Mild and efficient synthesis of 5,6-diamino-5,6-dideoxy-1,2-O-isopropylidene-3-O-methyl-β-L-idofuranose: Precursor of the first carbohydrate-derived chiral Mn(III)-salen complex

Article abstract of DOI:10.1016/S0040-4020(02)01294-2

Carbohydrates as multifunctional naturally occurred chiral products were used for the first time as chiral building blocks in Mn(III)-salen complexes as catalysts for the enantioselective epoxidation of alkenes. The pathways of the mild and efficient synthesis of a Mn(III)-salen complex and its diamino precursor 5,6-diamino-5,6-dideoxy-1,2-O-isopropylidene-3-O-methyl-β-L-idofuranose starting from D-(+)-glucose are described. The complex efficiently catalyzed the epoxidation of styrene and 1,2-dihydronaphthalene, using aqueous sodium hypochlorite in CH₂Cl₂ as terminal oxidant. The enantiomeric excesses were 13 and 33%, respectively. Mn(III)-salen catalyst with only one stereogenic carbon atom that is adjacent to nitrogen atom proved to be able to show enantioselectivity.

Full text of DOI:10.1016/S0040-4020(02)01294-2

Tetrahedron 58 (2002) 10065–10071
Mild and efficient synthesis of 5,6-diamino-5,6-dideoxy-1,2-O-iso-
propylidene-3-O-methyl-b-L-idofuranose: precursor of the first
carbohydrate-derived chiral Mn(III)–salen complex
*
Shanhong Yan and Dieter Klemm
¨ ¨
Institut fur Organische und Makromolekulare Chemie, Friedrich-Schiller-Universitat Jena, Lessingstr. 8, D-07743 Jena, Germany
Received 6 May 2002; revised 23 September 2002; accepted 9 October 2002
Abstract—Carbohydrates as multifunctional naturally occurred chiral products were used for the first time as chiral building blocks in
Mn(III)–salen complexes as catalysts for the enantioselective epoxidation of alkenes. The pathways of the mild and efficient synthesis of a
Mn(III)–salen complex and its diamino precursor 5,6-diamino-5,6-dideoxy-1,2-O-isopropylidene-3-O-methyl-b-L-idofuranose starting
from D-(þ)-glucose are described. The complex efficiently catalyzed the epoxidation of styrene and 1,2-dihydronaphthalene, using aqueous
sodium hypochlorite in CH2Cl2 as terminal oxidant. The enantiomeric excesses were 13 and 33%, respectively. Mn(III)–salen catalyst with
only one stereogenic carbon atom that is adjacent to nitrogen atom proved to be able to show enantioselectivity. q 2002 Elsevier Science Ltd.
All rights reserved.
1. Introduction
general sense, especially for the asymmetric epoxidation
of trans-substituted alkenes and terminal alkenes, still
constitutes a challenge for organic chemists, furthermore,
the controversial mechanism2c needs to be elucidated.
Since Jacobsen’s pilot work in 1990,1 chiral Mn(III)–salen
complexes (Scheme 1) have emerged as highly efficient
biomimetic catalysts for the asymmetric epoxidations of
unfunctionalized cis-disubstituted, tri- and tetra-substituted
alkenes,2 giving rise to optically active epoxides, which are
valuable intermediates for a wide variety of biologically and
pharmaceutically important compounds.3
Among the structural units in Mn(III)–salen catalysts that
affect the asymmetric induction in epoxidation reactions,
the diimine moiety plays an important role. Catalysts with
different diamine parts show not only different reactivity
and enantioselectivity but also different enantiofacial
selection, resulting in reversed enantioselectivity in some
cases. On the other hand, carbohydrates as naturally
occurring multifunctional products are cheap starting
materials with chiral molecule structures, these character-
istics make them ideal precursors for the introduction of
chiral building blocks into the molecule structures of the
catalysts. Surprisingly, while the derivatives of trans-1,2-
diaryldiamines and trans-1,2-diaminocyclohexane as pre-
cursors of the diimine units attracted much attention,
carbohydrate-derived Mn(III)–salen catalysts have never
been reported before, to our best knowledge.
Scheme 1.
The past decade has witnessed an explosive growth in the
chemistry of these chiral Mn(III)–salen species, with the
research topics varying from design and synthesis of salen
ligands, investigation of the steric and electronic effects of
the catalyst structure on stereoselectivity to rationales of the
mechanism of the asymmetric induction. Satisfactory
progress has been made toward catalytic enantiospecific
epoxidation of certain types of alkene substrates, however,
the development of high enantioselective catalysts of more
As a part of our research project ‘metal-mediated reactions
modelled after nature’, we have incorporated chiral
carbohydrate building blocks into the catalyst molecules
either as the diamine part or as the salicyaldehyde part or
both, in the hope of clarifying the catalytic mechanism and
obtaining chiral catalysts with generally good activity and
enantioselectivity. Here we report the preparation of the first
carbohydrate-based Mn(III)–salen complex and the facile
synthesis of its precursor 5,6-diamino-5,6-dideoxy-1,2-O-
isopropylidene-3-O-methyl-b-L-idofuranose starting from
Keywords: diamino sugars; (salen)manganese(III) complexes; Mn(III)–
salen catalysts; asymmetric reactions; enantiomeric epoxidations;
carbohydrate; Jacobsen’s catalyst.
*
Corresponding author. Tel.: þ49-3644-948260; fax: þ49-3644-948202;
e-mail: c9kldi@rz.uni-jena.de
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01294-2

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S. Yan, D. Klemm / Tetrahedron 58 (2002) 10065–10071
Scheme 2.
D-(þ)-glucose, followed by the evaluation of the catalytic
performance of this new type of complex in the epoxidation
of styrene and 1,2-dihydronaphthanene.
the final reaction mixture, trace of starting diol can be easily
removed by extracting with water, as it is water soluble.
Extended reaction time led to formation of ditosylate
resulting in a lower yield of the mono tosylate and the
separation of products became more troublesome.
2. Results and discussion
The monotosylate (4) was allowed to react with NaN3 in
DMF at about 1008C for 1 h to give chromatographically
pure 6-azido-1,2-O-isopropylidene-3-O-methyl-a-D-gluco-
furanose (6) in 96% yield. The conversion of (6) into ido-
azide (9) requires the introduction of another azido group at
C-5 position with a single inversion of configuration. Thus,
treatment of the mono-azide (6) with trifluoromethane-
sulphonic anhydride in dichloromethane in the presence of
pyridine at 2188C gave quantitatively the corresponding
triflate ester 7, which is kinetically stable and easily
handled. Compound 7 exhibited strong absorption at 1411
and 1206 cm21 (–SO2–) in IR spectrum and the peaks of
–OH group disappeared. When the triflate 7 in dimethyl-
formamide was treated with a suspension of sodium azide at
room temperature, a smooth nucleophilic displacement
reaction occurred within 35 min leading to the diazido
idofuranose derivative 9 in a yield of 92%, with no
concurrent formation of the epimeric gluco-azide 13.
D-(þ)-Glucose as a starting material was treated with
catalytic amounts of sulfuric acid in acetone for 5 h at room
temperature to give 1,2:5,6-di-O-isopropylidene-a-D-gluco-
furanose (1) (Scheme 2) according to literature.4 The
hydroxyl group at C-3 in (1) was methylated with CH3I
by the method of Bessodes5 with slight modifications. In our
preparation, the cheaper tetrabutylammonium bromide was
used as phase transfer catalyst instead of 18-crown-6, the
reaction completed smoothly within 40 min at room
temperature to give 1,2;5,6-di-O-isopropylidene-3-O-
methyl-a-D-glucofuranose (2) with the yield of 94%.
Selective hydrolysis of (2) in 75% aqueous acetic acid
under water bath (bath temperature 608C) for 50 min gave
1,2-isopropylidene-3-O-methyl-a-D-glucofuranose (3) in
90% yield.
The regioselective tosylation of the 6-OH group of (3) was
carried out in pyridine by reacting the diol (3) with tosyl
chloride at 2188C for 4 h in 94% yield, giving rise to
1,2-isopropylidene-3-O-methyl-6-O-tosyl-a-D-glucofura-
nose (4). Under this conditions, no ditosylate was found in
Alternatively, compound 9 can also be prepared from 4
following another route. On treatment with trifluoro-
methanesulphonic anhydride in dichloromethane in the
Table 1. Epoxidation of styrene and 1,2-dihydronaphthalene using Mn(III)–salen complex as catalyst
Entry
Substrate
Catalyst
Compound 12
Compound 12
(S,S)-Jacobsen’s catalyst
Without catalyst
Without catalyst
Time (h)
Ee (%)
Yield (%)
1
2
3
4
5
Styrene
3
6
3
16
16
13
33
52
–
75
52
59
0
1,2-Dihydronaphthalene
Styrene
Styrene
1,2-Dihydro-naphthalene
–
0

S. Yan, D. Klemm / Tetrahedron 58 (2002) 10065–10071
10067
Figure 1. NMR spectra of the epoxides obtained by using compound 12 as catalyst: (a) styrene oxide without Eu(hfc)3, (b) styrene oxide with 150 wt%
Eu(hfc)3, (c) 1,2-dihydronaphthalene oxide without Eu(hfc)3, (d) 1,2-dihydronaphthalene oxide with 50 wt% Eu(hfc)3, (e) 1,2-dihydronaphthalene oxide with
100 wt% Eu(hfc)3.
presence of pyridine, the tosylate 4 produced the triflate 5
within 1 h in quantitative yield. Compound 5 is a yellow
syrup, but slowly turns black on storage, and should be kept
at low temperature under Argon protection and light
prevention. Further analytical work and chemical treatment
should be done shortly. However, good analytical results
were also achieved 1 month later after passing the sample
though a column of silica gel, about 10% of the original
triflate has been degraded. The compound 5 showed
characteristic IR absorption for tosyl group at 1372 and
tosyl-b-L-idofuranose (8) in a yield of 95%. The character-
istic absorption of triflyl group disappeared in IR spectrum
after the formation of ido-azide while the characteristic
absorption peaks of tosyl group remained at 1365 and
1176 cm21, the newly incorporated 5-azido group accounts
for the additional strong peak at 2099 cm21. Compound 8
reacted with sodium azide in dimethylformamide at 1008C
for 1 h gave the diazido idofuranose derivative 9 in 94%
yield. Compound 9 can be obtained by treatment of 5
with sodium azide in excess, without separation of the
intermediate 8, thus shortened the synthetic pathway to final
product.
1177 cm21 as well as triflyl group at 1412 and 1209 cm21
.
When a solution of 5 in dimethylformamide was treated
with sodium azide at room temperature for 4 h, the SN2
substitution reaction occurred selectively at the C-5 position
giving rise to 5-azido-1,2-isopropylidene-3-O-methyl-6-O-
Reduction of compound (9) with hydrazine hydrate in
methanol catalyzed by Raney-nickel at room temperature

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S. Yan, D. Klemm / Tetrahedron 58 (2002) 10065–10071
led to the formation of the diamine 10, whose IR spectrum
showed new peaks at 3375, 3317, 1597 cm21 (6-NH2) and
3244, 3151, 1565 cm21 (5-NH2), while the strong azido-
absorption in IR spectrum disappeared. The yield of the
diamine 10 was 87%. The Schiff base 11 was prepared in
81% yield by refluxing the ethanol solution of the diamine
10 and 3,5-di-tert-butyl-2-hydroxybenzaldehyde for 3 h.
is described. The reaction conditions are mild and the yields
vary from high to excellent.
In view of the versatility of the derivatives of carbohydrate
and other natural chiral compounds, this work opens a wide
prospect of utilizing natural products as chiral templates for
the asymmetric epoxidative catalysis. Further synthesis and
investigations of the catalytic behavior of other types of
carbohydrate-based chiral Mn(III)–salen catalysts will be
published shortly.
Compound 11 showed strong absorption at 1628 cm21
,
which was attributed to the imine structure unit. Heating the
solution of the Schiff base 11 in ethanol with Mn(OAc)2·
4H2O in an atmosphere of oxygen under reflux, following
by treatment with lithium chloride gave the Mn(III)–salen
complex 12 in a yield of 92%.
4. Experimental
4.1. General
For the evaluation of the catalytic performance of the new
carbohydrate-based Mn(III)–salen catalyst, styrene as a
terminal alkene and 1,2-dihydronaphthalene as a cis-di-
substituted alkene were chosen as the substrates of the
catalytic epoxidation. NaOCl solution was used as the
terminal oxidant. The oxidation reactions were carried out at
208C. Table 1 summarizes the results obtained in the
epoxidation. Although carbohydrate structures are thought
to be sensitive to oxidative environment, its catalytic
behavior did not suggest of such kind of influence. Both
substrates in entries 1 and 2 were consumed completely
when 10 mol% of compound 12 was used as catalyst.
Entries 4 and 5 show that, when the oxidations were carried
out without any catalysts, no epoxidaton products could be
detected. The substrates could be recovered nearly
quantitatively.
Melting points were determined on a Kru¨ss apparatus, the
Digital Melting Point Analyzer KSPS 1000 or on a
microscopic analyzer DAW IMEJ Jena and were not
corrected. NMR spectra were recorded in CDCl3 at
250 MHz on a Bruker AC-200 spectrometer. IR spectra
were measured on a Perkin–Elmer 2000 spectrometer. Mass
spectra were carried out on a Finnigan MAT SSQ710 or a
Finnigan MAT 95XLTRAP. Elemental analyses were
acquired by use of a Leco CHNS 932. Optical rotation
was measured with a SchmidtþHaensch product, the
Polartronic E, at ambient temperature using a 50 mm
sample tube, the samples were dissolved in CHCl3 with
concentration of 1 g/100 ml unless otherwise stated. TLC
was conducted on Merck glass plates coated with silica gel
60, the plates were cut into small plates (2 cm£5 cm), the
solvent front was allowed to run 4 cm, sample spots were
visualized by spraying 1% vanillin/conc. H2SO4 solution
with subsequent heating at 2008C unless otherwise stated.
Chromatography was performed using silica gel 60 (particle
size 0.063–0.2 mm) from Fluka Chemie GmbH. Solvents
were distilled prior to use. Ethanol and pyridine were dried
before distillation. Other chemicals including D-(þ)-glu-
cose were obtained from Fluka Chemie GmbH and were
used directly. 3,5-di-tert-butyl-2-hydroxybenzaldehyde was
purchased from Aldrich Chem. Co. 1,2:5,6-di-O-isopropyl-
idene-a-D-glucofuranose 1 was prepared according to
literature.4
Interestingly, although compound 12 has only one stereo-
genic center (C-5) that is adjacent to nitrogen atom in the
diamine unit, it also showed definitely positive enantio-
selectivity. In the cases of styrene and 1,2-dihydronaphtha-
lene, the enantiomeric excesses of the oxidative products
1
were calculated to be 13 and 33%, respectively, from H
NMR spectra in the presence of europium tris[3-(hepta-
fluoropropylhydoxymethylene)-(þ)-camphorate] (Eu(hfc)3)
as the chiral shift reagent. Fig. 1 clearly shows that the peaks
of the enantiomers separated with the addition of Eu(hfc)3.
Spectrum (b) indicates that, in the case of epoxidation of
styrene, compound 12 showed the same enantiofacial
selection as (S,S)-Jacobsen’s catalyst, the major enantiomer
has the absolute configuration of S-(2), as was determined
by comparing the experimental results of entries 1 and 3 in
Table 1.
4.1.1. 1,2;5,6-Di-O-isopropylidene-3-O-methyl-a-D-gluco-
furanose (2). To a magnetically stirred solution of 26.3 g
(101.0 mmol) (1) in 150 ml acetone were added 7.4 g newly
powdered KOH and 1.2 g tetrabutylammonium bromide,
the mixture was cooled to 08C, 21.5 g CH3I (151.5 mmol)
was added within 20 min, the reaction was allowed to be
carried out at room temperature for a further 40 min, TLC
(ethyl acetate–n-hexane 1:1, Rf of starting sugar: 0.55, Rf of
product: 0.83) showed complete consumption of the starting
sugar. Acetone was evaporated under reduced pressure,
water was added and the mixture was three times extracted
with CH2Cl2, the combined organic phase was washed with
NH4Cl solution and water, dried over anhydrous Na2SO4,
filtered, evaporated under reduced pressure. Pure product
was obtained as a colorless syrup after vacuum distillation,
yield: 26.1 g (94%), [a]D¼238.08. IR(ATR): 2987, 2937,
2896, 2834, 1457, 1373, 1254, 1215, 1165, 1124, 1073,
3. Conclusion
In summary, this paper reports the preparation of the first
carbohydrate-derived chiral Mn(III)–salen complex, it can
efficiently catalyze the epoxidation of simple unfunctional-
ized olefins with positive enantioselectivity. Mn(III)–salen
catalyst with only one stereogenic center that is adjacent to
the nitrogen atom can also asymmetrically catalyze the
epoxidation of olefins, this helps to clarify the mechanism of
the epoxidation in the presence of chiral Mn(III)–salen
catalysts. The facile synthesis of its precursor 5,6-diamino-
5,6-dideoxy-1,2-O-isopropylidene-3-O-methyl-b-L-idofura-
nose from D-(þ)-glucose following two different pathways
1
1018, 847, 641 cm21. H NMR: d 5.83 (d, 1H, J¼3.7 Hz),
4.53 (d, 1H, J¼3.7 Hz), 4.27 (td, 1H, J¼7.8, 5.8 Hz), 3.96

S. Yan, D. Klemm / Tetrahedron 58 (2002) 10065–10071
10069
(dd, 1H, J¼8.6, 5.5 Hz), 4.01 (m, 2H), 3.74 (d, 1H, J¼
3.0 Hz), 3.42 (s, 3H), 1.47 (s, 3H), 1.40 (s, 3H), 1.33 (s, 3H),
1.29 (s, 3H). 13C NMR: d 112.0, 109.3, 105.5, 84.0, 82.3,
81.4, 72.7, 67.6, 58.5, 27.1, 27.1, 26.6, 25.7. MS(EI): m/z
275 (58%, [MþH]þ). Anal. calcd for C13H22O6: C, 56.92;
H, 8.08. Found: C, 56.90; H, 7.87.
DMF was added 0.385 g (5.92 mmol) NaN3, the mixture
was magnetically stirred and the flask was heated with an oil
bath (bath temperature: 1008C) for 1 h, TLC (ethyl acetate–
n-hexane 1:1, Rf of product: 0.61, yellow spot) showed
completion of the reaction, DMF was evaporated under
reduced pressure, 20 ml water was added, followed by
extracting the mixture with 100 ml ethyl acetate twice,
organic phase was combined and washed with 30 ml brine
three times, the inorganic phase was extracted once with
ethyl acetate, organic phased were combined, dried over
anhydrous Na2SO4, filtered and evaporated under reduced
pressure, the product was then dried in vacuo to give 6 as a
colorless syrup which is chromatographically pure, yield
0.98 g (96%). [a]D¼228.08. IR(ATR): 3470, 2989, 2938,
2835, 2100, 1445, 1376, 1295, 1257, 1217, 1194, 1164,
4.1.2. 1,2-O-Isopropylidene-3-O-methyl-a-D-glucofura-
nose (3). 345 ml acetic acid and 115 ml water were added
to a one-neck-round flask containing 33 g (120.3 mmol) (2)
and a magnetic stirrer, the flask was heated with a bath, the
temperature of the bath was adjusted to 608C, the reaction
mixture was stirred for 50 min until TLC showed the
completion of the reaction (ethyl acetate–n-hexane 1:1, Rf
of product: 0.10). Acetic acid and water were then removed
at 408C under reduced pressure, small amounts of toluene
were added repeatedly into the flask and were distilled under
reduced pressure to remove the remaining acetic acid. The
crude product was dried at 408C under vacuum to remove
trace of acetic acid. The product was purified by
chromatography (ethyl acetate–n-hexane 3:1) to give 3 as
colorless syrup, yield: 25.4 g (90%). [a]D¼252.08.
IR(ATR): 3412, 2986, 2937, 2834, 1458, 1376, 1297,
1256, 1215, 1195, 1164, 1120, 1074, 1012, 955, 891, 852,
642, 620 cm21. 1H NMR: d 5.85 (d, 1H, J¼3.8 Hz), 4.54 (d,
1H, J¼3.8 Hz), 4.05 (dd, 1H, J¼8.2, 3.2 Hz), 3.92 (m, 1H),
3.84 (d, 1H, J¼3.1 Hz), 3.76 (m, 1H), 3.64 (m, 2H), 3.46 (m,
1H), 3.42 (s, 3H), 1.45 (s, 3H), 1.28 (s, 3H). 13C NMR: d
112.1, 105.4, 84.5, 81.8, 80.1, 69.4, 64.7, 58.2, 27.0, 26.5.
MS(EI): m/z 235 (70%, [MþH]þ). Anal. calcd for
C10H18O6: C, 51.27; H, 7.75. Found: C, 50.71; H, 7.62.
1
1119, 1075, 1019, 956, 889, 855, 665, 642, 622 cm21. H
NMR: d 5.85 (d, 1H, J¼3.8 Hz), 4.56 (d, 1H, J¼3.8 Hz),
4.05 (s, 2H), 3.86 (d, 1H, J¼2.2 Hz), 3.51 (m, 1H), 3.42 (s,
3H), 3.38 (m, 1H), 2.98 (s, 1H), 1.45 (s, 3H), 1.29 (s, 3H).
13C NMR: d 112.2, 105.4, 84.5, 81.7, 80.3, 68.8, 62.5, 58.1,
55.0, 27.1, 26.6. MS(EI): m/z 260 (26%, [MþH]þ). Anal.
calcd for C10H17O5N3: C, 46.33; H, 6.61; N, 16.21. Found:
C, 46.59; H, 6.59; N, 15.80.
4.1.5. 6-O-Azido-6-deoxy-1,2-O-isopropylidene-3-O-
methyl-5-O-trifluromethanesulfonyl-a-D-glucofuranose
(7). A solution of 1.3 ml (16.2 mmol) pyridine in 20 ml
CH2Cl2 was cooled to 2188C with NaCl/ice bath. 1.3 ml
(7.88 mmol) Tf2O in 10 ml CH2Cl2 was added dropwise
with stirring into the solution in an atmosphere of Argon,
10 min later, 1.0 g (3.86 mmol) azide (6) in 10 ml CH2Cl2
was added slowly into the reaction vessel, the reaction
continued at that temperature with stirring, while moisture
was prevented by the inlet of Argon. 1.5 h later, TLC (ethyl
acetate–toluene 1:3, Rf of product: 0.78) showed the
reaction to be complete. 50 ml CH2Cl2 and 50 ml water
were added into the reaction mixture, after the extraction,
the organic phase was washed twice with 50 ml water,
organic phase was combined, dried over anhydrous Na2SO4,
filtered and evaporated under reduced pressure, the product
was purified by chromatography (ethyl acetate–toluene 1:6)
and then dried in vacuo at room temperature to give 7 as
a yellow liquid with low viscosity, yield 1.51 g (100%).
[a]D¼244.08. IR(ATR): 2993, 2942, 2841, 2110, 1411,
1379, 1294, 1244, 1206, 1164, 1141, 1123, 1081, 1027, 918,
4.1.3. 1,2-O-Isopropylidene-3-O-methyl-6-O-tosyl-a-D-
glucofuranose (4). 10.22 g (43.6 mmol) (3) was dissolved
in 50 ml pyridine, the solution was then cooled with a
NaCl/ice bath to 2188C, 9.1 g (47.2 mmol) tosyl chloride in
10 ml pyridine was added dropwise within 15 min, the
reaction mixture was kept in the cool bath for a further 4 h,
TLC (ethyl acetate–n-hexane 1:1, Rf of product: 0.49)
showed that only a very small amount of starting diol
remained and no ditosylate occurred, terminated the
reaction by adding water and extracting with ethyl acetate,
the organic phase was washed with 0.5 M HCl several
times, the inorganic phase was extracted once with ethyl
acetate, combined the organic phase and washed with brine.
Organic phase was dried over anhydrous Na2SO4, filtered,
evaporated under reduced pressure, the crude product was
purified by passing it through a column of silica gel giving
a colorless syrup, yield: 15.9 g (94%). [a]D¼228.08.
IR(ATR): 3483, 2989, 2938, 2833, 1599, 1454, 1356,
1
851, 760, 624 cm21. H NMR: d 5.87 (d, 1H, J¼3.6 Hz),
5.22 (m, 1H), 4.63 (d, 1H, J¼3.6 Hz), 4.46 (dd, 1H, J¼8.2,
3.3 Hz), 3.84 (m, 2H), 3.68 (dd, 1H, J¼14.3, 4.6 Hz), 3.43
(s, 3H), 1.50 (s, 3H), 1.33 (s, 3H). 13C NMR: d 121.2, 116.1,
113.0, 105.9, 82.9, 81.8, 81.0, 57.8, 51.9, 27.2, 26.6.
MS(DCI): m/z 392 (13%, [MþH]þ). Anal. calcd for
C11H16O7N3F3S: C, 33.76; H, 4.12; N, 10.74; S, 8.19.
Found: C, 33.59; H, 4.19; N, 10.68; S, 8.23.
1217, 1174, 1075, 1020, 967, 883, 614, 765, 666, 616 cm21
.
1H NMR: d 7.78 (d, 2H, J¼8.3 Hz), 7.33 (m, 2H), 5.83 (d,
1H, J¼3.7 Hz), 4.55 (d, 1H, J¼3.8 Hz), 4.26 (dd, 1H, J¼
9.6, 2.2 Hz), 4.10 (m, 3H), 3.86 (d, 1H, J¼3.1 Hz), 3.41 (s,
3H), 3.00 (s, 1H), 2.43 (s, 3H), 1.44 (s, 3H), 1.30 (s, 3H). 13C
NMR: d 145.4, 133.0, 130.3, 128.4, 112.2, 105.4, 84.4, 81.7,
79.5, 72.8, 67.6, 56.3, 27.1, 26.6, 22.0. MS(DCI): m/z 389
(88%, [MþH]þ). Anal. calcd for C17H24O8S: C, 52.57; H,
6.23; S, 8.26. Found: C, 52.72; H, 6.24; S, 8.43.
4.1.6. 5,6-Di-azido-5,6-dideoxy-1,2-O-isopropylidene-3-
O-methyl-a-D-glucofuranose (9). Method A, from 7. To a
solution of 1.32 g (3.37 mmol) (7) in 9 ml DMF was added
0.37 g (5.69 mmol) NaN3, the reaction continued at room
temperature for 35 min, TLC (ethyl acetate–toluene 1:4,
products ran slightly slower than starting sugar) showed the
complete consumption of 7, 10 ml water was added, the
mixture was extracted with 80 ml ethyl acetate, the organic
phase was washed once with 30 ml water and once with
4.1.4. 6-O-Azido-6-deoxy-1,2-O-isopropylidene-3-O-
methyl-a-D-glucofuranose (6). To a one-necked round-
bottom flask containing 1.535 g (3.95 mmol) (4) and 10 ml

10070
S. Yan, D. Klemm / Tetrahedron 58 (2002) 10065–10071
30 ml brine, organic phase was then combined, dried over
anhydrous Na2SO4, filtered, the solvent was removed under
reduced pressure and the product was dried in vacuo to
give pure 9 as a syrup, yield 0.88 g (92%). [a]D¼2628.
IR(ATR): 2990, 2938, 2835, 2094, 1453, 1375, 1258, 1216,
1193, 1163, 1114, 1076, 1017, 959, 888, 851, 667,
sugar, 100 ml ice water and 50 ml CH2Cl2 were added and
vigorously shaken in a separating funnel, the organic phase
was separated and washed with 80 ml ice brine three times,
the inorganic phase was extracted once with CH2Cl2, the
combined organic phase was dried over anhydrous Na2SO4
and decolorized by filtering though a short pad of silica gel,
the solution was then evaporated under reduced pressure to
give, after being dried in vacuo, a yellow syrup, which
turned brown easily on storage, yield: 7.4 g (100%). The
product should be kept at low temperature with prevention
of light and air. Immediate analyses or further chemical
treatments are recommended. [a]D¼2168. IR(ATR): 2992,
2939, 2840, 1412, 1372, 1244, 1209, 1192, 1177, 1141,
1080, 1005, 986, 918, 891, 856, 815, 792, 758, 661, 623,
617 cm21. 1H NMR: d 7.79 (d, 2H, J¼8.3 Hz), 7.35 (d, 2H,
J¼8.1 Hz), 5.82 (d, 1H, J¼4.4 Hz), 5.28 (m, 1H), 4.59 (d,
1H, J¼3.6 Hz), 4.46 (dd, 1H, J¼12.0, 2.0 Hz), 4.39 (dd, 1H,
J¼7.3, 2.0 Hz), 4.23 (dd, 1H, J¼12.0, 3.3 Hz), 3.83 (d, 1H,
J¼3.4 Hz), 3.41 (s, 3H), 2.45 (s, 3H), 1.47 (s, 3H), 1.32 (s,
3H). 13C NMR: d 145.7, 132.5, 130.3, 128.5, 113.0, 105.8,
83.0, 81.1, 80.9, 67.9, 57.9, 27.2, 26.6, 22.0. MS(DCI): m/z
521 (19%, [MþH]þ). Anal. calcd for C18H23O10F3S2: C,
41.54; H, 4.45; S, 12.32. Found: C, 42.06; H, 4.37; S, 12.37.
1
621 cm21. H NMR: d 5.93 (d, 1H, J¼3.8 Hz), 4.61 (d,
1H, J¼3.8 Hz), 4.21 (dd, 1H, J¼8.4, 3.5 Hz), 3.86 (m, 1H),
3.67 (d, 1H, J¼3.5 Hz), 3.40 (s, 3H), 3.28 (dd, 2H, J¼12.8,
6.6 Hz), 1.50 (s, 3H), 1.33 (s, 3H). 13C NMR: d 112.4,
105.2, 84.1, 81.6, 80.9, 61.5, 57.8, 52.0, 27.2, 26.6. MS(EI):
m/z 28 (31%), 43 (54%), 45 (12%), 59 (45%), 71 (13%), 84
(20%), 87 (99%), 98 (13%), 115 (54%), 145 (22%), 173
(99%), 174 (21%), 199 (30%), 269 (9%), 285 (2%,
[MþH]þ). Anal. calcd for C10H16O4N6: C, 42.25; H, 5.67;
N, 29.56. Found: C, 43.49; H, 5.66; N, 25.95.
Method B, from 8. A round-bottom flask containing 0.84 g
(2.0 mmol) (8) in 4 ml DMF and 0.4 g (6.2 mmol) NaN3
was heated with an oil bath (bath temperature: 1008C) with
stirring. 1 h later, TLC (ethyl acetate–toluene 1:4, Rf of
starting sugar: 0.66, Rf of product: 0.74) showed the reaction
to be complete. Water was added and the reaction mixture
was extracted with ethyl acetate, organic phase was washed
with water and brine, dried over anhydrous Na2SO4, filtered,
the solvent was removed under reduced pressure and the
product was dried in vacuo to give pure 9, yield 0.54 g
(94%). The analytical data were the same as in method A.
4.1.8. 5-Azido-5-deoxy-1,2-O-isopropylidene-3-O-
methyl-6-O-tosyl-a-D-glucofuranose (8). To a one-necked
round-bottom flask containing 1.6 g (3.07 mmol) (5) and
8 ml DMF was added 0.29 g NaN3, the reaction mixture was
stirred at room temperature for 4 h, until TLC (ethyl
acetate–toluene 1:4, Rf of starting sugar: 0.67, Rf of
product: 0.60) showed complete consumption of the starting
sugar, 20 ml water was added, the mixture was extracted
with 80 ml ethyl acetate, the inorganic phase was extracted
once with 50 ml ethyl acetate, the organic phase was
combined and wash successively with brine (3£30 ml), then
dried over anhydrous Na2SO4, filtered and then was passed
through a short pad of silica gel to decolorize the product,
solvent was removed under reduced pressure, the product
was dried in vacuo to give 8 as a yellow syrup, yield 1.21 g
(95%). [a]D¼40.08. IR(ATR): 2989, 2938, 2835, 2099,
1456, 1365, 1310, 1259, 1216, 1190, 1176, 1116, 1076,
Method C, from 5. 1.36 g (20.9 mmol) NaN3 was added to a
solution of 3.6 g (6.9 mmol) (5) in 15 ml DMF, the mixture
was stirred at room temperature for 4 h, TLC (ethyl
acetate–toluene 1:4) showed that the intermediate product
was slightly more polar than starting sugar. Then the
reaction mixture was heated with an oil bath, the bath
temperature was adjusted to be 1008C, the reaction was
terminated 1 h later, TLC (ethyl acetate–toluene 1:4)
showed that the final product was slightly less polar than
the intermediate product. DMF was removed under reduced
pressure, 50 ml water was added and the mixture was
extracted with 100 ml ethyl acetate twice, the combined
organic phase was washed with brine (3£30 ml), the
inorganic phase was washed with 100 ml ethyl acetate, the
organic phase was once again combined and dried over
anhydrous Na2SO4, the solution was decolorized by filtering
it through a short pad of silica gel to give a chromato-
graphically pure (9) 1.87 g (yield: 95%), the analytical data
were the same as in method A.
1
1018, 987, 939, 889, 854, 815, 770, 664, 615 cm21. H
NMR: d 7.79 (d, 2H, J¼8.3 Hz), 7.35 (d, 2H, J¼8.1 Hz),
5.89 (dd, 1H, J¼11.6, 3.8 Hz), 4.56 (d, 1H, J¼3.8 Hz), 4.16
(dd, 1H, J¼8.1, 3.4 Hz), 4.05 (m, 2H), 3.88 (m, 1H), 3.62 (d,
1H, J¼3.4 Hz), 3.31 (s, 3H), 2.43 (s, 3H), 1.45 (s, 3H), 1.29
(s, 3H). 13C NMR: d 145.7, 132.7, 130.4, 128.4, 112.4,
105.1, 83.9, 81.6, 79.8, 69.0, 60.0, 57.7. MS(DCI): m/z 69
(41%), 75 (36%), 93 (100%), 98 (20%), 115 (16%), 145
(16%), 173 (87%), 199 (46%), 242 (13%), 328 (23%), 386
(11%), 414 (3%, [MþH]þ). Anal. calcd for C17H23O7N3S:
C, 49.39; H, 5.61; N, 10.16; S, 7.76. Found: C, 49.34; H,
6.18; N, 10.57; S, 6.99.
4.1.7. 1,2-O-Isopropylidene-3-O-methyl-6-O-tosyl-5-O-
trifluromethanesulfonyl-a-D-glucofuranose
(5).
A
500 ml three-necked round-bottom flask was equipped
with a electric stirrer, an addition funnel and a device for
Argon introduction. The flask was charged with 5.7 ml
pyridine and 160 ml CH2Cl2, the solution was stirred and
was cooled to 2188C with a NaCl/ice bath. A solution of
triflic anhydride (4.73 ml, 28.67 mmol) in 40 ml CH2Cl2
was slowly added though the funnel under Argon protection,
10 min later, 5.514 g (14.2 mmol) (4) in 40 ml CH2Cl2 was
added dropwise through the funnel. The yellow reaction
mixture was stirred under argon atmosphere while cooled
with the bath for 1 h, TLC (ethyl acetate–toluene 1:4, Rf of
product: 0.67) showed the disappearance of the starting
4.1.9. 5,6-Di-amino-5,6-dideoxy-1,2-O-isopropylidene-3-
O-methyl-a-D-glucofuranose (10). To a stirred solution of
4.511 g (15.87 mmol) (9) in 30 ml methanol and 5.0 ml
N2H4·H2O was added catalytic Raney-nickel (freshly made)
slowly, gas evolved immediately, the reaction was allowed
to be carried out at room temperature over night. TLC (ethyl
acetate–toluene 1:4, product spot remained at the baseline)
showed no starting sugar was present. The reaction mixture
was filtered under suction, the filter and Raney-nickel were

S. Yan, D. Klemm / Tetrahedron 58 (2002) 10065–10071
10071
rinsed thoroughly with small amounts of methanol, solvents
and excess N2H4·H2O were removed under reduced
pressure, the product was then dried at 408C in vacuo to
give 3.21 g (87%) 10 as a pink wax. [a]D¼246.08.
IR(ATR): 3375, 3317, 3244, 3151, 2986, 2935, 2830,
1597, 1565, 1457, 1375, 1316, 1256, 1214, 1194, 1164,
IR(ATR): 2955, 2869, 1608, 1535, 1413, 1387, 1362, 1304,
1273, 1252, 1175, 1114, 1080, 1025, 882, 840, 812, 781,
1
750, 643, 616 cm21. H NMR (400 MHz): d 5.36, 3.66,
2.45, 1.33, from 0 to 4.4 ppm a very broad absorption
occurred. d MS(DEI): m/z 753 ([MþH]þ). Anal. calcd for
C40H58O6N2MnCl: C, 63.78; H, 7.76; N, 3.72; Cl, 4.71.
Found: C, 63.95; H, 7.87; N, 3.49; Cl, 4.41.
1
1116, 1074, 1010, 886, 851, 777, 682, 661, 615 cm21. H
NMR (400 MHz): d 5.80 (s, 1H), 4.49 (s, 1H), 3.82 (s, 1H),
3.56 (s, 1H), 3.29 (s, 3H), 2.96 (s, 1H), 2.68 (s, 1H), 2.49 (s,
1H), 1.39 (s, 3H), 1.22 (s, 3H), broad peaks between 1.65
and 0.96 (4H). 13C NMR (400 MHz): d 111.4, 104.5, 84.2,
82.8, 81.6, 57.5, 52.5, 45.0, 26.7, 26.1. MS(EI): m/z 233
(24%, [MþH]þ). Anal. calcd for C10H20O4N2: C, 51.71; H,
8.68; N, 12.06. Found: C, 51.60; H, 8.91; N, 11.86.
4.2. General procedure for the catalytic epoxidaton
To a solution of 0.1 g styrene or 0.125 g 1,2-dihydro-
naphthalene and 10% equiv. Mn(III)–salen catalyst in 2 ml
CH2Cl2 were added 8 ml 0.05 M Na2HPO4 and 8 ml sodium
hypochlorite solution (from Fluka, active chlorine: 13%),
the PH of the resulted buffered solution was adjusted to 11.3
by adding 1.3 g, 1.078 M HCl. The reaction flask was
capped with a cork, and the reaction mixture was violently
stirred at 208C with a magnetic bar until TLC showed the
completion of the reaction. The organic phase was
separated, CH2Cl2 was added to extract the inorganic
phase twice, the organic phase was combined, washed with
brine twice, dried over anhydrous Na2SO4, filtered, solvent
was evaporated under reduced pressure and the products
were purified by preparative TLC. The enantiomeric excess
of the products was determined by 1H NMR analysis6 in the
presence of Eu(hfc)3 as chiral shift reagent.
4.1.10. 5,6-Di(N-3,5-di-tert-butylsalicylidene)amino-5,6-
dideoxy-1,2-O-isopropylidene-3-O-methyl-a-D-glucofura-
nose (11). 20 ml ethanol solution containing 0.572 g
(2.46 mmol) (10) and 1.15 g (4.92 mmol) 3,5-di-tert-
butyl-2-hydroxybenzaldehyde was reflux for 3 h with
stirring, TLC (ethyl acetate–toluene 1:15 Rf of product:
0.50) showed the disappearance of the starting sugar.
Ethanol was removed under reduced pressure, the residue
was purified by chromatography (ethyl acetate–toluene
1:15) to give, after removal of the solvents, the Schiff
base (11) as a yellow solid, yield: 1.33 g (81%). Melting
point: 94.0–96.18C. IR(ATR): OH-absorption occurred as
shoulder of 2955, 2955, 2905, 2869, 1628, 1597, 1466,
1441, 1362, 1250, 1209, 1167, 1117, 1079, 1021, 854, 802,
772, 729, 703, 668, 645, 619 cm21. 1H NMR: 13.59 (d, 2H,
J¼11 Hz), 8.45 (d, 2H, J¼4.3 Hz), 7.41 (m, 1H), 7.27 (m,
1H), 7.12 (m, 2H), 5.99 (d, 1H, J¼3.9 Hz), 4.73 (d, 1H, J¼
3.9 Hz), 4.44 (dd, 1H, J¼8.0, 3.2 Hz), 3.95 (m, 4H), 3.56 (s,
3H), 1.3–1.5 (m, 42H). d 13C NMR: d 168.72, 168.67,
158.49, 158.47, 140.44, 140.32, 136.96, 136.74, 132.30,
129.47, 128.66, 128.28, 127.50, 127.39, 126.93, 126.57,
118.41, 118.25, 112.13, 105.11, 84.48, 81.79, 81.04, 68.71,
61.21, 57.90, 35.42, 35.14, 34.51, 34.49, 31.89, 31.77,
29.93, 29.85, 29.73, 27.18, 26.76. MS(DCI): m/z 665 (33%,
[MþH]þ). Anal. calcd for C40H60O6N2: C, 72.25; H, 9.10;
N, 4.21. Found: C, 72.12; H, 8.93; N, 4.11.
Acknowledgements
Shanhong Yan would like to thank the Deutscher Akade-
mischer Austauschdienst (DAAD) for a doctoral scholar-
ship. We thank the Deutsche Forschungsgemeinschaft
(DFG) for financial support.
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5,6-dideoxy-1,2-O-isopropylidene-3-O-methyl-a-D-gluco-
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while bubbling into oxygen slowly, shortly after adding into
Mn(OAc)2·4H2O, the solution became dark brown, 30 min
later, the introduction of oxygen was stopped, and air was
bubbled into the reaction system. Another 30 min later,
anhydrous LiCl 0.07 g was added, and the reflux continued
for an additional 2 h, water was added resulting in a dark
brown precipitate, which was collected by suction filtration.
The collected powder was re-dissolved in CH2Cl2 and
extracted with water and brine. The organic phase was dried
over anhydrous Na2SO4, and solvent evaporated to afford
a dark brown crystal, yield 0.396 g (92%). Mp .3008C.
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