Highly efficient synthesis of homoallylamines from aldimines with allylstannane promoted by MgI2 etherate

Article abstract of DOI:10.3184/030823410X12756737135354

We describe a mild and efficient procedure for the synthesis of homoallylamines by addition of allyltributylstannane to aldimines with promoted by MgI₂ etherate (MgI₂?(OEt₂)_n) in good to excellent yields.

Full text of DOI:10.3184/030823410X12756737135354

336 RESEARCH PAPER
JUNE, 336–339
JOURNAL OF CHEMICAL RESEARCH 2010
Highly efficient synthesis of homoallylamines from aldimines with
allylstannane promoted by MgI2 etherate
Xingxian Zhang*, Shenghui Hu and Junchen Shi
College of Pharmaceutical Sciences, Zhejiang University ofTechnology, Hangzhou, Zhejiang 310032, P. R. China
We describe a mild and efficient procedure for the synthesis of homoallylamines by addition of allyltributylstannane
to aldimines with promoted by MgI2 etherate (MgI2•(OEt2)n) in good to excellent yields.
Keywords: aldimine, allyltributylstannane, homoallylamine, MgI2 etherate
Lewis acid-catalysed carbon–carbon bond forming reactions
are of great importance in organic synthesis due to their high
rate of reaction and selectivity under mild reaction condi-
tions.1–3 Lewis acid-promoted nucleophilic addition of allylic
organometallics to aldimines is one of the most important
carbon–carbon bond forming reactions, and it provides a useful
method for the preparation of homoallylamines.4 Homoallyl-
amines are important building blocks for the preparation of
various biologically active molecules.5 Generally, the prepara-
tion of homoallylamines is accomplished either by nucleo-
philic addition of organometallic reagents6,7 or by addition
of allylsilane, allyltin, allylboron or allylgermane reagents to
imines in the presence of a variety of Lewis acids,8–10 transition
metallic reagents,11,12 lanthanide triflates,13,14 or other cata-
lysts.15 Recently, Li and Zhao have developed the allylation
of allyltributyltin promoted by the recoverable and reusable
polymer-supported sulfonamide of N-glycine.16 However, the
traditional methods using Lewis acids such as TiCl4, BF3•Et2O
and SnCl4 must be carried out under strictly anhydrous con-
ditions, which are difficult to achieve especially on a large
scale. Palladium complexes and water-tolerant Lewis acids
lanthanide triflates are rather expensive. From the above, it is
clear that the development of less expensive, environmentally
benign, and easily handled promoters for allylation of
aldimines is highly desirable.
% yield (entry 2). Furthermore, the allylation of imine 1c gave
the desired product in good yield (entry 3). Inspired by the
above results, we applied the MgI2 etherate catalyst system to
the allylation of a variety of imines. The results are summarised
in Table 1. As shown in Table 1, the reaction proceeded
smoothly at room temperature and provided good to excellent
yields. The reaction of the aldimines 1d and 1e, derived from
p-anisaldehyde and p-nitrobenzaldehyde, also proceded very
smoothly and provided the homoallylamines 2d and 2e respec-
tively in nearly quantitative yields (Table 1, entries 4 and 5).
The use of o-aminophenol as the imine component was exam-
ined and the allylation products 2f–i were obtained in good
yields (Table 1, entries 6–9). The allylation of the imine 1l
derived from cinnamaldehyde and p-methoxyaniline produced
the homoallylamine 2l in 90% yield (Table 1, entry 12).
Morever, the reaction of heteroaromatic imines 1j and 1k
derived from 2-thiophenealdehyde also proceeded in good
yields (Table 1, entries 10 and 11). Apparently, the use of aro-
matic amines as the imine component gave, in general, better
results than the use of benzylamine. The reactions of allyltri-
butylstannane with chiral imines, promoted by MgI2 etherate,
were also studied (Table 1, entries 13 and 14). The allylation
with chiral imines involving the S-l-phenylethylamine auxil-
iary afforded moderate stereoselection in excellent yield. In
addition, various ketoimine substrates are unreactive toward to
allyltributylstannane in the presence of MgI2 etherate (Table 1,
entries 15–17).
To examine the halide anion effect, MgCl2 etherate and
MgBr2 etherate were compared under parallel reaction condi-
tions (100 mol % of catalyst) in the allylation reaction of ben-
zylideneaniline 1a with allyltributylstannane. MgCl2 etherate
is almost inactive and MgBr2 etherate is less effective in terms
of substrate conversion and yield. The unique reactivity of
MgI2 etherate is attributed to the dissociative character of the
iodide counterion and a more Lewis acidic cationic [MgI]+
species as a result of Lewis base activation of Lewis acid.13
In conclusion, we have found an efficient and smooth
allylation of imines with allyltributylstannane in the presence
of the MgI2 etherate system. This catalytic reaction enables the
allylation to be carried out under essentially neutral conditions
at room temperature in good to excellent yields. We are
still working with other chiral imines to enhance the level
of the diastereoselectivity. We intend to study the addition
of stereogenic and heterosubstituted stannanes and an
enantioselective variant of this reaction.
In our previous paper,17 we have demonstrated that MgI2
etherate could efficiently promote the allylation of aldehydes
with allyltributylstannane. In the continuation of our research,
we now wish to describe a simple and efficient allylation of
aldimine with allyltributylstannane promoted by MgI2 etherate
under mild reaction conditions in good to excellent yields
(Scheme 1).
Results and discussion
Initially, we preformed a variety of imines derived from aro-
matic aldehydes and aromatic amines. We carried out our
first studies into the allylation of benzylideneaniline 1a with
allyltributylstannane using an equimolar amount of freshly
prepared MgI2 etherate in CH2Cl2 at room temperature. After
stirring for 1.0 h, the desired homoallylamine was afforded
in 92% yield. Then, under the similar reaction conditions, the
allylation of aldimine 1b and 1c, prepared from benzaldehyde
and 4-methylaniline or benzylamine, respectively, was exam-
ined, (Table 1, entries 2 and 3). The aromatic imine 1b also
produced the corresponding homoallylamine 2b in 95%
Scheme 1 MgI2 etherate-promoted allylation of aldimines with allyltributylstannane.
* Correspondent. E-mail: zhangxx@ zjut.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2010 337
a
Table 1 The allylation of aldimine with allyltributylstannane promoted by MgI2•(OEt2)n
Entry
Aldimine
Time/h
Productb
Yield/%c
92
1
1
2a
2
3
0.5
2
2b
2c
2d
2e
2f
95
89
98
97
90
91
87
88
93
86
90
4
1
5
0.5
0.5
0.5
0.5
0.5
0.5
1
6
7
2g
2h
2i
8
9
10
11
12
2j
2k
2l
1

338 JOURNAL OF CHEMICAL RESEARCH 2010
Table 1 Continued
Entry
Aldimine
Time/h
2
Productb
Yield/%c
13
2m
92 (dr 74:26)d
14
15
16
17
2
8
8
8
2n
94 (dr 62:38)d
NAe
NA
NA
NRf
NR
NR
a The reaction was carried out by addition of imine and allyltributylstannane promoted by 1.0 equivalent of MgI2•(OEt2)n at room
temperature in CH2Cl2.
b All products were identified by their 1H NMR spectra.
c Yields of products isolated by column chromatography.
d The ratio of dr value was determined by 1H NMR analysis.
e NA = Not available.
f NR = No reaction.
4-(4′-Methoxy-phenyl)-4-(N-phenyl)aminobut-1-ene (2d):22 δH
Experimental
2.48–2.52 (m, 1H), 2.58–2.61 (m, 1H), 3.68 (s, 3H,), 4.30 (dd, 1H,
For product purification by flash column chromatography, silica gel
J = 5.0, 8.0 Hz), 5.12–5.19 (m, 2H), 5.71–5.78 (m, 1H), 6.46 (d, 2H,
(200–300 mesh) and light petroleum ether (PE, b.p. 60–90 °C) were
used. 1H NMR spectra were taken on a Bruker AM-500 spectrometer
with TMS as an internal standard and CDCl3 as solvent. The reactions
monitoring was accomplished by TLC on silica gel polygram
J = 8.5 Hz), 6.67 (dd, 2H, J = 2.5, 7.0 Hz), 7.22–7.24 (m, 1H),
7.29–7.33 (m, 2H), 7.34–7.36 (m, 2H).
4-(4′-Nitrophenyl)-4-(N-4′-chloro-phenyl)aminobut-1-ene (2e):23
δH 2.45–2.52 (m, 1H), 2.59–2.64 (m, 1H), 4.26 (br s, 1H), 4.42–4.45
(m, 1H), 5.18–5.22 (m, 2H), 5.67–5.74 (m, 1H), 6.34 (d, 2H, J =
10.0 Hz), 7.01 (d, 2H, J = 10.0 Hz), 7.51 (d, 2H, J = 10.0 Hz), 8.17
(d, 2H, J = 10.0 Hz).
1
SILG/UV 254 plates. All compounds were identified by H NMR
and the spectra are in good agreement with those reported in the
literature.
4-(4′-Nitrophenyl)-4-(N-2′-hydroxy-phenyl)aminobut-1-ene (2f):24
δH 2.55–2.65 (m, 2H), 4.47 (t, 1H, J = 6.8 Hz), 5.18–5.24 (m, 2H),
5.71–5.82 (m, 1H), 6.23 (d, 1H, J = 8.0 Hz), 6.59 (t, 1H, J = 7.6 Hz),
6.67 (t, 1H, J = 7.6 Hz ), 6.72 (d, 1H, J = 4.4 Hz), 7.55 (d, 2H,
J = 9.2 Hz), 8.18 (d, 2H, J = 8.4 Hz).
Synthesis of homoallylamines; typical procedure
To a stirred benzylideneaniline 1a solution of (0.5 mmol) in CH2Cl2
(3 mL) was added freshly prepared MgI2 etherate (0.5 mmol) at room
temperature. After stirring for 10 min, a solution of allyltributylstan-
nane (0.6 mmol) in CH2Cl2 (2 mL) was added dropwise by a syringe.
The resulting homogeneous reaction mixture was stirred at r.t. for
1.0 h and quenched by saturated NaHCO3 aqueous solution. Extrac-
tive workup with ethyl acetate and chromatographic purification
of the crude product on silica gel gave the homoallylamine 2a in
92% yield. All the homoallylic amine products are pale yellowish to
yellowish oils.
4-(3′-Nitrophenyl)-4-(N-2′-hydroxy-phenyl)aminobut-1-ene (2g):24
δH 2.57–2.62 (m, 2H), 4.48 (t, 1H, J = 6.8 Hz), 5.17–5.23 (m, 2H),
5.73–5.78 (m, 1H), 6.27 (d, 1H, J = 7.6 Hz), 6.55–6.59 (m, 1H),
6.64–6.70 (m, 1H), 6.72 (d, 1H, J = 7.6 Hz), 7.47 (t, 1H, J = 8.0 Hz),
7.72 (d, 1H, J = 7.6 Hz), 8.08 (dd, 1H, J = 1.6, 8.0 Hz), 8.24 (dd, 1H,
J = 1.6, 4.0 Hz).
4-Phenyl-4-(N-phenyl)aminobut-1-ene (2a):16 δH 2.60–2.65 (m,
1H), 2.71–2.75 (m, 1H), 4.29 (br s, 1H), 4.50–4.53 (m, 1H), 5.26–5.33
(m, 2H), 5.85–5.92 (m, 1H), 6.63 (d, 2H, J = 7.5 Hz), 6.78 (t, 1H,
J = 7.5 Hz), 7.19–7.22 (m, 2H), 7.35–7.37 (m, 1H), 7.42–7.50 (m,
4H).
4-(4′-Chlorophenyl)-4-(N-2′-hydroxy-phenyl)aminobut-1-ene
(2h):24 δH 2.50–2.60 (m, 2H), 4.36 (t, 1H, J = 7.6 Hz), 5.13–5.21
(m, 2H), 5.71–5.76 (m, 1H), 6.34 (d, 1H, J = 8.0 Hz), 6.60 (t, 1H,
J = 7.6 Hz), 6.72 (d, 2H, J = 8.0 Hz), 7.26–7.31 (m, 4H).
4-(2′-Chlorophenyl)-4-(N-2′-hydroxy-phenyl)aminobut-1-ene (2i):24
δH 2.45–2.53 (m, 1H), 2.67–2.74 (m, 1H), 4.86 (m, 1H), 5.15–5.25
(m, 2H), 5.76–5.89 (m, 1H), 6.25 (d, 1H, J = 7.6 Hz), 6.56 (t, 1H,
J = 6.8 Hz), 6.67 (t, 2H, J = 7.2 Hz), 7.14–7.21 (m, 2H), 7.36–7.39
(m, 1H), 7.41–7.45 (m, 1H).
4-Phenyl-4-(N-4′-methyl-phenyl)aminobut-1-ene (2b):20 δH 2.28
(s, 3H), 2.56–2.60 (m, 1H), 2.67–2.71 (m, 1H), 4.14 (br s, 1H), 4.43–
4.46 (m, 1H), 5.22–5.29 (m, 2H), 5.82–5.90 (m, 1H), 6.52 (d, 2H,
J = 8.5 Hz), 6.99 (d, 2H, J = 8.0 Hz), 7.30–7.33 (m, 1H), 7.39–7.42
(m, 2H), 7.42–7.47 (m, 2H).
4-(2′-Thiophene)-4-(N-phenyl)aminobut-1-ene (2j):14 δH 2.64–2.68
(m, 2H), 4.12 (br s, 1H), 4.71 (t, 1H, J = 7.5 Hz), 5.15–5.21 (m, 2H),
5.76–5.83 (m, 1H), 6.60 (d, 2H, J = 9.0 Hz), 6.68–6.71 (m, 1H),
6.93–6.98 (m, 2H), 7.11–7.17 (m, 3H).
4-Phenyl-4-(N-benzyl)aminobut-1-ene (2c):21 δH 2.46–2.51 (m,
1H), 2.50–2.60 (m, 1H), 3.78 (s, 3H), 4.12 (s, 1H), 4.32–4.35 (m, 1H),
5.12–5.19 (m, 2H), 5.71–5.80 (m, 1H), 6.48–6.50 (m, 2H), 6.62–6.65
(m, 1H), 6.84–6.87 (m, 2H), 7.05–7.09 (m, 2H) 7.26–7.28 (m, 2H).

JOURNAL OF CHEMICAL RESEARCH 2010 339
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Received 27 April 2010; accepted 10 May 2010
Paper 1000090 doi:10.3184/030823410X12756737135354
Published online: 2 July 2010

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