Enantioselective epoxidation of non-functionalised alkenes using a urea-hydrogen peroxide oxidant and a dimeric homochiral Mn(III)-Schiff base complex catalyst

Article abstract of DOI:10.1016/S0957-4166(01)00057-X

The catalytic enantioselective epoxidation of chromenes, indene and styrene using a urea-hydrogen peroxide adduct as an oxidising agent and the novel dimeric homochiral Mn(III)-Schiff base catalyst 1 has been investigated in the presence of carboxylate salts and nitrogen and oxygen coordinating co-catalysts. Conversions of more than 99% were obtained with all alkenes except styrene. Absolute chiral induction, as determined by ¹H NMR using the chiral shift reagent (+)-Eu(hfc)₃, was obtained in the case of nitro- and cyanochromene. The catalyst could be re-used for up to five cycles with some loss of activity due to degradation of the catalyst under epoxidation condition with retention of e.e.'s.

Full text of DOI:10.1016/S0957-4166(01)00057-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 433–437
Enantioselective epoxidation of non-functionalised alkenes using
a urea–hydrogen peroxide oxidant and a dimeric homochiral
Mn(III)-Schiff base complex catalyst
Rukhsana I. Kureshy,* Noor-ul H. Khan, Sayed H. R. Abdi, Sunil. T. Patel and Raksh V. Jasra
Silicates and Catalysis Discipline, Central Salt and Marine Chemicals Research Institute, Bhavnagar 364 002, India
Received 22 December 2000; accepted 1 February 2001
Abstract—The catalytic enantioselective epoxidation of chromenes, indene and styrene using a urea–hydrogen peroxide adduct as
an oxidising agent and the novel dimeric homochiral Mn(III)-Schiff base catalyst 1 has been investigated in the presence of
carboxylate salts and nitrogen and oxygen coordinating co-catalysts. Conversions of more than 99% were obtained with all
alkenes except styrene. Absolute chiral induction, as determined by 1H NMR using the chiral shift reagent (+)-Eu(hfc)3, was
obtained in the case of nitro- and cyanochromene. The catalyst could be re-used for up to five cycles with some loss of activity
due to degradation of the catalyst under epoxidation condition with retention of e.e.’s. © 2001 Elsevier Science Ltd. All rights
reserved.
therefore be seen as co-catalysts.11 Sodium and ammo-
nium salts have also been reported previously as effec-
1. Introduction
tive co-catalysts in the metallo-porphyrin catalysed
The enantioselective epoxidation of prochiral non-func-
tionalised alkenes constitutes an important tool in
organic synthesis.1–3 Chiral Mn(III)-SALEN type com-
plexes using PhIO,4 NaOCl,5 m-CPBA,6 molecular oxy-
gen/aldehyde,7 dimethyldioxirane,8 periodate9 and
potassium monopersulphate10 as oxidising agents have
been extensively studied for the enantioselective epoxi-
dation of mono-, tri- and tetra-substituted alkenes.
However, all of these oxidants are either expensive or
result in undesirable by-products. Hydrogen peroxide
was considered as an oxygen source as it is reasonably
stable, readily available, inexpensive and generates only
water as a by-product.11 However, the use of hydrogen
peroxide in transition metal catalysed epoxidation reac-
tions has limitations because, as a result of homolytic
cleavage of the weak OꢀO bond, peroxy radicals are
produced that oxidatively degrade the catalyst. Never-
theless, it is possible to mimic the function of the
enzyme cytochrome P450, which also uses H2O2 as an
oxidant and generate an active high valent metal–oxo
intermediate, leading to selective alkene epoxidation.12
The reactive metal–oxo species is known to be further
stabilised by using nitrogenous bases including imida-
zole, pyridine and tertiary amine N-oxides, which can
epoxidation of alkenes by hydrogen peroxide.12
Katsuki et al.13 and Pietika¨inan14 reported the use of
aqueous hydrogen peroxide in the Mn(III)-SALEN
catalysed enantioselective epoxidation of alkenes in the
presence of substituted imidazoles. We felt that urea–
hydrogen peroxide (UHP), an anhydrous source of
H2O2, a stable and inexpensive solid, would be an
attractive oxygen source and we therefore decided to
examine its use in this study.
Increasing the molecular weight of the catalyst would
lower its solubility, aiding product isolation and cata-
lyst recovery, whilst increasing the number of active
reaction sites on the catalyst would also result in higher
reactivity catalyst and aid turnover. With these points
in mind, we designed and synthesised the homochiral
dimeric Mn(III) complex, 5,5-methylene di-[(R,R)-{N-
(3-tert-butyl salicylidine)-N%-(3%,5%-di-tert-butyl salicyli-
dene)}-1,2-cyclohexanediaminato(2-)
manganese(III)
chloride] 1 which carries two active catalytic metal
centres.
Herein, we report the highly enantioselective epoxida-
tion of non-functionalised alkenes using 1 as a catalyst
and UHP as the oxidising agent in the presence of an
ammonium salt or a nitrogen and oxygen coordinating
* Corresponding
salt@csir.res.in
author.
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434
R. I. Kureshy et al. / Tetrahedron: Asymmetry 12 (2001) 433–437
co-catalyst. In practice, 1 was found to be less soluble
than its monomeric counterpart, and precipitated from
hexane; separation of 1 from the product after the
reaction then allowed the catalyst to be recycled for a
number of reactions.
chromene, 6-nitro-2,2-dimethyl chromene, 6-methoxy-
2,2-dimethyl chromene, spiro[cyclohexane-1,2%-[2H][1]-
chromene, styrene and indene using a UHP adduct as
an oxidant in the presence of ammonium acetate co-
catalyst at 2°C in a 1:1 mixture of CH2Cl2–CH3OH.
Data regarding the observed enantioselectivities is given
in Table 1.
2. Results and discussion
Conversions of ]99% were obtained with all alkenes
As shown in Scheme 1, the pentacoordinate dimeric
complex 1 was formed by condensing first the monotar-
trate salt of (1R,2R)-(−)-cyclohexanediamine with 3,5-
di-tert-butyl salicylaldehyde in a 1:1 molar ratio in
CHCl3 at low temperature. The free amine function of
2 was then condensed further with the 5,5-methylene-
bis-salicylaldehyde 3, followed by metallation with
Mn(III). Complex 1 was characterised by microanaly-
sis, conductance, optical rotation, UV–vis and IR
spectroscopy.
except styrene, and the reaction was faster in the case of
2,2-dimethyl
chromene,
6-methoxy-2,2-dimethyl-
chromene and spiro[cyclohexane-1,2%-[2H][1]chromene
(entries 3–5) compared with the electron deficient nitro-
and cyanochromenes. Of the compounds examined, the
best chiral induction, with excellent e.e.’s of 100%, was
seen in the epoxidation of the electron deficient
nitrochromene and cyanochromene (entries 6 and 7).
However, the e.e. was a poor 23% in the epoxidation of
styrene (entry 1).
2.1. Enantioselective epoxidation of non-functionalised
alkenes
To compare these results with that of Jacobsen’s
reagent,5 the epoxidation reaction was conducted with
cyanochromene using 2 mol% of Jacobsen’s catalyst
under similar reaction conditions, which gave an excel-
lent 95% conversion with an e.e. of 98% after 15 h.
Complex 1 was then used as a catalyst in the epoxida-
tion of 2,2-dimethyl chromene, 6-cyano-2,2-dimethyl
Scheme 1.

R. I. Kureshy et al. / Tetrahedron: Asymmetry 12 (2001) 433–437
435
Table 1. Conversion and e.e. in the UHP/1 epoxidation of non-functionalised alkenes in the presence of ammonium acetate
However, using 1 in an identical reaction, epoxidation
was complete in 5 h with 100% conversion and 100%
e.e. (Table 1, entry 6). This enhanced activity of the
dimeric catalyst 1 indicates that the two metal centres
are not working in isolation but have some co-operative
interaction.
conversion. There was marginal improvement in e.e.
values in the presence of an oxygen coordinating co-
catalyst whilst both conversion and the e.e. decreased in
the presence of a nitrogen coordinating co-catalyst. The
loading of the catalyst could not be reduced below 0.5
mol%.
Catalytic runs were also conducted with 2,2-
dimethylchromene by changing the co-catalyst used.
Pyridine N-oxide, 4-phenyl pyridine N-oxide, 4-(3-
phenyl propyl pyridine N-oxide), 4-methyl morpholine
N-oxide and 1-methyl imidazole were examined as co-
catalysts. The results are listed in Table 2.
To investigate recycling of the catalyst, after comple-
tion of the reaction, the organic phase of the reaction
mixture was washed with water and brine, and then
concentrated. The catalyst was precipitated by adding
hexane and used in an identical reaction. This recycling
procedure was repeated a further four times and the
results obtained are shown in Table 3.
The reaction time increased to ꢀ8 h with all other
nitrogen and oxygen coordinating co-catalysts com-
pared to 2.5 h when ammonium acetate was used. The
change in co-catalyst had no significant effect on the
The activity of 1 decreased steadily upon successive use
possibly due to minor degradation (weight loss) under
the reaction conditions. Whilst the yield of the reaction
Table 2. UHP/1 catalysed enantioselective epoxidation of 2,2-dimethyl chromene in the presence of different co-catalysts
Entry
Co-catalyst
Conversion (%)a
Time (h)
e.e. (%)b
Configuration
1
2
3
4
5
NMO
\99
\99
\99
\99
95
8
7
6.5
7
7
86
86
86
86
81
3R,4R
3R,4R
3R,4R
3R,4R
3R,4R
4-PhPyNO
4-PPPyNO
PyNO
NMeIm
Reactions were carried out in CH2Cl2–MeOH (1.6 mL) with catalyst (0.025 mmol), substrate (2.5 mmol), co-catalyst (0.2 mmol), and oxidant (3.0
mmol) at 2°C.
a Determined by GC.
b Determined by 1H NMR using the chiral shift reagent (+)-Eu(hfc)3.

436
R. I. Kureshy et al. / Tetrahedron: Asymmetry 12 (2001) 433–437
Table 3. UHP/1 catalysed enantioselective epoxidation of
2,2-dimethyl chromene in the presence of ammonium acet-
ate co-catalyst: catalyst recycling investigations
GTA chiral capillary column or 1H NMR using the
chiral shift reagent (+)-Eu(hfc)3.
Run
1
2
3
4
5
4.2. Synthesis of 5,5-methylene-di-3-tert-butyl salicyl-
aldehyde 3
Conversion (%)
e.e. (%)
Time (h)
100
84
2.5
85
84
3
70
84
5
59
84
6.5
53
84
10
3-tert-Butyl salicylaldehyde (0.12 mol) was treated with
a solution of paraformaldehyde (0.06 mol) in glacial
acetic acid (16 mL) and sulphuric acid (2 mL) under
nitrogen. The resulting solution was allowed to heat to
90°C with stirring for 24 h. The reaction mixture was
poured into cold water and allowed to stand overnight.
The deposited dark brown solid was extracted with
petroleum ether (3×15 mL). The organic phase was
dried over sodium sulphate. The dark brown com-
pound was purified by silica gel column chromatogra-
phy using hexane–ethyl acetate as eluent to yield 3 as a
reduced with repeated use of 1, the e.e. values remained
consistent through the recycling process.
3. Conclusion
1
solid (30.9 g, 70%), mp 99–100°C; H NMR (CDCl3,
The dimeric Mn(III)-Schiff base complex 1 successfully
catalysed the enantioselective epoxidation of the
non-functionalised alkenes examined in this study. The
best chiral induction, with excellent e.e. of 100%, was
obtained in the epoxidation of nitro- and
cyanochromene. The reaction rate was found to be
slower in the presence of nitrogen and oxygen coordi-
nating co-catalysts compared to reactions in which
ammonium acetate was used.
200 MHz): l ppm 11.72 (s, 2H, OH), 9.82 (s, 2H,
HCO), 7.37 (d, 2H, aromatic Jm=2.14), 7.14 (d, 2H,
aromatic, Jm=2.14), 3.93 (s, 2H, methylene), 1.40 (s,
9H, methyl). Anal. calcd for C23H28O4: C, 74.97; H,
7.66. Found: C, 74.80; H, 7.58%.
4.3. Synthesis of N-(2-hydroxy-3,4-di-tert-butyl benz-
aldehyde)-1-amino-2-cyclohexeneimine 2
The catalyst could be recovered after the reaction and
re-used without purification. The activity of the
recycled catalyst gradually decreased upon successive
use, possibly due to minor degradation during the
reaction. Whilst the reaction times increased and the
yields reduced, the enantioselectivity of the reactions
was unaffected on recycling the catalyst five times.
Synthesis of the chiral Schiff base was carried out with
a minor modification to the reported method.18 The
monotartarate salt of (1R,2R)-(−)-cyclohexane diamine
(0.0112 mol) and K2CO3 (0.0225 mol) were dissolved in
distilled water (15 mL) with stirring. Ethanol (6 mL)
was added and the resulting cloudy mixture was heated
under reflux at 70–80°C for 2 h. The solvent was
completely removed and the liberated diamine was
extracted with chloroform (4×5 mL). The free diamine
was stirred with a solution of 3,5-di-tert-butyl salicyl-
aldehyde (0.0112 mol) in CHCl3 (20 mL) for 48 h at
0°C. Removal of the solvent gave 2 as a yellow solid.
1H NMR (CDCl3, 200 MHz): l ppm 1.23 (s, 9H), 1.41
(s, 9H), 1.58–2.25 (m, 11H, 2H exchangeable with
D2O), 3.34 (1H), 6.89 (s, 1H), 7.26 (s, 1H), 13.72 (b,
1H, exchangeable with D2O). Anal. calcd for
C21H34N2O: C, 76.31; H, 10.37; N, 8.48. Found: C,
76.26; H, 10.30; N, 8.40%.
4. Experimental
4.1. Methods
All the solvents used were purified by a known proce-
dure. Indene and styrene were both passed through a
pad of neutral alumina before use. (1R,2R)-(−)-Cyclo-
hexane diamine was resolved from the technical grade
cis–trans mixture by the reported procedure.15 2,2-
Dimethyl chromene, 6-cyano-2,2-dimethyl chromene, 6-
nitro-2,2-dimethyl chromene, 6-methoxy-2,2-dimethyl
chromene, and spiro[cyclohexane-1,2%-[2H][1]chromene
were synthesised by known methods.16 3,5-Di-tert-butyl
salicylaldehyde was synthesised by a reported proce-
dure.17 The purity of the solvents, substrates and prod-
ucts was determined by GLC using a Shimadzu GC
14B machine with a 2 m long, 3 mm ID, 4 mm OD
stainless steel column packed with SE30, 5% mesh size
60–80 and an FID detector. For styrene and indene, the
column temperature was programmed between 70 and
150°C while for chromenes it was 150°C isothermal.
Nitrogen was used as the carrier gas with a flow of 30
mL min−1 and an injection temperature of 200°C. Inter-
nal standard methods were used to determine yields by
comparison of peak height and area. The enantiomeric
purity of the product was determined using a Chiraldex
4.4. Synthesis of 5,5-methylene di-[(R,R)-{N-(3-tert-
butyl salicylidine)-N%-(3%,5%-di-tert-butyl salicylidene)}-
1,2-cyclohexanediamine] 4
A solution of 2 (0.002 mol) in dichloromethane and
5,5-methylene-di-3-tert-butyl salicylaldehyde 3 (0.002
mol) in ethanol was refluxed for 6–8 h. The resulting
solution, on concentration, precipitated out the desired
chiral ligand, which was isolated in 85% yield. IR
1
(KBr): 1620 cm−1 w(HꢀCꢁN); H NMR (CDCl3, 200
MHz): l ppm 1.23 (s, 18H), 1.40 (s, 36H), 1.54–2.0 (m,
16H), 3.2 (s, 4H), 3.68 (s, 2H), 6.74 (s, 4H), 7.05 (s,
4H), 8.21 (s, 4H), 13.69 (bs, 4H exchangeable with
D2O). Anal. calcd for C65H92N4O4: C, 78.58; H, 9.34;
N, 5.64. Found: C, 78.26; H, 9.30; N, 5.47%.

R. I. Kureshy et al. / Tetrahedron: Asymmetry 12 (2001) 433–437
437
The catalyst was separated from the epoxide by precip-
itation with hexane for further use.
4.5. Synthesis of 5,5-methylene di-[(R,R)-{N-(3-tert-
butyl salicylidine)-N%-(3%,5%-di-tert-butyl salicylidene)}-
1,2-cyclohexanediaminato(2-) manganese(III) chloride] 1
Acknowledgements
Schiff base 4 (0.001 mol in CH2Cl2) was stirred under
reflux with manganese acetate (0.002 in CH3OH) under
an inert atmosphere for 8–10 h. The reaction mixture
was cooled to room temperature. Lithium chloride
(0.006 mol) was added and the mixture was stirred for
a further 5 h while exposed to air. The mixture was
filtered and the solvent was removed from the filtrate.
The evaporation residue was extracted with
dichloromethane, and the dichloromethane extracts
were combined and washed with water, brine and dried
over sodium sulphate. On partial removal of the solvent
and addition of petroleum ether (40–60°C fraction), 1
precipitated from solution. The mixture was filtered and
the filter cake dried to afford 1 (4.45 g, 90%). Anal.
calcd for C65H92Cl2Mn2N4O6: C, 67.81; H, 8.06; 4.87.
Found: C, 67.60; H, 8.02; N, 4.83%. IR (KBr): 3431
(br), 2947 (s), 2866 (s), 1612 (s), 1538 (s), 1475 (sh),
1435 (s), 1388 (m), 1342 (s), 1309 (s), 1285 (sh), 1238
(sh), 1201 (m), 1170 (m), 1100 (w), 1030 (m), 940 (w),
833 (m), 780 (w), 731 (w), 690 (w), 568 (s), 475 (w)
cm−1. UV–vis (CH2Cl2): umax (m) 250 (50000), 266
(49960), 345 (47540), 420 (41460), 451 (41040), 510
(36060). [h]3D0=−50.4 (c 0.12, CH2Cl2). Absolute
configuration (R); \M (MeOH) 4 mho cm−1 mol−1.
R.I.K. and N.H.K. are grateful to the DST and TWAS
for financial assistance and to Dr. P. K. Ghosh, the
Director of the Institute, for providing the necessary
facilities.
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Enantioselective epoxidation reactions were typically
performed according to the established procedure1
using complex 1 (1 mol%) with 2,2-dimethylchromene,
6-cyano-2,2-dimethylchromene,
6-nitro-2,2-dimethyl-
chromene, 6-methoxy-2,2-dimethylchromene, spiro[cy-
clohexane-1,2%-[2H][1]chromene, styrene and indene
(2.5 mmol) as substrate in 1:1 dichloromethane:
methanol (1.6 mL) in the presence of a co-oxidant viz.
ammonium acetate, pyridine N-oxide, 4-phenyl pyri-
dine N-oxide, 4-(3-phenyl propyl pyridine N-oxide),
4-methyl morpholine N-oxide and 1-methyl imidazole
(0.2 mmol) using a urea–H2O2 adduct (3.0 mmol) in six
equal portions as an oxidant at a reaction temperature
of 2°C. The progress of the epoxidation reaction was
monitored by GC. After completion of the reaction, the
solvent was removed and the residue was extracted with
CH2Cl2, washed with water and dried over sodium
sulphate.
17. Deng, L.; Jacobsen, E. N. J. Org. Chem. 1992, 57,
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18. Janssen, K. B. M.; Laquiere, I.; Dehaen, W.; Parton, R.
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.