Heterogenisation of ketone catalysts within mesoporous supports for asymmetric epoxidation

Article abstract of DOI:10.1039/c2ra21837b

The synthesis of the first mesoporous silica (150 A) anchored carbohydrate-derived chiral ketone is described. This new heterogeneous catalyst has been shown to be effective in the asymmetric epoxidation of olefins by oxone. The heterogeneous ketone catalyst has comparable activity to that of its homogeneous counterpart and returned enantioselectivities up to 90% e.e.

Full text of DOI:10.1039/c2ra21837b

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Heterogenisation of ketone catalysts within
mesoporous supports for asymmetric epoxidation3
Cite this: RSC Advances, 2013, 3, 843
Lynda J. Brown,* Richard C. D. Brown and Robert Raja
Received 16th August 2012,
Accepted 30th October 2012
The synthesis of the first mesoporous silica (150 Å) anchored carbohydrate-derived chiral ketone is
described. This new heterogeneous catalyst has been shown to be effective in the asymmetric epoxidation
of olefins by oxone. The heterogeneous ketone catalyst has comparable activity to that of its
homogeneous counterpart and returned enantioselectivities up to 90% e.e.
DOI: 10.1039/c2ra21837b
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tivities9 and the lactam ketone 1c could be utilised to epoxidise
a variety of 1,1-disubstituted terminal olefins using oxone as
Introduction
the oxidant, giving up to 88% e.e.10 However, it is known that
these chiral ketones can undergo undesired Baeyer–Villiger
side reactions leading to their inactivation, necessitating
relatively high catalyst loadings (typically 20–30 mol%).11
It was envisaged that heterogenisation of optically pure
chiral ketones 1b within the interior of mesoporous silicas
would afford asymmetric epoxidation catalysts with the
potential benefits of ease of product separation, and catalyst
recovery. Additionally, the environment within the pore
structure could influence the reactivity and selectivity of the
heterogeneous catalyst (Fig. 2). Indeed, Armstrong et al.
showed that immobilisation of an a-fluorotropinone on silica
gave a material with comparable catalytic efficiency and
selectivity to the homogeneous system.12
Stereoselective catalytic transformations are of central impor-
tance in modern organic synthesis. Homogenous asymmetric
catalysis affords many effective transformations1 accelerating
reactions with minimal energy input, however the removal of
the catalyst can be challenging resulting in inefficient
purifications and catalyst recovery and recycling. Separation
of catalysts and reagents by heterogenisation overcomes some
of these difficulties by offering simplified product isolation.2
Furthermore, heterogenisation can facilitate implementation
of continuous flow processes.3 With respect to selectivity, it
has been established that by anchoring a homogeneous
catalyst within the pores of a suitable silica support reactivities
and enantioselectivities can be conserved or even enhanced.4
Mesoporous silicas, such as the M41S (e.g. MCM-41), can be
synthesised with structurally ordered nanopores in a range
sizes, with narrow pore size distributions. These solid supports
can act as scaffolds for catalysis when modified with
homogeneous catalysts and influence the yield, configuration
or constitution of the final products.5
Herein we describe the first successful application of a novel
heterogeneous system based on an oxazolidinone catalyst to the
asymmetric oxidation of a range of conjugated olefins to their
corresponding epoxides in high yields and selectivities.
Asymmetric alkene epoxidation is one of the most useful
synthetic transformations in the preparation of chiral building
blocks for the synthesis of biologically active molecules.6 Non
racemic chiral ketones, which generate chiral dioxiranes in situ
in the presence of an oxidising agent such as oxone, have been
well documented to effectively promote asymmetric epoxida-
tions.7 Early reports from the Shi group described fructose-
derived ketone 1a as a successful epoxidation catalyst for trans
1,2-disubstituted and trisubstituted olefins (Fig. 1).8
Subsequent studies from the same group showed that
oxazolidinone-bearing ketone (catalyst 1b) catalysed the
epoxidation of a wide range of olefins with high enantioselec-
Results and discussion
Our study commenced by modifying a homogeneous chiral
ketone with a linker that terminated in a suitable functionality
for attachment on to a solid support, under immobilisation
School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ,
UK. E-mail: ljb2@soton.ac.uk; Fax: +44-(0)23-8059-5919; Tel: +44-(0)23-8059-6757
Electronic supplementary information (ESI) available: 1H and 13C NMR of
3
compounds 2–7, 1H NMR and HPLC of epoxides and 13C and 29Si CP-MAS NMR
of silicas 8a–10a. See DOI: 10.1039/c2ra21837b
Fig. 1 Shi’s chiral ketone catalysts
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Fig. 2 Representation of heterogeneous epoxidation
Scheme 1 Synthesis of chiral ketone catalyst-linker conjugate 5.
conditions compatible with the functionality present in the
catalyst (Scheme 1).12 In the present case a terminal alkene
linker was selected, which would be coupled to a thiol
functionalised support using a thiyl radical coupling pro-
cess.13 The synthesis of the catalyst-linker conjugate 5 was
adapted from the method of Shi,14 commencing with the
Amadori rearrangement of D-glucose and aniline 7 to produce
the tetraol 2.15 Ketalisation, oxazolidinone formation and
oxidation of the resulting secondary alcohol 4 provided the
desired ketone 5 with the appended linker.
In order to prepare the supported catalyst, dry calcined (T =
550 uC) mesoporous silica was first reacted with dichlorodi-
phenylsilane with the objective to preferentially cap the more
accessible Si–OH functionality following a method previously
described for capping external sites (Scheme 2).16,17 This left
the surface of the inner walls of the mesoporous silicas free for
catalyst attachment, thus confining the ketone predominately
within its interior pores. With the intent of securing the
catalyst to the internal siloxyl functionality of the support, the
silica was then reacted with 3-mercaptopropyl trimethoxysi-
lane to provide thiol functionalisation ready for radical
mediated addition to the olefin moiety of the ketone 5.
Refluxing the thiol modified silica 9 in a CHCl3 solution of
catalyst 5 and AIBN in the dark completed the heterogenisa-
tion of the ketone catalyst.12 Elemental analysis of both silicas
9a and 10a showed clear incorporation of the thiol, and from
nitrogen analysis of 10a the loading of the catalyst was
estimated to be 0.20 mmol g21 (entries 3 and 4, Table 1). IR
spectroscopy confirmed the presence of the ketone (vCO 1770
cm21).
Confirmation of the immobilisation of the ketone catalyst
within the pores of the supports, not just on the more
accessible outer surface sites, came from nitrogen adsorption
isotherms. Firstly, there was a clear drop in BET surface area
from 263 m2 g21 for the underivatised mesoporous silica
(entry 1, Table 1) to 210 m2 g21 after heterogenisation of the
catalyst (entry 4, Table 1). The total pore volume showed no
decrease after capping, when the linker was attached there was
a small decrease in volume, however when the catalyst was
attached there was a large decrease from 0.152 mL g21 to 0.122
mL g21. These data provide strong evidence for the anchoring
of the ketone catalyst within the pores of the support.
Evidence to support covalent functionalisation of the
mesoporous framework was provided by solid-state NMR
spectroscopy; 29Si CP-MAS (cross-polarized magic angle spin-
ning) NMR spectra of the silica 8a showed three signals: Q2
signals (292 ppm) derived from a low level of silandiol groups
(Si(OH)2), Q4 signals (2102 ppm) from the siloxanes (Si(OSi)4)
and stronger Q3 signals (2111 pm) from the silanol groups (Si–
OH) (Fig. 3). The presence of Si environments due to the
capping was below the detection levels of the experiment. The
29Si NMR spectrum of silica 9a containing the mercaptopropyl
linker showed a decreased relative intensity of the Q3 signal
compared to silica 8a and Q2 almost disappeared, providing a
clear indication that the 3-mercaptopropyl trimethoxysilane
reacted with the available Si–OH groups. The presence of three
new resonances in the 29Si NMR spectrum of 9a (247 ppm T1,
844 | RSC Adv., 2013, 3, 843–850
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functionality rather than disulfides or higher sulfur oxidation
states. The 29Si CP-MAS NMR spectra for the heterogeneous
catalyst 10a did not display any new signals as anticipated,
whereas the 13C NMR showed characteristic signals for the
immobilised catalyst consistent with the presence of aromatic,
C–O and aliphatic carbon signals. The ketone carbon signal
was too weak to be observed due to its high anisotropic
environment and splitting between
a centre band and
spinning sidebands under experimental conditions.
However, the presence of the chiral ketone was strongly
supported by IR spectroscopy and the ability of the modified
silica to mediate the asymmetric epoxidation of olefins.
To enable us to probe the influence of pore size and
application of the capping protocol upon the reactivity and
selectivity of the heterogeneous chiral ketone catalysts, two
uncapped silica supported catalysts 11a,b were also prepared
from KG-60 Å and KG-150 Å (Scheme 2).{ The epoxidation of
the chromene 12 was selected as a test reaction and the four
heterogeneous catalysts, 10a, 10b, 11a and 11b were evaluated
under these conditions. Our preliminary results (Table 2,
entries 1–4) were obtained with low catalyst loadings (typically
2.5 mol%). Interestingly, a substantial drop in e.e. was
observed for the epoxidations conducted in the presence of
the heterogenised catalysts prepared without capping (entries
2 and 4, Table 2) relative to the capped catalysts (entries 1 and
3, Table 2). These results indicate that capping the more
accessible Si–OH functionalities is a significant factor in
gaining high enantioselectivities in this system, which could
be due to confinement of the catalyst within the pores of the
silica. It was possible that without capping there was a
separate, unselective background epoxidation reaction occur-
ing.17
Scheme 2 Derivatisation of mesoporous silica.
Table 1 Physical data supporting heterogenisation of the catalyst into the internal pores of 150 Å silica
Elemental analysis by combustion (%)
Entry
Catalyst sample
SBET/m2 g21
Pore volumea/mL g21
C
H
N
S
Loadingb/mmol g21
1
2
3
4
SG-150 Å silica
8a
9a
10a
263
266
262
210
0.156
0.158
0.152
0.122
—
—
1.97
8.39
—
—
1.19
1.53
—
—
,0.10
0.29
—
—
2.78
2.05
—
—
—
0.20
a
b
Total pore volume was measured at P/Po = 0.410. Loading based on N%.
(RSi(OSi)–(OH)2), 257 ppm T2, (RSi(OSi)2–(OH)), 267 ppm, T3,
(RSi(OSi)3)) further confirmed the incorporation of organic
silanes on the silica surface.
Fig. 4 shows the 13C CP-MAS NMR spectrum of 9a, with
three resonances (27.9, 22.8, 10.6 ppm) corresponding to the
CH2SH, CH2 and CH2Si methylene carbons of the propyl linker
respectively. Oxidation of surface thiol groups to disulfides
may occur in air under ambient conditions, however, the
Our results indicated that the KG-150 Å (10a) gave better
conversions which may be due to enhanced site isolation of
the catalyst molecules within this larger polymeric framework.
Subsequent optimisation showed that using the KG-150 Å
{ KG-60 Å: particle size 70-230 mesh; 63-200 mm; pore size 0.8 cm3 21; pore
g
volume 60 Å; surface area 500 m2 g21; pH 6.0-7.5 (10% in H2O); bp 2230 uC; mp
1600 uC. KG-150 Å: particle size 100-200 mesh; 75-150 mm; pore size 1.15 cm3
g
21; pore volume 150 Å; surface area 300 m2 21; pH 7.0 (5% in slurry); bp 2230
g
chemical shift data are consistent with the presence of thiol
uC; mp 1600 uC.
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Table 2 Effect of heterogenisation and capping on ketone catalyst
Entry Catalyst Pore size Capping conv (%) e.e. (%) TON
1
2
3
4
5
6
10a
11a
10b
11b
10a
5
150
150
60
60
150
—
3
x
3
x
3
—
23a
20a
16a
8a
65
32
69
32
88
93
9.2
8
6.4
3.2
4.8
3.2
96b
80c
a
Catalyst (2.5 mol%), oxone (2.7 equiv.), K2CO3 (10.5 equiv.), 0 uC to
b
rt, 24 h. Catalyst (20 mol%), oxone (2.7 equiv.), K2CO3 (10.5 equiv.),
0 uC to rt, 6 h. Catalyst (25 mol%), oxone (2.7 equiv.), K2CO3 (10.5
equiv.), 0 uC to rt, 24 h.
c
Fig. 3 29Si CP-MAS NMR of (a) silica 8a (b) silica 9a.
epoxidation was also comparable to that attained by the
homogeneous equivalent, again with a small drop in enantios-
electivity (homogeneous 74%, 93% e.e.; heterogeneous 70%,
86% e.e.).
mesoporous silica with the more accessible sites capped
(catalyst 10a) with loadings of 20 mol% (Table 2 entry 5) gave
excellent conversions in reasonable timescales and therefore
all ensuing reactions were performed under these conditions.
Comparing the heterogeneous catalyst 10a to its homogeneous
counterpart 5 (Table 2, entries 5 and 6) showed that the
heterogeneous ketone gave improved conversion, with only a
modest drop in e.e. This conversion required 20 mol% of the
heterogeneous catalyst and was almost complete within 6 h,
whereas but the homogeneous catalyst used 25 mol% and had
not reached completion after 24 h. This was reflected in the
improved turnover number (TON = moles of product/moles of
catalyst). The conversion of trans-stilbene by heterogeneous
The heterogeneous catalyst 10a was employed in the
epoxidation of a range of olefins and the conversions and
e.e. were measured (Table 3). In all cases the epoxidation
reactions were very efficient giving high conversions and good
isolated yields. A major advantage of the heterogeneous
catalyst was the ease of purification. Unlike its homogeneous
equivalent which required separation from the product by
chromatography, the supported catalyst was removed by
simple filtration. The TON in all reactions ranged from 3.5
to 5.0 indicating that the heterogeneous catalyst was as
effective as its homogeneous equivalent. The addition of the
oxone was performed as described by Shi involving the
simultaneous and separate addition of aqueous oxone and
aqueous K2CO3 at 0 uC to buffer the effect of KHSO4 and
ensure that a mildly basic pH was maintained through the
reaction.18 With slower addition times, the e.e. values were
typically higher whilst retaining good conversions. trans-
Stilbene gave a slightly lower conversion than expected, which
was attributed to its insolubility in the mixed aqueous/organic
solvent medium.
The choice of epoxidation conditions has been noted to be
substrate dependant11 and a modified procedure where oxone
and NaHCO3 were added as solids proved advantageous
raising the conversion to 70%.
The Shi catalysts are well documented to undergo an
undesirable Baeyer–Villiger side reaction resulting in their
deactivation, thereby impeding a high number of catalytic
cycles. Therefore the recyclability of the heterogeneous catalyst
10a was investigated by the epoxidation of the chromene
substrate 12. It was observed that after two cycles there was
only a minor reduction in catalytic ability and enantioselec-
tivity. However, by the third cycle a significant drop in
conversion was noted and a small drop in enantioselectivity
due to the increased significance of the background reaction
Fig. 4 13C CP-MAS NMR of (a) silica 9a (b) catalyst 10a.
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Table 3 Epoxidation data for a range of olefins
Entry
1a
Substrate
Add. time (h)c
6h
Conv.(%)d
100
Yielde [Sel]f(%)
79 [79]i
e.e.g (%)
Configj
90
(1S,2R)20
2b
3a
3.5h
70
96
63 [90]
93 [97]
86
88
(R,R)21
6
(3R,4R)22
4a
5a
6
6
93
75
82 [88]
65 [86]
80
79
(3R,4R)22
(3R,4R)23
6a
7a
6
6
93
90
80 [86]
77 [86]
83
81
(3R,4R)22
(3R,4R)20
(1R,2S)24
8a
9a
4
6
100
100
75 [75]
83 [83]
68
18
k
—
a
Typical procedure: olefin (0.2 mmol), silica supported ketone catalyst 10a (200 mg, 0.04 mmol, 20 mol%, based on a calculated loading of
0.20 mmol g21), K2CO3 (0.84 M in aq. Na2EDTA (4 6 1024 M), 2.52 mL, 2.11 mmol, 10.5 equiv.), oxone (0.212 M in aq. Na2EDTA (4 x 1024
M), 2.52 mL, (0.53 mmol, 2.7 equiv.), Bu4NHSO4 (0.0015 mmol) in DME : DMM (3 : 1, v/v, 3.0 mL) and K2CO3–AcOH buffer (0.1 M, pH 9.3, 2.0
b
mL) at 0 uC. Olefin (0.1 mmol), silica supported ketone catalyst 10a (100 mg, 0.02 mmol, 20 mol%, based on a calculated loading of 0.20
mmol g21), NaHCO3 (3.1 mmol, 30 equiv.), oxone (1.0 mmol, 10 equiv.), in DME : DMM (3 : 1, v/v, 1.5 mL) and Na2EDTA buffer (4 6 1024 M,
c
d
1.0 mL) at 0 uC. Time allowed for complete simultaneous addition of the K2CO3 and oxone. The conversions were determined by 1H NMR.
e
f
g
Yields of isolated products. (Yield/conv.) 6 100. Enantioselectivites were determined by chiral HPLC using a Chiralcel ODH or a Chiralcel
OBH column. Total reaction time 24 h. Product isolated as a mixture of epoxide (54%) and diol (46%). The absolute configurations were
determined by comparing HPLC retention times and orders of elution with reported values. The absolute configuration was not determined.
h
i
j
k
dry glassware and in an atmosphere of nitrogen.
Dichloromethane was dried by distillation from CaH2. 1H
NMR and 13C NMR spectra were recorded in CDCl3 solution
using Bruker AC300, AV300 (300 and 75 MHz respectively) or
Bruker DPX400 (400 and 100 MHz respectively) spectrometers.
Chemical shifts are reported in d units using CHCl3 as an
(racemic epoxidation by oxone alone) which becomes more
apparent at lower conversions.19
Conclusion
In summary, we have synthesised and heterogenised a chiral
ketone catalyst on the inner walls of mesoporous silica
supports. Capping of the more accessible siloxyl groups, prior
to catalyst immobilisation, was found to be advantageous in
terms of enantioselectivities for the epoxidation of a number
of olefin substrates. The heterogeneous catalyst has been
applied to the epoxidation of a range of olefins with good
conversions and enantioselectivities.
internal standard (d 7.27 ppm 1H,
d
77.00 ppm 13C
respectively). Infrared spectra were recorded on a Nicolet 380
spectrometer fitted with a Diamond platform, as solids or neat
liquids. Electrospray mass spectra were obtained using a
Micromass platform mass analyser with an electrospray ion
source. Chiral HPLC separations were performed on a Agilent
1120 Compact LC using a Chiralcel ODH or OBH column
eluting with isopropanol : hexane mixtures monitored by UV
detection at 220 or 254 nm. Elemental analyses were
performed at Medac Ltd, Chobham Business Centre, Surrey,
UK. BET-Nitrogen asorption isotherms were obtained with a
Gemini 2375 volumetric gas adsorption apparatus (micro-
meritics) at 77 K.
Experimental
General
(2R,3S,4R,5R)-2-(((4-(BUT-3-EN-1-YL)PHENYL)AMINO)METHYL)TETRAHYDRO-
2H-PYRAN-2,3,4,5-TETRAOL (2). A solution of D-glucose (3.00 g, 16.7 mmol)
All reagents were purchased from Sigma–Aldrich and used
without further purification. All reactions were performed in
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and aniline 7 (2.95 g, 20.0 mmol, 1.2 equiv.) in acetic acid (40.0
mg, 0.67 mmol, 0.04 equiv.) and H2O (1.0 mL) was heated at 95
uC (bath temp.). After 10 min the reaction was dark red and after
1 h had formed a dark red solid. The heat was removed, EtOH
(1.0 mL) added, and the reaction allowed to cool with stirring
for 30 min. The reaction was then diluted with Et2O and the
resultant precipitate removed by filtration. The crude product
remaining in the filtrate was purified by silica gel column
chromatography eluting with 2 to 5% MeOH : CH2Cl2. The
combined solids were dried in vacuo to give the title compound
as an off white solid (2.58 g, 8.35 mmol, 50%). IR nmax(neat)/
4.38–4.24 (m, 4H), 4.18–4.10 (m, 1H), 3.85–3.74 (m, 2H), 3.05
(d, J = 7.7 Hz, 1H), 2.74–2.63 (m, 2H), 2.40–2.29 (m, 2H), 1.57
(s, 3H), 1.39 (s, 3H); 13C NMR (CDCl3, 75 MHz): d 153.0, 138.1,
137.7, 135.3, 129.0, 118.6, 115.1, 109.8, 100.8, 76.4, 73.1, 71.4,
61.7, 53.0, 35.4, 34.6, 28.0, 26.0; LRMS (ESI+) m/z 396.2
([M+H]+).
( 3 A R , 5 9 S , 7 A R ) - 3 9 - ( 4 -( B U T -3 - E N -1 - Y L ) P H E N Y L )- 2 , 2 -
DIMETHYLDIHYDROSPIRO[[1,3]DIOXOLO[4,5-C]PYRAN-6,59-OXAZOLIDINE]-
29,7-(7AH)-DIONE (5). To a suspension of the alcohol 4 (0.2 g,
0.53 mmol) and crushed 3 Å molecular sieves (dried, 1.00 g) in
dry CH2Cl2 (5 mL) was added PDC (0.35 g, 1.6 mmol, 3.0
equiv.) portionwise over 20 min. Glacial acetic acid (30 mL) was
added and the reaction stirred at room temperature overnight.
The reaction was filtered through short pad of silica gel eluting
with 40% EtOAc : hexane the resultant off white foam was
recrystallised from hot Et2O to give the title ketone as a white
solid (168 mg, 0.45 mmol, 85%). IR nmax(neat)/cm21 1755 (s),
1518 (m); 1H NMR (CDCl3, 400 MHz): d 7.43 (d, J = 8.5 Hz, 2H),
7.21 (d, J = 8.5 Hz, 2H), 5.83 (ddt, J = 16.9, 10.3, 6.5 Hz, 1H),
5.08–4.93 (m, 2H), 4.87 (d, J = 5.5 Hz, 1H), 4.75 (d, J = 10.3 Hz,
1H), 4.57–4.68 (m, 2H), 4.27 (d, J = 13.6 Hz, 1H), 3.76 (d, J =
10.3 Hz, 1H), 2.75–2.63 (m, 2H), 2.36 (q, J = 7.2 Hz, 2H), 1.49 (s,
3H), 1.44 (s, 3H); 13C NMR (CDCl3, 100 MHz): d 195.0, 151.2,
138.7, 137.7, 134.8, 129.3, 118.7, 115.1, 111.1, 99.1, 77.5, 75.5,
60.9, 49.8, 35.3, 34.6, 27.0, 25.9; LRMS (EI+) m/z 398 ([M+Na]+).
4-(BUT-3-EN-1-YL)ANILINE (7).25,26. To a stirred solution of
trifluoroacetic anhydride (75 mL) at 0 uC containing 4-phe-
nyl-1-butene (10.0 g, 75.6 mol) was added copper(II) nitrate (9.1
g, 37.7 mol) portionwise. After 30 min at 0 uC, the reaction was
allowed to warm to room temperature and stirred for 2 h
becoming dark green. The reaction was poured onto ice and
extracted with Et2O (x 3) the combined organics were washed
with sat. NaHCO3, brine and dried (MgSO4) and concentrated
in vacuo to a brown crude oil (14.5 g) which was used directly
in the next step.
1-(But-3-en-1-yl)-4-nitrobenzene (14.5 g, ca. 75.6 mol) was
dissolved in EtOH (300 mL), SnCl2?2H2O (85.0 g, 0.38 mol, 5.0
equiv.) was added and the reaction allowed to stir for 2 days.
The reaction was poured onto water (250 mL) and the pH
raised to 9 with 1 M NaOH, the cloudy mixture was extracted
with EtOAc (x 3), Rochelle’s salt was added to aid separation.
Combined organics were washed with brine and dried (MgSO4)
and concentrated in vacuo to a brown oil which was purified by
silica gel column chromatography eluting with 25 to 30%
EtOAc : hexane gave a the title para-isomer as a pale oil (6.40 g,
43.5 mmol, 58%) and the undesired ortho-isomer as a pale oil
(2.10 g, 14.30 mmol, 19%). Data consistent with reported
values27 IR nmax(neat)/cm21 1640 (m), 1515 (s), 1342 (s); 1H
NMR (CDCl3, 400 MHz): d 7.01 (d, J = 8.0 Hz, 2H), 6.65 (d, J =
8.0 Hz, 2H), 5.88 (ddt, J = 16.9, 10.3, 6.7 Hz, 1H), 5.11–4.93 (m,
2H), 3.50 (br s, 2H), 2.68–2.55 (m, 2H), 2.35 (q, J = 7.2 Hz, 2H);
13C NMR (CDCl3, 101 MHz): d 144.2, 138.4, 132.0, 129.1, 115.2,
114.6, 35.8, 34.5; LRMS (ESI+) m/z 464.2 ([3M+Na]+).
1
cm21 3345 (s), 1616 (m); H NMR (DMSO-d6, 300 MHz): d 6.89
(d, J = 7.9 Hz, 2H), 6.55 (d, J = 7.9 Hz, 2H), 5.69–5.93 (m, 1H), 5.47
(s, 1H), 5.01 (d, J = 17.2 Hz, 1H), 4.94 (d, J = 9.1 Hz, 2H), 4.24–
4.56 (m, 3H), 3.84 (d, J = 12.1 Hz, 1H), 3.71–3.22 (m, 5H), 3.05–
2.93 (m, 1H), 2.50 (t, J = 7.1 Hz, 2H), 2.32–2.18 (m, 2H); 13C NMR
(DMSO-d6, 75 MHz): d 147.2, 138.4, 128.6, 128.5, 114.9, 112.3,
98.1, 70.0, 69.2, 68.7, 63.3, 49.6, 35.6, 33.8; LRMS (ESI+) m/z
310.2 ([M+H]+).
(3AR,6R,7S,7aS)-6-(((4-(BUT-3-EN-1-YL)PHENYL)AMINO)METHYL)-
2,2-DIMETHYLTETRAHYDRO-3AH-[1,3]DIOXOLO[4,5-C]PYRAN-6,7-DIOL
(3). To a suspension of the tetraol 2 (0.34 g, 1.10 mmol) in dry
acetone (11 mL) at 0 uC, under N2, was added CH(OCH3)3 (0.29
mL, 2.64 mmol, 2.4 equiv.), followed by concentrated H2SO4
(96 mL, 1.79 mmol, 1.63 equiv.). After addition of the acid the
reaction was clear but quickly became cloudy and thick and
with vigorous stirring was complete within 15 min. The pH
was adjusted to 8.9 by the addition of a few drops of NH4OH
solution and the reaction filtered through a pad of silica gel
with suction to remove NH4Cl, and washed through with
acetone. Concentration in vacuo gave a yellow oil which was
purified by silica gel column chromatography eluting with 2 to
3% MeOH : CH2Cl2 to give the title compound as a clear oil
(383 mg, 1.10 mmol, 100%). IR nmax(neat)/cm21 3393 (s), 2985
(m), 2932 (m), 1616 (m); 1H NMR (CDCl3, 300 MHz): d 7.04 (d, J
= 8.4 Hz, 2H), 6.73 (d, J = 8.4 Hz, 2H), 5.86 (ddt, J = 17.0, 10.3,
6.4 Hz, 1H), 5.11–4.92 (m, 2H), 4.33–4.10 (m, 3H), 4.01 (d, J =
13.0 Hz, 2H), 3.55–3.70 (m, 2H), 3.23 (d, J = 13.0 Hz, 1H), 2.56–
2.69 (m, 2H), 2.25–2.39 (m, 2H), 1.57 (s, 3H), 1.40 (s, 3H); 13C
NMR (CDCl3, 75 MHz): d 145.9, 138.3, 132.9, 129.2, 114.7,
109.3, 96.3, 77.4, 73.6, 72.1, 59.5, 50.5, 35.8, 34.4, 28.1, 26.1;
LRMS (ESI+) m/z 350.2 ([M+H]+), 332.2 ([M–OH]+).
(3AR,59S,7S,7AS)-39-(4-(BUT-3-EN-1-YL)PHENYL)-7-HYDROXY-2,2-
D I M E T H Y L T E T R A H Y D R O S P I R O [[1,3]D I O X O L O [4,5-C ]P Y R A N -
6,59-OXAZOLIN]-29-ONE (4). Diol 3 (0.80 g, 2.29 mmol) was
suspended in CH2Cl2 (3 mL), cooled to 0 uC and NaHCO3
(1.16 g, 13.75 mmol, 6.0 equiv.) added followed by 20%
phosgene in toluene (1.68 mL, 3.2 mmol, 1.4 equiv.) dropwise
over 10 min. The reaction was stirred for a further 2 h at 0 uC
and then triethylamine added (1.28 mL, 9.17 mmol, 4.0
equiv.). The reaction was filtered through a short pad of silica
and eluted with EtOAc, and concentrated in vacuo to an orange
oil. Purification by silica gel column chromatography eluting
with 30 to 40% EtOAc : hexane gave the title oxazolidinone as
a pale yellow foam (702 mg, 1.87 mmol, 82%). IR nmax(neat)/
cm21 3395 (w), 2985 (w), 2935 (w), 1754 (s), 1518 (m); 1H NMR
(CDCl3, 300 MHz): d 7.40 (d, J = 8.8 Hz, 2H), 7.17 (d, J = 8.8 Hz,
2H), 5.83 (ddt, J = 17.0, 10.3, 6.4 Hz, 1H), 5.08–4.94 (m, 2H),
Derivitisation of 150 Å silica
CAPPING OF EXTERNAL SI–OH FUNCTIONALITIES (8a). To dry (heated
at 550 uC) calcined 150 Å silica (Grace-Davidson 644, BET
surface area 262.79 m2
g
21, pore volume 0.156 mL g21
848 | RSC Adv., 2013, 3, 843–850
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determined by N2 adsorption, 1.50 g) in dry THF (25 mL) was
added dichlorodiphenylsilane (51 mL, 0.2 mmol) and turned
slowly§ for 1 h at room temperature.
IPA : hexane, UV 220 nm, flowrate: 1.0 mL min21 (peak 1
10.96 min, 94.01%; peak 2 13.31 min, 5.94%).
(3R,4R)-2,2-DIMETHYLCHROMENE OXIDE. (Table 3, entry 4):22
Eluent: 10% EtOAc : hexane. Off white solid (yield 82%, e.e.
80%). Chiral HPLC: Chiralcel ODH column, eluent 10%
IPA : hexane, UV 220 nm, flowrate: 1.0 mL min21 (peak 1
5.62 min, 89.91%; peak 2 6.34 min, 10.09%).
(3R,4R)-2,2-DIMETHY-6-CHLORO-CHROMENE OXIDE. (Table 3, entry
5):22 Eluent: 10% EtOAc : hexane. White solid (yield 65%, e.e.
79%). Chiral HPLC: Chiralcel ODH column, eluent 10%
IPA : hexane, UV 220 nm, flowrate: 1.0 mL min21 (peak 1
5.36 min, 89.25%; peak 2 5.83 min, 10.75%).
(3R,4R)-2,2-DIMETHY-6-BROMO-CHROMENE OXIDE. (Table 3, entry
6):22 Eluent: 10% EtOAc : hexane. Pale yellow oil (yield 80%,
e.e. 83%). Chiral HPLC: Chiralcel ODH column, eluent 10%
IPA : hexane, UV 220 nm, flowrate: 1.0 mL min21 (peak 1 5.41
min, 87.79%; peak 2 6.15 min, 8.29%).
ACTIVATION OF THE INTERNAL SURFACES OF SILICA (9a). To the above
solution was added 3-mercaptopropyl trimethoxysilane (1.50
mL, 8.00 mmol) and the reaction was turned gently for 24 h§.
The resultant solution was filtered and washed with CH2Cl2
(65), Et2O (65) and then purified by Soxhlet extraction with
Et2O for 4 h and dried in vacuo at room temperature.
Elemental analysis found (%): C 1.97, H 1.19, S 2.78; BET
surface area 266.97 m2 g21, pore volume 0.152 mL g21
.
IMMOBILISATION OF (3AR,59S,7AR)-39-(4-(BUT-3-EN-1-YL)PHENYL)-2,2-
DIMETHYLDIHYDROSPIRO[[1,3]DIOXOLO[4,5-C]PYRAN-6,59-OXAZOLIDINE]-29,
7(7AH)-DIONE (10a). The activated 150 Å silica (9a, 600 mg),
a,a9-azoisobutyronitrile (AIBN, 131 mg, 0.80 mmol), and ketone
catalyst (5, 300 mg, 0.8 mmol) were heated at reflux, in the dark, in
dry, degassed CHCl3 under nitrogen for 16 h. After this time the
silica was removed by filtration and washed with CH2Cl2 (65),
Et2O (65) and then purified by Soxhlet extraction with Et2O for 4
h and dried in vacuo at room temperature. ATR-IR vmax 1770
cm21; Elemental analysis found (%): C 8.39, H 1.53, N 0.29, S 2.05;
(3R,4R)-2,2-DIMETHY-6-FLUORO-CHROMENE OXIDE. (Table 3, entry
7):22 Eluent: 10% EtOAc : hexane. Pale yellow oil (yield 77%,
e.e. 81%). Chiral HPLC: Chiralcel ODH column, eluent 10%
IPA : hexane, UV 220 nm, flowrate: 1.0 mL min21 (peak 1 5.28
min, 90.65%; peak 2 5.95 min, 9.35%).
BET surface area 210.00 m2 g21, pore volume 0.122 mL g21
.
(1R,2S)-INDENE OXIDE. (Table 3, entry 8):29 Eluent: 20%
EtOAc : hexane. Pale yellow oil (yield 75%, e.e. 68%). Chiral
HPLC: Chiralcel OBH column, eluent 0.5% IPA : hexane, UV
220 nm, flowrate: 1.0 mL min21 (peak 1 20.63 min, 16.06%;
peak 2 32.18 min, 83.94%).
1-PHENYLCYCLOHEXENE OXIDE. (Table 3, entry 9):28 Eluent: 5%
Et2O : pentane. Colourless oil (yield 83%, e.e. 18%). Chiral
HPLC: Chiralcel ODH column, eluent 1% IPA : hexane, UV 220
nm, flowrate: 1.0 mL min21 (peak 1 6.45 min, 59.18%; peak 2
6.98 min, 40.82%).
General catalysis procedure
A mixture of the olefin (0.2 mmol), silica supported ketone
catalyst 10a (200 mg, 0.04 mmol), Bu4NHSO4 (1.00 mg, 0.003
mmol) in DME : DMM (3 : 1, v/v, 3.0 mL) were stirred at room
temperature for 5 min and then cooled to 0 uC. K2CO3–AcOH
buffer (0.1 M in aq. Na2EDTA (4 6 1024 M), pH 9.3, 2.0 mL)
was added and the mixture stirred for a further 10 min at 0 uC.
K2CO3 (0.84 M in aq. Na2EDTA (4 6 1024 M), 2.52 mL, 2.11
mmol, 10.5 equiv.) and oxone (0.212 M in aq. Na2EDTA (4 6
1024 M), 2.52 mL, 0.53 mmol, 2.7 equiv.) were then added
simultaneously through separate syringes using a syringe
pump. Addition times and final reaction times were as
denoted in Table 3. The reaction was then diluted with Et2O
(20 mL) and water (20 mL), and extracted further with Et2O (20
mL, 62). Combined organics were washed with brine, dried
(MgSO4) and concentered in vacuo and then purified by silica
gel column chromatography using the eluents described
below.
Acknowledgements
We are grateful to generous financial support of The Royal
Society (Dr L. J. Brown, Dorothy Hodgkin Research
Fellowship). Solid-state NMR spectra were obtained at the
EPSRC UK National Solid-state NMR Service at Durham
University, the authors thank Dr David Apperley.
(1S,2R)-1,2-DIHYDRONAPHTHALENE OXIDE. (Table 3, entry 1):28
Eluent: 10% Et2O : pentane. White solid (yield 43% epoxide;
36% diol, e.e. 90%). Chiral HPLC: Chiralcel OBH column,
eluent 1% IPA : hexane, UV 254 nm, flowrate: 1.0 mL min21
(peak 1 15.59 min, 95.16%; peak 2 19.63 min, 4.84%).
(R,R)-TRANS-STILBENE OXIDE. (Table 3, entry 2):28 Eluent: 40%
CH2Cl2 : hexane. Pale yellow oil (yield 63%, e.e. 86%). Chiral
HPLC: Chiralcel ODH column, eluent 2% IPA : hexane, UV 254
nm, flowrate: 1.0 mL min21 (peak 1 8.05 min, 6.90%; peak 2
8.77 min, 93.10%).
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