (m, 2 H), 6.72 (t, J = 7.4 Hz, 2
H), 6.64 (t, J = 7.5 Hz, 2 H), 3.41–3.40 (m, 2 H), 3.35 (s, 3 H), 1.90–1.81
(m, 4 H), 1.64–1.57 (m, 4 H).
13C NMR(100 MHz, CDCl3): δ = 146.3, 129.3, 117.8, 113.9, 75.1, 55.6,
50.9, 28.0, 27.4.
Lett. 2013, 15, 4900. (e) Wen, J.; Wei, W.; Xue, S.; Yang, D.; Lou,
Y.; Gao, C.; Wang, H. J. Org. Chem. 2015, 80, 4966. (f) Imrich, H.-
G.; Conrad, J.; Bubrin, D.; Beifuss, U. J. Org. Chem. 2015, 80, 2319.
(g) Cui, H.; Wei, W.; Yang, D.; Zhang, J.; Xu, Z.; Wen, J.; Wang, H.
RSC Adv. 2015, 5, 84657. (h) Zhao, F.; Li, B.; Huang, H.; Deng, G.-
J. RSC Adv. 2016, 6, 13010.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19NONa: 228.1364; found:
228.1365.
(4) (a) Magano, J.; Dunetz, J. R. Chem. Rev. 2011, 111, 2177. (b) Ricci,
A. Amino Group Chemistry: From Synthesis to the Life Sciences;
Wiley-VCH: Weinheim, 2008. (c) Wei, W.; Wen, J.; Yang, D.; Sun,
X.; You, J.; Suo, Y.; Wang, H. Tetrahedron 2013, 69, 10747.
(d) Wei, W.; Wen, J.; Yang, D.; Du, J.; You, J.; Wang, H. Green
Chem. 2014, 16, 2988. (e) Wei, W.; Wen, J.; Yang, D.; Liu, X.; Guo,
M.; Dong, R.; Wang, H. J. Org. Chem. 2014, 79, 422. (f) Wei, W.;
Cui, H.; Yang, D.; Yue, H.; He, C.; Zhang, Y.; Wang, H. Green
Chem. 2017, 19, 5608.
trans-N-(4-Methoxycyclohexyl)aniline
Purified by preparative TLC (hexanes/EtOAc) to give a pale yellow oil;
yield: 8.2 mg (19%).
1H NMR (400 MHz, CDCl3): δ = 7.19 (t, J = 7.5 Hz, 2 H), 6.72 (t, J = 7.3
Hz, 2 H), 6.64 (t, J = 7.7 Hz, 2 H), 3.39 (s, 3 H), 3.32–3.27 (m, 1 H),
3.24–3.17 (m, 1 H), 2.20–2.10 (m, 4 H), 1.39–1.20 (m, 4 H).
(5) Deng, G.; Chen, W.; Li, C.-J. Adv. Synth. Catal. 2009, 351, 353.
(6) (a) Yamane, Y.; Liu, X.; Hamasaki, A.; Ishida, T.; Haruta, M.;
Yokoyama, T.; Tokunaga, M. Org. Lett. 2009, 11, 5162.
(b) Sreedhar, B.; Reddy, P.; Devi, D. J. Org. Chem. 2009, 74, 8806.
(7) (a) Feng, C.; Liu, Y.; Peng, S.; Shuai, Q.; Deng, G.; Li, C.-J. Org. Lett.
2010, 12, 4888. (b) Liu, Y.; Chen, W.; Feng, C.; Deng, G. Chem.
Asian J. 2011, 6, 1142. (c) Gelman, F.; Blum, J.; Avnir, D. New J.
Chem. 2003, 27, 205. (d) Tang, C.-H.; He, L.; Liu, Y.-M.; Cao, Y.;
He, H.-Y.; Fan, K.-N. Chem. Eur. J. 2011, 17, 7172.
(8) (a) Xie, Y.; Liu, S.; Liu, Y.; Wen, Y.; Deng, G.-J. Org. Lett. 2012, 14,
1692. (b) Sutter, M.; Duclos, M.-C.; Guicheret, B.; Raoul, Y.;
Metay, E.; Lemaire, M. ACS Sustainable Chem. Eng. 2013, 1, 1463.
(c) Wei, W.; Wen, J.; Yang, D.; Guo, M.; Wang, Y.; You, J.; Wang,
H. Chem. Commun. 2015, 51, 768.
13C NMR (100 MHz, CDCl3): δ = 146.7, 129.3, 117.6, 113.6, 78.6, 55.9,
51.7, 30.9, 30.2.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19NONa: 228.1364; found:
228.1369.
N-(p-Tolyl)-1,2,3,4-tetrahydronaphthalen-2-amine (3ag)10g
Yellow solid; yield: 19.3 mg (42%).
1H NMR (400 MHz, CDCl3): δ = 7.19–7.15 (m, 3 H), 7.12–7.11 (m, 1 H),
7.04 (d, J = 8.0 Hz, 2 H), 6.63 (d, J = 8.0 Hz, 2 H), 3.86–3.79 (m, 1 H),
3.28–3.21 (m, 1 H), 2.96–2.93 (m, 2 H), 2.75–2.71 (m, 1 H), 2.29 (s, 3
H), 2.24–2.20 (m, 1 H), 1.85–1.74 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 144.6, 135.9, 134.8, 129.9, 129.5,
128.8, 126.9, 126.0, 125.9, 113.9, 49.0, 36.5, 28.8, 27.5, 20.4.
HRMS (ESI): m/z [M + Na]+ calcd for C17H19NNa: 260.1415; found:
260.1419.
(9) (a) Upton, B. M.; Kasko, A. M. Chem. Rev. 2016, 116, 2275. (b) Li,
C.; Zhao, X.; Wang, A.; Huber, G. W.; Zhang, T. Chem. Rev. 2015,
115, 11559. (c) Huber, G. W.; Corma, A. Angew. Chem. Int. Ed.
2007, 46, 7184.
(10) (a) Su, B.; Cao, Z.-C.; Shi, Z.-J. Acc. Chem. Res. 2015, 48, 886.
(b) Tobisu, M.; Chatani, N. Acc. Chem. Res. 2015, 48, 1717.
(c) Tobisu, M.; Morioka, T.; Ohtsuki, A.; Chatani, N. Chem. Sci.
2015, 6, 3410. (d) Zarate, C.; Manzano, R.; Martin, R. J. Am.
Chem. Soc. 2015, 137, 6754. (e) Cornella, J.; Zarate, C.; Martin, R.
Chem. Soc. Rev. 2014, 43, 8081. (f) Tasker, S. Z.; Standley, E. A.;
Jamison, T. F. Nature (London) 2014, 509, 299. (g) Chen, Z.; Zeng,
H.; Gong, H.; Wang, H.; Li, C.-J. Chem. Sci. 2015, 6, 4174.
(h) Chen, Z.; Zeng, H.; Girard, S. A.; Wang, F.; Chen, N.; Li, C.-J.
Angew. Chem. Int. Ed. 2015, 54, 14487. (i) Jumde, V. R.; Petricci,
E.; Petrucci, C.; Santillo, N.; Taddei, M.; Vaccaro, L. Org. Lett.
2015, 17, 3990. (j) Meng, Q.; Hou, M.; Liu, H.; Song, J.; Han, B.
Nat. Commun. 2017, 8, 14190. (k) Qiu, Z.; Li, J.-S.; Li, C.-J. Chem.
Sci. 2017, 8, 6954. (l) Bisz, E.; Szostak, M. ChemSusChem 2017,
10, 3964.
Funding Information
We are grateful for financial support from the post-funded projects of
Hunan University of Science and International Cooperation Project of
Qinghai Province (2018-HZ-806, 2018-HZ-706).
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Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610231.
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References and Notes
(11) Entwistle, I. D.; Jackson, A. E.; Johnstone, R. A. W.; Telford, R. P.
J. Chem. Soc., Perkin Trans. 1 1977, 443.
(1) (a) Rylander, P. N. Hydrogenation Methods; Academic: London,
1985, 104–117. (b) Nishimura, S. Handbook of Heterogeneous
Catalytic Hydrogenation for Organic Synthesis; Wiley: New York,
2001, 315–387.
(2) (a) Adams, J. P.; Paterson, J. R. J. Chem. Soc., Perkin Trans. 1 2000,
3695. (b) Lawrence, S. A. Amines: Synthesis Properties and Appli-
cations; Cambridge University Press: Cambridge, 2004.
(c) Corma, A.; Serna, P. Science (Washington, D. C.) 2006, 313,
332. (d) Ono, N. The Nitro Group in Organic Synthesis; Wiley-
VCH: New York, 2011.
(12) (a) Li, W.; Yin, G.; Huang, L.; Xiao, Y.; Fu, Z.; Xin, X.; Liu, F.; Li, Z.;
He, W. Green Chem. 2016, 18, 4879. (b) Wu, C.; Xin, X.; Fu, Z.-M.;
Xie, L.-Y.; Liu, K.-J.; Wang, Z.; Li, W.; Yuan, Z.-H.; He, W.-M.
Green Chem. 2017, 19, 1983. (c) Xie, L.-Y.; Duan, Y.; Lu, L.-H.; Li,
Y.-J.; Peng, S.; Wu, C.; Liu, K.-J.; Wang, Z.; He, W.-M. ACS Sustain-
able Chem. Eng. 2017, 5, 10407. (d) Xie, L.-Y.; Li, Y.-J.; Qu, J.;
Duan, Y.; Hu, J.; Liu, K.-J.; Cao, Z.; He, W.-M. Green Chem. 2017,
19, 5642. (e) Liu, K.-J.; Fu, Y.-L.; Xie, L.-Y.; Wu, C.; He, W.-B.;
Peng, S.; Wang, Z.; Bao, W.-H.; Cao, Z.; Xu, X.; He, W.-M. ACS Sus-
tainable Chem. Eng. 2018, 6, 4916. (f) Liu, K.-J.; Jiang, S.; Lu, L.-
H.; Tang, L.-L.; Tang, S.-S.; Tang, H.-S.; Tang, Z.; He, W.-M.; Xu, X.
Green Chem. 2018, 20, 3038. (g) Wu, C.; Wang, Z.; Hu, Z.; Zeng,
F.; Zhang, X.-Y.; Cao, Z.; Tang, Z.; He, W.-M.; Xu, X.-H. Org.
(3) (a) Xiao, F.; Liu, Y.; Tang, C.; Deng, G.-J. Org. Lett. 2012, 14, 984.
(b) Pereira, M. F.; Thiéry, V. Org. Lett. 2012, 14, 4754.
(c) Nguyen, T. B.; Ermolenko, L.; Al-Mourabit, A. Org. Lett. 2013,
15, 4218. (d) Wang, H.; Cao, X.; Xiao, F.; Liu, S.; Deng, G.-J. Org.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

H
K.-J. Liu et al.
Paper
Synthesis
Biomol. Chem. 2018, 16, 3177. (h) Wu, C.; Wang, J.; Zhang, X.-Y.;
Jia, G.-K.; Cao, Z.; Tang, Z.; Yu, X.; Xu, X.; He, W.-M. Org. Biomol.
Chem. 2018, 16, 5050. (i) Xie, L.-Y.; Qu, J.; Peng, S.; Liu, K.-J.;
Wang, Z.; Ding, M.-H.; Wang, Y.; Cao, Z.; He, W.-M. Green Chem.
2018, 20, 760. (j) Wu, C.; Lu, L.-H.; Peng, A.-Z.; Jia, G.-K.; Peng,
C.; Cao, Z.; Tang, Z.; He, W.-M.; Xu, X. Green Chem. 2018, 20,
3686. (k) Xie, L.-Y.; Peng, S.; Lu, L.-H.; Hu, J.; Bao, W.-H.; Zeng,
F.; Tang, Z.; Xu, X.; He, W.-M. ACS Sustainable Chem. Eng. 2018, 6,
7989.
Q.-H.; Liu, H.-C. Green Chem. 2014, 16, 2664. (c) Wang, Y.; Yao,
J.; Li, H.; Su, D.; Antonietti, M. J. Am. Chem. Soc. 2011, 133, 2362.
(d) Makowski, P.; Cakan, R. D.; Antonietti, M.; Goettmann, F.;
Titirici, M. M. Chem. Commun. 2008, 999. (e) Li, Y.; Xu, X.;
Zhang, P.; Gong, Y.; Li, H.; Wang, Y. RSC Adv. 2013, 3, 10973.
(f) Chen, A.; Li, Y.; Chen, J.; Zhao, G.; Ma, L.; Yu, Y. ChemPlus-
Chem 2013, 78, 1370.
(15) For reviews on the catalytic reduction of imines, see: (a) Xie, J.-
H.; Zhu, S.-F.; Zhou, Q.-L. Chem. Rev. 2011, 111, 1713.
(b) Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069.
(13) Rajagopal, S.; Spatola, A. F. J. Org. Chem. 1995, 60, 1347.
(14) For selected examples of reduction of phenols, see: (a) Liu, H.;
Jiang, T.; Han, B.; Liang, S.; Zhou, Y. Science (Washington, D. C.)
2009, 326, 1250. (b) Zhu, J.-F.; Tao, G.-H.; Liu, H.-Y.; He, L.; Sun,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H