Catalytic heterogeneous aziridination of alkenes using microporous materials

Article abstract of DOI:10.1039/a801997e

Copper-exchanged zeolite Y is a highly active catalyst for the aziridination of alkenes; modification using bis(oxazo-lines) leads to preparation of the first heterogeneous enantioselective aziridination catalyst.

Full text of DOI:10.1039/a801997e

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Catalytic heterogeneous aziridination of alkenes using microporous materials
Christopher Langham,a Paola Piaggio,a Donald Bethell,b Darren F. Lee,b Paul McMorn,a Philip C. Bulman
Page,c David J. Willock,a, Chris Sly,d Frederick E. Hancock,e Frank Kinge and Graham J. Hutchingsa,b
†
a Department of Chemistry, University of Wales Cardiff, PO Box 912, Cardiff, UK CF1 3TB
b Leverhulme Centre for Innovative Catalysis, Department of Chemistry, University of Liverpool, Liverpool, UK L69 3BX
c Department of Chemistry, Loughborough University, Loughborough, Leicestershire, UK LE11 3TU
d Robinson Brothers Ltd., Phoenix Street, PO Box, West Bromwich, West Midlands, UK B70 OAH
e ICI Katalco, R & T Division, Street, PO Box 1, Billingham, Teeside, UK TS23 1LB
Copper-exchanged zeolite Y is a highly active catalyst for
the aziridination of alkenes; modification using bis(oxazo-
lines) leads to preparation of the first heterogeneous
enantioselective aziridination catalyst.
initial results confirmed our contention that cations within
zeolites could be used as heterogeneous counterparts of known
homogeneous catalysts, and, to the best of our knowledge, this
is the first example of an aziridination reaction catalysed
heterogeneously.
The design of asymmetric catalysts is of intense current
interest,1 and procedures making use of chiral transition metal
complexes have been described for epoxidation, cyclopropana-
tion, aziridination and hydrogenation of alkenes in homo-
geneous solution.2–6 There is increasing recognition that
heterogeneous catalysts have practical advantages over homo-
geneous ones.6–8 We describe here a generic approach to the
design of heterogeneous transition-metal catalysts by making
use of the well-known ability of zeolites to undergo metal cation
exchange,9 together with their acid–base properties.10 By
constructing transition-metal complexes within the spatially
restricted environment of the zeolite pores, enantioselective
organic transformations can be catalysed with comparable or
even greater efficiency than in the corresponding homogeneous
process. We exemplify this approach with the first hetero-
geneous catalyst for asymmetric aziridination of alkenes.
We have found that CuHY zeolite is successful in catalysing
the aziridination of a range of alkenes employing [N-(tolyl-
p-sulfonyl)imino]phenyliodinane (PhI = NTs) as the nitrogen
source. The results are shown in Table 1. The Cu-exchanged
zeolite (CuHY) was prepared by conventional ion-exchange
methods with aqueous Cu(OAc)2 solution, the concentration of
which was chosen so as to obtain the required exchange level
(ca. 50–60% of available H+). The cation-exchanged zeolite
was then washed with distilled water and dried at 110 °C in air.
CuHY was initially screened in the aziridination of styrene
(Table 1, entries 1–3), since this alkene affords good yields of
aziridine when copper triflate is used as a homogeneous
catalyst.4 Using a five-fold molar excess of styrene, the desired
N-tosylaziridine was obtained in 90% yield (entry 1). These
In order to confirm the absence of homogeneously catalysed
reaction, following reaction the zeolite catalyst was recovered
by filtration and another aliquot of reactants (styrene: PhINNTs
= 5 : 1 molar ratio) was added to the recovered filtrate; no
further product was observed. Further, the removed catalyst was
reused with fresh reagents and solvent, and the zeolite
demonstrated similar activity to when it was used initially.
It was noted in earlier studies that, in the homogeneously
catalysed reaction,4 the yield of aziridine decreased to 37%
when the molar ratio of styrene : PhINNTs
= 1: 1 was
employed, due to the competing breakdown of the PhINNTs
reagent. This decrease was found to be less significant using our
heterogeneous catalyst, where 87% yield was obtained when a
styrene : PhINNTs = 1: 1 molar ratio was used (Table 1, entry 2)
as compared to a yield of 90% when a styrene : PhINNTs = 1 : 1
molar ratio was used (Table 1, entry 1).
CuHY was found to be successful in catalysing the
aziridination of a range of alkenes (Table 1) in addition to
styrene. It is observed that the catalyst gives best results with
phenyl-substituted alkenes and lower yields are observed with
cyclohexene and trans-hex-2-ene. Interestingly, for the azir-
idination of trans-stilbene no product could be observed. This
was considered to be the due to the relatively bulky aziridine
product being too large to be accommodated within the
supercages of CuHY. However, the aziridination of trans-
methyl cinnamate inside CuHY proceeded in 84% yield, despite
being similar in structure type to the trans-stilbene product. We
used molecular modeling to investigate the ease with which
these two aziridines could be placed into the pore structure of
zeolite Y. These calculations suggest that the N-tosylaziridine
formed from trans-methyl cinnamate can adopt a conformation
which can easily be accommodated in the pores of zeolite Y.
The aziridine derived from trans-stilbene can be constructed
within the supercages but is indeed too bulky to diffuse through
the connecting channels of the zeolite. We consider this to be a
crucial piece of evidence since it shows that the aziridination
reaction with the CuHY catalyst occurs within the intracrystal-
line space. Furthermore, this exciting result illustrates the
potential for a heterogeneous catalyst to possess size-specificity
to a precise degree. Such a property could be exploited by
constructing zeolites with a range of pore sizes, and could also
be developed to achieve regioselectivity in a reagent containing
two or more double bonds.
Table 1 CuHY-catalysed aziridination of representative alkenes
Cu
(mol%)
Yield
(%)b
Entry
Alkenea
1
2
3
Styrene
25
25
5
90 (92)
87 (35)
62
Styrenec
Styrene
4
5
6
7
8
9
10
a-Methylstyrene
p-Chlorostyrene
p-Methylstyrene
Cyclohexene
Methyl cinnamate
trans-Stilbene
trans-Hex-2-ene
25
25
25
25
25
25
25
33
76
66
50 (60)
84 (73)
0 (52)
44
Evans et al.4 have shown that modification of the copper
homogeneous catalysts using chiral bis(oxazoline) ligands
induces enantioselectivity. We have examined modification of
the CuHY catalyst with a range of oxazolines and have observed
N-tosylaziridine products with up to 61% ee. The optimum
conditions for racemic heterogeneous aziridination of alkene, in
a
Unless otherwise specified reaction conditions were: MeCN, 25 °C,
b
styrene:PhINNTs = 5:1. Isolated yield of aziridine based on PhINNTs.
Values in parentheses indicate yields obtained from homogeneous reac-
tions. c styrene:PhINNTs = 1:1 molar ratio.
Chem. Commun., 1998
1601

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the absence of bis(oxazoline), was observed to be at 25 °C using
MeCN as solvent. As expected, for the enantioselective
reaction, the use of lower reaction temperatures was found to
give the highest enantioselectivities. We have found that a
temperature of 210 °C provides the highest enantioselectivity
of 42% ee without compromising yield when using MeCN
solvent and 2,2-bis{2-[(4R)-1-phenyl-1,3-oxazolinyl]}propane
1 as the chiral modifier. It would be reasonable to assume that
one chiral modifier would be required per zeolite supercage to
obtain maximum enantioselectivity. We have, however, found
that very low levels of the expensive modifier can be used
without resulting in decreases in yield or enantioselectivity. An
this bis(oxazoline). Support for this interpretation comes from
our observation that, by carrying out the reaction using styrene
as the solvent, enantioselectivity was restored, although both
yield and ee were then lower than for the homogenous reaction.
To provide further evidence that the reaction is proceeding
within the supercages of the zeolite, reactions were carried out
using a simple phenyl-substituted bis(oxazoline) 3, which is
known to fit inside the zeolite, and using a diphenyl substituted
analogue 4, which was considered as the result of molecular
simulations to be too bulky to fit inside the zeolite pores. At
25 °C the smaller bis(oxazoline) 3 gave 10% ee for both the
heterogeneous and homogeneous reactions. However, for the
heterogeneously catalysed reaction, using CuHY as catalyst, the
bulky diphenyl bis(oxazoline) 4 gave racemic product, despite
inducing 15% ee for the equivalent homogeneously catalysed
reaction. This is again evidence that the reaction is truly
heterogeneous and is occurring within the pores of the zeolite.
Further modification of the bis(oxazaline) has shown that the
pyridine-bridged bis(oxazoline) 5 gives the highest enantio-
selectivity of 61% ee for the aziridination of styrene (Table 2).
We consider that these initial results are encouraging and that
careful optimization of the chiral ligand will result in further
improvements in ee and yield.
R3
R3
N
O
O
O
O
N
R2
R2
N
N
N
R1
R1
Pri
Pri
1 R1 = Ph, R2 = H, R3 = Me
2 R1 = But, R2 = H, R3 = Me
3 R1 = Ph, R2 = R3 = H
5
4 R1 = R2 = Ph, R3 = H
The major advantage of the use of CuHY as a catalyst for this
reaction is the ease with which it can be recovered from the
reaction mixture by simple filtration if used in a batch reactor
(alternatively it can be used in a continuous flow fixed bed
reactor). We have carried out the heterogeneous asymmetric
aziridination of styrene until completion, filtered and washed
the zeolite then added fresh styrene, PhINNTs and solvent,
without further addition of bis(oxazoline) 1, for several
consecutive experiments and have found that both yield and
enantioselectivity are retained. After each consecutive experi-
ment a portion of CuHY was retained to determine the
concentration of copper still present in the zeolite. For each
experiment we found that only traces of the copper were
removed from the catalyst ( < 0.5% of the total Cu2+ is lost from
the catalyst). Filtrate containing trace Cu2+ has been used in a
reaction and was not found to catalyse aziridination. We have
noted that adsorbed water can build up within the pores of the
zeolite on continued use and this can lead to some loss of
activity. However, full enantioselectivity and yield can be
recovered if the catalyst is simply dried in air prior to reuse. We
are therefore confident that this catalyst system can form the
basis of a commercial heterogeneous catalyst for the aziridina-
tion of alkenes.
excess of 1 significantly reduces the yield of aziridine, due to
pore-blocking, but both yield and enantioselectivity were
maximized with a molar ratio of only PhINNTs: 1 = 1: 0.05.
This corresponds to a molar ratio of Cu2+ : 1 of 2: 1, indicating
that not all the Cu2+ cations are modified in our experiments. In
a subsequent experiment, an excess of 1 was stirred with CuHY
(Cu2+ : 1 = 1 : 60) in MeCN. The zeolite was filtered and
washed with acetonitrile, then used as the catalyst in fresh
solvent and reactants. Both yield and enantioselectivity ob-
served were identical to that obtained when 1 was added directly
to the reaction mixture (molar ratio of PhINNTs: 1 = 1 : 1.05).
It is clear that very low levels of the modifier are required to
obtain the enantioselectivities reported.
With the optimum conditions established for the enantio-
selective aziridination of styrene, other bis(oxazolines) and
alkenes were screened with CuHY as the catalyst (Table 2).
trans-b-Methylstyrene was found to show similar degrees of
enantioselectivity to styrene. However, trans-methyl cinnamate
gave a much higher result of 61% ee, albeit in poorer yield. The
tert-butyl substituted bis(oxazoline) 2, when used in MeCN,
gave racemic aziridine. We suggest this is because MeCN, a
ligand for Cu2+, binds more strongly to the active sites than does
Table 2 Representative bis(oxazolines) for the enantioselective aziridina-
tion of alkenes
Notes and References
† E-mail: hutch@cf.ac.uk
Oxazoline Alkenea
T/°C
Yield (%)b
Ee (%)b,c
1 R. Noyari, Asymmetric Catalysis in Organic Synthesis, Wiley, New
York, 1994.
2 T. Katsuki and K. B. Sharpless, J. Am. Chem. Soc., 1980, 102, 5974.
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Chem. Soc., 1991, 113, 726.
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116, 2742.
5 K. Srinivasan, P. Michaud and J. K. Kochi, J. Am. Chem. Soc., 1986,
108, 2309; W. Zhang, J. L. Loebach, S. R. W. Wilson and E. N.
Jacobsen, J. Am. Chem. Soc., 1990, 112, 2801.
6 K. T. Wan and M. E. Davis, Nature 1994, 370, 449.
7 H. U. Blasser, Tetrahedron: Asymmetry, 1997, 8, 1693.
8 P. P. Knops-Gerrits, D. De Vos, F. Thibault-Starzyk and P. A. Jacobs,
Nature, 1994, 369, 543.
9 K. Klier, Langmuir, 1998, 4, 13.
10 C. B. Dartt and M. E. Davis, Catal. Today, 1994, 19, 151.
1
1
1
1
2
2
3
4
5
trans-Methyl cinnamate 210
trans-b-Methylstyrene 210
8 (21)
74
82
87
64
15 (89)
78 (75)
73 (74)
4
61 (70)
36
44
29
0
18 (63)
10 (10)
0 (15)
61
Styrene
Styrene
Styrene
Styrened
Styrene
Styrene
Styrene
210
25
220
220
25
25
210
a
Unless otherwise specified, reaction conditions were: MeCN, alkene:
b
PhINNTs = 5 : 1. Values in parentheses indicate yields obtained from
homogeneous reactions. Enantioselectivity determined by chiral HPLC.
c
Absolute configurations of major products, determined by optical rotation,
are (S) for trans-b-methylstyrene and trans-b-methyl cinnamate, (R) for
styrene. d Styrene was used as solvent.
Received in Cambridge, UK, 12th March 1998; 8/01997E
1602
Chem. Commun., 1998