Catalytic enantioselective epoxidation with arabinose-derived uloses containing tunable steric sensors

Article abstract of DOI:10.1016/j.tetlet.2003.09.226

Readily available arabinose-derived 4-uloses, containing a tunable butane-2,3-diacetal as the steric sensor, displayed increasing enantioselectivity (up to 93 percent ee) with the size of the acetal alkyl group in catalytic asymmetric epoxidation of trans-disubstituted and trisubstituted alkenes.

Full text of DOI:10.1016/j.tetlet.2003.09.226

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 9225–9228
Catalytic enantioselective epoxidation with arabinose-derived
uloses containing tunable steric sensors
Tony K. M. Shing,* Gulice Y. C. Leung and Kwan W. Yeung
Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong, PR China
Received 16 July 2003; revised 19 August 2003; accepted 25 September 2003
Abstract—Readily available arabinose-derived 4-uloses, containing a tunable butane-2,3-diacetal as the steric sensor, displayed
increasing enantioselectivity (up to 93% ee) with the size of the acetal alkyl group in catalytic asymmetric epoxidation of
trans-disubstituted and trisubstituted alkenes.
© 2003 Elsevier Ltd. All rights reserved.
Recently, chiral dioxiranes, generated in situ from chi-
ral ketones and Oxone®, have become promising
reagents for asymmetric epoxidation of unfunction-
room for the discovery of easily accessible ulose cata-
lysts in catalytic enantioselective epoxidation. Our long-
term interest4 in the application of carbohydrates in
asymmetric synthesis has prompted us to search for an
efficient ulose catalyst to induce chirality with high ee
alised alkenes.1
D-Fructose-derived 1,2:4,5-di-O-iso-
propylidene-3-ulose, reported by Shi, was the most
impressive and had demonstrated excellent enantiose-
lectivity towards trans-disubstituted and trisubstituted
alkenes.2 However, this 3-ulose underwent decomposi-
tion under the reaction conditions and had to be used
in high loading, thus rendering the reaction non-cata-
in asymmetric epoxidation.
D- and L-Arabinose are
both commercially available in large quantities and
therefore are the first choice for our investigation. We
recently described our studies on enantioselective epoxi-
dation of alkenes catalyzed by uloses derived from
lytic. The preparation of a more robust
D
-fructose-
D
-glucose5 as well as by 2-uloses and 3-uloses derived
derived catalyst containing a fused oxazolidinone has
from L
-arabinose.6 Now, we report our results on
recently been improved to a six-step synthesis.3 Unfor-
asymmetric epoxidation of trans-disubstituted and
trisubstituted alkenes, using Oxone® as oxidant, cata-
lyzed by readily available arabinose-derived 4-uloses
containing tunable steric sensors that control the enan-
tioselectivity of the epoxidation.
tunately, L-fructose is not commercially available and
its scarcity diminishes its attractiveness as the enantio-
complement since a short and facile preparation of
L
-fructose remains elusive.2 Consequently, there is
Scheme 1. Reagents and conditions: (a) BnOH, AcCl (0.6 equiv.), rt, 5 days, 87%; (b) 2,2,3,3-tetramethoxybutane (1.2 equiv.),
CH(OMe)3 (4 equiv.), ( )-CSA (0.1 equiv.), reflux, 12 h, 76% for 2; 2,2,3,3-tetraethoxybutane (1.2 equiv.), CH(OEt)3 (4 equiv.),
( )-CSA (0.1 equiv.), reflux, 12 h, 50% for 3; (c) 2-methyl-1-propanol (4 equiv.), p-TsOH, PhH, Dean & Stark trap, reflux, 12 h,
,
85%; (d) PDC (1.5 equiv.), 3 A MS, CH2Cl2, rt, 12 h, 90% for 5, 85% for 6, 95% for 7.
* Corresponding author. E-mail: tonyshing@cuhk.edu.hk
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.09.226

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T. K. M. Shing et al. / Tetrahedron Letters 44 (2003) 9225–9228
Figure 2. X-Ray structure alcohol 3 (CCDC no. 184257)
(ORTEP view).
Figure 1. X-Ray structure alcohol 2 (CCDC no. 184258)
(ORTEP view).
Uloses 5–7 were readily accessible from
L
-arabinose via
2,2,3,3-tetramethoxybutane in 76% yield. Similar reac-
tion of 1 with 2,2,3,3-tetraethylbutane afforded diethyl
acetal 3.7 The structures of 2 and 3 were confirmed by
X-ray crystallography (Figs. 1 and 2), thereby demon-
strating that the benzyl aglycone and the alkoxy groups
a reaction sequence involving Fischer glycosidation,
transacetalization, and oxidation (Scheme 1). The
known benzyl glycoside 1,6 readily obtained from
L-
arabinose, was converted into dimethyl acetal 26 with
Table 1. Asymmetric epoxidation of alkenes using uloses 5, 6, 7 as catalysts at room temperature
Entrya
Catalysts
Substrates
Yield (%)b
Ee (%)c
Config.d
1
2
3
4
5
6
7
8
5
6
7
5
6
7
5
6
7
5
6
7
5
6
7
a
a
a
b
b
b
c
c
c
d
d
d
e
89
95
93
82
81
92
90
88
90
97
95
96
80
88
95
42
54
65
43
60
68
43
56
67
68
78
85
75
75
83
(−)-(S,S)8
(−)-(S,S)8
(−)-(S,S)8
(−)-(S,S)9
(−)-(S,S)9
(−)-(S,S)9
(−)
(−)
(−)
9
10
11
12
13
14
15
(+)-(S)9
(+)-(S)9
(+)-(S)9
(−)-(S,S)9
(−)-(S,S)9
(−)-(S,S)9
e
e
a All epoxidations were carried out with substrate (0.1 mmol), ulose catalyst (0.01 mmol), Oxone® (1 mmol) and NaHCO3 (3.1 mmol) in
CH3CN:4×10−4 M aqueous EDTA (5:1, v/v) for 2.5 h.
b Isolated yield.
c Enantioselectivity was determined by 1H NMR analysis of the epoxide products directly with shift reagent Eu(hfc)3.
d The absolute configurations were determined by comparing the measured optical rotations with the reported ones.

T. K. M. Shing et al. / Tetrahedron Letters 44 (2003) 9225–9228
9227
of the acetal occupy axial positions. It is noteworthy
that transacetalisation of dimethyl acetal 2 with 2-
methyl-1-propanol furnished di-isobutyl acetal 4 in 85%
yield. In fact, diethyl acetal 3 could also be obtained
from 2 using this transacetalisation protocol. Oxidation
of the free alcohol in acetals 2–4 with pyridinium
dichromate (PDC) gave the respective uloses 5–7 in
good yields. Uloses 5–7 had steric sensors, i.e. the acetal
alkyl group, of different sizes that might induce differ-
ent degree of enantioselectivity in catalytic epoxidation
of alkenes.
60%). Encouraged by these results, we therefore
prepared ulose 7 in order to improve the enantioselec-
tivity of the epoxidation. The results of asymmetric
epoxidation of trans-disubstituted and trisubstituted
alkenes with uloses 5–7 are shown in Table 1. Indeed,
the ee’s enhanced with the size of the acetal alkyl group
from 5 to 7 as anticipated. Ulose 7 was the most
efficient catalyst (90–96% conversions) and displayed
good stereochemical communication with the substrate
(65–85% ee) (Table 1, entries 3, 6, 9, 12, 15).
Under improved reaction conditions at 0°C, the cata-
lytic and chiral induction properties of 7 were further
studied together with additional alkenes and the results
are summarized in Table 2. The chemical yields
remained high and the enantioselectivity improved sig-
nificantly (up to 11% ee increase). Simple trans-disub-
stituted alkene without a phenyl substituent displayed
the highest ee of 93% (Table 2, entry 5). It is notewor-
thy that ulose 7 could be recovered in no less than 95%
yield after work-up (Table 2, entry 1) and the recovered
catalyst 7 was subject to an epoxidation/recovery cycle
without loss of catalytic and chiral induction power.
Facile formation of other steric sensors via the transac-
etalisation protocol described in this paper was feasible
Initially, we prepared only uloses 5 and 6 to test our
design of catalyst. On the basis of our previous stud-
ies,5,6 we reasoned that the enantioselectivity should be
sensitive to the size of the acetal steric sensor. The
epoxidation reactions were carried out at room temper-
ature with 0.1 mmol of substrate (disubstituted alkenes)
and 10 mol% of catalyst in aqueous CH3CN at almost
neutral conditions (pH 7–7.5). These uloses 5 and 6
were found to be efficient catalysts with high chemical
conversions (82–95% yields) as shown in Table 1
(entries 1, 2, 4, 5, 7, 8). Ulose 6 with a more bulky ethyl
acetal group consistently displayed better chiral induc-
tion than 5, although the ees were still moderate (54–
Table 2. Asymmetric epoxidation of alkenes using ulose 7 as catalyst at 0°C
Entrya
Substrates
Yield (%)b
Ee (%)c
Config.d
1
2
3
4
5
6
7
8
a
b
c
d
e
f
g
h
97
89
93
85
92
99
93
92
76
79
77
75
93
90
87
85
(−)-(S,S)8
(−)-(S,S)9
(−)
(−)-(S,S)11,12
(−)
(+)-(S)9
(−)-(S,S)10
(−)-(S,S)13,14
a All epoxidations were carried out with substrate (0.1 mmol), ulose catalyst (0.01 mmol), Oxone® (1 mmol) and NaHCO3 (3.1 mmol) in
CH3CN:4×10−4 M aqueous EDTA (10:1, v/v) for 12 h.
b Isolated yield.
c Enantioselectivity was determined by 1H NMR analysis of the epoxide products directly with shift reagent Eu(hfc)3.
d The absolute configurations were determined by comparing the measured optical rotations with the reported ones.

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T. K. M. Shing et al. / Tetrahedron Letters 44 (2003) 9225–9228
noteworthy that the benzyl aglycone in ulose 7 is
amenable for elaboration into a polymer support and
hence opens an avenue for the development of solid-
phase catalysis. The research in this direction is
underway.
and uloses with various acetals, such as an isopropyl
group, benzyl group, cyclohexylmethyl, an
isopentyl and a neopentyl group, had been readily
synthesised. The enantioselectivity displayed by these
uloses in catalytic asymmetric epoxidation is under
investigation and will be reported in the full paper.
a
a
Acknowledgements
The preponderant formation of the (S,S)-enantiomer
may be rationalised by the spiro2,3 transition state
resulted from a minimum steric interaction between
the steric sensor and the alkene substrate, using trans-
stilbene as an example (Fig. 3). Firstly, attack on the
equatorial oxygen in dioxirane should be preferred
because the axial approach of the alkene would be
hindered by the axial proton of the pyran ring. Sec-
ondly, the steric repulsion between the phenyl group
and the acetal alkyl group in transition state (spiro-2)
is absent in (spiro-1). We have also prepared the
This research was supported by the CUHK Direct
Grant.
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Figure 3. Spiro transition states for trans-stilbene epoxidation
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