Sn-mediated one-pot four-component allylation of aldimines

Article abstract of DOI:10.1002/aoc.3122

A convenient and facile method for the synthesis of homoallylic amines was disclosed. The one-pot reaction of aldehydes, aromatic amines and allylic bromide with tin powder at room temperature could afford the homoallylic amines in good to excellent yield

Full text of DOI:10.1002/aoc.3122

Full Paper
Received: 31 October 2013
Revised: 17 December 2013
Accepted: 21 December 2013
Published online in Wiley Online Library: 30 January 2014
(wileyonlinelibrary.com) DOI 10.1002/aoc.3122
Sn-mediated one-pot four-component
allylation of aldimines
Jian Li, Wenxian Lv, Danfeng Huang*, Ke-Hu Wang, Teng Niu,
Yingpeng Su* and Yulai Hu
A convenient and facile method for the synthesis of homoallylic amines was disclosed. The one-pot reaction of aldehydes,
aromatic amines and allylic bromide with tin powder at room temperature could afford the homoallylic amines in good to
excellent yield without any promoter or additive. The method is highly efficient and environmentally benign with low cost
and concise manipulation. Copyright © 2014 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web-site.
Keywords: tin powder; one-pot; allylation; homoallylic amines
Introduction
Results and Discussion
Nucleophilic addition of allylic organometallics to carbonyl com-
pounds or their derivatives constitutes a representative method
for preparing homoallylic compounds,[1–4] which are versatile
building blocks and synthons in the synthesis of many biologi-
cally active molecules and natural products.[5–16] Among the
existing methods to construct these biologically active molecules
and natural products, the Barbier[17–19] or Barbier-type reac-
tion[20–25] is one of the easiest and most convenient strategies.
In the past few decades, several kinds of allylic organometallics
such as allyl Si,[26,27] Sn,[28–31] Sm,[32,33] Mg,[34,35] Zn,[36–38] B[37,39]
and In[40–43] have been intensively investigated in allylation reac-
tion.[44–47] Among these, allyltributyltin is an effective and com-
monly used reagent for allylation of aldehydes or imines to give
homoallylic alcohols or amines.[8] Although it has several advan-
tages such as easy availability, air and moisture stability and com-
patibility with a variety of functional groups,[48] its application is
still limited because of the toxicity of organotin compounds
and the formation of an unwanted byproduct containing the
SnBu3 group during the reaction.[49–52] Furthermore, only the allyl
group in allyltributyltin is delivered into the product molecule
and the SnBu3 group is usually discarded as waste after the reac-
tion. Thus, this transformation is not an efficient method from the
viewpoint of atom economy. Moreover, Lewis acids or Brønsted
acids are often needed in the allylation of imines with
allyltributyltin to activate the substrates,[52–61] generally because
of the lower reactivity of imine compared with the corresponding
aldehyde.[44,46,62–64] In this context, there is ongoing interest in
developing an environmentally benign and bench-friendly pro-
cess for allylation of imines with non-toxic tin reagents. As we
know, tin powder is much less toxic than the organostannes. If
the organostannes can be replaced by tin powder in organic re-
actions, the process would be more environmentally benign. To
our knowledge, there are few reports on four-component
allylation in the presence of tin powder.[65] Herein, we report a
one-pot four-component procedure for preparation of
homoallylic amines, involving in situ generation[66–68] of imines
and allyltin without any additive.
Initially, the one-pot allylation was performed in 1,4-dioxane
using benzaldehyde(1 equiv.), aniline (1 equiv.), allylic bromide
(1 equiv.) and tin powder (1 equiv.) at room temperature. The cor-
responding homoallylic product was readily formed, but the yield
was only 12% (Table 1, entry 1). In order to optimize the product
yield, the different mole ratios of the substrates and solvents
were checked. As summarized in Table 1, the best product yield
was obtained by carrying out the reaction at room temperature
in 1,4-dioxane with a mole ratio of benzaldehyde/aniline/
allylbromide/tin of 1.0/1.5/1.5/2.0. Under these conditions 4a
was obtained in 87% yield in 12 h (Table 1, entry 6).
In order to study the scope of this new protocol, reactions of
various aromatic amines with benzaldehyde were investigated
first (Table 2, entries 1–12). Anilines bearing electron-withdrawing
groups such as Cl and Br in the para position underwent allylation
smoothly to furnish the desired adducts 4 in good yields (Table 2,
entries 2 and 3). However, para-NO2-substituted aniline could
not give the desired product (Table 2, entry 4). Anilines with
electron-donating groups in both the ortho and para position
could also provide the corresponding homoallylic amines with
slightly low yields (Table 2, entries 5–8). This is possibly due to
the lower stability of the formed imines compared with the
electron-withdrawing ones. Interestingly, when bulky anilines
2i and 2j were exposed under the optimal condition, the de-
sired products 4i and 4j were obtained in good yield (Table 2,
entries 9 and 10). 2-Naphthyl amine gave the product 4k in
moderate yield. Unfortunately, aliphatic amine could not be-
have well in this transformation. The reason for this may be that
*
Correspondence to: D. Huang or Y. Su, College of Chemistry and Chemical
Engineering, Northwest Normal University, Anning East Road 967#, Lanzhou,
Gansu 730070, People’s Republic of China. Email: huangdf@nwnu.edu.cn or
suyingp@gmail.com
College of Chemistry and Chemical Engineering, Northwest Normal University,
Anning East Road 967#, Lanzhou, Gansu 730070, People’s Republic of China
Appl. Organometal. Chem. 2014, 28, 286–289
Copyright © 2014 John Wiley & Sons, Ltd.

Sn-mediated one-pot four-component allylation
Table 1. Optimization of reaction conditions for one-pot four-com-
imines formed from the aliphatic amines are labile and amena-
ble to side reactions. (Table 2, entry 12).
ponent allylationa
We next examined the substrate scope of aldehydes. As shown
in Table 3, a variety of aromatic aldehydes with both electron-
withdrawing groups and electron-donating groups could react
with aniline under the optimized reaction conditions to produce
homoallylic amines in good yield. Nevertheless, the former gave
better yields than the latter (Table 3, entries 1–3 versus 4). 2-
Furaldehyde and 2-thenaldehyde also afforded appropriate prod-
ucts in fair yield (Table 3, entries 5 and 6). As reported in the
literature, for aliphatic aldehydes having α-protons, the allylation
reaction usually takes place with many side reactions to dramat-
ically decrease the product yield.[62,63] Keeping this in view,
pivaldehyde without α-protons was used in our reaction, and
the product 4s was obtained in 73% yield (Table 3, entry 7).
As indicated above, the use of an electron-deficient aldehyde
and amine is beneficial to this allylation reaction. To further con-
firm this fact, electron-rich para-anisaldehyde and electron-poor
ortho-fluorobenzaldehyde were selected as substrates to react
anilines with different electronic properties. As expected, the
reactions of electron-rich para-anisaldehyde with electron-poor
anilines could furnish the desired products in higher yield than
the reaction with electron-rich anilines (Table 4, entries 1–4).
These results are in agreement with those obtained from the re-
action of electron-poor ortho-fluorobenzaldehyde with various
anilines (Table 4, entries 5–8). Based on the above investigation,
it is further confirmed that the use of electron-poor aromatic
aldehydes and/or anilines is more suitable in the present four-
component allylation protocol.
Entry
Mole ratio of
1a/2a/3/Sn
Solvent
Time (h) Yield (%)b
1
1.0/1.0/1.0/1.0
1.0/1.0/1.0/1.5
1.0/1.0/1.5/2.0
1.0/1.0/2.0/2.0
1.0/1.0/2.0/2.5
1.0/1.5/1.5/2.0
1.0/2.0/2.0/2.0
1.0/2.0/2.0/2.5
1.0/1.5/1.5/2.0
1.0/1.5/1.5/2.0
1.0/1.5/1.5/2.0
1.0/1.5/1.5/2.0
1.0/1.5/1.5/2.0
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
THF
24
24
24
12
12
12
12
12
24
24
24
24
24
12
24
63
83
85
87
86
87
78
72
47
60
66
2
3
4
5
6
7
8
9
10
11
12
13
Ether
Toluene
DCM
EtOH
aReaction conditions: benzaldehyde (1a, 1.0 mmol), aniline (2a,
1.0–2.0 mmol), allylic bromide (3, 1.0–2.0 mmol), tin (1.0–2.0
mmol), solvent (3.0 mL).
bIsolated yield.
A plausible mechanism for this tin-mediated allylation process
is proposed in Scheme 1 on the basis of experimental results and
previous reports.[29,69,70] As illustrated by Chan and co-
workers,[29] allyltin bromide 5 and diallyltin dibromide 6 are gen-
erated as organometallic intermediates in this process. According
to the optimized condition, the ratio of allylic bromide and tin
powder is 1:1.3. Thus we believe that the intermediate 5 is the
favored intermediate. Moreover, neither Brønsted acid nor Lewis
acid is required for the reaction, which indicates that the nucleo-
philicity of organometallic intermediate 5 is enough to react with
Table 2. Results of the allylation of benzaldehyde with various aminesa
Table 3. Results of the allylation of aniline with various aldehydesa
Entry
R2
Product
Yield (%)b
1
Ph
4a
4b
4c
—
4e
4f
87
78
75
NR
62
69
61
64
83
81
63
ND
2
p-Cl-C6H4
3
p-Br-C6H4
p-NO2-C6H4
p-CH3-C6H4
o-CH3-C6H4
p-CH3O-C6H4
p-C2H5O-C6H4
2,6-(i-Pr)2-C6H3
Mes-
4
Entry
R1
Product
Yield (%)b
5
6
1
2
3
4
5
6
7
p-CF3-C6H4
o-Cl-C6H4
o-F-C6H4
p-CH3O-C6H4
2-Thienyl
2-Furyl
4m
4n
4o
4p
4q
4r
83
82
88
72
68
74
73
7
4g
4h
4i
8
9
10
11
12
4j
2-Naphthyl
t-Bu
4k
—
t-Bu
4s
aReaction conditions: benzaldehyde (1.0 mmol), amines (1.5 mmol),
allylic bromide (1.5 mmol), tin (2.0 mmol), 1,4-dioxane (3.0 mL).
bIsolated yield.
aReaction conditions: aldehydes (1.0 mmol), aniline (1.5 mmol),
allylic bromide (1.5 mmol), tin (2.0 mmol), 1,4-dioxane (3.0 mL).
bIsolated yield.
Appl. Organometal. Chem. 2014, 28, 286–289
Copyright © 2014 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

J. Li et al.
Table 4. Results of the allylation of various aromatic aldehydes with
Experimental
aromatic aminesa
A solution of R1CHO (1 mmol), R2NH2 (1.5 mmol), allylic bromide
(1.5 mmol) and Sn powder (2 mmol) in 1,4-dioxane (3 mL) was
stirred at room temperature for 12–24 h (monitored by thin-layer
vhromatography), then quenched with saturated NH4Cl aq.,
extracted with EtOAc and dried over anhydrous MgSO4. The
solvent was removed under vacuum, and the crude product
was purified by column chromatography on silica gel (petroleum
ether/EtOAc) to afford the desired product.
Entry
R1
R2
Product
Yield (%)b
1
2
3
4
5
6
7
8
p-CH3O-C6H4
p-CH3O-C6H4
p-CH3O-C6H4
p-CH3O-C6H4
o-F-C6H4
o-CH3-C6H4
p-CH3-C6H4
p-Cl-C6H4
4t
4u
4v
68
67
89
90
89
86
92
96
Acknowledgments
We are thankful for financial support from the National Natural
Science Foundation of China (Grant No. 21062016); Key Labora-
tory Polymer Materials of Gansu Province (Northwest Normal
University); Bioactive Product Engineering Research Center for
Gansu Distinctive Plants; and State Key Laboratory of Applied
Organic Chemistry, Lanzhou University.
p-Br-C6H4
o-CH3-C6H4
p-CH3-C6H4
p-Cl-C6H4
4w
4x
o-F-C6H4
4y
o-F-C6H4
4z
o-F-C6H4
p-Br-C6H4
4aa
aReaction conditions: aldehydes (1.0 mmol), amines (1.5 mmol),
allylic bromide (1.5 mmol), tin (2.0 mmol), 1,4-dioxane (3.0 mL).
bIsolated yield.
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Appl. Organometal. Chem. 2014, 28, 286–289
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