Synthesis of aziridines from imines and ethyl diazoacetate in room temperature ionic liquids

Article abstract of DOI:10.1016/S0040-4039(03)00185-0

The synthesis of aziridines from imines and ethyl diazoacetate in room temperature ionic liquids is reported. The reactions proceed readily under mild conditions with high cis selectivities and high yields.

Full text of DOI:10.1016/S0040-4039(03)00185-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2409–2411
Synthesis of aziridines from imines and ethyl diazoacetate in
room temperature ionic liquids
Wei Sun, Chun-Gu Xia* and Hong-Wang Wang
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics,
Chinese Academy of Sciences, Lanzhou 730000, PR China
Received 28 October 2002; revised 9 January 2003; accepted 17 January 2003
Abstract—The synthesis of aziridines from imines and ethyl diazoacetate in room temperature ionic liquids is reported. The
reactions proceed readily under mild conditions with high cis selectivities and high yields. © 2003 Elsevier Science Ltd. All rights
reserved.
Due to their highly regio- and stereoselective ring-open-
ing reactions, aziridines are valued as building blocks
for the synthesis of a wide range of nitrogen-containing
compounds.1 Therefore, a general methodology for
one-step formation of aziridines would be very useful.
Recently, several groups have developed transition
metal catalyzed aziridinations based on [N-(-p-toluene-
sulfonyl)imino] phenyliodinane (PhI=NTs) as the
nitrene source2 and transition metal-catalyzed aziridina-
tion processes using chloramine-T (Ts-N-ClNa) and
bromamine-T (Ts-N-BrNa).3 Routes to aziridines start-
ing from imines have also been reported. For example,
Jorgensen has reported reactions of imines with ethyl
diazoacetate (EDA) catalyzed by Cu(OTf)2.4 The same
reaction was also effectively catalyzed by methylrhe-
nium trioxide5 and Lewis acids such as BF3·OEt2,
extremely exciting result in the chiral arylborate
(derived from VAPOL and VANOL) catalyzed reaction
of ethyl diazoacetate and imines.9
Recent exploration of the industrial potential of green
chemistry using room-temperature ionic liquids, partic-
ularly those based on 1,3-dialkylimidazolium cations
such as 1-n-butyl-3-methylimidazolium tetrafluoro-
borate (bmimBF4) and 1-n-butyl-3-methylimidazolium
hexafluorophosphate (bmimPF6), as novel reaction
media has become an exciting area of research. Their
utility in alkylation, esterification, acylation, hydro-
formylation, alkoxycarbonylation, hydrogenation, the
Beckmann rearrangement, Baylis–Hillman, Biginelli,
Diels–Alder and Heck reactions as well as in other
organic transformations has been demonstrated.10
Herein, we wish to report a convenient synthesis of
aziridines from imines and EDA in ionic liquids at
room temperature (Scheme 1).
AlCl3, TiCl4 and InCl3.7 A recent report demonstrated
6
that Ln(OTf)3 also catalyzed the synthesis of aziridines
from imines and EDA.8 Wulff has disclosed an
Scheme 1.
* Corresponding author. Tel.: +86-931-827-6531; fax: +86-931-827-7088; e-mail: cgxia@ns.lzb.ac.cn
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00185-0

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W. Sun et al. / Tetrahedron Letters 44 (2003) 2409–2411
Table 1. Formation of azridines 2a–h from imines 1a–h and EDA in room temperature ionic liquidsa
Entry
Ionic liquid
Imine
R1
R2
Product (yield%)b
1c
2c
3
bmimBF4
bmimPF6
bmimPF6
bmimPF6
bmimPF6
bmimPF6
bmimPF6
bmimPF6
bmimPF6
bmimPF6
bmimPF6
bmimPF6
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
p-Me-Ph
Ph
Ph
2a (82, cis:trans=29.6:1)
2a (95, cis only)
2a (93, cis only)
0
3a (3)
3a (2)
3a (3)
0
4d
5e
6
Ph
0
0
p-Me-Ph
p-Me-Ph
o-MeO-Ph
p-Cl-Ph
o-Cl-Ph
p-NO2-Ph
p-Br-Ph
2b (83, cis only)
2c (91, cis only)
2d (85, cis only)
2e (98, cis only)
2f (97, cis only)
2g (98, cis:trans=33.7:1)
2h (98, cis only)
3b (8)
7
8
9
10
11
12
Ph
Ph
Ph
1g
1h
a All reactions were carried out using 0.5 mmol of imine and 0.5 mmol of EDA in 1.5 ml of ionic liquid at room temperature for 5 h.
b Isolated yield, the ratio of cis and trans isomers was determined by GC–MS and 1H NMR.
c 1 mmol of imine and 0.5 mmol of EDA.
d 0.5 mmol of imine, 0.5 mmol of EDA and 0.1 mmol of bmimPF6 in 3 ml of CH2Cl2 at room temperature for 7 h.
e 0.5 mmol of imine, 0.5 mmol of EDA and 0.1 mmol of bmimPF6 in 3 ml of hexane at room temperature for 7 h.
Table 2. Formation of azridines 2a from imine 1a and
products were extracted with petroleum ether and ethyl
acetate (5:1) and purified by column chromatography
on silica gel with petroleum ether and ethyl acetate (5:1)
as eluent. The room temperature ionic liquid
(bmimPF6) was dried under vacuum for the next run.
The resulting products were analyzed by NMR and
GC–MS.
EDA in bmimPF6 recyclinga
Entry
Recycle no.
Product (yield%)b
1
2
3
4
5
1
2
3
4
5
2a (93, cis only)
3a (3)
3a (3)
3a (3)
3a (2)
3a (4)
2a (93, cis only)
2a (93, cis only)
2a (94, cis only)
2a (91, cis only)
Being composed entirely of ions, ionic liquids are
immiscible with some organic solvents. When the reac-
tion is over, the products are easily extracted from the
ionic liquids with petroleum ether and ethyl acetate
(5:1). The ionic liquid (bmimPF6) could be dried under
vacuum for further use. The procedure was repeated
five times and the results are shown in Table 2. It is
obvious that the ionic liquid (bmimPF6) still retains
high conversion and cis selectivities during the fifth
cycle. In addition, these reactions proceed readily at
room temperature and do not need another Lewis acid
promoter, such as BF3·OEt2, AlCl3, TiCl4, etc.
a 0.5 mmol of imine and 0.5 mmol of EDA in 1.5 ml of bmimPF6 at
room temperature for 5 h.
b Isolated yield, the ratio of cis and trans isomers was determined by
GC–MS and 1H NMR.
BmimBF4 and bmimPF6 ionic liquids were synthesized
according to the procedures reported in the literature.11
Entry 1 in Table 1 shows that bmimBF4 produces an
82% yield of the aziridines 2a with a diastereoselectivity
of about 30:1, from 1 equiv. of imine 1a and 0.5 equiv.
of ethyl diazoacetate in bmimBF4 for 5 h. When
bmimPF6 is used, a 95% yield of cis-2a12 was obtained
as a single product (Table 1, entry 2). With equimolar
amounts of imine 1a and EDA in bmimPF6 for 5 h at
the room temperature, a 93% yield of cis-2a was
obtained (Table 1, entry 3). However, when a catalytic
amount of bmimPF6 was used, no aziridine was
observed. As summarized in Table 1, arylimines with
either electron donating or electron withdrawing groups
react readily with EDA in bmimPF6, affording the
corresponding aziridines with high cis selectivities. In
fact, for most of the reactions examined, only the cis
aziridines were isolated. No carbene-coupling product
was detected under these reaction conditions, however
a small amount of 3 was obtained in some cases. It has
been suggested that the formation of aziridines in ionic
liquids proceeds in a similar manner to that previously
proposed for typical Lewis acids.6,8 A typical procedure
was as follows: A mixture of the imine (0.5 mmol) and
EDA (0.5 mmol) was stirred in 1.5 ml of the ionic
liquid (bmimPF6) at room temperature for 5 h. The
In summary, we have demonstrated an aziridine synthe-
sis in ionic liquids at room temperature. The reactions
proceed readily under mild conditions and show high
yields and cis selectivity. Further study regarding the
mechanism is underway.
Acknowledgements
We thank the National Natural Science Foundation of
China for financial support of this work (29933050).
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