Electrochemical allylation reactions of simple imines in aqueous solution mediated by nanoscale zinc architectures

Article abstract of DOI:10.1002/anie.201004852

I zinc we're alone now: The title reactions were achieved in an undivided cell fitted with a pair of zinc electrodes in aqueous solution. A preliminary study on the relationship of reaction activity and surface morphology showed that the deposited zinc powders with nanoscale architectures had very high activity.

Full text of DOI:10.1002/anie.201004852

Communications
DOI: 10.1002/anie.201004852
Electrochemistry
Electrochemical Allylation Reactions of Simple Imines in Aqueous
Solution Mediated by Nanoscale Zinc Architectures**
Jing-Mei Huang,* Xu-Xiao Wang, and Yi Dong
=
Addition of allylmetal reagents to C N double bonds is one
Table 1: Optimization of the reaction conditions for the electrochemical
allylation of the simple imine 1a.[a]
of the most important and straightforward methods to afford
homoallylic amines, which are useful building blocks for many
biologically active compounds and nitrogen-containing natu-
ral products.[1] In recent years, organic reactions that can be
performed in aqueous media have attracted great interest
because of significant environmental and economical advan-
tages,[2] especially for the Barbier-type reactions in aqueous
media.[3] However, owing to the lower electrophilicity of
simple imines and their instability in water, most of the
previously reported metal-mediated aqueous allylation reac-
tions were focused on the use of special imines, such as
sulfonimines, tosyl or aryl hydrazones, and glyoxylic oxime
ethers.[4] The limited scope of these reported systems encour-
ages us to search for methods to achieve the allylation
reactions of simple imines in aqueous media. Electrochemical
methods are another approach to efficient organic trans-
formations and sustainable chemistry,[5,6] and we have also
been interested in developing new electrochemical process in
aqueous solution.[7] Herein, we reported a zinc-mediated
electrochemical allylation reaction of simple imines in a
mixture of saturated aqueous NH4Br and tetrahydrofuran
(9:1) at room temperature; this method is also suitable for the
alkylation and benzylation of simple imines.
Entry
Anode–cathode
Electrolyte
Yield [%][b]
1
2
3
4
5
6
7
8
Zn–Zn
Zn–Zn
Zn–Zn
Zn–Zn
Zn–Zn
Zn–Zn
Zn–Zn
Zn–Zn
Zn–Zn
Zn–Zn
Zn–Zn
Zn–Zn
Pt–Pt
LiClO4 (0.1 m)/THF (9:1)
NaOH (0.1 m)/THF (9:1)
HCl (0.1 m)/THF (9:1)
0
0
trace
<5
15
20
60
92
70
35
72
74
0
HOAc (0.1 m)/THF (9:1)
NH3·H2O (4.5 m)/THF (9:1)
NH4Cl (0.1 m)/THF (9:1)
sat. aq NH4Cl/THF (9:1)
sat. aq NH4Br/THF (9:1)
sat. aq NH4Br/THF (95:1)
sat. aq NH4Br/MeOH (9:1)
sat. aq NH4Br/THF (9:1)
sat. aq NH4Br/THF (9:1)
sat. aq NH4Br/THF (9:1)
sat. aq NH4Br/THF (9:1)
sat. aq NH4Br/THF (9:1)
9
10
11[c]
12[d]
13
14
15
Al–Al
Sn–Sn
10
15
[a] Standard condition: imine (0.5 mmol), allyl bromide (1 mmol) in
electrolyte was electrolyzed at a constant current of 30 mA in a round-
bottomed-flask cell equipped with a pair of zinc electrodes (1.5 cm2) at
RT. [b] Yield of isolated product. [c] 15 mA. [d] 45 mA. THF=tetrahydro-
furan.
Initial studies were performed at room temperature under
neutral aqueous conditions of 0.1m LiClO4/tetrahydrofuran
(9:1; Table 1, entry 1) in a one-compartment cell under a
constant current (30 mA), and zinc foils (1.5 cm2 each) were
chosen as both the anode and cathode. After electrolysis for
75 minutes, none of the desired product was obtained. The
same result was observed in 0.1m NaOH solution (Table 1,
entry 2), whilst in an acidic 0.1m HCl solution (Table 1,
entry 3), only a trace amount of the desired product was
detected. In 0.1m HOAc solution and ammonia solution
(4.5m)[7a], the desired homoallylic amine was obtained with
yields of < 5% and < 15%, respectively (Table 1, entries 4
and 5). When ammonium salts were employed, the results
were more promising (Table 1, entries 6–8), and NH4Br was
found to be superior (92% yield) to NH4Cl as an electrolyte
salt. Reducing the amount of the tetrahydrofuran or using
methanol instead resulted in lower yields (Table 1, entries 9
and 10). Studies on the effect of current density (Table 1,
entries 11 and 12) showed that an increase or decrease of the
current resulted in a decrease in the yield. No allylation
occurred when the electrolysis was carried out with platinum
electrodes (Table 1, entry 13). Other electrodes (aluminium
and tin) showed low yields (10% and 15%, respectively,
Table 1, entries 14 and 15). Therefore, our optimized reaction
conditions were found to be those given in Table 1, entry 8.
Next, a wide variety of simple imines were investigated,
and the results are summarized in Table 2. Imines derived
from aromatic, heteroaromatic, aliphatic aldehydes, and
aromatic or aliphatic amines were all suitable substrates and
produced the corresponding homoallylic amines in good
yields. The functionalities including methoxyl, chloro, bromo,
hydroxy, and cyano[8] were tolerated by this mild method.
Encouraged by the above results, we applied this reaction
system to chiral imines to explore a new method for the
synthesis of enantiomerically enriched homoallylic amines in
aqueous solution. By using the imines derived from l-valine
methyl ester, l-phenylalanine methyl ester, and l-phenyl-
glycinol, it was found that the reaction worked well in the
[*] Prof. Dr. J.-M. Huang, X.-X. Wang, Y. Dong
School of Chemistry and Chemical Engineering, South China
University of Technology
Guangzhou, Guangdong, 510640 (P. R. China)
Fax: (+86)20-8711-0622
E-mail: chehjm@scut.edu.cn
[**] We express appreciation to Prof. Ye Jian-Shan for valuable
discussions on the electrochemical process. We are grateful to the
National Natural Science Foundation of China (Grant 20972055).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201004852.
924
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Angew. Chem. Int. Ed. 2011, 50, 924 –927

Table 2: Zinc-mediated electrochemical allylation of imines in an
Table 3: Zinc-mediated electrochemical benzylation and alkylation of
aqueous solution.[a]
imines in aqueous solution.[a]
Entry
R1
R2
R4
X
5
Yield [%][b]
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
n-C4H9
Ph
Ph
PhCH2
PhCH2
PhCH2
PhCH2
c-C6H11
i-C3H7
n-C4H9
i-C3H7
Br
Br
Br
Br
I
I
I
I
5a
5b
5c
5d
5e
5 f
95
96
92
76
86
90
68
76
4-MeO-C6H4
Entry
R1
R2
R3
3
Yield [%][b]
2-furyl
Ph
Ph
Ph
Ph
1
2
3
4
5
6
Ph
2-OH-C6H4
4-MeO-C6H4
4-Cl-C6H4
4-CN-C6H4
2-furyl
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
H
H
3a
3b
3c
3d
3e
3 f
3g
3h
3i
92
96
95
90
88
86
67
61
79
75
62
97[e]
Ph
PhCH2
5g
5h
Ph
[a] Imine (0.5 mmol), benzyl bromide (1 mmol) or alkyl iodide (2 mmol),
electrolyte (sat. aq NH4Br/THF (9:1), 6 mL), constant current (60 mA for
benzylation and 15 mA for alkylation), zinc electrodes (1.5 cm2), RT.
[b] Yield of isolated product.
7[c]
8[c]
9
10
11
12[d]
C6H4CH2CH2
nPr
=
Ph
Ph
Ph
Ph
CH2 CHCH2
PhCH2
n-C4H9
Ph
H
H
CH3
3j
3k
3l
a three-dimensional (3D) Tremella fuciformis-like hierarch-
itecture (with pore diameters in the range of 150–400 nm, and
wall thicknesses at about 50 nm).
13
14
Ph
Ph
H
H
3m
3n
88 (98:2[f])
90 (>99:1[f])
15
Ph
H
3o
91 (>99:1[f])
[a] Imine (0.5 mmol), allyl bromide (1 mmol), electrolyte (sat. aq NH4Br/
THF (9:1), 6 mL), constant current (30 mA), zinc electrodes (1.5 cm2),
RT. [b] Yield of isolated product, d.r. in parentheses. [c] One-pot reaction
of aliphatic aldehyde (0.5 mmol), amine (0.5 mmol), and allyl bromide
(1 mmol); see the Supporting Information. [d] Allyl bromide was
replaced with crotyl bromide. [e] Anti/syn=44:56 (determined by
1H NMR analysis). [f] d.r. was determined by 1H NMR spectroscopic
analysis of crude product.
system to afford the desired products in both good yields (88–
91%) and good diastereoselectivities of up to greater than
99:1 d.r. (Table 2, entries 13–15).
Figure 1. SEM image of deposits (Zn-1) from the reaction mixture.
Furthermore, this electrochemical method was also effec-
tive for the benzylation and alkylation of simple imines in
aqueous solution,[9] which have received much less attention
compared with the allylation of imines. After a brief screening
of reaction conditions, it was found that benzylation and
alkylation reactions proceeded smoothly under similar con-
ditions, with only a minor adjustment in the applied current
necessary. A substrate screen showed that both aromatic and
heteroaromatic imines were good substrates for the benzyla-
tion and alkylation reactions (Table 3). It was notable that a
primary iodide (Table 3, entry 7) could also be used for the
alkylation reaction.
During the electroallylation process, we observed that the
zinc deposited on the cathode was of a metallic luster, instead
of a dark-gray color as for the commercial zinc powder.
Further investigations using X-ray diffraction (XRD) analysis
showed that the deposits (represented as Zn-1) consisted of
pure zinc(0) with a good crystalline structure. Scanning
electron microscopy (SEM; Figure 1) showed that Zn-1 had
Attempts to obtain the Zn-1 by deposition of zinc in the
electrolyte (sat. aq NH4Br/THF, 9:1) without the imine or
allyl bromide failed, and instead Zn-2 was obtained,[10] which
indicated that the morphology of the deposited zinc was
controlled by the organic composition in the electrolyte.
Therefore, the effects of imine and allyl bromide on the
controlling of morphology were investigated by SEM. It was
found that with only allyl bromide in the electrolyte, Zn-3 was
obtained,[10] whilst with only imine in the electrolyte, Zn-4 was
obtained;[10] zinc with nano-hierarchitectures could not be
obtained in both cases. Finally, the deposition of Zn-1 was
reproduced in the real reaction mixture (in the presence of
imine and allyl bromide), and 36 mg of Zn-1 was obtained
after 75 minutes.
At present, it is still not clear why Zn-1 could only be
obtained under the actual reaction conditions. It was tenta-
tively suggested that the nitrogen atom of the imine coordi-
nated with zinc(II) in the solution to form a complex, which
Angew. Chem. Int. Ed. 2011, 50, 924 –927
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925

Communications
might account for the unique deposition of Zn-1 with
nanoscale hierarchitectures. However, the allyl bromide
turned out to be another determining factor for producing
such hierarchitectures: in the presence of allyl bromide, the
deposition potential was lowered.[11]
We propose that the distinct activity of Zn-1 towards the
allylation of simple imines might be attributed to its special
nanoscale hierarchitectures. Different from low dimensional
nanomaterials, materials with nanoscale hierarchitectures
showed the features of both micrometer-scaled (e.g. highly
stabilized, easily operated) and nanometer-scaled (e.g. highly
activated) building blocks.[12] A preliminary study on the
relationship between reaction activity and surface morphol-
ogy was carried out using the zinc(0) powders under non-
electrochemical processes (Table 4). Here, Zn-1 to Zn-6
Table 4: Studies on the relationship of reaction activity and surface
morphology.[a]
Entry Zinc powders[b]
Composition of product mixture
product 3a [%] aniline [%] unreacted
Imine 1a [%]
1
2
3
4
Zn-1
Zn-2
Zn-3
Zn-4
Zn-5
Zn-6
Zn-1
78
18
42
44
55
5
13
10
10
<10
15
<10
62
43
41
30
70
0
5
6
<10
92
7[c]
0
[a] Standard conditions: Zn (1 mmol), sat. aq NH4Br-THF (9:1)
(1.0 mL), 1a (0.5 mmol), 2 (1 mmol), RT, 75 min, non-electrochemical
process. [b] Zn-1: zinc with 3D nano-hierarchitectures; Zn-2: zinc
deposited from sat. aq NH4Br/THF (9:1); Zn-3: zinc deposited from
sat. aq NH4Br/THF (9:1) with only allyl bromide; Zn-4: zinc deposited
from sat. aq NH4Br/THF (9:1) with only imine; Zn-5: zinc deposited
from 4.5m aqueous ammonia solution. Zn-6: commercial zinc. [c] Stan-
dard electrochemical process listed under Table 2.
Figure 2. a) SEM image of Zn-5 and b) SEM image of Zn-6.
represented zinc(0) powders[13] with different surface mor-
phologies (for their SEM images, see the Supporting Infor-
mation). As we can see from Table 4, the activity of zinc
towards the allylation reaction is strongly dependent on its
morphology. Zn-1, which has a nanoscale hierarchitecture
(Figure 1), showed the highest reactivity towards the allyla-
tion of simple imine 1a in water (78%, Table 4, entry 1). Zn-
5,[7a] with a porous network structure (Figure 2a), was the
second most effective (55%, Table 4, entry 5). Commercial
zinc (Zn-6),[14] which contained irregular and relatively larger-
sized particles (Figure 2b), showed very low activity (yield
< 10%, Table 4, entry 6).
Figure 3. pH values for solutions of the reaction mixtures from
Table 4.
However, under non-electrochemical conditions, the
allylation reaction mediated by preformed Zn-1 was not as
active as in the electrochemical process (78% vs 92%;
Table 4, entries 1 and 7). Thus, the pH value was carefully
monitored under electrochemical and non-electrochemical
(Figure 3) reaction conditions. It was found that under the
electrochemical process, the pH value of the reaction solution
increased to pH 6.7 from pH 5.4 very fast (less than 10 min)
and maintained at pH 6.7 during the remaining reaction
time,[15] whilst in the non-electrochemical process, the pattern
of the pH curves was different, and decomposition of the
imine was observed. These results suggested that at lower pH
values, the imines were prone to hydrolysis to produce aniline
and benzaldehyde (see Table 4), which is one of the reasons
for the lower yield under non-electrochemical reaction
conditions. Furthermore, during the electrochemical process,
direct electroreduction of the imine and the halides at the
cathode to produce active intermediates may also assist the
desired reactions of simple imines.[16] Therefore, it can be
concluded that, besides the promotion of active Zn-1 with 3D
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Angew. Chem. Int. Ed. 2011, 50, 924 –927

b) T. H. Chan, W. Lu, Tetrahedron Lett. 1998, 39, 8605; c) W.
Lu, T. H. Chan, J. Org. Chem. 2000, 65, 8589; d) W. Lu, T. H.
Chan, J. Org. Chem. 2001, 66, 3467; e) H. M. S. Kumur, S.
Anjaneyulu, E. J. Reddy, J. S. Yadav, Tetrahedron Lett. 2000, 41,
9311; f) D. J. Ritson, R. J. Cox, J. Berge, Org. Biomol. Chem.
2004, 2, 1921; g) L. Bernardi, V. Cere, C. Fermoni, S. Pollicino, A.
Ricci, J. Org. Chem. 2003, 68, 3348; h) H. Miyabe, Y. Yamaoka,
T. Naito, Y. Takemoto, J. Org. Chem. 2003, 68, 6745; i) H.
Miyabe, Y. Yamaoka, T. Naito, Y. Takemoto, J. Org. Chem. 2004,
69, 1415; j) G.-Q. Lin, X.-W. Sun, M. H. Xu, Org. Lett. 2008, 10,
1259; k) I. H. S. Estevam, L. W. bieber, Tetrahedron Lett. 2003,
44, 667; l) S. Kumar, P. Kaur, Tetrahedron Lett. 2004, 45, 3413.
[5] a) P. T. Anastas, J. C. Warner, Green Chemistry: Theory and,
Practice, Oxford University Press, New York, 1997; b) P. T.
Anastas, M. M. Kirchhoff, Acc. Chem. Res. 2002, 35, 686.
[6] a) K. Uneyama, H. Matsuda, S. Torii, Tetrahedron Lett. 1984, 25,
6017; b) R. Grigg, B. Putnikovic, C. J. Urch, Tetrahedron Lett.
1997, 38, 6307; c) S. Seka, O. Burize, J. Y. Nꢁdꢁlec, J. Pꢁrichon,
Chem. Eur. J. 2002, 8, 2534; d) G. Hilt, K. I. Smolko, Angew.
Chem. 2001, 113, 3514; Angew. Chem. Int. Ed. 2001, 40, 3399;
e) G. Hilt, Angew. Chem. 2002, 114, 3737; Angew. Chem. Int. Ed.
2002, 41, 3586; f) D. Nematollahi, R. A. Rahchamani, J. Elec-
troanal. Chem. 2002, 520, 145; g) G. Hilt, Angew. Chem. 2003,
115, 1760; Angew. Chem. Int. Ed. 2003, 42, 1720; h) P. Gomes, C.
Gosmini, J. Pꢁrichon, J. Org. Chem. 2003, 68, 1142; i) Z. Zha, A.
Hui, Y. Zhou, Q. Miao, Z. Wang, H. Zhang, Org. Lett. 2005, 7,
1903; j) G. Hilt, K. I. Smolko, C. Waloch, Tetrahedron Lett. 2002,
43, 1437; k) Z. Li, Z. Zha, Z. Zhang, Y. Li, Z. Wang, Chem.
Commun. 2010, 46, 7196; l) L. Zhang, Z. Zha, Z. Wang, Synlett
2010, 1915.
nano-hierarchitectures, the electrochemical process is
another factor for the excellent yield of allylation of simple
imines in water.
In conclusion, an efficient electrosynthesis of amines from
simple imines with allylic bromides, benzyl bromides, and
alkyl iodides in aqueous solution has been developed. This
preliminary study showed that the deposited zinc(0) powder
with nanoscale hierarchitectures played an important role in
the reaction of simple imines in aqueous media. High
efficiencies and environmental friendliness rendered this
methodology as an attractive alternative synthetic route to
amines. Further investigation to determine the mechanism of
this reaction and to expand its scope is underway in our
laboratory.
Experimental Section
General procedure for the allylation of imines: A mixture of 1a
(0.5 mmol) in THF (0.6 mL) and allyl bromide (1.0 mmol) was added
to a saturated aqueous NH4Br solution (5.4 mL). The stirring mixture
was then electrolyzed at a constant current of 30 mA in a round-
bottom-flask cell equipped with a pair of zinc electrodes (1.5 cm2) at
RT. The electrolysis was stopped when the imine had been completely
consumed (monitored by TLC, 75 min, 2.6 FmolÀ1). After the
electrolysis, THF was removed on a rotary evaporator. The residue
was extracted with ethyl acetate (2 ꢀ 10 mL). The combined organic
layer was washed with brine (5 mL), dried over Na2CO3, filtered, and
concentrated under vacuum. The crude product was purified by
column chromatography on silica gel (petroleum ether/ethyl acetate
10:1) and the product was obtained as a colorless oil (3a, 103 mg,
92%).
[7] a) J.-M. Huang, Y. Dong, Chem. Commun. 2009, 3943; b) J.-M.
Huang, H. R. Ren, Chem. Commun. 2010, 46, 2286.
[8] For the reduction of the CN group in an electrochemical process,
see Ref. [6j].
[9] To the best of our knowledge, it is the first report of the
benylation of simple imines in aqueous media. The alkylation of
simple imines in aqueous media has only recently been reported;
see: T.-S. Huang, C. K. K. Keh, C.-J. Li, Chem. Commun. 2002,
2440, and Ref. [3d].
Received: August 4, 2010
Published online: November 25, 2010
Keywords: allylation · aqueous reactions · electrochemistry ·
.
[10] For the SEM images of the depositions from different electrolyte
solutions, see the Supporting Information.
imines · zinc
[11] In the absence of allyl bromide, the deposition potential was
0.6 V, whilst in the presence of allyl bromide, the potential was
0.2 V. It has been reported that the deposition potential was
critical for controlling the morphology of deposited particles.
See: L. Xiao, L. Zhuang, Y. Liu, J. Lu, H. D. Abrunda, J. Am.
Chem. Soc. 2009, 131, 602.
[12] a) Z. L. Sun, S. C. Liufu, X. H. Chen, L. D. Chen, Chem.
Commun. 2010, 46, 3101; b) B. F. Lu, W. P. Cai, Y. G. Zhang,
Adv. Funct. Mater. 2008, 18, 1047, and references therein.
[13] XRD analysis has shown that all of the powders contain zinc in
its zero valence state, with good crystalline forms. XRD patterns
demonstrated that these crystals are in different shapes; for
further information, see the Supporting Information.
[14] The commercial zinc powder was activated before used for
allylation and SEM studies. For the procedure of activating zinc,
see: C. L. K. Lee, H.-Y. Ling, T.-P. Loh, J. Org. Chem. 2004, 69,
7787.
[15] It is believed that the electrolysis process helped to maintain a
suitable proton concentration.
[1] a) C. Agami, F. Coutyand, G. Evano, Tetrahedron: Asymmetry
2000, 11, 4639; b) H. Ding, G. K. Friestad, Synthesis 2005, 2815;
c) A. M. Schmidt, P. Eilbracht, J. Org. Chem. 2005, 70, 5528;
d) J. E. Kropf, I. C. Meigh, M. W. P. Bebbington, S. M. Weinreb,
J. Org. Chem. 2006, 71, 2046; e) C. Denhez, J.-L. Vasse, D.
Harakat, J. Szymoniak, Tetrahedron: Asymmetry 2007, 18, 424.
[2] For recent leading reviews, see: a) C.-J. Li, Chem. Rev. 2005, 105,
3095; b) C.-J. Li, Acc. Chem. Res. 2002, 35, 533; c) C.-J. Li, Chem.
Rev. 1999, 99, 2023; d) C.-J. Li, Tetrahedron 1996, 52, 5643.
[3] a) C. C. K. Keh, C.-M. Wei, C.-J. Li, J. Am. Chem. Soc. 2003, 125,
4062; b) W.-C. Zhang, C.-J. Li, J. Org. Chem. 1999, 64, 3230;
c) T. H. Chan, M. B. Isaac, Pure Appl. Chem. 1996, 68, 919;
d) Z.-L. Shen, T.-P. Loh, Org. Lett. 2007, 9, 5413; e) Z.-L. Shen,
H.-L. Cheong, T.-P. Loh, Chem. Eur. J. 2008, 14, 1875; f) Z.-L.
Shen, Y.-L. Yeo, T.-P. Loh, J. Org. Chem. 2008, 73, 3922; g) H.
Miyabe, T. Naito, Org. Biomol. Chem. 2004, 2, 1267; h) F. F.
Fleming, S. Gudipati, Org. Lett. 2006, 8, 1557; i) F. F. Fleming, S.
Gudipati, J. A. Aitken, J. Org. Chem. 2007, 72, 6961; j) Z.-L.
Shen, H.-L. Cheong, T. P. Loh, Tetrahedron Lett. 2009, 50, 1051.
[4] For examples, see: a) X. Piao, J. K. Jung, H. Y. Knag, Bull.
Korean Chem. Soc. 2007, 28, 139, and references therein;
[16] Reductive waves were observed for imine 1a, allylic bromide,
benzyl bromide, and cyclohexane iodide by cyclic-voltammetry
studies. For further details, see the Supporting Information.
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