Solvent-free allylation and benzylation of aldimines mediated by zinc powder

Article abstract of DOI:10.1016/j.tetlet.2009.03.184

A rapid and efficient procedure for allylation and benzylation of aldimines mediated by zinc powder under solvent-free conditions is described. The procedure is operationally simple, higher regioselective, and gives good to excellent yields.

Full text of DOI:10.1016/j.tetlet.2009.03.184

Tetrahedron Letters 50 (2009) 2925–2928
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Tetrahedron Letters
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Solvent-free allylation and benzylation of aldimines mediated by zinc powder
*
Yumei Zhang , Tingli Yan, Wei Cheng, Jianming Zuo, Weijie Zhao
The School of Chemical and Biological Engineering, Lanzhou Jiaotong University, 88 West Anning Road, Lanzhou 730070, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A rapid and efficient procedure for allylation and benzylation of aldimines mediated by zinc powder
under solvent-free conditions is described. The procedure is operationally simple, higher regioselective,
and gives good to excellent yields.
Received 4 November 2008
Revised 26 March 2009
Accepted 27 March 2009
Available online 1 April 2009
Ó 2009 Published by Elsevier Ltd.
Allylation and benzylation of imines are an established
route to homoallylic and homobenzylic amines, which are fun-
damental building blocks for many biologically active com-
pounds and the synthesis of many nitrogen containing
natural products.1–3 The reactions are generally carried out by
addition of organometallic reagents to imines in the presence
of acid catalysts in anhydrous organic solvents. Acid catalysts
hyde imines (entries 8 and 9) were produced by grinding to-
gether furfuraldehyde with aniline with a mortar in an ice-
bath.
We studied the reactions of allyl bromide and imines mediated
by zinc powder under solvent-free conditions.8 The range of differ-
ent types of aryl aldimines studied in this reaction is summarized
in Table 1. Imines containing both electron donating and electron-
withdrawing groups in the aromatic rings proceeded smoothly.
The corresponding homoallylic secondary amines were obtained
in yields ranging from 76% to 94%. Other solventless methods6
include
TiCl4,
BF3.OEt2,
PdCl2(PPh3)2,
Pd2(dba)3,
or
PtCl2(PPh3)2.1a,b,4 However, many of these reagents are expen-
sive, hygroscopic, and difficult to handle. Therefore current
investigation has focused on developing more benign protocols
for the allylation of aldimines.5 Solvent-free synthesis of homo-
allylic amines has also been considered.6 However, the previ-
ous solvent-free method has certain drawbacks such as
requirement of expensive Ga metal, supersonic irradiation with
long reaction time, or unsatisfactory yields (especially with
have been found to be unsuitable for the
–OH substituted imines. However, our approach only proceeded
with 1,2-additions for ,b-unsaturated, and compatible with the
a,b-unsaturated and the
a
–OH substituted imines, and the yields were high (Table 1, entries
5–7 and 10).
Compared to the extensive studies on the allylation of imines,
the benzylation of imines has received much less scrutiny.7 We re-
port herein benzylation of imines under solvent-free conditions
mediated by zinc powder. The results are listed in Table 2. Aro-
matic and hetoroaromatic imines gave the products in high yields
a,b-unsaturated and the –OH substituted imines). In this Letter,
we report the reactions of allyllation and benzylation of aldi-
mines mediated by zinc powder under solvent-free conditions.
Allyl bromide and benzyl bromide can react with aryl aldi-
mines without other assistance or any catalysts, and the reac-
tion is completed within 20–30 min.8
Also, the reactions of organozinc reagents always require strict
reaction conditions such as N2 atmosphere, anhydrous solvent, and
low temperature. However, our present route proceeds well in
atmosphere at room temperature. The yields are high and the reac-
tion time is very short.
(Table 2, entries 1–5, 7 and 8), and a,b-unsaturated imine only pro-
ceeded with 1,2-addition (Table 2, entry 6), while imines derived
from hydroxyl substituted aldehydes did not give the desired
product.
In conclusion, we have developed a new and simple procedure
for the allylation and benzylation of aryl aldimines mediated by
zinc powder under solvent-free and catalyst-free conditions at
room temperature. The reaction here has the following advanta-
ges: mild conditions, short reaction time, environmentally benign
procedure, and high yield.
Imines 1 listed in Table 1 were prepared by mixing various
aldehydes with aniline in the presence of a catalytic amount of
toluene-4-sulfonic acid at room temperature.6 The furfuralde-
* Corresponding author. Tel.: +86 0931 4938803.
E-mail address: zhangym@mail.lzjtu.cn (Y. Zhang).
0040-4039/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2009.03.184

2926
Y. Zhang et al. / Tetrahedron Letters 50 (2009) 2925–2928
Table 1
Zinc powder mediated allylation of imines under solvent-free conditionsa
Zn*
R2
R2
Br
+
R1
Solvent-free
r.t. 20-30 min
N
R1
N
H
1
3a -j
2
Entry
1
R1
R2
Productb
Yieldc (%)
NH
p-Br–C6H4
C6H5
3a
3b
3c
86
Br
NH
Cl
2
3
C6H5
p-Cl–C6H4
93
94
NH
p-F–C6H4
C6H5
F
NH
NH
4
5
6
7
C6H5
C6H5
3d
3e
3f
91
88
76
82
o-OH–C6H4
o-OH–C6H4
o-OH–C6H4
C6H5
OH
OH
NH
NH
CH3
p-CH3–C6H4
H3C
o-CH3–C6H4
3g
OH
NH
NH
CH3
8
9
2-Furyl
p-CH3–C6H4
p-Cl–C6H4
C6H5
3h
3i
85
92
88
O
O
Cl
2-Furyl
NH
10
C6H5–CH@CH
3j
a
Reaction condition: activated zinc powder (6 mmol), imines (4 mmol), and allyl bromide (5 mmol) at room temperature for 20–30 min.
b
c
All products were characterized by IR, 1H NMR, 13C NMR, and MS.
Isolated yield.

Y. Zhang et al. / Tetrahedron Letters 50 (2009) 2925–2928
2927
Table 2
Zinc powder mediated benzylation of imines under solvent-free conditionsa
Ph
Zn*
R2
+
PhCH2Br
4
R2
R1
N
Solvent-free
r.t. 20-30 min
R1
N
H
1
5a -h
Entry
1
R1
R2
Productb
Yieldc (%)
NH
NH
C6H5
C6H5
5a
5b
5c
5d
5e
5f
87
Cl
2
3
4
5
6
7
C6H5
p-Cl–C6H4
89
83
94
91
72
70
83
NH
p-F–C6H4
p-CH3O–C6H4
p-CH3O–C6H4
C6H5-CH@CH
2-Furyl
C6H5
F
NH
NH
CH3
p-CH3–C6H4
p-Cl–C6H4
C6H5
H3CO
Cl
H3CO
NH
NH
NH
Cl
p-Cl–C6H4
5g
O
O
CH3
8
2-Furyl
p-CH3–C6H4
5h
a
Reaction condition: activated zinc powder(6 mmol), imines (4 mmol), and benzyl bromide (5 mmol) at room temperature for 20–30 min.
b
c
All products were characterized by IR, 1H NMR, 13C NMR, MS.
Isolated yield.

2928
Y. Zhang et al. / Tetrahedron Letters 50 (2009) 2925–2928
I.; Jun, Y. M.; Lee, B. M.; Kim, B. H. Synth. Commun. 2005, 35, 1725; (d) Vilaivan, T.;
Acknowledgment
Winotapan, C.; Shinada, T.; Ohfune, Y. Tetrahedron Lett. 2001, 42, 9073.
6. Andrews, P. C.; Peatt, A. C.; Raston, C. L. Tetrahedron Lett. 2004, 45, 243.
7. Hatano, M.; Suzuki, S.; Isbibara, K. J. Am. Chem. Soc. 2006, 128, 9998.
8. General experimental procedure for preparation of homobenzylamine and
homoallylamine: Activated zinc powder9,10 (0.39 g, 6 mmol) was placed in
a dried round-bottomed flask fitted with a magnetic stir bar. Then imine
(4 mmol) was added immediately. After this step, allyl (or benzyl)
bromide (5 mmol) was added dropwise in 2 min and then stirred for
20–30 min at room temperature. After the reaction was completed, as
indicated by TLC, saturated aqueous ammonium chloride was poured
into the mixture and stirred for 5 min. Ethyl ether was added to the
reaction mixture and the organic layer was separated. The organic
extracts were dried over anhydrous MgSO4. The residue was purified by
column chromatograph on silica gel using petroleum/ethyl acetate as an
eluent. Typical spectral data are as follows: 2-(1-(p-toluidino)but-3-
This work was supported by ‘Qing Lan’ Talent Engineering
Funds of Lanzhou Jiaotong University.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.03.184.
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