Direct electrochemical reductive amination between aldehydes and amines with a H/D-donor solvent

Article abstract of DOI:10.1039/d0ob01163k

A novel electrochemical synthesis protocol has been achieved for reductive amination between aldehydes and amines in undivided cells at room temperature. Under metal-free and external-reductant-free electrolysis conditions, various important secondary amine products are obtained in moderate-to-high yields. Deuterium-labeling experiments have demonstrated that low-toxicity DMSO acts both as a solvent and a H-donor in the reaction. On this basis, various deuterium-labeled products with good-to-excellent D-incorporation have been synthesized by using DMSO-d6 as a solvent. Furthermore, a molecule with GR-antagonistic activity has been synthesized through further sulfonylation.

Full text of DOI:10.1039/d0ob01163k

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DOI: 10.1039/D0OB01163K
Journal Name
ARTICLE
Direct Electrochemical Reductive Amination between Aldehydes and
Amines with H/D-donor Solvent
Huanliang Hong,+ Zirong Zou,+ Gen Liang, Suyun Pu, Jinhui Hu, Lu Chen, Zhongzhi Zhu, Yibiao Li*
and Yubing Huang*
Received 00th January
20xx,
Accepted 00th January
20xx
A novel electrochemical synthesis protocol has been achieved for reductive amination between aldehydes and amines in
undivided cells at room temperature. Under metal-free and external-reductant-free electrolysis conditions, various
important secondary amine products are obtained in moderate to high yields. Deuterium-labeling experiments have
demonstrated that low-toxicity DMSO acts both as a solvent and a H-donor in the reaction. On this basis, various
deuterium-labeled products with good to excellent D-incorporation have been synthesized by using DMSO-d6 as a solvent.
Furthermore, molecule with GR-antagonistic activity has been synthesized through further sulfonylation.
DOI: 10.1039/x0xx00000x
www.rsc.org/
O
N
N
F
O
H
Introduction
N
HN
O
N
S
O2N
NH2
OH
Amines are an essential class of bioactive chemicals, existing in a
myriad of natural products, agrochemicals and pharmaceuticals,1
such as anti-parkinson’s disease drugs (A-B), anti-chagas disease
drug (C), antihistamines for the treatment of rhinitis (D-E) and so on
(Figure 1). Multiple synthetic methods have been established for
the construction and functionalization of amines,2 and reductive
amination is considered to be one of the most versatile and
efficient means.1f For efficient and highly selective reductive
amination, great efforts had been made to find a suitable reductant
(Scheme 1, a-d). Since the mid-20th century, Borch et al. had applied
the stoichiometric amounts of NaBH4 and NaBH3CN as strong
reductants for reductive amination.3 Later, the more stable
hydrosilanes gradually became effective reductants,4 and their
application in reductive amination usually required high
temperatures without the need for inert atmosphere and dry
solvents. In response to the call for green chemistry,5 molecular
hydrogen had been widely utilized as a reductant in recent years for
transition-metal-catalyzed or lewis pair-catalyzed reductive
amination studies,6,7 which generally required high-pressure
hydrogen. Simultaneously, several examples of Rh-catalyzed
reductive amination of aldehydes with CO as a reductant had also
been achieved.8 For the development of greener and sustainable
methods for the synthesis of secondary amines, researchers are
turning to metal-free catalytic systems that uses simple and mild
reaction conditions, cheap and readily available reaction materials
and low-toxicity solvents, which is extremely challenging.
Safinamide
(A)
Rotigotine
(B)
Benznidazole
(C)
F
O
H
N
N
N
N
HN
N
N
N
N
O
N
N
N
S
O
Antazoline
(D)
Tripelennamine
(E)
Butenafine
(F)
CRTH2 (DP2) Receptor antagonists
(G)
Figure 1. Selected bioactive molecules containing amines.
Electrochemical synthesis is recognized as an environmentally
friendly and sustainable synthesis tool that has received much
attention in recent years.9 A range of redox reactions can be
achieved by efficiently utilizing energy to activate the substrate on
the electrode surface.10 On the cathode surface, electrons can be an
ideal alternative to reductants for a range of reduction reactions to
achieve more efficient synthesis of organic molecules.11 So far, a
number of electrochemical hydrogenations have been reported,
wherein the constantly exploration of low-cost, safe and
conveniently stored hydrogen sources is still of great concern.12 As
a common and inexpensive solvent, DMSO can act as a H-donor for
organic reactions in the presence of a base, while converting to a
stable DMSO free radical.13 Moreover, DMSO is considered
compatible with multiple electrochemical reactions.14 To develop
more hydrogenation reactions, herein, we propose
a room-
temperature electrochemical reductive amination of aldehydes and
amines. The reaction is conducted under metal-free and external-
reductant-free conditions with low-toxicity DMSO/DMSO-d6 as a
H/D-donor solvent for the synthesis of a series of secondary amines
and deuterium-labeled secondary amines (Scheme 1, e).
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020
(China, E-mail: wyuchemhyb@126.com, leeyib268@126.com
Scheme 1. Reductive amination between aldehydes and amines
with different reductants.
+These authors contributed equally to this work.
†Electronic Supplementary Information (ESI) available: General experimental
information, and NMR spectra. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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9
8 mA instead of 10mA
5 mA instead of 10mA
No electricity
86
12
(a) NaBH4 or NaBH3CN as a
reductant
View Article Online
DOI: 10.1039/D0OB01163K
10
80
0
17
88
<5
<5
(b) PhMe2SiH or PhSiH3 as a
reductant
11
R1
O
H/D
R2
12
13
C(+) | Pt(-)
11
0
+
R1
N
(c) [Au], [Ru], [Ir], [Co], lewis, etc.,
H2 as a reductant
H
Without nBu4NHSO4
NH2
R2
a
Reaction conditions: undivided cell, graphite anode, graphite cathode, constant
 undivided cell
 metal-free
 external-reductant-free
 low energy consumption
 DMSO as a H-donor
(d) [Rh], CO as a reductant
current = 10 mA, 1a (0.1 mmol), 2a (0.12 mmol), electrolyte, solvent, air, 2.5 h. Yield
determined by GC analysis with n-dodecane as the internal standard.
This work
(e) electron as a reductant
 DMSO-D6 as a D-donor
With the optimized conditions established, the
electrochemical reductive amination of aldehydes 1a-1t was
subsequently examined with aniline (2a) (Table 2). To our
satisfaction, aldehyde substrates (1b-1l) bearing methyl (Me),
isopropyl (iPr), tert-butyl (tBu), methoxy (MeO), phenyl (Ph) or
fluorine (F) on the phenyl ring could undergo the reaction
smoothly, and the reaction delivered the corresponding
products (3aa-3la) in moderate to excellent yields. Among
them, aldehydes containing a methyl group at the para- or
meta-position of benzene ring gave lower yields (3ba and 3ha).
It was noteworthy that the use of 2-substituted aldehydes
allowed the reaction to proceed smoothly (3ja-3ka),
demonstrating that the steric hindrance of the 2-position did
not affect the substrate reactivity. Naphthaldehyde substrates
could transfer to the corresponding products 3ma-3na in 93%
and 70% isolated yield, respectively. Aldehydes containing
heterocycles such as furan, thiophene and pyridine appeared
to be easily oxidized and decomposed at the anode, resulting
in a lower yield of the products (3oa-3qa). Moreover,
reductive amination of cyclic aliphatic aldehydes could also be
performed (3ra-3sa), where the yield of the more stable
cyclohexanecarboxaldehyde (44%) was superior to that of
cyclopentanecarbaldehyde (12%). Finally, the reaction of 2-
phenylpropionaldehyde was found to be feasible with aniline
to afford desired product (3ta) in 82% yield.
Results and discussion
To achieve this electrochemical reductive amination,
benzaldehyde (1a) and aniline (2a) were selected as model
substrates for condition optimization (Table 1). The reaction was
initially electrolyzed in an undivided cell equipped with a graphite
anode and a graphite cathode using nBu4NHSO4 in DMSO as
electrolyte under a constant current of 10 mA. Satisfyingly, the
initial attempt went smoothly, delivering the desired product (3aa)
in excellent yield (>98%) (entry 1). Changing electrolyte
concentration by increasing the amount of DMSO or increasing the
amount of electrolyte could result in a decrease in the yield of 3aa
(entries 2-3), which indicated that appropriate electrolyte
concentration was required for effective reductive amination.
According to the subsequent solvent screening, other solvents, such
as MeOH, MeCN and DMF, were considered unsuitable for this
reaction (entries 4-6). When NaHSO4 was used instead of
nBu4NHSO4, no desired product was detected, but the imine (4aa)
was formed in a yield of 36% (entry 7). The addition of HOAc (acetic
acid) did not show an improvement in the yield (entry 8). As the
current was gradually reduced, a gradually decreasing yield was
obtained (entries 9-10). The reaction did not give 3aa without
electricity, but delivered imine product (4aa) in 88% yield (entry
11). Replacing the graphite cathode with a platinum plate resulted
in a low yield (entry 12). Additionally, no expected product was
obtained in the absence of nBu4NHSO4 (entry 13).
Table 2. Scope of aldehydes. a, b
C(+) | C(-), I = 10 mA
nBu4NHSO4 (1 equiv)
H
NH2
R1
R1
N
O
+
DMSO, r.t.
H
Table 1. Optimization of reaction conditions. a
undivided cell
1
2a
3 (3aa-3ta)
H
H
H
H
H
C(+) | C(-), I = 10 mA
nBu4NHSO4 (1 equiv)
NH2
N
N
N
N
O
N
N
H
H
H
H
+
+
H
Me
Ph
iPr
iBu
Me
DMSO (1 mL)
r.t., 2.5 h
undivided cell
3aa (96%)
H
3ba (62%)
H
3ca (85%)
H
3da (98%)
H
1a
2a
3aa
4aa
MeO
N
H
N
H
N
H
N
H
Yield (%)
Variation from standard
conditions
MeO
F
Entry
3ea (58%)
H
3fa (98%)
3ga (83%)
3ha (52%)
H
3aa
4aa
OMe H
Me
H
MeO
MeO
1
2
3
4
5
6
7
8
none
>98
81
67
18
8
0
N
H
N
N
H
N
H
H
DMSO (2.5 mL) as solvent
12
<5
<5
0
3ia (89%)
H
3ja (97%)
H
3ka (85%)
H
3la (86%)
nBu4NHSO4 (2 equiv) was used
MeOH (1 mL) as solvent
MeCN (1 mL) as solvent
DMF (1 mL) as solvent
H
N
H
N
H
N
H
N
H
O
S
3ma (93%)
H
3na (70%)
H
3oa (50%)
H
3pa (31%)
Me
H
36
0
0
N
N
H
N
H
N
H
NaHSO4 instead of nBu4NHSO4
HOAc (1 equiv) was added
36
<5
N
H
3qa (12%)
3ra (44%)
3sa (12%)
3ta (82%)
95
2 | J. Name., 2012, 00, 1-3
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a
Reaction conditions: graphite anode, graphite cathode, constant current = 10 mA, 1 (Eqn. c). Part of 4aa in the reaction was decomposed into
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DOI: 10.1039/D0OB01163K
(0.5 mmol), 2a (0.6 mmol), nBu4NHSO4 (1 equiv), DMSO (5 mL), undivided cell, r.t., 5 h. benzaldehyde, and 40% of 3aa was formed, from which we
Isolated yields.
speculated the reaction was via the formation of imine-like
intermediates. In order to explore the source of hydrogen in this
electrochemical reductive amination, the deuterium-labeling
experiments were then conducted. Surprisingly, when performing
the reaction with DMSO-d6 as a solvent, the ratio of 3aa-d1 and 3aa
was confirmed by 1H NMR to be 97:3 among 92% isolated yield
(Eqn. d), wherein 3aa-d1 had been confirmed through NMR and
HRMS analysis. Subsequently, the transformation with DMSO/D2O
(30:1) as a solvent was also performed (Eqn. e), and it was noted
that no deuterated product 3aa-d1 was detected in the reaction
except that 77% of 3aa was detected. In addition, no 3aa-d1 was
produced after the treatment of 3aa under the conditions of using
DMSO-d6 as a solvent, which proved that no H/D exchange occurred
(Eqn. f). The above experiments confirmed that one hydrogen atom
in the product 3aa was derived from the methyl hydrogen of DMSO
in this electrochemical reductive amination.
Next, the scope of amines 2 for this electrochemical reductive
amination was investigated (Table 3). Electron-rich groups (Me, nBu,
tBu, MeO, PhO and Ph) and halogen groups (F and Cl) on the phenyl
ring were well tolerated in the conversion (3ab-3am). By
comparison, substrates containing a meta-substituent on the
phenyl ring (3aj-3ak) were better converted than those containing
an ortho-substituent (3al-3am), which might be due to steric
hindrance. Moreover, a higher yield of 98% was obtained when
using 3,5-dimethylaniline (3ao) as a substrate, while the reaction
yield was lower when dimethoxy-substituted aniline (3ap) was
used, possibly because the electron-rich substrate was prone to
oxidation. 2,3-Dihydro-1H-inden-5-amine and benzo[d][1,3]dioxol-
5-amine were also proved to be useful and the corresponding
products (3aq-3ar) were afforded in lower yields. In addition, the
reaction with 3 equivalents of cyclohexylamine delivered 3as in an
acceptable yield, suggesting that aliphatic amines were equally Scheme 2. Mechanistic studies.
applicable to the reaction.
C(+) | C(-), I = 10 mA
nBu4NHSO4 (1 equiv)
H
NH2
OH
Table 3. Scope of amines. a, b
N
Eqn. a
+
H
DMSO, r.t., 2.5 h
undivided cell
1a
2a
(1.2 equiv)
3aa (0%)
H
(0.1 mmol)
C(+) | C(-), I = 10 mA
nBu4NHSO4 (1 equiv)
H
R2
C(+) | C(-), I = 10 mA
nBu4NHSO4 (1 equiv)
O
O
NH2
R2
2
N
+
H
N
H
DMSO, r.t.
undivided cell
N
Eqn. b
Eqn. c
H
DMSO, r.t., 2.5 h
undivided cell
1a
3 (3ab-3as)
H
3aa (0%)
(0.1 mmol)
Me
nBu
tBu
OMe
H
H
H
C(+) | C(-), I = 10 mA
nBu4NHSO4 (1 equiv)
H
N
N
N
H
N
O
N
N
H
H
H
+
H
DMSO, r.t., 2.5 h
undivided cell
3ab (98%)
H
3ac (98%)
H
3ad (86%)
3ae (47%)
4aa
(0.1 mmol)
3aa
by-product
(40% GC yield)
OPh
Ph
F
Cl
H
H
C(+) | C(-), I = 10 mA
nBu4NHSO4 (1 equiv)
D/H
NH2
N
H
N
H
N
N
H
O
+
H
Eqn. d
Eqn. e
N
H
DMSO-d6, r.t., 3 h
undivided cell
3af (92%)
H
3ag (62%)
H
3ah (61%)
H
3ai (65%)
H
2a
(2 equiv)
1a
3aa-d1/3aa = 97:3
(92%)
(0.3 mmol)
C(+) | C(-), I = 10 mA
nBu4NHSO4 (1 equiv)
H
N
H
Me
N
H
OMe
N
H
N
H
NH2
O
OMe
N
H
+
3aa-d1 (0%)
+
dry DMSO/D2O (30:1)
r.t., 2.5 h
undivided cell
3aj (71%)
3ak (52%)
3al (33%)
3am (49%)
Me
OMe
1a
2a
(2 equiv)
3aa
Me
H
(0.1 mmol)
(77% GC yield)
H
H
H
C(+) | C(-), I = 10 mA
nBu4NHSO4 (1 equiv)
N
H
N
Me
N
OMe
N
H
D
H
H
Me
N
N
H
Eqn. f
H
3an (47%)
H
3ao (98%)
H
3ap (30%)
3aq (50%)
DMSO-d6, r.t., 2.5 h
undivided cell
3aa
(0.1 mmol)
3aa-d1 (0%)
O
O
N
H
N
H
3as (69%) b
Deuterium-labeled molecules have received significant attention
from organic and medicinal chemists because of their important
applications in mechanistic studies and drug modification.15 After
learning that DMSO-d6 could provide a deuterium atom to construct
various deuterium-labeled secondary amines through the formation
of a C-D bond, we subsequently investigated the substrate scope for
the reductive amination (Table 4). Both electron-rich groups (Me,
3ar (30%)
a
Reaction conditions: graphite anode, graphite cathode, constant current = 10 mA, 1a
(0.5 mmol), 2 (0.6 mmol), nBu4NHSO4 (1 equiv), DMSO (5 mL), undivided cell, r.t., 5 h.
Isolated yields. b Cyclohexylamine (3 equiv).
To gain mechanistic insight into this electrochemical reductive
amination, some control experiments were then conducted
(Scheme 2). The reaction of benzyl alcohol and aniline did not
produce the desired product 3aa, proving that benzyl alcohol was
only a by-product formed in the reaction (Eqn. a). Subsequently, N-
phenylbenzamide proved to be unable to form 3aa in this
electrochemical reduction system (Eqn. b). In order to verify
whether the reaction was via the formation of an imine-like
intermediate and further reduction to a product, we used (E)-N-
benzylideneaniline (4aa) as a substrate to carry out the reaction
t
iPr, Bu, MeO and Ph) and electron-poor groups (F) on the aromatic
ring of aldehyde were tolerated in the transformation, and the
corresponding products (3ca-d1-3ka-d1) were given with good to
excellent D-incorporation. Among them, p-phenylbenzaldehyde and
o-methoxybenzaldehyde were good substrates, and both reactions
delivered the corresponding products (3fa-d1 and 3ja-d1) in 98%
yields. Naphthaldehyde with a large conjugated structure could also
be applied in the reaction, and 3ma-d1 was obtained with 86% D-
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1a
2a
incorporation in 77% yield. Gratifyingly, the reactions of
benzaldehyde and amines containing different groups (Me, nBu, tBu,
OPh and Cl) on the aromatic ring could give products (3ab-d1-3ao-
d1) with good to excellent D-incorporation.
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DOI: 10.1039/D0OB01163K
3aa
120
100
80
60
40
20
0
4aa
benzyl alcohol
Table 4. Deuterium-labeled substrate scope for the electrochemical
reductive amination. a, b
C(+) | C(-), I = 10 mA
nBu4NHSO4 (1 equiv)
D
R2
NH2
O
R1
R2
N
R1
H
+
DMSO-d6, r.t.
undivided cell
1
2
3-d1
D
D
D
D
N
N
N
N
H
H
H
H
0.0
0.5
1.0
1.5
2.0
iPr
Ph
tBu
3aa-d1
3ca-d1
3da-
d1
3fa-d1
reaction time (h)
(92%, 97%-D)
(56%, 94%-D)
(79%, 96%-D)
(98%. 82%-D)
D
D
Me
D
OMe D
Figure 2. Sampling experiment. Standard conditions: graphite rod
(ϕ 6 mm) anode, graphite rod (ϕ 6 mm) cathode, constant current =
10 mA, benzaldehyde 1a (0.1 mmol), aniline 2a (0.12 mmol),
nBu4NHSO4 (1 equiv), DMSO (1 mL), room temperature, GC yields.
OMe
F
N
H
N
H
N
N
H
H
3ga-d1
(75%, 72%-D)
3ia-d1
(82%, 94%-D)
3ka-d1
(58%, 78%-D)
3ja-d1
(98%, 91%-D)
Me
nBu
tBu
D
D
D
D
N
H
N
H
N
H
N
H
3ac-d1
(70%, 90%-D)
3ad-d1
(75%, 80%-D)
3ab-d1
(76%. 77%-D)
Based on the above experimental results and previous reports, a
plausible reaction mechanism for the formation of 3aa in
electrochemical conditions was depicted in Scheme 3. Firstly,
3ma-d1
(77%, 86%-D)
Cl
OPh
D
D
D
N
H
N
H
N
H
benzaldehyde
1a
and
aniline
2a
could
form
a
3ao-d1
3af-d1
3ai-d1
phenyl(phenylamino)methanol intermediate A, followed by the
departure of OH- to form imine cation B. Subsequently, imine cation
B obtained an electron through electrochemical reduction to form a
radical intermediate C.16 Then, radical Intermediate B abstracted a
hydrogen atom from DMSO to form 3aa and a DMSO radical,13
which could re-form DMSO via reduction and protonation at the
cathode. At the anode, DMSO was oxidized to provide electrons for
the reduction of substrate.17
(48%, 91%-D)
(68%, 91%-D)
(85%, 97%-D)
a
Reaction conditions: graphite anode, graphite cathode, constant current = 10 mA,
aldehydes 1 (0.3 mmol), amines 2 (0.6 mmol), nBu4NHSO4 (1 equiv), DMSO-d6 (3 mL),
undivided cell, r.t., 3 h. Isolated yields.
To gain more insight into this transformation, we monitored the
electrochemical reductive amination of benzaldehyde and aniline at
room temperature by GC-MS analysis, as shown in Figure 2. During
the first 0.5 h, 1a and 2a were rapidly consumed, the concentration
of 3aa in the reaction gradually increased, and the by-product 4aa
reached the maximum at 0.29 h. Over the next period,
accompanied by the continuous accumulation of 3aa, the
concentration of 4aa gradually decreased to zero. Among them, a
trace amount of benzyl alcohol was detected in the reaction.
According to these interesting conversion processes, we speculated
that 4aa may be an intermediate in the reaction, and 3aa was
obtained by the reduction of 4aa.
Scheme 3. Proposed mechanism.
anode
cathode
e-
e-
1a
2a
+
- OH-
OH
Ph
Ph
N
Ph
H
Ph
N
B
H
e-
A
reduction
H
H
NH2
standard conditions
O
Ph
N
N
Ph
N
H
+
+
C (+)
C (-)
Ph
Ph
3aa
N
undivided cell
H
C
H
1a
2a
3aa
4aa
O
S
O
S
2e-
O2
O
S
e-
+
H
O
Finally, we found the products from this electrochemical
reductive amination could be applied to the synthesis of active aryl
sulfonyl tertiary amine molecules (Scheme 4). The reaction of N-
benzylaniline and 4-methylbenzenesulfonyl chloride in the presence
of triethylamine could deliver the sulfonylated product 5a in 82%
isolated yield (A). Moreover, with pyridine as the solvent, the
reaction of N-acetylsulfanilyl chloride with 3aa or 3af gave products
4 | J. Name., 2012, 00, 1-3
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5b and 5c in isolated yields of 72% and 84%, respectively (B).
Among them, 5c has been reported as a novel class of nonsteroidal
glucocorticoid receptor (GR) modulators, which is expected to be a
drug candidate for treating immune-related disorders.18
Training Program (201911349031 and 3344100114) for financial
support.
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DOI: 10.1039/D0OB01163K
Notes and references
1
Scheme 4. Construction of aryl sulfonyl tertiary amine molecules
from 3aa and 3af.
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O
S
Cl
O
S
Et3N (1 equiv)
N
(A)
N
H
O
+
O
DCM, 0 °C, 24 h
5a (82%)
R3
0.5 mmol
1.2 equiv
R3
O
S
O
Cl
pyridine
O
(B)
+
N
S
N
H
60 °C, 4 h
AcHN
O
AcHN
0.5 mmol
1.2 equiv
R3 = H, 5b (72%)
R3 = OPh, 5c (84%)
Conclusions
2
3
4
In conclusion, we have developed a novel electrochemical
reductive amination between aldehydes and amines at room
temperature. The reaction proceeds in undivided cells to deliver
various important secondary amine products in moderate to high
yields, some of which can be converted to molecules with GR-
antagonistic activity by further sulfonylation. Interestingly,
deuterium-labeling experiments have demonstrated that DMSO is
not only the solvent in the reaction, but also the H-donor in the
reaction, providing a hydrogen atom for the product. Based on the
experiments, various deuterium-labeled secondary amines with
good to excellent D-incorporation are subsequently synthesized by
using DMSO-d6 as a solvent. Compared with previous reductive
amination reactions, no metal or external-reductant is required in
this protocol. Furthermore, inexpensive and readily available
substrates, simple and mild electrolysis conditions and low energy
consumption make this transformation extremely attractive. Our
further efforts are to elucidate the mechanism of this novel
reaction and develop more hydrogenation and deuteration
reactions by cathodic reduction.
5
6
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
The authors thank the Foundation of the Department of Education
of Guangdong Province (2017KZDXM085, 2018KZDXM070 and
2019KZDXM052), the Foundation of Guangdong Basic and Applied
Basic Research (2019A1515110516, 2019A1515110266 and
2019A1515110522), the Foundation for Young Talents
(2019KQNCX159, 2019KQNCX160 and 2018KQNCX273), Science
Foundation for Young Teachers of Wuyi University (pdjh2020a0595)
and National College Students Innovation and Entrepreneurship
7
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6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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DOI: 10.1039/D0OB01163K
H
R2
R1
N
H
C(+) | C(-), I = 10 mA
nBu4NHSO4
38 examples
up to 98% yield
NH2
R1
+
R2
or
O
DMSO or DMSO-d6
D
r.t.
R1, R2 = aryl, het and alkyl
R2
R1
N
H
15 examples
 low energy consumption
 undivided cell
up to 98% yield
up to 97% D-incorporation
 metal-free
 external-reductant-free
 DMSO as a H-donor solvent
 DMSO-d6 as a D-donor solvent
Electrochemical reductive amination of aldehydes and amines was first realized at room
temperature by using DMSO/DMSO-d6 as a H/D-donor solvent.