Efficient Ruthenium(II)-Catalyzed Direct Reductive Amination of Aldehydes under Mild Conditions Using Hydrosilane as the Reductant

Article abstract of DOI:10.1055/s-0036-1588092

A direct reductive amination of aldehydes with anilines is performed with a ruthenium(II)-(arene) catalyst. The [RuCl₂(p-cymene)]₂/Ph₂SiH₂ catalytic system is very efficient for the synthesis of secondary amines and tertiary amines in good yields, and is highly chemoselective, tolerating a wide range of functional groups, such as NO₂, CN, CO₂Me, F, Cl, Br, OMe, Me, furyl and alkyl. We also report an interesting direductive amination of 2-ethylbutanal.

Full text of DOI:10.1055/s-0036-1588092

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–G
paper
A
B. Li et al.
Paper
Synthesis
Efficient Ruthenium(II)-Catalyzed Direct Reductive Amination of
Aldehydes under Mild Conditions Using Hydrosilane as the
Reductant
Bin Li*
R3
R2 = H
R1
N
Jianxiong Zheng
Weifeng Zeng
Yibiao Li*
H
17 examples, 40–90% yields
Ru(II)
H
R1 CHO
+
N
Lu Chen
R2
R3
silane
R3
School of Chemical & Environmental Engineering, Wuyi University,
Jiangmen 529020, Guangdong Province, P. R. of China
binli@wyu.edu.cn
R2 = Me
R1
N
leeyib268@126.com
8 examples, 68–84% yields
Received: 12.10.2016
Accepted after revision: 14.10.2016
Published online: 13.12.2016
secondary amines, the more challenging synthesis of tertia-
ry amines through reductive amination of aldehydes with
secondary amines is less developed. Herein, we have devel-
oped the first ruthenium(II)-catalyzed reductive amination
of aldehydes for the synthesis of secondary amines, and im-
portantly, tertiary amines, by employing hydrosilanes and
an easily available [RuCl2(p-cymene)]2 complex under mild
conditions (Scheme 1).
DOI: 10.1055/s-0036-1588092; Art ID: ss-2016-h0571-op
Abstract A direct reductive amination of aldehydes with anilines is
performed with
a ruthenium(II)-(arene) catalyst. The [RuCl2(p-cy-
mene)]2/Ph2SiH2 catalytic system is very efficient for the synthesis of
secondary amines and tertiary amines in good yields, and is highly che-
moselective, tolerating a wide range of functional groups, such as NO2,
CN, CO2Me, F, Cl, Br, OMe, Me, furyl and alkyl. We also report an inter-
esting direductive amination of 2-ethylbutanal.
R3
R2 = H
N
H
R1
Key words ruthenium catalysis, hydrosilane, reductive amination,
amines, aldehydes
CHO
Ru(II)
H
N
+
R2
R3
silane
R1
R3
Amines are very important compounds because they
constitute a central class of compounds in natural products,
agrochemicals, pharmaceuticals, and valuable fine chemi-
cals.1 Among the numerous synthetic methodologies to
produce amine derivatives, the reduction of imines is one of
the most efficient methods, through hydrogenation,2,3 hy-
drogen transfer reactions,4,5 or stoichiometric reactions us-
ing reactive alkali hydrides.6 Hydrosilylation reactions have
attracted interest from chemists due to their mild condi-
tions and good chemoselectivities.7,8 In addition, compared
to the reduction of imines, direct reductive amination from
carbonyl derivatives in the presence of primary amines via
sequential condensation/catalytic reduction is a ‘greener’
process in the area of amine synthesis.
In the field of transition-metal-catalyzed hydrosilyla-
tion reductions, there are several catalysts9–13 that have
been utilized for the synthesis of secondary amines via re-
ductive amination of aldehydes with primary amines, how-
ever, only a few reports14–16 describe the hydrosilylation of
imines using ruthenium complexes, whilst the rutheni-
um(II)-catalyzed direct reductive amination had not been
developed. Furthermore, compared with the synthesis of
R2 = Me
N
R1
Scheme 1 Ru(II)-catalyzed direct reductive amination of aldehydes us-
ing silane as the reductant
To start our investigation, we selected benzaldehyde
(1a) and aniline (2a) as the model substrates in the pres-
ence of [RuCl2(p-cymene)]2 as the catalytic system with si-
lane at room temperature under air conditions (Table 1).
Firstly, full conversion was detected, but with an imine 3a
to amine 4a ratio of 53:46, by using 5 mol% of [RuCl2(p-cy-
mene)]2 and Ph2SiH2 as the hydrogen source in ethanol at
room temperature in four hours (Table 1, entry 1). However,
the reactions performed in Et2O or toluene gave better con-
versions and were selective for benzylamine product 4a
(Table 1, entries 2 and 3). When the reaction was per-
formed in dichloromethane, complete conversion was
reached yielding benzylamine 4a in 97% yield (Table 1, en-
try 4). Among the variety of silanes tested in dichlorometh-
ane at room temperature in the presence of 5 mol% of
[RuCl2(p-cymene)]2, Ph2SiH2 and PhSiH3 were optimum hy-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–G

B
B. Li et al.
Paper
Synthesis
drogen sources toward the formation of benzylamine 4a
(Table 1, entries 4 and 7). It was shown that 1,1,3,3-te-
tramethyldisiloxane (TMDS) and polymethylhydroxysilox-
ane (PMHS) did not give better results under similar condi-
tions (Table 1, entries 5 and 6). The amount of catalyst could
be decreased to 2 mol% in dichloromethane in the presence
of 4 Å molecular sieves under air, reaching complete con-
version and affording amine 4a in 82% isolated yield (Table
1, entry 10). However, decreasing the amount of catalyst to
1 mol% led to lower selectivity (Table 1, entry 11). By con-
trast, other catalysts such as [RuCl2(PPh3)3] and RuCl3·xH2O
were unsatisfactory for this reaction under hydrosilylation
conditions (Table 1, entries 12 and 13).
[RuCl2(p-cymene)]2 (2 mol%)
R2
R1 CHO
R1
N
H
H2N R2
+
Ph2SiH2 (1.5 equiv)
CH2Cl2 (2 mL), r.t., 4 h
4 Å M.S., air
1
2
4
4b: R1 = H 85%
4c: R1 = m-Me 86%
4d: R1 = p-Me 90%
4e: R1 = p-MeO 85%
4f: R1 = p-Br 82%
N
N
H
H
R1
4a: 82%
N
N
N
H
H
H
O
O2N
NC
O
4i: 86%
4g: 46%
(4 mol%, 50 °C, 24 h)
4h: 40%
(4 mol%, 50 °C, 24 h)
Table 1 Optimization of the Ruthenium-Catalyzed Direct Reductive
Amination of Benzaldehyde and Anilinea
N
H
O
CHO
NH2
N
H
N
H
NH
N
[RuCl2(p-cymene)]2
+
+
4j: 80%
4k: 85%
4p: 65%
silane (1.5 equiv)
solvent, r.t., 4 h
under air
R2
4l: R1 = H, R2 = o-F 70%
1a
2a
3a
4a
N
H
4m: R1 = H, R2 = p-MeO 83%
4n: R1 = H, R2 = p-Cl 75%
4o: R1 = p-Me, R2 = p-Br 72%
N
H
Entry Catalyst (mol%)
Silane
Solvent
Conv. Ratio
4q: 84%
R1
(%)b (3a/4a)
Scheme 2 [RuCl2(p-cymene)]2-catalyzed direct reductive amination of
aldehydes with anilines. Reagents and conditions: aldehyde (1.1 mmol),
aniline (1.0 mmol), [RuCl2(p-cymene)]2 (2 mol%), PH2SiH2 (1.5 equiv),
4 Å MS (200 mg), CH2Cl2 (2 mL), r.t., air, 4 h.
1
[RuCl2(p-cymene)]2 (5)
PhSiH3
PhSiH3
PhSiH3
PhSiH3
TMDS
EtOH
99
89
89
98
83
87
99
99
99
99
97
98
83
53:46
9:80
2
3
[RuCl2(p-cymene)]2 (5)
Et2O
[RuCl2(p-cymene)]2 (5)
[RuCl2(p-cymene)]2 (5)
[RuCl2(p-cymene)]2 (5)
[RuCl2(p-cymene)]2 (5)
[RuCl2(p-cymene)]2 (5)
[RuCl2(p-cymene)]2 (5)
[RuCl2(p-cymene)]2 (3)
[RuCl2(p-cymene)]2 (2)
[RuCl2(p-cymene)]2 (1)
[RuCl2(PPh3)3] (2)
PhMe
1:90
4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
1:97
At first, different aromatic aldehydes 1 were reacted
with aniline (2a) to successfully produce secondary amines
4 by employing the optimized conditions (see Table 1, entry
10). Secondary amine 4b, which was produced from benz-
aldehyde and p-methylaniline, was isolated in 85% yield.
The reaction could be carried out with aromatic aldehydes
bearing a methyl group at the para- or meta-positions to
give the corresponding amines 4c and 4d in 86% and 90%
isolated yields, respectively. The reductive amination of 4-
bromobenzaldehyde (1f) and aniline (2a) under hydrosi-
lylation conditions exhibited no dehalogenation, and no re-
ductive amination occurred at the C–Br bond with -NH2;
only the corresponding amine 4f was generated in an isolat-
ed yield of 82%. The reductive amination was more difficult
to perform in the presence of a nitro group or a cyano
group, and it was necessary to use 4 mol% of the [RuCl2(p-
cymene)]2 catalyst with a longer time at 50 °C to reach 46%
and 40% yields of 4g and 4h. Moreover, the reductive ami-
nation of aliphatic aldehydes, such as cyclohexane carboxal-
dehyde (1j) and pivalaldehyde (1q) successfully led to the
corresponding amines 4j and 4q in 80% and 84% yields. The
reaction also proceeded well with the heteroaromatic alde-
hyde 2-furaldehyde (1k) leading to 2-furylamine 4k in 85%
isolated yield.
5
5:78
6
PMHS
65:22
1:98
7
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
c
c
c
c
c
c
8
0:99
9
0:99
10
11
12
13
0:99 (82)d
8:89
65:33
82:1
RuCl3·xH2O (2)
a Reaction conditions: benzaldehyde (1a) (0.55 mmol), aniline (2a) (0.5
mmol), catalyst, silane (0.75 mmol), solvent (2 mL), r.t., air, 4 h.
b Determined by GC.
c Reactions performed in the presence of 4 Å MS.
d Yield of isolated product 4a.
The scope and limitations of the ruthenium-catalyzed
reductive amination of aldehydes 1 and anilines 2 with
Ph2SiH2 were then explored by using 2 mol% of [RuCl2(p-cy-
mene)]2 to directly produce secondary amines 4 at room
temperature under air conditions. As shown in Scheme 2,
various aldehydes 1 and anilines 2 were applied to synthe-
size secondary amines 4.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–G

C
B. Li et al.
Paper
Synthesis
CHO
H
[RuCl2(p-cymene)]2 (4 mol%)
N
+
N
R1
Ph2SiH2 (1.5 equiv)
CH2Cl2 (2 mL), r.t., 24 h
4 Å M.S., air
R1
5
6
1
N
N
N
N
MeO
6a: 80%
6d: 80%
6c: 75%
6b: 68%
N
O
N
N
N
O
Br
O
6h: 82%
6g: 84%
6f: 78%
6e: 82%
Scheme 3 [RuCl2(p-cymene)]2-catalyzed direct reductive amination of aldehydes with N-methylaniline. Reagents and conditions: aldehyde (1.1 mmol),
N-methylaniline (5) (1.0 mmol), [RuCl2(p-cymene)]2 (4 mol%), PH2SiH2 (1.5 equiv.), 4 Å MS (200 mg), CH2Cl2 (2 mL), r.t., air, 24 h.
More importantly, the reductive amination tolerates the
ester functional group of aldehyde 1i, and the correspond-
ing amine 4i (86%) was directly obtained. On the other
hand, several anilines bearing functional groups, such as p-
Br, p-Cl, o-F and p-MeO were tested with benzaldehyde or
p-methyl benzaldehyde under similar conditions, leading to
the corresponding amines 4l–o in 72–83% isolated yields.
The reductive product from the reaction of benzylamine
with benzaldehyde, dibenzylamine (4p), could also be syn-
thesized and isolated in 65% yield.
Additionally, we investigated the reactions of secondary
amines with various aldehydes in order to test the efficien-
cy of the [RuCl2(p-cymene)]2/Ph2SiH2 catalytic system in
the synthesis of tertiary amines by direct reductive amina-
tion (Scheme 3), but which were more difficult than the re-
actions with primary amines. A simple increase of the
amount of the catalyst to 4 mol% at room temperature for
24 hours in dichloromethane under air, to perform the re-
action of p-methoxybenzaldehyde with N-methylaniline
(5), led to the corresponding tertiary amine 6a in 80% iso-
lated yield.
ic aldehyde, and generated the corresponding tertiary
amines 6b–e in 68%, 75%, 80%, and 82% yields, respectively.
The tertiary amine 6f containing an ester group, and origi-
nating from the aldehyde 1i, was obtained in 86% yield
without reduction of the ester carbonyl moiety. The ali-
phatic tertiary amine 6g containing a cyclohexane group
and the heterocyclic tertiary amine 6h containing a 2-furyl
group were also successfully obtained in good yields (84%
and 82%, respectively) (Scheme 3).
Moreover, an intermolecular competition experiment
between aniline and N-methylaniline in the reaction with
aldehyde 1i in the presence of 2 mol% of [RuCl2(p-cy-
mene)]2 and 1.5 equivalents of Ph2SiH2 in CH2Cl2 at room
temperature for four hours resulted in a 93% yield (by GC) of
a mixture of the aniline derivatives N-[4-(methyloxycar-
bonyl)benzyl]aniline (4i) and N-[4-(methyloxycarbon-
yl)benzyl]-N-methylaniline (6f) in a ratio of 85:8 (Scheme
4). This result showed that a primary amine is more reac-
tive than a secondary amine in this reaction.
Interestingly, when the reaction of 2-ethylbutanal (1r)
(1.1 equiv) with p-toluidine (2b) (1.0 equiv) was performed
in the presence of 2 mol% of [RuCl2(p-cymene)]2 and
Ph2SiH2 (1.5 equiv) at room temperature, a 40% isolated
Using the optimized conditions, this reductive amina-
tion reaction also tolerated several functional groups (o-
Me, m-Me, p-Me, and p-Br) on the arene ring of the aromat-
CHO
NH2
MeO2C
+
N
N
[RuCl2(p-cymene)]2 (2 mol%)
H
+
MeO2C
MeO2C
Ph2SiH2 (1.5 equiv)
CH2Cl2 (2 mL), r.t.
4 Å MS (200 mg), 4 h
H
N
4i
GC yield = 93%, 4i/6f = 85:8
6f
Scheme 4 An intermolecular competition reaction between aniline and N-methylaniline
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–G

D
B. Li et al.
Paper
Synthesis
yield of the direductive amination product, N,N-bis(2-ethyl-
butyl)-4-methylaniline (7), was obtained after four hours
(Scheme 5).
All reagents were obtained from commercial sources and were used
as received. CH2Cl2 (anhydrous) was used as received. Technical grade
petroleum ether (bp 40–60 °C) and EtOAc were used for column chro-
matography. Silica Gel 200–300F (Qingdao Haiyang Chemical Co. Ltd)
was employed. Melting points were obtained using an RY-1G melting
point apparatus system. IR spectra were recorded on a Nicolet 6700
NH2
O
[RuCl2(p-cymene)]2 (2 mol%)
1
N
spectrometer as KBr pellets. H NMR spectra were recorded in CDCl3
+
Ph2SiH2 (1.5 equiv)
CH2Cl2 (2 mL)
r.t., air, 4 h
at ambient temperature on a Bruker AVANCE I 300 spectrometer at
300 MHz using the solvent as the internal standard (7.26 ppm). 13C
NMR spectra were obtained at 75 MHz and referenced to the internal
solvent signals (central peak at 77.2 ppm). The chemical shifts (δ) and
coupling constants (J) are given in ppm and Hz, respectively. The peak
patterns are indicated as follows: s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet; br, broad. Elemental analyses were carried out
on a PE EA2400 CHN analyzer. GC analyses were performed with a
Shimadzu GC-2010 instrument equipped with a 30 m capillary col-
umn (Supelco, SPBTM-20, fused silica capillary column, 30 m × 0.25
mm × 0.25 mm film thickness), with N2/air as the vector gas. The fol-
lowing GC conditions were used: initial temperature = 80 °C for 2
min, then increasing at a rate of 10 °C/min until 260 °C, and then
260 °C for 10 min.
1r
2b
7 40%
Scheme 5 [RuCl2(p-cymene)]2/Ph2SiH2-catalyzed direductive amina-
tion of 2-ethylbutanal
Based on the previous work of Darcel and Tuttle, we
have proposed a mechanism (Scheme 6) for the direct re-
ductive amination of aldehydes with the [RuCl2(p-cy-
mene)]2/Ph2SiH2 catalytic system. The process is expected
to be initiated by the oxidative addition of the hydrosilane
to the ruthenium center.17,18 Next, the imine generated in
situ from the aldehyde and the aniline would coordinate
and undergo insertion with the ruthenium species A, af-
fording the ‘N–Ru–Si’ complex B. After reductive elimina-
tion, the N-silylamine is obtained and the resulting product
would be produced by the hydrolysis with H2O.
Anilines 4; General Procedure
[RuCl2(p-cymene)]2 (0.02 mmol, 12.2 mg), aldehyde 1 (1.1 mmol), an-
iline 2 (1.0 mmol), Ph2SiH2 (1.5 mmol, 277 μL), 4 Å molecular sieves
(200 mg) and CH2Cl2 (2 mL) were added to a Schlenk tube (equipped
with a magnetic stir bar) under air, and the mixture was stirred at r.t.
After 4 h, the extent of the conversion of the reaction was analyzed by
GC. The solvent was then evaporated under vacuum and the residue
was purified by silica gel column chromatography (PE–EtOAc) to af-
ford the desired product 4.
R2
[Si]
H
H
Ru
H
N
Cl
Cl
R1
[Si]
N-Benzylaniline (4a)11
Light yellow oil; yield: 150 mg (82%).
1H NMR (300 MHz, CDCl3): δ = 7.29–7.44 (m, 5 H), 7.19–7.25 (m, 2 H),
6.74–6.79 (m, 1 H), 6.67–6.70 (m, 2 H), 4.38 (s, 2 H), 4.08 (br s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 148.29, 139.58, 129.44, 128.81, 127.69,
127.41, 117.77, 113.05, 48.52.
[Si]
Ru
H
Cl
Cl
Ru
Cl
Cl
H
[Si]
N
R2
H
R1
B
A
N-Benzyl-4-methylaniline (4b)14
R2 NH2
+
R1 CH=O
Light yellow oil; yield: 167 mg (85%).
1H NMR (300 MHz, CDCl3): δ = 7.31–7.46 (m, 5 H), 7.03–7.07 (m, 2 H),
6.61–6.65 (m, 2 H), 4.37 (s, 2 H), 3.95 (br s, 1 H), 2.31 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 146.1, 139.8, 129.9, 128.8, 127.7, 127.3,
R2
H
C
N
R1
H2O
Scheme 6 Proposed catalytic cycle for the Ru(II)-catalyzed direct re-
126.9, 113.1, 48.8, 20.6.
ductive amination of aldehydes and anilines
4-Methyl-N-(3-methylbenzyl)aniline (4c)19
In summary, we have developed a procedure that utiliz-
es a readily available [RuCl2(p-cymene)]2 complex as an ef-
ficient catalyst for the reductive amination of aldehydes
with diphenylsilane to access secondary amines and tertia-
ry amines. These reactions were performed under air at
room temperature via a compatible convenient process.
Furthermore, many functional groups, such as nitro, cyano,
halide, heterocyclic, and ester were tolerated under this re-
ductive amination process. An interesting direductive ami-
nation product was obtained from 2-ethylbutanal under
similar conditions.
Light yellow oil; yield: 181 mg (86%).
1H NMR (300 MHz, CDCl3): δ = 7.25–7.35 (m, 4 H), 7.09 (d, J = 7.8 Hz, 2
H), 6.67 (d, J = 7.8 Hz, 2 H), 4.35 (s, 2 H), 3.97 (br s, 1 H), 2.45 (s, 3 H),
2.34 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 148.1, 139.7, 138.5, 129.9, 128.7, 128.5,
128.1, 127.0, 124.8, 113.3, 49.0, 21.6, 20.6.
4-Methyl-N-(4-methylbenzyl)aniline (4d)14
White solid; yield: 190 mg (90%); mp 54–56 °C.
1H NMR (300 MHz, CDCl3): δ = 7.31 (d, J = 8.1 Hz, 2 H), 7.20 (d, J = 7.8
Hz, 2 H), 7.04 (d, J = 8.4 Hz, 2 H), 6.60–6.63 (m, 2 H), 4.31 (s, 2 H), 3.90
(br s, 1 H), 2.40 (s, 3 H), 2.30 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–G

E
B. Li et al.
Paper
Synthesis
13C NMR (75 MHz, CDCl3): δ = 146.2, 136.9, 136.8, 129.9, 129.4, 127.7,
13C NMR (75 MHz, CDCl3): δ = 153.1, 145.5, 142.0, 129.9, 127.4, 113.6,
126.8, 113.1, 48.6, 21.3, 20.6.
110.5, 107.1, 42.0, 20.6.
N-(4-Methoxybenzyl)-4-methylaniline (4e)14
N-Benzyl-2-fluoroaniline (4l)21
Light yellow solid; yield: 193 mg (85%); mp 79–81 °C.
Colorless oil; yield: 141 mg (70%).
1H NMR (300 MHz, CDCl3): δ = 7.35 (d, J = 8.4 Hz, 2 H), 7.05 (d, J = 8.1
Hz, 2 H), 6.94 (d, J = 8.1 Hz, 2 H), 6.62 (d, J = 8.1 Hz, 2 H), 4.29 (s, 2 H),
3.86 (br s, 1 H), 3.86 (s, 3 H), 2.31 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 158.9, 146.1, 131.8, 129.9, 128.9, 126.8,
114.1, 113.1, 55.4, 48.2, 20.5.
1H NMR (300 MHz, CDCl3): δ = 7.29–7.41 (m, 5 H), 6.97–7.06 (m, 2 H),
6.64–6.74 (m, 2 H), 4.41 (s + br s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 153.1 (d, JC–F = 238.5 Hz), 139.0, 134.4,
128.7, 127.4, 127.3, 124.6 (d, JC–F = 3.8 Hz), 118.9 (d, JC–F = 6.8 Hz),
114.5 (d, JC–F = 18.8 Hz), 112.4 (d, JC–F = 3.0 Hz), 47.9.
N-(4-Bromobenzyl)-4-methylaniline (4f)14
N-Benzyl-4-methoxyaniline (4m)14
Light yellow solid; yield: 226 mg (82%); mp 89.5–91 °C.
Light yellow solid; yield: 177 mg (83%); mp 47–49 °C.
1H NMR (300 MHz, CDCl3): δ = 7.48 (d, J = 8.4 Hz, 2 H), 7.27 (d, J = 8.4
Hz, 2 H), 7.01 (d, J = 8.1 Hz, 2 H), 6.56 (d, J = 8.4 Hz, 2 H), 4.30 (s, 2 H),
3.96 (br s, 1 H), 2.27 (s, 3 H).
1H NMR (300 MHz, CDCl3): δ = 7.28–7.42 (m, 5 H), 6.79–6.82 (m, 2 H),
6.62–6.65 (m, 2 H), 4.32 (s, 3 H), 3.81 (br s, 1 H), 3.77 (s, 2 H).
13C NMR (75 MHz, CDCl3): δ = 152.3, 142.6, 139.8, 128.7, 127.7, 127.3,
115.1, 114.2, 55.9, 49.4.
13C NMR (75 MHz, CDCl3): δ = 145.7, 139.0, 131.8, 130.0, 129.2, 127.2,
121.0, 113.2, 48.1, 20.6.
N-Benzyl-4-chloroaniline (4n)22
4-Methyl-N-(4-nitrobenzyl)aniline (4g)14
Light yellow oil; yield: 163 mg (75%).
Red oil; yield: 111 mg (46%).
1H NMR (300 MHz, CDCl3): δ = 7.36–7.43 (m, 5 H), 7.17–7.20 (m, 2 H),
6.59–6.62 (m, 2 H), 4.35 (s, 2 H), 4.01 (br s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 146.7, 139.0, 129.2, 128.8, 127.5, 127.4,
122.2, 114.1, 48.4.
1H NMR (300 MHz, CDCl3): δ = 8.20 (d, J = 9.0 Hz, 2 H), 7.55 (d, J = 9.0
Hz, 2 H), 7.02 (d, J = 7.8 Hz, 2 H), 6.54 (d, J = 8.4 Hz, 2 H), 4.48 (s, 2 H),
4.18 (br s, 1 H), 2.27 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 148.0, 147.2, 145.2, 130.0, 127.8, 127.5,
4-Bromo-N-(4-methylbenzyl)aniline (4o)23
123.9, 113.2, 48.0, 20.5.
Light yellow oil; yield: 198 mg (72%).
1H NMR (300 MHz, CDCl3): δ = 7.23–7.33 (m, 6 H), 6.54–6.57 (m, 2 H),
4.31 (s, 2 H), 3.98 (br s, 1 H), 2.44 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 147.2, 137.1, 135.9, 132.0, 129.5, 127.5,
N-(4-Cyanobenzyl)-4-methylaniline (4h)14
Orange solid; yield: 44 mg (40%); mp 88–90 °C.
1H NMR (300 MHz, CDCl3): δ = 7.61–7.65 (m, 2 H), 7.50 (d, J = 8.1 Hz, 2
H), 7.00–7.03 (m, 2 H), 6.51–6.55 (m, 2 H), 4.43 (s, 2 H), 4.13 (br s, 1
H), 2.27 (s, 3 H).
114.5, 109.1, 48.1, 21.2.
13C NMR (75 MHz, CDCl3): δ = 145.8, 145.3, 132.5, 130.0, 127.8, 127.4,
119.1, 113.1, 110.9, 48.2, 20.5.
Dibenzylamine (4p)11
Colorless oil; yield: 128 mg (65%).
1H NMR (300 MHz, CDCl3): δ = 7.29–7.38 (m, 10 H), 3.85 (s, 4 H), 1.87
(br s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 140.5, 128.6, 128.3, 127.1, 53.3.
N-[4-(Methyloxycarbonyl)benzyl]aniline (4i)19
White solid; yield: 207 mg (86%); mp 46–48 °C.
1H NMR (300 MHz, CDCl3): δ = 8.04 (d, J = 7.8 Hz, 2 H), 7.47 (d, J = 7.8
Hz, 2 H), 7.20 (t, J = 7.5 Hz, 2 H), 6.77 (t, J = 7.2 Hz, 1 H), 6.65 (d, J = 7.8
Hz, 2 H), 4.29 (s, 2 H), 4.32 (br s, 1 H), 3.94 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 166.8, 147.8, 145.1, 129.8, 129.2, 128.9,
127.0, 117.6, 112.8, 51.9, 47.7.
N-Neopentylaniline (4q)24
Light yellow oil; yield: 137 mg (84%).
1H NMR (300 MHz, CDCl3): δ = 7.21–7.25 (m, 2 H), 6.67–6.75 (m, 3 H),
4.81 (br s, 1 H), 2.96 (s, 2 H), 1.06 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 149.2, 129.4, 117.1, 112.8, 56.0, 32.0,
27.8.
N-(Cyclohexylmethyl)-4-methylaniline (4j)20
Light yellow oil; yield: 162 mg (80%).
1H NMR (300 MHz, CDCl3): δ = 7.07 (d, J = 7.8 Hz, 2 H), 6.62 (d, J = 7.8
Hz, 2 H), 3.63 (br s, 1 H), 3.02 (d, J = 6.6 Hz, 2 H), 2.34 (s, 3 H), 1.63–
1.93 (m, 5 H), 1.13–1.46 (m, 4 H), 1.01–1.09 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 146.5, 129.9, 126.3, 113.0, 51.2, 37.7,
31.5, 26.8, 26.2, 20.5.
N-Methylanilines 6; General Procedure
[RuCl2(p-cymene)]2 (0.04 mmol, 24.4 mg), aldehyde 1 (1.1 mmol), N-
methylaniline (5) (1.0 mmol), Ph2SiH2 (1.5 mmol, 277 μL), 4 Å molec-
ular sieves (200 mg) and CH2Cl2 (2 mL) were added to a Schlenk tube
(equipped with a magnetic stir bar) under air, and the mixture was
stirred at r.t. After 24 h, the extent of the conversion of the reaction
was analyzed by GC. The solvent was then evaporated under vacuum
and the residue was purified by silica gel column chromatography
(PE–EtOAc) to afford the desired product 6.
N-(Furan-2-ylmethyl)-4-methylaniline (4k)20
Light yellow oil; yield: 159 mg (85%).
1H NMR (300 MHz, CDCl3): δ = 7.42 (d, J = 1.5 Hz, 1 H), 7.06 (d, J = 8.4
Hz, 2 H), 6.65–6.68 (m, 2 H), 6.37–6.38 (m, 1 H), 6.28 (d, J = 3.3 Hz, 1
H), 4.35 (s, 2 H), 3.83 (br s, 1 H), 2.31 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–G

F
B. Li et al.
Paper
Synthesis
N-(4-Methoxybenzyl)-N-methylaniline (6a)10a
N-(Furan-2-ylmethyl)-N-methylaniline (6h)29
Colorless oil; yield: 182 mg (80%).
Light yellow oil; yield: 153 mg (82%).
1H NMR (300 MHz, CDCl3): δ = 7.40 (t, J = 7.5 Hz, 2 H), 7.32 (d, J = 8.1
Hz, 2 H), 7.02 (d, J = 8.1 Hz, 2 H), 6.88–6.96 (d, J = 8.4 Hz, 3 H), 4.62 (s,
2 H), 3.92 (s, 3 H), 3.14 (s, 3 H).
1H NMR (300 MHz, CDCl3): δ = 7.32–7.44 (m, 3 H), 6.83–6.95 (m, 3 H),
6.38–6.40 (m, 1 H), 6.23–6.24 (m, 1 H), 4.56 (s, 2 H), 3.08 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 152.5, 142.0, 134.5, 129.2, 117.3, 113.2,
110.3, 107.4, 50.0, 38.4.
13C NMR (75 MHz, CDCl3): δ = 158.7, 149.9, 130.9, 129.2, 128.1, 116.6,
114.0, 112.6, 56.1, 55.3, 38.3.
N,N-Bis(2-ethylbutyl)-4-methylaniline (7)
N-Methyl-N-(2-methylbenzyl)aniline (6b)25
Light yellow oil; yield: 104 mg (40%).
Yellow oil; yield: 143 mg (68%).
1H NMR (300 MHz, CDCl3): δ = 7.24–7.35 (m, 6 H), 6.81 (d, J = 7.8 Hz, 3
H), 4.56 (s, 2 H), 3.13 (s, 3 H), 2.42 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 149.9, 136.5, 135.7, 130.4, 129.3, 126.9,
IR (KBr): 2961, 2927, 1618, 1518, 1459, 1369, 803 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.05 (d, J = 8.4 Hz, 2 H), 6.65 (d, J = 8.4
Hz, 2 H), 3.21 (d, J = 8.4 Hz, 4 H), 2.29 (s, 3 H), 1.72–1.80 (m, 2 H),
1.28–1.45 (m, 8 H), 0.92 (t, J = 7.5 Hz, 12 H).
126.5, 126.2, 116.5, 112.3, 54.9, 38.5, 19.1.
13C NMR (75 MHz, CDCl3): δ = 146.6, 129.7, 124.4, 113.3, 56.4, 38.3,
24.6, 20.4, 10.9.
N-Methyl-N-(3-methylbenzyl)aniline (6c)
Anal. Calcd for C19H33N: C, 82.84; H, 12.07; N, 5.08. Found: C, 82.63; H,
12.11; N, 5.25.
Light yellow oil; yield: 158 mg (75%).
IR (KBr): 3028, 2951, 1601, 1506, 1372, 1251, 748, 693 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.22–7.29 (m, 3 H), 7.06–7.11 (m, 3 H),
6.76–6.82 (m, 3 H), 4.53 (s, 2 H), 3.05 (s, 3 H), 2.37 (s, 3 H).
Acknowledgment
13C NMR (75 MHz, CDCl3): δ = 139.0, 138.2, 134.4, 129.2, 128.5, 127.7,
127.5, 123.9, 116.7, 112.5, 56.8, 38.6, 21.5.
We are grateful for the support of the Science Foundation for Young
Teachers of Wuyi University (No: 2014zk04 and No: 2015td01), the
Natural Science Foundation of Guangdong Province (No:
2014A030310211), the Foundation of the Department of Education of
Guangdong Province (No: 2014KQNCX156 and No: YQ2015162), SRF
for ROCS, SEM (No: [2015]311), and the National Natural Science
Foundation of China (No: 21302146).
Anal. Calcd for C15H17N: C, 85.26; H, 8.11; N, 6.63. Found: C, 85.48; H,
8.06; N, 6.46.
N-Methyl-N-(4-methylbenzyl)aniline (6d)26
Colorless oil; yield: 169 mg (80%).
1H NMR (300 MHz, CDCl3): δ = 7.30–7.43 (m, 6 H), 6.87–6.95 (m, 3 H),
4.66 (s, 2 H), 3.16 (s, 3 H), 2.51 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 149.5, 136.5, 130.0, 129.4, 129.3, 126.9,
116.6, 112.5, 56.5, 38.5, 21.2.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588092.
S
u
p
p
o
nrtIo
g
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
N-(4-Bromobenzyl)-N-methylaniline (6e)10a
Colorless oil; yield: 226 mg (82%).
References
1H NMR (300 MHz, CDCl3): δ = 7.48 (d, J = 8.1 Hz, 2 H), 7.28 (t, J = 7.8
Hz, 2 H), 7.16 (d, J = 8.1 Hz, 2 H), 6.77–6.79 (m, 3 H), 4.52 (s, 2 H), 3.05
(s, 3 H).
(1) For selected representative books, see: (a) Larock, R. C. Compre-
hensive Organic Transformations, A Guide to Functional Group
Preparations; Wiley-VCH: New York, 1989. (b) Ricci, A. Modern
Amination Methods; Wiley-VCH: New York, 2000. (c) Lawrence,
S. A. Amines: Synthesis, Properties and Applications; Cambridge
University Press: Cambridge, 2004. (d) Amino Group Chemistry.
From Synthesis to the Life Sciences; Ricci, A., Ed.; Wiley-VCH:
Weinheim, 2008.
(2) For reviews, see: (a) Spindler, F.; Blaser, H.-U. In Transition
Metals for Organic Synthesis, 2nd ed., Vol. 2; Beller, M.; Bolm, C.,
Eds.; Wiley-VCH: Weinheim, 2004, 113. (b) Blaser, H.-U.;
Spindler, F. In The Handbook of Homogeneous Hydrogenation;
Vol. 3; de Vries, J. G.; Elsevier, C. J., Eds.; Wiley-VCH: Weinheim,
2007, 1193. (c) Blaser, H.-U.; Malan, C.; Pugin, B.; Spinder, F.;
Steiner, H.; Studer, M. Adv. Synth. Catal. 2003, 345, 103. (d) Tang,
W.; Zhang, X. Chem. Rev. 2003, 103, 3029. (e) Nugent, T. C.; El-
Shazly, M. Adv. Synth. Catal. 2010, 352, 753. (f) Rueping, M.;
Sugiono, E.; Schoepke, F. R. Synlett 2010, 852.
13C NMR (75 MHz, CDCl3): δ = 138.1, 134.4, 131.7, 129.3, 128.6, 120.7,
117.0, 112.6, 56.3, 38.6.
N-[4-(Methyloxycarbonyl)benzyl]-N-methylaniline (6f)27
Colorless oil; yield: 199 mg (78%).
1H NMR (300 MHz, CDCl3): δ = 8.02 (d, J = 8.1 Hz, 2 H), 7.34 (d, J = 8.1
Hz, 2 H), 7.29–7.33 (m, 2 H), 6.75–6.78 (m, 3 H), 4.61 (s, 2 H), 3.94 (s, 3
H), 3.07 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 167.1, 144.7, 134.5, 130.1, 129.4, 129.1,
128.2, 126.9, 112.7, 56.9, 52.2, 38.9.
N-(Cyclohexylmethyl)-N-methylaniline (6g)28
Light yellow oil; yield: 171 mg (84%).
1H NMR (300 MHz, CDCl3): δ = 7.30–7.36 (m, 2 H), 6.77 (d, J = 8.4 Hz, 3
H), 3.22 (d, J = 6.6 Hz, 2 H), 3.05 (s, 3 H), 1.83–1.87 (m, 6 H), 1.28–1.35
(m, 3 H), 1.03–1.10 (m, 2 H).
(3) (a) Xie, J.-H.; Zhu, S.-F.; Zhou, Q.-L. Chem. Rev. 2011, 111, 1713.
(b) Fleury-Brégeot, N.; de la Fuente, V.; Castillon, S.; Claver, C.
ChemCatChem 2010, 2, 1346. (c) Transition Metals for Organic
13C NMR (75 MHz, CDCl3): δ = 149.8, 129.2, 115.6, 111.8, 59.9, 39.7,
37.1, 31.5, 26.8, 26.2.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–G

G
B. Li et al.
Paper
Synthesis
Synthesis, 2nd ed.; Beller, M.; Bolm, C., Eds.; Wiley-VCH: Wein-
heim, 2004. (d) Fabrello, A.; Bachelier, A.; Urrutigoïty, M.; Kalck,
P. Coord. Chem. Rev. 2010, 254, 273.
(9) Mizuta, T.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2005, 70, 2195.
(10) (a) Sousa, S. C. A.; Fernandes, A. C. Adv. Synth. Catal. 2009, 352,
2218. (b) Bernardo, J. R.; Sousa, S. C. A.; Florindo, P. R.; Wolff,
M.; Machura, B.; Fernandes, A. C. Tetrahedron 2013, 69, 9145.
(c) Das, B. G.; Ghorai, P. Org. Biomol. Chem. 2013, 11, 4379.
(11) Zheng, J.; Roisnel, T.; Darcel, C.; Sortais, J.-B. ChemCatChem
2013, 5, 2729.
(4) (a) Gladiali, S.; Alberico, E. In Transition Metals for Organic Syn-
thesis; Beller, M.; Bolm, C., Eds.; Wiley-VCH: Weinheim, 2004.
(b) Clapham, S. E.; Hadzovic, A.; Morris, R. H. Coord. Chem. Rev.
2004, 248, 2201. (c) Samec, J. S. M.; Bäckvall, J.-E. Chem. Eur. J.
2002, 8, 2955. (d) Casey, C. P.; Johnson, J. B. J. Org. Chem. 2003,
68, 1998. (e) Zhu, C.; Saito, K.; Yamanaka, M.; Akiyama, T. Acc.
Chem. Res. 2015, 48, 388.
(5) (a) Xiong, B.; Zhang, S.; Jiang, H.; Zhang, M. Org. Lett. 2016, 18,
724. (b) Xiong, B.; Li, Y.; Lv, W.; Tan, Z.; Jiang, H.; Zhang, M. Org.
Lett. 2015, 17, 4054. (c) Xie, F.; Zhang, M.; Jiang, H.; Chen, M.;
Lv, W.; Zheng, A.; Jian, X. Green. Chem. 2015, 17, 279.
(12) Enthaler, S. Catal. Lett. 2011, 141, 55.
(13) (a) Enthaler, S. ChemCatChem 2010, 2, 1411. (b) Jaafar, H.; Li, H.;
Misal Castro, L. C.; Zheng, J.; Roisnel, T.; Dorcet, V.; Sortais, J.-B.;
Darcel, C. Eur. J. Inorg. Chem. 2012, 3546.
(14) Li, B.; Sortais, J.-B.; Darcel, C.; Dixneuf, P. H. ChemSusChem 2012,
5, 396.
(15) (a) Li, B.; Bheeter, C. B.; Darcel, C.; Dixneuf, P. H. ACS Catal. 2011,
1, 1221. (b) Li, B.; Bheeter, C. B.; Darcel, C.; Dixneuf, P. H. Top.
Catal. 2014, 57, 833.
(6) Seyden-Penne, J. Reductions by the Alumino- and Borohydrides
in Organic Synthesis, 2nd ed.; Wiley: New York, 1997.
(7) For selected representative books and reports, see: (a) Ojima, I.
In The Chemistry of Organic Silicon Compounds; Vol. 1; Patai, S.;
Rappoport, Z., Eds.; Wiley: Chichester, 1989. (b) Pukhnarevich,
V. B.; Lukevics, E.; Kopylova, L. T.; Voronkov, M. G. In Perspec-
tives of Hydrosilylation; Lukevics, E., Ed.; Institute of Organic
Synthesis: Riga, 1992. (c) Brook, M. A. In Silicon in Organic,
Organometallic, and Polymer Chemistry; Wiley: New York, 2000.
(d) Nishiyama, H. In Transition Metals for Organic Synthesis;
Beller, M.; Bolm, C., Eds.; Wiley-VCH: Weinheim, 2004.
(e) Marciniec, B. Coord. Chem. Rev. 2005, 249, 2374. (f) Riant, O.
In Modern Reduction Methods; Anderson, P. G.; Munslow, I. J.,
Eds.; Wiley-VCH: Weinheim, 2008, 321. (g) Arena, C. G. Mini
Rev. Org. Chem. 2009, 6, 159. (h) Nishiyama, H. In Comprehensive
Chirality; Vol. 5; Carreira, E. M.; Yamamoto, H., Eds.; Elsevier:
Amsterdam, 2012, 318.
(8) For representative examples, see: (a) Kennedy-Smith, J. J.; Nolin,
K. A.; Gunterman, H. P.; Toste, F. D. J. Am. Chem. Soc. 2003, 125,
4056. (b) Nolin, K. A.; Ahn, R. W.; Toste, F. D. J. Am. Chem. Soc.
2005, 127, 12462. (c) Abbina, S.; Bian, S.; Oian, C.; Du, G. ACS
Catal. 2013, 3, 678. (d) Zhou, S.; Junge, K.; Addis, D.; Das, S.;
Beller, M. Angew. Chem. Int. Ed. 2009, 48, 9507. (e) Misal Castro,
L. C.; Sortais, J.-B.; Darcel, C. Chem. Commun. 2012, 48, 151.
(f) Lipshutz, B. H.; Shimizu, H. Angew. Chem. Int. Ed. 2004, 43,
2228. (g) Volkov, A.; Tinnis, F.; Slagbrand, T.; Pershagen, I.;
Adolfsson, H. Chem. Commun. 2014, 50, 14508. (h) Sunada, Y.;
Kawakami, H.; Imaoka, T.; Motoyama, Y.; Nagashima, H. Angew.
Chem. Int. Ed. 2009, 48, 9511. (i) Das, S.; Wendt, B.; Möller, K.;
Junge, K.; Beller, M. Angew. Chem. Int. Ed. 2012, 51, 1662.
(16) (a) Nishibayashi, Y.; Takei, I.; Uemura, S.; Hidai, M. Organome-
tallics 1998, 17, 3420. (b) Hashimoto, H.; Aratani, I.; Kabuto, C.;
Kira, M. Organometallics 2003, 22, 2199.
(17) Li, B.; Sortais, J.-B.; Darcel, C. Chem. Commun. 2013, 49, 3691.
(18) Tuttle, T.; Wang, D.; Thiel, W.; Köhler, J.; Hofmann, M.; Weis, J.
Dalton Trans. 2009, 5894.
(19) Cui, X.; Zhang, Y.; Shi, F.; Deng, Y. Chem. Eur. J. 2011, 17, 2581.
(20) Zhou, W.; Fan, M.; Yin, J.; Jiang, Y.; Ma, D. J. Am. Chem. Soc. 2015,
137, 11942.
(21) Zhao, Y.; Foo, S. W.; Saito, S. Angew. Chem. Int. Ed. 2011, 50,
3006.
(22) Zhan, L.-W.; Han, L.; Xing, P.; Jiang, B. Org. Lett. 2015, 17, 5990.
(23) Motoyama, Y.; Taguchi, M.; Desmira, N.; Yoon, S.-H.; Mochida, I.;
Nagashima, H. Chem. Asian J. 2014, 9, 71.
(24) Sorribes, I.; Junge, K.; Beller, M. J. Am. Chem. Soc. 2014, 136,
14314.
(25) Lepley, A. R.; Becker, R. H.; Guimanini, A. G. J. Org. Chem. 1971,
36, 1222.
(26) Sueki, S.; Kuninobu, Y. Org. Lett. 2013, 15, 1544.
(27) Numata, M.; Tamesue, S.; Fujisawa, T.; Haraguchi, S.; Hasegawa,
T.; Bae, A.-H.; Li, C.; Sakurai, K.; Shinkai, S. Org. Lett. 2006, 8,
5533.
(28) Kovalenko, O. O.; Volkov, A.; Adolfsson, H. Org. Lett. 2015, 17,
446.
(29) Nayal, O. S.; Bhatt, V.; Sharma, S.; Kumar, N. J. Org. Chem. 2015,
80, 5912.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–G