Ruthenium nanoparticle catalyzed selective reductive amination of imine with aldehyde to access tertiary amines

Article abstract of DOI:10.1039/c8cc05437a

Reductive amination is one of the most frequently used transformations in organic synthesis. Herein, we developed a novel ruthenium nanoparticle embedded ordered mesoporous carbon catalyst (Ru-OMC) and a new hydrosilylation process for the synthesis of tertiary amines. We present a direct reductive amination of imines (CN bond) with aldehydes (CO bond) using hydrosilane as the reducing reagent under mild conditions. Moreover, the Ru-OMC catalysts can be reused for up to 14 runs without noticeably losing activity.

Full text of DOI:10.1039/c8cc05437a

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Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc
first methanofullerene derivatives of Sc
3
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Ruthenium Nanoparticles Catalyzed Selective Reductive
Amination of Imine with Aldehyde to Access Tertiary
Amines
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
a
a
a
Bin Li,* Shun liu, Qiao Lin, Yan Shao,* Shiyong Peng and Yibiao Li
DOI: 10.1039/x0xx00000x
www.rsc.org/
10
Reductive amination is one of the most frequently used catalysts (Scheme 1). However, these transformations always
transformations in organic synthesis. Herein, by developing a stopped in the first reductive amination step to formation of
novel ruthenium nanoparticles embedded within ordered secondary amines, and the second reductive amination of
mesoporous carbon catalyst (Ru-OMC) and
a
new aldehydes with secondary amines is always slower, this mainly
hydrosilylation process for the synthesis of tertiary amines. We because of the reaction difficulty on the steric effect and pꢀᴨ
present a direct reductive amination of imines (C=N bond) with conjugated effect between nitrogen atom and aromatic ring.
aldehydes (C=O bond) using hydrosilane as reducing reagent Furthermore, compared to the reductive amination of secondary
under mild conditions. Moreover, the Ru-OMC catalytst can be amines with carbonyl derivatives, the direct reductive amination of
reused up to 14 runs without noticeable losing activities.
imine with carbonyl derivatives is a more “greener” process without
amine pre-reduction step in the area of tertiary synthesis. We
envisioned a new synthetic protocol to produce tertiary amines from
the reaction of imines and aldehydes under hydrosilylation
conditions (Scheme 1). Hence, to achieve selective generation of
tertiary amine product, at least three challenging issues have to be
solved: (1) There should be an compatible catalytic system able to
perform two times hydrosilylation of imine or iminium. (2) This
catalytic system ensure the reducing rate of C=N bond is much faster
than reduction of C=O bond. (3) This catalytic system could also
react with aromatic aldehydes which overcome the steric effect and
pꢀᴨ conjugated effect between nitrogen atom and aromatic ring, thus
enrich the molecular diversities of tertiary amine products.
The development of synthetic strategies to access tertiary amines is
of significant importance due to their widespread occurrence in
natural products, agrochemicals, pharmaceuticals, and valuable fine
1
chemicals . Pioneered by N-alkylation using alcohols or haloalkanes
2
3
with amines , amine-carbonyl reductive amination , or C-N cross
coupling are simple methods for the synthesis and functionalization
4
of tertiary amines . Despite these significant achievement, the
control of the degree of N-alkylation, the limitation of molecular
diverse of tertiary amides still remains elusive and highly
challenging. Importantly, reductive amination has become the sixth
most frequently used transformation in medical chemistry from a
recent analysis of drug candidate synthesis by three pharmaceutical
5
companies . Very recently, Doyle reported an efficient Ni-catalyzed
reductive amination to access tertiary alkylamines with N-
6
trimethylsilyl amines. Within the mild conditions and good
chemoselectivities, transition metal catalyzed reductive amination
using hydrosilane as a suitable hydrogen donor has emerged as a
7
competitive alternative method to access tertiary amines , which
8
compared to the classical hydrogenation and hydrogen transfer
9
reactions .
During the last few years, the amine synthesis via reductive
amination of aldehydes with primary amines under hydrosilylation
conditions has been developed by using some transition metal
a.
Scheme 1. Previous work and new synthetic protocol
School of Chemical & Environmental Engineering, Wuyi University, Jiangmen
5
29020, Guangdong Province, P.R. China
Recently, heterogenous metal oxide nanocatalysts have attracted
more and more attention on organic transformations, mainly
Eꢀmail: Dr. Bin Li: andonlee@163.com ; Dr. Yan Shao:wyuchemsy@126.com
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See because of their high stability, easy recyclability and different
DOI: 10.1039/x0xx00000x
reaction pathway, such as hydrogenation or transfer hydrogenation
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1
1
12
of nitro compounds , selective reduction of N-heteroaromatics ,
1
3
oxidation of alcohols to esters . Ordered mesoporous carbon (OMC)
1
4
is a kind of mesoporous material , with typical mesoporous
structures like a 2-D hexagonal ordered structure. After introducing
Ru, to some extent, parts of pore may be blocked by RuOx. However,
the large amount of mesopore volume with high specific surface
area still benefit for decreasing diffusion resistance and increasing
mass transfer. The another advantage is that this material can be
prepared with adjustable pore diameter by changing raw material
ratio, which would offer a promising way in the field of organic
synthesis. Herein, nanoparticles embedded within ordered
mesoporous carbon catalyst (Ru-OMC), and demonstrate for the
first application in catalytic reductive amination of imines and
aldehydes to selective access tertiary amine derivatives using
hydrosilane as the hydrogen source.
Fig. 2. SEM photograph and elemental mapping images of as-
synthesized Ru-OMC catalyst for C, O, and Fe with color
superposition (C = red; O = green; and Ru = blue).
The new Ru-OMC catalyst was prepared using RuCl3 as the
ruthenium precursor and resorcinol formaldehyde resin precursor
as the sources of carbon material. As depicted in Fig. 1, resorcinol
formaldehyde resin precursor synthesized using soft template
procedure. Next, the RuCl3 was then added to this resorcinol
formaldehyde resin precursor with
5 wt% Ru contents by
impregnating method. Finally, the resulting composites were dried
o
o
in an oven at 90 C for 12 h and then carbonized at 1000 C for 2 h
under a N2 atmosphere. Finally, the Ru-OMC catalysts were
obtained after cooling down the materials to room temperature.
Fig. 3. XPS results of as-synthesized Ru-OMC catalysts.
X-ray photoelectron spectroscopy (XPS) was employed to
investigate the oxidation state of Ru and the surface composition of
the catalysts. The C 1s, O 1s and Ru 3d for Ru-OMC catalysts are
shown in Fig.3, indicating the Ru-OMC catalyst was composed of C,
O and Ru elements. Due to the strong overlap of the C 1s and Ru 3d
peaks around 284.6 eV, it can be seen from Fig. 3a that the C 1s
high-resolution spectrum, revealed a peak at 284.6 eV ascribed to
the sp 2 RuC bond of pure carbon. The C 1s signal is deconvoluted
into two distinguishable component peaks. The peak at about 284.6
eV is assigned to aromatic carbon and RuC while the peak at about
Fig. 1. Schematic illustration for the preparation of catalyst.
Fig.2 shows the SEM–EDS micrographs of surfaces of particle
morphology of Ru-OMC materials after calcination. As shown in the
Figure 2(a), the porous structure in the material, which has loose
network micro structure, is still be obviously observed after the
impregnation of Ru. The Ru nanoparticles were dispersed on the
surface of OMC almost without aggregation. As seen in Fig.2(a)-(c),
lots of ruthenium oxide composite crystallites distribute evidently
inside or on the surface of the carbon matrix. The EDS mapping
results shown in Fig. 2(d)-(f) confirm that C, O, and Ru elements are
highly dispersed in Ru-OMC catalyst.
1
5
2
85.9 eV is assigned to single C-O bonds (hydroxyl group) . The
deconvolution of the O 1s spectra yielded the following three peaks:
peak I (531.0 eV), metal oxides such as RuO ; peak II (532.3 eV),
2
carbonyl oxygen atoms in esters, anhydrides and oxygen atoms in
hydroxyl groups; peak III (533.1 eV), non-carbonyl (ether-type)
oxygen atoms in esters or aromatic ring. Fig. 3d shows the
absorptions located at 284.6 eV for Ru 3d, revealing the Ru element
1
6
that covered on the surface of Ru-OMC exists as metallic Ru .
To test the catalytic efficiency of the prepared novel Ru-OMC
material, we selected imine 1a and benzaldehyde 2a as the model
substrates to evaluate different reaction parameters, such as
solvents, silane and temperature. (Table 1) As shown in table 1, no
2
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GC-yield of tertiary amine 3a was detected in the absence of group containing imines afforded the desired tertiary amine
catalyst (table 1, entry 1). 27 % GC-yield of tertiary amine 3a was products in higher yields (see 3a and 3b) than the electron-poor one
obtained by using 1 mol% of Ru-OMC catalyst, 1.5 equiv. of Ph
2
SiH
CN at 80 C for 16 h (Table 1, entry 2). heteroaromatic aldehydes, including thiophene-2-carbaldehyde, 2-
Next, after tested different hydrosilanes under similar conditions for furaldehyde and 2-chloronicotinaldehyde leading to corresponding
this reductive amination, PhSiH as the best hydrosilane was found, tertiary amines (3k-3n) in good yields. More importantly, the
and yielding tertiary amine 3a in 83% yield (table 1, entry 10), other functional ester group on imine aryl ring could be tolerated, and the
hydrosilanes including Et SiH , TMDS (1,1,3,3-tetramethyldisiloxane), corresponding tertiary amine 3r were directly obtained without the
PMHS (polymethylhydroxysiloxane), PhMe SiH, Ph ClSiH, PhMeSiH reduction of the carbonyl moiety. Additionally, the reaction of
MeO) SiH can not give the better results (Table 1, entries 3-9). different imines containing thiophene, benzyl and alkyl groups with
However, when this reaction was performed in MeOH instead of aldehydes were well performed and produce corresponding tertiary
2
(3p and 3q). Moreover, the reaction also proceeded well with the
o
as hydrogen source in CH
3
3
2
2
2
2
2
,
(
3
o
3
CH CN at 40 C, almost complete conversion was reached and amines (3s-3u) in 64-80% yields. However, when using
tertiary amine 3a was obtained in 82% isolated yield (Table 1, acetophenone instead of aldehyde react with imine, no desired
entries 13). By contrast, other solvents such as EtOAc, EtOH, DMC tertiary amine was occurred. This indicated that the reductive
were disfavor for this reductive amination (Table 1, entries 11, 12, amination of imine with ketone is more difficult than aldehydes.
14).
Table 1. Optimization of the Ru-OMC catalyzed selective reductive
[a]
amination of benzaldehyde and imine 1a
Entry
Solvent
CH CN
CH CN
Silane
Ph SiH
Ph SiH2
GC-yield. (%)
1
2
3
4
5
6
7
8
9
3
2
2
---
27
24
---
6
3
2
CH
CH
3
3
CN
CN
2 2
Et SiH
TMDS
PMHS
CH CN
3
CH
CH
3
3
CN
CN
PhMe
2
SiH
12
60
63
---
83
60
Ph
2
ClSiH
CH CN
3
PhMeSiH2
(MeO) SiH
CH
CH
3
3
CN
CN
3
10
11
12
13
14
PhSiH
PhSiH
PhSiH
PhSiH
PhSiH
3
3
3
3
3
EtOAc
EtOH
[
b]
61
[
b]
[c]
MeOH
DMC
96 (82 )
3
Imine (0.5 mmol), aldehyde (0.75 mmol), Ru-OMC (5 wt%, 1 mol%), PhSiH (1.5 equiv.),
o
---
3
CH OH (2 mL), at 40 C, under air for 16 h.
[
a] imine 1a (0.5 mmol), benzaldehyde 2a (0.75 mmol), Ru-OMC catalyst (5 wt%, Scheme 2. Ru-OMC catalyzed reductive amination of imines with
o
mol%), Silane (1.5 equiv.), Solvent (2 mL), at 80 C for 16 h. [b] at 40 C. [c]
o
1
Isolated yield of 3a
aldehydes.
.
Further, we examined the stability and reusability for our developed
new Ru-OMC catalyst with the reaction of imine 1a and
benzaldehyde 2a under the reductive amination conditions. The
Within the optimal conditions (table 1, entry 13), the scope and
limitations of this first Ru-OMC catalyzed reductive amination of
imines 1 with aldehydes 2 were then explored. Various imines 1 and results listed in Fig. 4, and shown the catalytic system could be
aldehydes 2 were applied to synthesize tertiary amines 3, and the reused up to 14 runs while retaining the catalytic activity, without
substantially decrease of the yield. However, after 14 times
results were shown in scheme 2. As shown in scheme 2, different
consecutive experiments, the surface of RuOx particles appeared
some matters, which was corresponding with the surface scaling
formation. Morphological information of the used Ru-OMC catalyst
catalyst shows that the active RuOx component could not uniformly
aromatic and alkyl aldehydes 2 were reacted with imines 1a or 1b to
successfully produce tertiary amines 3a-3j in 45-86% isolated yields.
Notably, no dehalogenation occurred during the reductive
amination process. It is noteworthy that the electron-donating disperse on the surfaces of Ru-OMC catalyst. (see in Figure S1).
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In summary, we have developed a novel ruthenium nanoparticles
embedded within ordered mesoporous carbon catalyst, and
demonstrated a direct reductive amination to produce tertiary
amines of imines with aldehydes under hydrosilylation conditions
for the first time. Many functional groups, such as halides, ester,
furan, thiophene are tolerated under this reductive amination.
Moreover, the Ru-OMC catalytst can be easily separated and
recovered from the reaction mixture by filtration and reuse up to 14
runs without noticeable losing activities. Further development of
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Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
We thank the Support of the National Natural Science Foundation of
China (No: 21702148), the Foundation of Department of Education
of Guangdong Province (No: YQ2015162, No: 2017KZDXM085)..
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