Allylation of aldimines promoted by NbCl5

Article abstract of DOI:10.1016/S0040-4039(02)00167-3

Niobium chloride promoted the addition of allylstannanes to aromatic aldimines. Excellent syn diastereoselectivity was obtained in the addition of crotylstannane to N-benzylideneaniline (46:1).

Full text of DOI:10.1016/S0040-4039(02)00167-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1935–1937
Allylation of aldimines promoted by NbCl5
Carlos Kleber Z. Andrade* and Guilherme R. Oliveira
Instituto de Qu´ımica, Universidade de Bras´ılia, C.P. 4478, 70910-970 Bras´ılia, DF, Brazil
Received 20 December 2001; revised 18 January 2002; accepted 23 January 2002
Abstract—Niobium chloride promoted the addition of allylstannanes to aromatic aldimines. Excellent syn diastereoselectivity was
obtained in the addition of crotylstannane to N-benzylideneaniline (46:1). © 2002 Elsevier Science Ltd. All rights reserved.
Although the Lewis acid-promoted addition of allyl-
stannane to aldehydes is a well-established synthetic
method,1 the allylation of aldimines still needs further
development. The homoallylic amines thus obtained are
of great interest since the CꢀC double bond of the allyl
moiety can be further functionalized.
improves the yields but is not critical to the success of
the reaction, except when Et2O was used (entry 2). The
lower yields obtained with 1 equiv. of allystannane may
be due to its slight decomposition in the presence of
NbCl5.
Table 1. Experimental conditions and yields of the reac-
tions between N-benzylideneaniline (1) and allyltri-n-
butylstannanea
Due to the low reactivity of imines towards nucleophilic
addition of allylstannanes, additives such as Lewis acids
must be used. Thus, BF3·OEt2, TiCl4, MgBr2, Et2AlCl,
among others, have been reported to accelerate the
reaction rate.2 Recent improvements in this reaction
deal with imine activation by chlorotrimethylsilane,3
catalytic lanthanide triflates4 and catalytic Pd(II) or
Pt(II) complexes.5
Entry
Solvent
Yields (%)b
In our previous work in this area,6 we studied the
niobium(V) chloride-mediated allylation of aldehydes.
NbCl5 has proved to be a versatile Lewis acid7 and is
readily available in our country since Brazil accounts
for about 60% of total niobium production.8 Now we
wish to report our results on the allylation of imines.
0°C“rt
−15°C
−78°C
1
2
3
CH2Cl2
Et2O
CH3CN
27
18
62
82
41
80
83
-
-
a 1 equiv. of NbCl5 and 2 equiv. of allylstannane were employed.
b Isolated yields of the chromatographically pure products.
We initiated our study by searching for the best solvent
system. Ethyl ether, acetonitrile and dichloromethane
were investigated in the allylation of N-benzylideneani-
line (1) at different temperatures. The results are shown
in Table 1. Either CH3CN or CH2Cl2 gave satisfactory
results at −15°C.9 The yields were the same at lower
temperatures using CH2Cl2 (entry 1) and decreased in
all cases when the reaction was allowed to reach room
temperature. A control experiment indicated that no
reaction takes place in the absence of NbCl5.
Table 2. Influence of an excess of allylstannane on the
allylation of N-benzylideneaniline (1), at −15°C
Entry
Solvent
Yields (%)a
−15°Cc
−15°Cb
1
2
3
CH2Cl2
Et2O
CH3CN
72
17
60
82
41
80
Next, the stoichiometry of the reaction was assessed
(Table 2). We found that an excess of stannane
a Isolated yields of the chromatographically pure products.
b Imine:NbCl5:stannane=1:1:1
c Imine:NbCl5:stannane=1:1:2
* Corresponding author. E-mail: ckleber@unb.br
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00167-3

1936
C. K. Z. Andrade, G. R. Oli6eira / Tetrahedron Letters 43 (2002) 1935–1937
mixture of isomers) and imine 1 in the presence of
In this way, we defined the ideal conditions for the
NbCl5-mediated allylation of imines as being CH2Cl2 as
the solvent,10 at −15°C and using an excess of allylstan-
nane. Under these conditions a variety of aromatics
aldimines11 were allylated in reasonable to good yields
(Table 3).12
NbCl5 (Table 4).
The reaction proved to be regiospecific in that no linear
products were formed under any conditions. The allyl-
ated products were obtained in good yields and excel-
lent diastereoselectivities (entries
1 and 2). The
In some cases, bis-allylated13 by-products were also
obtained (ca. 10–15%) when 2 equiv. of allylstannane
were used (Fig. 1). This can be circumvented using only
a slight excess of this reagent.
diastereomeric ratio was determined by GC analysis of
1
the mixture of products and by H NMR integration of
the proton on the carbon attached to the nitrogen (syn:
l 4.33, J=4.5 Hz and anti: l 4.07, J=7.2 Hz) and
methyl groups (syn: l 1.01, J=6.9 Hz and anti: l 0.99,
J=6.9 Hz). These data are in accordance with those
reported.2b
The activation of the imines probably occurs via the
formation of an iminium salt with NbCl5 (Scheme 1).
As an example, a dark-orange precipitate forms when
imine 1 is added to a suspension of NbCl5 in CH2Cl2.14
At −78°C, the syn isomer is obtained almost exclu-
sively, regardless of the stereochemistry of the stannane
double bond.15 These results are even superior to those
obtained with other Lewis acids such as BF3·OEt2 and
TiCl4.2
The stereo- and regioselectivity of these NbCl5-pro-
moted allylation reactions were assessed in the reaction
between crotylstannane (3-methyl-allylstannane, 1:1
Although the mechanism of these reactions is still con-
troversial, the observed syn selectivity could be
explained through an acyclic antiperiplanar transition
state16 (Fig. 2). Among the possible geometries, includ-
ing the synclinals, the antiperiplanar (ET1) seems to be
preferred since it has less steric crowding as compared
to the others.
Table 3. Results of the reactions between aldimines and
allyltri-n-butylstannane
In summary, the scope of the NbCl5-mediated allyla-
tion of imines has been studied. Homoallylic amines
were obtained in good yields with excellent regio- and
stereoselectivities. These results confirm the effective-
Entry
Imine
R
R1
Yielda (%)
1
2
3
4
5
6
1
2
3
4
5
6
Ph
Ph
Ph
Ph
n-Bu
Ph
82
80
59
35
51
85
p-NO2Ph
2-Furyl
p-ClPh
p-ClPh
p-OMePh
Table 4. Results of the reaction between crotylstannanea
and N-benzylideneaniline (1) in CH2Cl2
Ph
a Isolated yields of the chromatographically pure products.
Entry
Temp (°C)
Mode of
addition
Syn:anti
Yieldb (%)
1
2
−15
−78
Normal
Normal
9:1
46:1
60
62
a 2 equiv. of crotylstannane were used.
b Isolated yields of chromatographically pure products (syn/anti mix-
Figure 1. Bis-allylated by-products.
ture).
Scheme 1. Activation of the imine by NbCl5.

C. K. Z. Andrade, G. R. Oli6eira / Tetrahedron Letters 43 (2002) 1935–1937
1937
6641; (c) Nakamura, H.; Nakamura, K.; Yamamoto, Y.
J. Am. Chem. Soc. 1998, 120, 4242; (d) Bao, M.; Naka-
mura, H.; Yamamoto, Y. Tetrahedron Lett. 2000, 41,
131; (e) Bao, M.; Nakamura, H.; Yamamoto, Y. Angew.
Chem., Int. Ed. 2001, 40, 3208.
6. Andrade, C. K. Z.; Azevedo, N. R. Tetrahedron Lett.
2001, 42, 6473.
7. Other examples on the use of NbCl5 as a Lewis acid: (a)
Suzuki, K.; Hashimoto, T.; Maeta, H.; Matsumoto, T.
Synlett 1992, 125; (b) Maeta, H.; Nagasawa, T.; Handa,
Y.; Takei, T.; Osamura, Y.; Suzuki, K. Tetrahedron Lett.
1995, 36, 899; (c) Howarth, J.; Gillespie, K. Tetrahedron
Lett. 1996, 37, 6011; (d) Yamamoto, M.; Nakazawa, M.;
Kishikawa, K.; Kohmoto, S. Chem. Commun. 1996, 2353;
(e) Chandrasekhar, S.; Takhi, M.; Reddy, Y. R.; Mohap-
atra, S.; Rao, C. R.; Reddy, K. V. Tetrahedron 1997, 53,
14997; (f) Kobayashi, S.; Busujima, T.; Nagayama, S.
Chem. Eur. J. 2000, 6, 3491.
Figure 2. Antiperiplanar transition states proposed for the
allylation of imines.
ness of NbCl5 as a Lewis acid in these allylation
reactions and make the procedure an attractive choice
because of the simplicity and mildness of this
methodology.
8. For a review on niobium compounds, see: Nowak, I.;
Acknowledgements
Ziolek, M. Chem. Rev. 1999, 99, 3603.
9. In contrast, Et2O was the best solvent in the allylation of
aldehydes (see Ref. 6).
10. The choice for CH2Cl2 was based on the fact that the
reaction in this solvent could be run at lower temperature
(−78°C) as compared to CH3CN.
11. Prepared from the corresponding aldehydes (1 equiv.)
and primary amines (1 equiv.), in Et2O, in the presence of
Na2SO4.
The authors thank the Instituto de Qu´ımica, Universi-
dade de Bras´ılia, for financial support during the early
stages of this work. We also thank CBMM for NbCl5
samples, Professor Antoˆnio Gilberto Ferreira (UFS-
Car) for high field NMR spectra and Prof. Peter
Bakuzis (UnB) for helpful suggestions and revision of
this manuscript.
12. Typical experimental procedure: To a fresh sublimed
NbCl5 (1 mmol) suspension in CH2Cl2 at –15°C, under
an argon atmosphere, was added a solution of the imine
in CH2Cl2 (1 mmol), followed by the addition of allyl-
stannane (2 mmol), after 10 min. The reaction was moni-
tored by TLC and after the consumption of the imine
(1–2 h) it was quenched with sat. NH4Cl, extracted with
diethyl ether (3×15 mL) and stirred for 2 h with 10% KF
in H2O (10 mL). The reaction mixture was then washed
with brine, dried with Na2SO4 and concentrated at
reduced pressure to furnish the crude product which was
purified by silica gel chromatography (hexanes:EtOAc).
13. An example of palladium-catalyzed double allylation
reaction has recently been reported: Nakamura, H.; Aoy-
agi, K.; Shim, J.-G.; Yamamoto, Y. J. Am. Chem. Soc.
2001, 123, 372.
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