α-fluorotropinone immobilized on silica: A new stereoselective heterogeneous catalyst for epoxidation of alkenes with oxone

Article abstract of DOI:10.1021/jo034044c

The dioxirane-mediated epoxidation of alkenes in the presence of supported α-fluorotropinones 5 and 9 has been evaluated. The catalysts anchored onto silica supports 5 have shown comparable activity with respect to the homogeneous counterpart 10 and good stability on recycling. In the second part of this paper the enantiomerically enriched α-fluorotropinone 4* was anchored onto both mesoporous MCM-41 and amorphous KG-60 silicas. The chiral-supported catalysts promoted the stereoselective epoxidation of several trans-substituted and trisubstituted alkenes with ee values up to 80% and were perfectly reusable with the same performance for at least three catalytic cycles.

Full text of DOI:10.1021/jo034044c

r-F lu or otr op in on e Im m obilized on Silica : A New Ster eoselective
Heter ogen eou s Ca ta lyst for Ep oxid a tion of Alk en es w ith Oxon e
,
†
,‡
†
†
Giovanni Sartori,* Alan Armstrong,* Raimondo Maggi, Alessandro Mazzacani,
†
†
‡
Raffaella Sartorio, Franca Bigi, and Belen Dominguez-Fernandez
Clean Synthetic Methodologies Group, Dipartimento di Chimica Organica e Industriale dell’Universit a` ,
Parco Area delle Scienze 17A, I-43100 Parma, Italy, and Department of Chemistry,
Imperial College of Science, Technology and Medicine, London SW7 2AY, United Kingdom
sartori@unipr.it
Received J anuary 15, 2003
The dioxirane-mediated epoxidation of alkenes in the presence of supported R-fluorotropinones 5
and 9 has been evaluated. The catalysts anchored onto silica supports 5 have shown comparable
activity with respect to the homogeneous counterpart 10 and good stability on recycling. In the
second part of this paper the enantiomerically enriched R-fluorotropinone 4* was anchored onto
both mesoporous MCM-41 and amorphous KG-60 silicas. The chiral-supported catalysts promoted
the stereoselective epoxidation of several trans-substituted and trisubstituted alkenes with ee values
up to 80% and were perfectly reusable with the same performance for at least three catalytic cycles.
In tr od u ction
can be utilized as isolated pure reagents or, more
conveniently, generated in situ by oxidation of ketones
Preparation of fine chemicals by catalytic oxidation1
with particular interest in nonracemic epoxides has been
extensively studied in recent years since these com-
pounds represent useful building blocks in stereoselective
7
with Oxone (2KHSO
5
‚KHSO
4
‚K
2
SO
4
). The entire oxida-
tive process consists of a ketone-mediated oxygen transfer
from Oxone to the selected substrate affording the
oxidation product and restoring the starting ketone,
which is consequently required in catalytic amount.
2
synthesis, and the epoxide functionality constitutes the
essential framework of various naturally occurring and
Some of the most efficient ketones useful in this
reaction are expensive and/or undergo unwanted side
3
biologically active compounds. Among the impressive
number of papers published on this topic, some general
methods appear as fundamental routes for the synthesis
of enantiomerically enriched epoxides. These include
reactions with the oxidant, i.e. Baeyer-Villiger oxidation,
dimerization, etc.6
The heterogenization of the ketone by supporting it on
an insoluble material increases its stability, allows its
easy recovery and reuse, and makes easier the reaction
workup and product purification.8
4
metal-catalyzed synthesis such as the Sharpless- and
the J acobsen-type5 approaches and the use of chiral
6
oxidizing nonmetal reagents such as dioxiranes. These
compounds represent classes of versatile and powerful
oxidants showing a widespread applicability. Dioxiranes
9
In view of the increasing interest in this field and in
continuation of our involvement in this area,1 we report
here the preparation and use of an R-fluorotropinone
derivative supported on silica materials, providing ef-
ficient and reusable solid catalysts for the epoxidation
0
*
To whom correspondence should be addressed.
Parma University.
Imperial College London.
†
‡
(1) (a) Arends, I. W. C. E.; Sheldon, R. A.; Wallau, M.; Schuchardt,
U. Angew. Chem., Int. Ed., Engl. 1997, 36, 1144. (b) Sheldon, R. A.
Chemtech 1991, 566.
(7) (a) Curci, R. In Advances in Oxygenated Process; Baumstark, A.
L., Ed.; J AI: Greenwich CT, 1990; Vol. 2, Chapter 1, p 1. (b) Adam,
W.; Hadjiarapoglou, L. P.; Curci, R.; Mello, R. In Organic Peroxides;
Ando, W., Ed.; J ohn Wiley & Sons: New York, 1992; Chapter 4, p 195.
(c) Adam, W.; Smerz, A. K. Bull. Soc. Chim. Belg. 1996, 105, 581. (d)
Adam, W.; Smerz, A. K.; Zhao, C.-J . J . Prakt. Chem. 1997, 339, 298
and references therein.
(8) (a) Boehlow, T. R.; Buxton, P. C.; Grocock, E. L.; Marples, B. A.;
Waddington, V. L. Tetrahedron Lett. 1998, 39, 1839. (b) Shiney, A.;
Rajan, P. K.; Sreekumar, K. Polym. Int. 1996, 41, 377. (c) Song, C. E.;
Lim, J . S.; Kim, S. C.; Lee, K.-J .; Chi, D. Y. Chem. Commun. 2000,
2415.
(2) (a) Sharpless, K. B. Aldrichim. Acta 1983, 16, 67. (b) Behrens,
C. H.; Katsuki, T. Coord. Chem. Rev. 1995, 140, 189. (c) Tokunaga,
M.; Larrow, J . F.; Kakiuchi, F.; J acobsen, E. N. Science, 1997, 277,
9
36. (d) Bonini, C.; Righi, G. Tetrahedron 2002, 58, 4981.
3) See, for example: (a) Paquette, L. A.; Gao, Z.; Ni, Z.; Smith, G.
(
F. J . Am. Chem. Soc. 1998, 120, 2543. (b) Taylor, R. J . K.; Alcaraz, L.;
Kapfer-Eyer, I.; Macdonald, G.; Wei, X.; Lewis, N. Synthesis 1998, 775.
(4) J ohnson, R. A.; Sharpless, K. B. Addition Reactions with Forma-
tion of Carbon-Oxygen Bonds (II): Asymmetric Methods of Epoxidation
in Comprehensive Organic Synthesis; Trost, B. M., Fleming, J ., Eds;
Pergamon Press: Oxford, 1991; Vol. 7, p 389.
(
5) (a) Zhang, W.; Loebach, J . L.; Wilson, S. R.; J acobsen, E. N. J .
(9) Chiral Catalyst Immobilization and Recycling; De Vos, D. E.,
Vankelecom, I. F. J ., J acobs, P. A., Eds; Wiley-VCH: Weinheim,
Germany, 2000.
(10) (a) Bigi, F.; Moroni, L.; Maggi, R.; Sartori, G. Chem. Commun.
2002, 716. (b) Carloni, S.; De Vos, D. E.; J acobs, P. A.; Maggi, R.;
Sartori, G.; Sartorio, R. J . Catal. 2002, 205 (1), 199. (c) Demicheli, G.;
Maggi, R.; Mazzacani, A.; Righi, P.; Sartori, G.; Bigi, F. Tetrahedron
Lett. 2001, 42, 2401.
Am. Chem. Soc. 1990, 112, 2801. (b) J acobsen, E. N.; Wu, M. H. In
Comprehensive Asymmetric Catalysis; J acobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds; Springer: Berlin, Germany, 1999; Vol. II, p 649.
(6) (a) Murray, R. W. Chem. Rev. 1989, 89, 1187. (b) Curci, R.; Dinoi,
A.; Rubino, M. F. Pure Appl. Chem. 1995, 67, 811. (c) Adam, W.; Saha-
Moller, C. R.; Ganeshpure, P. A. Chem. Rev. 2001, 101, 3499. (d) Frohn,
M.; Shi, Y. Synthesis 2000, 1979.
1
0.1021/jo034044c CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/22/2003
3
232
J . Org. Chem. 2003, 68, 3232-3237

Epoxidation of Alkenes with Oxone
SCHEME 1. P r ep a r a tion of Silica -Bou n d r-F lu or otr op in on es KG-60-F T a n d MCM-41-F T
SCHEME 2. P r ep a r a tion of P olystyr en e-Bou n d
r-F lu or otr op in on e P OLY-F T
of alkenes with Oxone. This particular ketone was
selected since one of us recently reported11 the epoxida-
tion of alkenes with Oxone promoted by R-fluoro-N-
carbethoxytropinone via the corresponding dioxirane
under homogeneous conditions. Good stereoselective
control could be achieved by using an enantiomerically
pure R-fluorotropinone. Tropinone derivatives of this type
are conformationally well defined, efficient catalysts
which do not undergo Baeyer-Villiger decomposition
under the reaction conditions.
In the first part of the present study we tested three
heterogeneous catalysts prepared by anchoring R-fluo-
rotropinone to the surface of the commercially available
amorphous silica KG-60, the mesoporous silica MCM-41,
of the loading values of the 3-mercaptopropylsilica in-
termediates 3 with those of the final catalysts 5 suggests
that some unreacted thiol groups exist in the silica-bound
R-fluorotropinones 5, namely 0.56 mmol/g in KG-60-FT
and 0.37 mmol/g in MCM-41-FT. As expected, the higher
surface area and the ordered mesoporous structure of
MCM-41 allow it to accommodate a larger amount of
catalyst.
prepared in our laboratory by the method reported in the
literature,12 and a Merrifield resin. The activity of the
heterogeneous catalysts was compared with that of the
homogeneous counterpart.
In the second part, we analyzed the efficiency of the
enantiomerically enriched heterogeneous catalysts and
we report the enantioselective epoxidation of alkenes
with Oxone under heterogeneous catalysis.
The Merrifield resin-bound R-fluorotropinone 9, called
POLY-FT, was prepared as shown in Scheme 2.
Chloromethylated styrene-divinylbenzene resin 6 (load-
ing value 2.0-2.5 mmol/g) was reacted with 1,2-ethane-
dithiol (7) in dry THF in the presence of sodium ethoxide
affording the modified resin 8 (loading value 0.60 mmol/
g). This material was subjected to the previously de-
scribed reaction with 4 in the presence of AIBN to afford
the Merrifield resin-supported R-fluorotropinone 9 (load-
ing value 0.56 mmol/g) with a lower amount of unreacted
thiol groups (∼0.04 mmol/g).
Resu lts a n d Discu ssion
Our plan to support R-fluorotropinone on different
silica materials is shown in Scheme 1 and it was
performed by slightly modifying a procedure reported in
1
3
the literature for immobilization of cinchona alkaloids
and trifluoroketones.8c
The siliceous supports 1 (KG-60 or MCM-41) were first
reacted with 3-mercaptopropyltrimethoxysilane (2) in
refluxing toluene to give the corresponding 3-mercapto-
propylsilicas 3 respectively called KG-60-SH (loading
value 1.14 mmol/g) and MCM-41-SH (loading value 1.15
mmol/g). Further treatment of these modified materials
with R-fluoro-N-carballyloxytropinone (4) in the presence
of R,R′-azoisobutyronitrile (AIBN) as radical initiator in
refluxing chloroform readily led to silica-supported R-flu-
orotropinones 5 through the formation of the sulfide
linkage. The heterogeneous catalysts thus obtained were
designated as KG-60-FT (loading value 0.58 mmol/g) and
MCM-41-FT (loading value 0.78 mmol/g). The comparison
Finally, the homogeneous counterpart 10 of the sup-
ported R-fluorotropinone was prepared by a similar
AIBN-promoted coupling reaction between 1-propane-
thiol and compound 4 (Figure 1).
F IGURE 1. Homogeneous catalyst utilized in the model
epoxidation reaction.
In addition to elemental analyses (giving the loading
values), the anchoring of the R-fluorotropinone moiety to
silica and Merrifield resin was confirmed via FT-IR
spectroscopy. The presence in the supported R-fluorotro-
pinone spectra of the same pattern of bands characteristic
of the homogeneous counterpart 10 demonstrates that
the anchored catalyst does not experience any further
interaction with the support surface.
(
11) (a) Armstrong, A.; Hayter, B. R. Chem. Commun. 1998, 621.
b) Armstrong, A.; Ahmed, G.; Dominguez-Fernandez, B.; Hayter, B.
R.; Wailes, J . S. J . Org. Chem. 2002, 67, 8610.
12) Beck, J . S.; Vartuli, J . C.; Roth, W. J .; Leonowicz, M. E.; Kresge,
(
(
C. T.; Schmitt, K. D.; Chu, C. T.-W.; Olson, D. H.; Sheppard, E. W.;
McCullen, S. B.; Higgins, J . W.; Schlenker, J . L. J . Am. Chem. Soc.
1
992, 114, 10834.
13) (a) Minutolo, F.; Pini, D.; Petri, A.; Salvadori, P. Tetrahedron:
(
After modification, the starting siliceous materials
showed a considerable lowering of the surface area (from
Asymmetry 1996, 7, 2293. (b) Song, C. E.; Lim, J . S.; Kim, S. C.; Lee,
K.-J .; Chi, D. Y. Chem. Commun. 2000, 2415.
J . Org. Chem, Vol. 68, No. 8, 2003 3233

Sartori et al.
TABLE 1. Ep oxid a tion of 1-P h en ylcycloh exen e
a
yielda of 12
Sel.] (%)
surface area
loading
(mmol/g)
oxone
(equiv)
t
conv. of 11
2
b
entry
catalyst
(m /g)
(h)
(%)
a
b
c
d
e
f
10
2.5
5.0
5.0
5.0
5.0
5.0
5.0
0.5
1.0
1.0
1.0
1.0
1.0
1.0
100
62
65
60
98
98 [98]
58 [93]
63 [98]
18 [30]
96 [98]
98 [98]
19 [34]
KG-60-FT
MCM-41-FT
POLY-FT
KG-60-FT (A)
MCM-41-FT (A)
POLY-FT (A)
200
670
0.58
0.78
0.56
0.58
0.78
0.56
200
670
100
56
g
a
Determined by 1H NMR and GC. b (Yield/conv.) × 100.
2
2
3
00 to 200 m /g for KG-60 and from 1050 to 670 m /g for
0.37 mmol/g in MCM-41-FT) could undergo oxidation to
sulfonic acid.16 Thus we preoxidized the supported cata-
lysts with Oxone [the preoxidized materials were named
KG-60-FT(A), MCM-41-FT(A), and POLY-FT(A)] and the
activity of the so-obtained catalysts was compared with
that of the parent ones. Results from Table 1 (compare
entries b-d with entries e-g) allow us to conclude that
the oxidative pretreatment of the catalysts provided a
remarkable increase in product 12 yield. For example,
in the presence of KG-60-FT(A) the original conversion
of 62% was improved to 98%. Similar enhancement was
observed with MCM-41-FT(A); on the contrary the
Merrifield resin supported catalyst showed unchanged
low activity.
MCM-41). Moreover, since the X-ray diffraction patterns
of the MCM-41 functionalized materials resemble that
of the original MCM-41 silica, we argue that during the
immobilization treatments the mesoporous structure of
the support remains undisrupted and the molecules of
R-fluorotropinone should be dispersed on the surface of
the support and easily accessible to reagents.
Our catalytic studies begun by comparing the efficiency
of all catalysts in the epoxidation of 1-phenylcyclohexene
with Oxone. All reactions were carried out in acetonitrile
containing aqueous Na
stirring, portions of a Oxone (2.5 equiv)/NaHCO
2
EDTA by adding, under vigorous
(3.9
3
equiv) mixture each 30 min for the selected time. The
amount of both homogeneous and heterogeneous cata-
lysts was chosen in order to utilize a 0.4 molar ratio
between the R-fluorotropinone and the reagent 11. The
results are summarized in Table 1.
Reference experiments performed without any catalyst
and in the presence of KG-60 and KG-60-SH silicas
showed a low conversion with poor yield and selectivity
The relationship between the oxidation state of the
linker and the catalyst activity is not easily rationaliz-
able; however, the beneficial effect of the catalyst pre-
oxidation on both stability and efficiency of similar
17
catalysts has been previously observed. We tentatively
ascribe this enhancement to, at least, two facts: (i) part
of the Oxone is consumed in the oxidation of the linker
(
10-15% of 12 was obtained with 5 equiv of Oxone in all
and (ii) the -SH f -SO
3
H and -S- f -SO -oxidation
2
experiments). Moreover, as expected, the homogeneous
catalyst 10, bearing at the nitrogen atom of the R-fluo-
rotropinone the same chain of the spacer present in the
heterogeneous catalyst, afforded the product 12 in quan-
titative yield and excellent selectivity (entry a). It was
noted that quite similar satisfactory results were achieved
with both silica-supported catalysts independent from
whether the amorphous or the mesoporous silica was
utilized as the solid support (entries b and c). Surpris-
ingly a very poor efficiency was observed by using
R-fluorotropinone supported on the Merrifield resin
18
were shown to be ketone-catalyzed via oxirane, which
consequently represents a further competitive reaction
affecting the desired epoxidation process.
To support this hypothesis we analyzed the progress
of the yield of product 12 versus time in the model
reaction performed in the presence of freshly prepared
KG-60-FT ([, Figure 2) and preoxidized KG-60-FT(A)
(9, Figure 2) catalysts. Experiments were carried out by
3
adding a single portion of Oxone (2.5 equiv)/NaHCO (3.9
equiv) mixture to substrate 11 (Figure 2).
In the presence of KG-60-FT(A) the yield reaches 60%
after 30 min; the data were better described by a first-
(
entry d). This result can partly be attributed to a low
degree of swelling of the styrene-divinylbenzene poly-
meric support in the acetonitrile/water polar and hydro-
philic reaction medium.14
While the silica-supported catalysts show good ef-
ficiency in the model reaction, we suspected that in the
strongly oxidizing reaction medium the sulfide groups of
the spacer arm could be converted to sulfoxide or sul-
fone15 and the free mercaptopropyl groups still present
on the surface of the silica (0.56 mmol/g in KG-60-FT and
-
1
-2
order irreversible kinetic with k ) 4.2 × 10 (3 × 10
)
-
1
min . On the contrary, with the catalyst KG-60-FT the
yield reaches only 25% after 30 min; in this case data
were fitted by assuming that the apparent kinetic
constant is proportional to the catalyst amount (i.e. k )
k′Ccat). A first-order kinetic for the catalyst oxidation
(
16) (a) Kennedy, R. J .; Stock, A. M. J . Org. Chem. 1960, 25, 1901.
(
b) Van Rhijn, W. M.; De Vos, D. E.; Sels, B. F.; Bossaert, W. D.; J acobs,
P. A. Chem. Commun. 1998, 317.
(
14) Sherrington, D. C. Chem. Commun. 1998, 2275.
(17) Kim, B. M.; Sharpless, K. B. Tetrahedron Lett. 1990, 31, 3003.
(18) Adam, W.; Haas, W.; Seiker, G. J . Am. Chem. Soc. 1984, 106,
5020.
(15) Kropp, P. J .; Breton, G. W.; Fields, J . D.; Tung, J . C.; Loomis,
B. R. J . Am. Chem. Soc. 2000, 122, 4280.
3
234 J . Org. Chem., Vol. 68, No. 8, 2003

Epoxidation of Alkenes with Oxone
TABLE 2. Recyclin g of th e KG-60-F T in th e Ep oxid a tion
of 1-P h en ylcycloh exen e by Oxon e
a
yielda of 12
[Sel.] (%)
conv. of
b
entry
cycle
11 (%)
a
b
c
d
e
f
1
2
3
4
5
6
62
98
95
96
98
96
58 [93]
96 [98]
94 [99]
95 [99]
96 [99]
93 [97]
a
Determined by 1H NMR and GC. b (Yield/conv.) × 100.
(ee 78%), which was prepared by desymmetrization of the
parent ketone with (R,S,S,R)-1,2-diphenyl-N,N′-bis(1-
phenylethyl)ethane-1,2-diamine.19 It was anchored to
amorphous silica KG-60 and to mesoporous silica MCM-
4
1 by using the same strategy described in Scheme 1.
Both KG-60-FT* and MCM-41-FT* materials were acti-
vated by reaction with Oxone before use in the first cycle
giving the heterogeneous catalysts called KG-60-FT(A)*
and MCM-41-FT(A)*. Results of their efficiency in the
model reaction of 1-phenylcyclohexene (0.4 molar ratio
between supported tropinone and alkene) with Oxone,
including ee values, are reported in Table 3. The eemax
value is the expected epoxide ee if enantiomerically pure
catalysts were used, based on a linear relationship
between catalyst ee and product ee, which has been
1
1b
shown for the homogeneous catalytic system.
Results from Table 3 show good levels of enantioselec-
tivity achieved in all cases with only a 10% difference
between the homogeneous (0.1 molar ratio between
F IGURE 2. (A) [12] ) f(t). The continuous line refers to the
previously oxidized catalyst KG-60-FT(A) and plots the func-
-
2
tion [12] ) 0.02[1 - exp((-4.2 × 10 )t)], whereas the dotted
supported tropinone and alkene) and heterogeneous
line refers to the catalyst KG-60-FT and plots the function [12]
-2
11a
)
0.02(1 - exp[(-4.4 × 10 )0.02[1 - exp(-0.14t)]t]). (B) log10-
catalysts.
Moreover, the products isolated in all the
[
11] ) f(t).
homogeneous and heterogeneous experiments showed the
same (S,S)-absolute configuration indicating that the
ability of the catalyst to effectively differentiate the faces
of reagent 11 is only slightly affected by the siliceous
support.
Finally we faced the problem of the catalyst recycling
and we found that both heterogeneous catalysts showed
the same high level of activity and good stereochemical
control on recycling.
Having found satisfactory catalytic conditions for the
model reaction, a number of different alkenes were
subjected to the standard reaction with use of KG-60-
FT(A)* as the enantiomerically enriched heterogeneous
catalyst, this being more easily available than MCM-41-
FT(A)*. As previously shown,11 each substrate requires
specific reaction time and Oxone amount (Table 4).
Usually, if the alkene is poorly soluble in the reaction
mixture (i.e. trans-stilbene) or if it bears bulky groups
reaction was supposed and consequently a k ) 4.4 ×
-
1
-2
-1
1
0
(4 × 10 ) min was calculated, in very good agree-
ment with that obtained for the reaction carried out with
the preoxidized catalyst. In addition, in a comparative
experiment the model compound 10 was treated with the
3
Oxone (2.5 equiv)/NaHCO (3.9 equiv) mixture under the
same reaction conditions. The reaction after a few
minutes showed complete conversion of 10 into the
corresponding sulfone 13. All these results are in satis-
factory agreement with the hypothesis that Oxone is
initially involved in the fast oxidation of -S- and -SH
groups.
Recycling studies were successively carried out with
the catalyst KG-60-FT in the model reaction performed
under the above-reported experimental conditions. To
this end, after the first cycle the catalyst was filtered,
(i.e. TBS-cinnamyl alcohol), a higher amount of oxidant
3
washed with CH CN, dried, and immediately reused. On
and longer reaction times are required. It can be seen
from the results in Table 4 that the catalyst promotes
the reaction with high yield and excellent selectivity with
a satisfactory to high level of stereocontrol for a variety
of substrates showing the generality of this method for
trans-substituted and trisubstituted olefins. For all ex-
amined alkenes the observed enantiomeric excesses are
comparable to those previously obtained with the homo-
the basis of the results shown in Table 1 and Figure 2,
the reused catalyst showed higher activity affording
product 12 in almost quantitative yield and selectivity
for at least five successive cycles (see Table 2). Elemental
analysis of the recovered catalyst confirmed its good
stability.
Our next objective was to support the nonracemic
R-fluorotropinone to both KG-60 and MCM-41 silicas and
to examine the chemical behavior of the nonracemic
heterogeneous catalysts prepared. We utilized enantio-
merically enriched R-fluoro-N-carballyloxytropinone 4*
11
geneous R-fluoro-N-carbethoxytropinone, evidencing
(19) Bambridge, K.; Begley, M. J .; Simpkins, N. S. Tetrahedron Lett.
1994, 35, 3391.
J . Org. Chem, Vol. 68, No. 8, 2003 3235

Sartori et al.
TABLE 3. En a n tioselective Ep oxid a tion of 1-P h en ylcycloh exen e
a
yielda of
12 [Sel] (%)
eemaxc
[eeobs] (%)
oxone
(equiv)
t
conv. of
a
entry
catalyst
(h)
cycle
11 (%)
a
b
c
d
e
f
10*
KG-60-FT(A)*
2.5
5.0
5.0
5.0
5.0
5.0
5.0
0.5
1.0
1.0
1.0
1.0
1.0
1.0
1
1
2
3
1
2
3
100
96
98 [98]
94 [98]
97 [97]
97 [97]
98 [98]
99 [99]
98 [98]
69 [54]
58 [45]
61 [48]
63 [49]
62 [48]
63 [49]
62 [48]
100
100
100
100
100
MCM-41-FT(A)*
G
a
Determined by 1H NMR and GC. b (Yield/conv.) × 100. eemax ) (eeobs/eecat) × 100.
c
TABLE 4. En a n tioselective Ep oxid a tion of Va r iou s Alk en es over KG-60-F T(A)*
a
Determined by H NMR and GC. (Yield/conv.) × 100. Enantiomeric excess calculated by NMR with chiral Eu(hfc)3. d Enantiomeric
1
b
c
excess calculated by chiral HPLC (CHIRACEL OD).
that the heterogenization of the catalyst led only to a
slight lowering of the ee values.
mode at 70 eV. Microanalyses were carried out by the
Dipartimento di Chimica Generale ed Inorganica, Chimica
Analitica, Chimica Fisica dell’Universit a` di Parma, Italy. TLC
analyses were performed on Merck 60 PF254 silica gel plates
with mixtures of hexanes-ethyl acetate (25-35%). All the
reagents were of commercial quality from freshly opened
containers and were used as received without further purifica-
tion. Solvents were distilled under nitrogen and dried before
use. The amorphous silica used was the commercial Kieselgel
Con clu sion s
We have shown that R-fluorotropinone supported on
silica materials represents the first example of efficient
heterogenized chiral ketone for the stereoselective ep-
oxidation of alkenes with Oxone. The activity of the
supported catalyst is comparable to that of the homoge-
neous counterpart and of the reported R-fluoro-N-carbe-
thoxytropinone even though a larger amount of oxidant
and longer reaction times are required to obtain the same
high level of yields and selectivities. Moreover the
homogeneous and heterogeneous chiral catalysts pro-
moted the reaction with similar values of enantiomeric
excess, proving that the support does not significantly
interfere with the chirality transfer. Finally from elemen-
tal analysis and recycling experiments we can conclude
that all the silica-supported catalysts are stable in the
strong oxidizing and aqueous reaction medium and that
they can be easily recovered by filtration and reused with
unchanged high activity and stereoselectivity.
6
0 (KG-60) purchased from Merck. MCM-41 mesoporous
material was prepared, according to the procedure reported
in the literature,12 by mixing, at room temperature and under
vigorous stirring, a 25% sodium silicate solution, tetramethy-
lammonium hydroxide, a 25% cetyltrimethylammonium chlo-
ride solution, and water and aging at 110 °C for 4 days the
resulting gel (composition: SiO
2
‚0.39Na O‚0.25CTMACl‚
2
0.24TMAOH‚50.7H O). The XRD pattern and the high surface
2
area of the material are characteristic of MCM-41 silica with
a long-range order in the mesopore arrangement. The Merri-
field’s peptide resin 2% cross-linked used contains 2.0-2.5
-
mmol Cl /g and was purchased from Aldrich. The surface area
was measured by the B.E.T. method,20 using a PulseChemi-
Sorb 2705 Micromeritics instrument. Pore dimensions were
2
determined by N adsorption on a C. Micromeritics ASAP 2010
instrument. Elemental analyses were Performed on a Carlo
Erba CHNS-O EA1108 Elemental Analyser.
Exp er im en ta l Section
Rea ction P r oced u r e. All reactions were carried out in a
Schlenk tube equipped with a magnetic stirrer. In a typical
experiment, the selected alkene (0.1 mmol) was added to a
1
Gen er a l. Melting points are uncorrected. H NMR spectra
were recorded at 300 MHz. Mass spectra were obtained in EI
3
236 J . Org. Chem., Vol. 68, No. 8, 2003

Epoxidation of Alkenes with Oxone
-
2
suspension of KG-60-FT(A)* (4.0 × 10 mmol of supported
(S,S)-2-[(ter t-Bu t yld im et h ylsiloxy)m et h yl]-3-p h en yl-
oxir a n e (18): Colorless oil, yield 95%, eemax 48%.
-4
21
catalyst, 69 mg) in acetonitrile (3 mL) and 4 × 10 M aqueous
Na EDTA (2 mL). Then, under vigorous stirring, portions of
Oxone (0.25 mmol, 0.154 g) and NaHCO (0.39 mmol, 0.033
g) were added each 30 min for the selected time. Finally, water
10 mL) and methylene chloride (10 mL) were added, the
catalyst was filtered off on a B u¨ chner funnel, and the organic
phase was dried with MgSO . The solvent was distilled off
2
3
Ack n ow led gm en t. The authors are indebted to
Prof. Dario Pini (University of Pisa) for helpful sugges-
tions on Merrifield’s peptide resins and to Prof. Giovanni
Mori (University of Parma) for the treatment of kinetic
data. The support of the University of Parma and MIUR
(
4
under reduced pressure and the product identified by GLC
analysis.
(
National Project “Stereoselezione in Sintesi Organica.
S,S)-1-P h en ylcycloh exen e oxid e (12):21 Colorless oil,
Metodologie e Applicazioni”) is acknowledged. A.A.
thanks the EPSRC (GR/M84534) for support. We are
also grateful to Mr. Pier Antonio Bonaldi (Lillo) for
technical assistance and to the Centro Interdipartimen-
tale Misure (CIM) for the use of NMR and mass
instruments.
(
yield 94%, eemax 58%.
S,S)-tr a n s-Stilben e oxid e (14):21 White solid, yield 97%,
eemax 66%.
(
(
S,S)-tr a n s-Meth ylstilben e oxid e (15):21 White solid,
yield 93%, eemax 67%.
(
S,S)-tr a n s-P h en ylstilben e oxid e (16):22 White solid,
yield 91%, eemax 80%.
S,S)-3-P h en yloxir a n em eth a n ol (17):21 Colorless oil, yield
0%, eemax 50%.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails. This material is available free of charge via the Internet
at http://pubs.acs.org.
(
9
J O034044C
(
20) Braunauer, S.; Emmet, P. H.; Teller, E. J . Am. Chem. Soc. 1938,
0, 309.
21) Shu, L.; Shi, Y. Tetrahedron 2001, 57, 5213.
6
(
(22) Fleischer, R.; Galle, D.; Braun, M. Liebigs Ann. 1997, 1189.
J . Org. Chem, Vol. 68, No. 8, 2003 3237