Iron-catalysed aziridination reactions promoted by an ionic liquid

Article abstract of DOI:10.1039/b813655f

A catalytic system based on iron(II) triflate, quinaldic acid and an ionic liquid allows the aziridination of olefins with equimolar amounts of iminoiodinane providing products in good to moderate yields. The Royal Society of Chemistry.

Full text of DOI:10.1039/b813655f

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Iron-catalysed aziridination reactions promoted by an ionic liquidw
´ ´
Agathe C. Mayer, Anne-Frederique Salit and Carsten Bolm*
Received (in Cambridge, UK) 5th August 2008, Accepted 12th September 2008
First published as an Advance Article on the web 9th October 2008
DOI: 10.1039/b813655f
Table 1 Ligand effects in the iron-catalysed aziridinationa
A catalytic system based on iron(II) triflate, quinaldic acid and an
ionic liquid allows the aziridination of olefins with equimolar
amounts of iminoiodinane providing products in good to moderate
yields.
The preparation of aziridines is an important transformation in
organic synthesis.1 Aziridines are encountered in pharmaceutical
and natural products that exhibit potent biological activity,2 and
constitute versatile building blocks for a number of nitrogen-
containing compounds.3 Transition metal complex-mediated
aziridinations of alkenes using nitrene sources are among the
most powerful methods developed until now. A large number of
efficient catalytic systems involving manganese,4 ruthenium,5
silver,6 gold,7 and cobalt8 have been introduced but most of
them suffer from the use of a large excess of olefin to achieve
reasonable yields. Although the copper9 and rhodium10
complex-mediated aziridination account for the best methods,
iron-based catalysts are receiving more and more attention due
to their lower cost and toxicity.11–13
Entry
Ligand
—
(mol%)
Yield (%)
1
2
—
5
23
31
4
4
5
5
6
3
4
5
15
5
40
53
15
15
60
6
Traces
Recently, we reported a method for the conversion of olefins
into aziridines13 using iron(II) triflate14 in the presence of the
preformed iminoiodinanes PhINSO2Ar.15 Moderate to good
yields were obtained using a 7-fold excess of the styrene
derivative. Herein we describe a more practical and efficient
iron-based catalytic system that allows the conversion of
various alkenes into the corresponding aziridines with only
one equivalent of olefin.
a
Reaction conditions: 1a (1.0 equiv.) and 2a (1.0 equiv.) were used.
However, the addition of 15 mol% of 6 afforded only traces
of aziridine 3aa (Table 1, entry 6).
For the further optimisation of the system the use of 15 mol%
of quinaldic acid (5) was retained. Unexpectedly, the addition of
5 mol% of NaCl drastically improved the yield in the formation
of aziridine 3aa to 73% (Table 2, entry 1). The best result (79%)
was obtained with 20 mol% of NaCl (Table 2, entry 2). The
addition of anhydrous LiCl or KCl afforded N-tosylaziridine 3aa
in lower yields of 73% and 61%, respectively (Table 2, entries 3
and 4). Realising that ionic species notably contributed to the
nitrene transfer onto alkenes, the replacement of NaCl by a small
amount of an ionic liquid was envisaged.17 Since metal-catalysed
aziridination reactions can be sensitive to water, the hydro-
phobic ethylmethylimidazolium bis[(trifluoromethyl)sulfonyl]-
amide (emim BTA) (7) was chosen.18 To our delight we found
that the addition of 8 mol% of 7 furnished aziridine 3aa in 89%
yield (Table 2, entry 5). The effect of the counter anion BTA was
evaluated by using 8 mol% of LiBTA. However, the latter
promoted the reaction to a smaller extent (73%, Table 2, entry
6), pointing out the efficiency of ionic liquid 7.
Initially, we studied the influence of a ligand in the iron
catalytic system with styrene (1a) as a model substrate.
Pyridine type molecules were chosen due to their known
affinity to iron.16 When one equivalent of styrene was sub-
mitted to aziridination conditions without any ligand, the yield
of N-tosylaziridine 3aa was only 23% (Table 1, entry 1).
Under the same conditions, the addition of picolinic acid (4)
(5 and 15 mol%) increased the yield (to 31% and 40%,
respectively; Table 1, entries 2 and 3). The best results were
obtained by using 5 and 15 mol% of quinaldic acid (5) giving
the desired product in 53% and 60%, respectively (Table 1,
entries 4 and 5). When more than 15 mol% of 5 were used,
problems of solubility were encountered and no significant
improvement of the yield could be achieved. In order to
increase the number of chelating points between the ligand
and iron, pyridine-2,6-dicarboxylic acid (6) was tested.
Next, the iminoiodinane was modified in order to
reinforce the electronic and/or chelating properties of the
catalytic system. A comparison of the three preformed imi-
noiodinanes 2a–c revealed significant reactivity differences
(Table 3). Pleasingly, the nitrene transfer to styrene (1a) with
5-methyl-2-pyridinesulfonyliminophenyliodinane (2c) under
Institute of Organic Chemistry, RWTH Aachen University,
Landoltweg 1, 52074 Aachen, Germany.
E-mail: carsten.bolm@oc.rwth-aachen.de; Fax: (+49)-241-809-391
w Electronic supplementary information (ESI) available: Experimental
details. See DOI: 10.1039/b813655f
ꢀc
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Table 2 Additive effects in the iron-catalysed aziridinationa
Table 4 Substrate scope
Producta
Yield (%)
Entry
Additive
(mol%)
Yield (%)
Entry Substrate
1
2
3
4
5
6
a
NaCl
NaCl
LiCl
KCl
emim BTA (7)
LiBTA
5
20
20
20
8
73
79
73
61
89
73
1
1a
3ac
3bc
495b
2
1b
1c
1d
1e
1f
495b
8
Reaction conditions: 1a (1.0 equiv.) and 2a (1.0 equiv.) were used.
3
4
5
6
7
8
3cc
3dc
3ec
3fc
3gc
3hc
3ic
60c
Table 3 Variation of iminoiodinane 2a
95b
36c
Entry
2
X
Y
Product
Yield (%)
1
2
3
a
a
b
c
CH
CH
N
Me
NO2
Me
3aa
3ab
3ac
89
39
495
70c
Reaction conditions: 1a (1.0 equiv.) and 2 (1.0 equiv.) were used.
1g
1h
60b
65b
50c
the optimised conditions led to quantitative formation of aziri-
dine 3ac (Table 3, entry 3). Presumably, coordination
effects were responsible for the enhanced reactivity of this
iminoiodinane.19
Encouraged by these results, the substrate scope of the iron-
catalysed aziridination reaction was examined (Table 4). With
styrene derivatives 1a–h it proceeded well giving products with
moderate to good yields (entries 2–8). The best results were
achieved with p-methylstyrene and p-nitrostyrene (entries 2
and 4). p-Acetoxystyrene, p-cyanostyrene and p-trifluoro-
methylstyrene (entries 6–8) gave the corresponding aziridines
in reasonable yields (70, 60 and 65%, respectively), while the
reaction with p-chlorostyrene led to only 36% of aziridine 3ec
(entry 5). No by-products other than traces of sulfonamide
were detected (by TLC or NMR). Apparently, the results were
irrespective of the electronic effect of the substituents, and thus
a clear-cut rationale regarding the reactivity of the styrene
derivatives could not be deduced.
9
1i
1j
8
10
3ic (trans) 55c
3jc (cis)
11
9
57c
a
b
c
R = 5-methyl-2-pyridinesulfonyl. Use of 1.0 equiv. of 2c. Use of
1.2 equiv. of 2c.
Whereas the nitrene transfer onto trans-methylstyrene (1i)
led exclusively to the corresponding trans-aziridine 3ic
(50% yield; Table 4, entry 9), the aziridination of cis-methyl-
styrene (1j) afforded an inseparable trans–cis mixture of 3ic
and 3jc in a 70 : 30 ratio (55% yield; entry 10). Thus, as in the
previously described iron-catalysed aziridination,13 only the
former olefin reacted stereospecifically. This result suggests the
presence of radical intermediates during the nitrene transfer
process.20
Finally, the reaction was carried out with cyclooctene (8) as
substrate affording 57% of the corresponding aziridine 9
(entry 11).
In conclusion, we have developed a catalytic system for the
aziridination of olefins using ligand-modified Fe(OTf)2 as
the catalyst and a preformed iminoiodinane with a pyridine
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backbone as the nitrene source. Remarkable features are the
substrate-to-iminoiodinane ratio of 1 : 1 and the pronounced
additive effect.
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Institute for Technical and Macromolecular Chemistry,
RWTH Aachen University, for a donation of ionic liquid
emim BTA 7. Support by the Fonds der Chemischen Industrie
is acknowledged.
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