Glycosyl hydroperoxides derived from 2-deoxysugars

Article abstract of DOI:10.1016/j.carres.2010.09.005

Oxidation of 3,4,6-tri-O-benzyl-2-deoxy-d-glucose and d-galactose or their t-butyl glycosides to the corresponding glycosyl hydroperoxides can be performed with hydrogen peroxide in the presence of an acid catalyst. Several reaction conditions and their i

Full text of DOI:10.1016/j.carres.2010.09.005

Carbohydrate Research 345 (2010) 2464–2468
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Glycosyl hydroperoxides derived from 2-deoxysugars
⇑
´
Barbara Szechner, Zofia Urbanczyk-Lipkowska, Marek Chmielewski
Institute of Organic Chemistry of the Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 15 July 2010
Received in revised form 30 August 2010
Accepted 2 September 2010
Available online 7 September 2010
Oxidation of 3,4,6-tri-O-benzyl-2-deoxy-D-glucose and D-galactose or their t-butyl glycosides to the cor-
responding glycosyl hydroperoxides can be performed with hydrogen peroxide in the presence of an acid
catalyst. Several reaction conditions and their influence on the effectiveness of the oxidation are dis-
cussed. Separation of the
a - and b-anomers of the glycosyl hydroperoxides was achieved through mixed
peroxide formation by reaction of the hydroperoxide group with 2-methoxypropene and subsequent
deprotection.
Keywords:
Ó 2010 Elsevier Ltd. All rights reserved.
Glycosyl hydroperoxides
Anomeric peroxides
Hydrogen peroxides
1. Introduction
2. Results and discussion
Recently, we have reported on the oxidation of 2-deoxysugars
or their glycosides with 50% hydrogen peroxide, in the presence
of molybdenum trioxide or in dioxane with sulfuric acid, to the
corresponding glycosyl hydroperoxides.1–3 Hydroperoxides 1–3
are relatively stable; they can be purified by silica gel chromatog-
raphy and stored for months in the refrigerator without visible
decomposition.
The attractiveness of glycosyl hydroperoxides as chiral epoxi-
dising reagents prompted us to find an easier and more effective
way of synthesising them. The use of pure
help clarify the reaction mechanism and the calculations. The read-
ily available 3,4,6-tri-O-benzyl- -glucal (4) and 3,4,6-tri-O-benzyl-
a- or b-anomers would
D
D
-galactal (5) were selected as starting materials.4 Both glycals
were transformed into the corresponding 2-deoxysugars5 6, 7 or
their t-butyl glycosides 8–116 for use in the oxidation experiments.
Compounds 8–11 have been obtained earlier by the other method,
but their spectral and analytical data have been reported only
partly.7 Previously we found that the configuration of the anomeric
CH2OBn
BnOH2C
CH2OBn
O
OOH
BnO
O
O
OBn
OBn
OOH
OOH
centre in the starting sugar does not influence the ratio of
anomers of the resulting hydroperoxides and so inseparable mix-
tures of ,b-anomers of free sugars 6 and 7, as well as t-butyl gly-
a- and b-
OBn
BnO
a
3
1
2
cosides 8 and 9, were used for the oxidation.
Compounds 1–3 were used for enantioselective epoxidation of
electrophilic olefins such as 2-methylnaphthoquinone, chalcone,
(E)-1,2-dibenzoylethylene and (E)-iso-butyrylphenylethylene.3 In
the presence of sodium hydroxide the epoxidations showed
exceptionally high asymmetric induction; the exchange of so-
dium by potassium ion resulted in a lower asymmetric induction.
These results pointed to the crucial role of the counterion and
strongly suggested the coordination of the alkali metal ion in
the transition state of the epoxidation process by both reactants,
the hydroperoxide and the olefin. DFT theoretical studies of the
reaction mechanism were in good agreement with the experi-
mental facts.3
Three methods of oxidation were chosen for comparison. Previ-
ously we used a method proposed by Snatzke and co-workers8 and
Taylor and co-workers9, that is, hydrogen peroxide in dioxane in
the presence of concd sulfuric acid. For the synthesis of glycosyl
peroxides directly from glycals or 2,3-unsaturated glycosides, the
Taylor group9 used a solution of hydrogen peroxide in diethyl ether
(prepared by extracting 50% hydrogen peroxide with ether), with
concd sulfuric acid. We turned our attention to a softer version
of this method, preparing a solution of hydrogen peroxide in ether
by extraction of 30% hydrogen peroxide. This solution, described by
Ma˛kosza and Surowiec,10 has been used by them for multi-gram
reactions without any problems. Finally, we proposed a new meth-
od of oxidation—a solution of hydrogen peroxide in tert-butanol
prepared according to Milas and Sussman,11 using commercially
available 50% hydrogen peroxide instead of 30%.
⇑
Corresponding author. Tel.: +48 226318788; fax: +48 226326681.
E-mail address: chmiel@icho.edu.pl (M. Chmielewski).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.09.005

B. Szechner et al. / Carbohydrate Research 345 (2010) 2464–2468
2465
CH2OBn
CH2OBn
CH2OBn
CH2OBn
BnO
BnO
O
O
O
O
OBn
OBn
OBn
OBn
OH
OH
BnO
BnO
BnO
6
5
7
4
CH2OBn
CH2OBn
CH2OBn
CH2OBn
BnO
Ot-Bu
O
O
Ot-Bu
O
O
OBn
OBn
OBn
OBn
BnO
Ot-Bu
BnO
Ot-Bu
9
10
8
11
CH2OBn
CH2OBn
CH2OBn
CH2OBn
BnO
BnO
OOCMe OMe
OOCMe OMe
O
2
O
O
O
2
OBn
OBn
OBn
OBn
OOCMe2OMe
BnO
BnO
OOCMe2OMe
12
14
13
15
All three methods provided similar ratios of anomers 1
a
,1b and
16 (a,a-anomeric configuration) is the result of a sequence of reac-
2
a
,2b (Table 1). The highest yield (up to 95%) and the shortest reac-
tions involving formation of the hydroperoxide followed by its
addition to the anomeric oxonium cation. Peroxide 16 was syn-
thesised in our laboratory previously13 but this time we were able
to grow a suitable crystal for an X-ray measurement. The X-ray
structure of compound 16 is shown in Figure 1.14
tion time (1 h) were obtained for the H2O2/Et2O solution. Lowering
the temperature of the oxidation experiment (procedure D) led to a
higher yield of the b-anomer of 2.
Since chromatographic separation of hydroperoxides 1
,2b is not easy, we devised an efficient protection/deprotection
methodology which enabled their separation. A mixture of the
,b-anomers of hydroperoxides 1 or 2 was treated with 2-methoxy-
propene in the presence of pyridinium p-toluenesulfonate12 to yield
,b-anomer mixtures of the corresponding (1-methoxy-1-methy-
a,1b and
2a
Similarly, crystal structure of compounds 1a and 2b is presented
in Figures 2 and 3, respectively. Intramolecular hydrogen bonds be-
tween hydroperoxide protons and the corresponding ring oxygen
atoms, postulated by us previously for both compounds in solu-
tion3,15 was notobserved in the solid state. Instead, a helicalarrange-
ment of molecules connected by intermolecular hydrogen bonds
was the dominating structural pattern for both hydroperoxides.
a
a
l)ethyl peroxides 12, 13 and 14, 15. The mixtures were separated
by chromatography and then each compound was deprotected with
diluted sulfuric acid in acetone solution giving anomerically pure
hydroperoxides. Also pyridine p-toluenesulfonate in acetone could
be used for deprotection but the reaction was very slow.
3. Experimental
Mixed (1-methoxy-1-methyl)ethyl peroxides are usually quite
stable compounds, and we were surprised to notice that b-anomer
15 started spontaneously losing its protecting group and that prod-
uct 2b was accompanied by bisglycosyl peroxide 16. Formation of
3.1. General methods
1H and 13C NMR spectra were recorded on a Brucker DRX 500
Avance Spectrometer, using deuteriated solvents and TMS as an
internal standard. Chemical shifts are reported as d values in
ppm and coupling constants are in Hertz. Infrared spectra were re-
corded on a FT-IR-1600 Perkin–Elmer spectrophotometer. The
optical rotations were measured with a JASCO J-2000 digital polar-
imeter. High-resolution mass spectra were recorded on an ESI-TOF
Mariner Spectrometer (Perspective Biosystem). Thin layer chroma-
tography was performed on aluminium sheet Silica Gel 60 F254
(20 Â 20 Â 0.2) from Merck. Column chromatography was carried
out using Merck silica gel (230–400 mesh). X-Ray experiment
was performed on Bruker X8APEX diffractometer equipped with
APEXII CCD detector. 1H and 13C NMR spectral data matched those
reported before2 were not provided.
Table 1
Results of the oxidation experiments
Compound
Reaction conditionsa
Yield (%)
a
:b ratio from HPLCb
6
6
6
8/9
8/9
8/9
8/9
7
7
7
10
10
10
A
B
C
A
B
C
D
A
B
C
A
B
C
78.2
89.3
89.8
82.2
85.6
94.9
84.9
74.4
79.1
83.7
91.3
87.8
95.0
68.6:31.4
61.5:38.5
65.1:34.9
62.1:37.9
58.0:42.0
63.3:36.7
58.8:41.2
80.4:19.6
84.7:15.3
88.7:11.3
86.5:13.5
77.0:23.0
89.5:10.4
3.2. Synthesis of tert-butyl glycosides
3.2.1. tert-Butyl 3,4,6-tri-O-benzyl-a- and b-D-arabino-
hexopyranoside (8) and (9)
tert-Butanol (0.67 g, 9 mmol) and triphenylphosphine hydro-
bromide (TPHB, 51.6 mg, 0.15 mmol) were added to a solution of
3,4,6-tri-O-benzyl-D-glucal (1) (1.29 g, 3 mmol) in dry dichloro-
methane (15 mL) and the reaction mixture was stirred at rt for
5 h. Then it was diluted with ethyl acetate (100 mL) and washed
a
(A) 0.25 mmol substrate, Milas solution (H2O2 in t-BuOH, ca. 3.2 M, 15 mL)
concd H2SO4 (225 L), rt; (B) 0.25 mmol substrate, 50% H2O2 (3 mL), dioxane (3–
4 mL), concd H2SO4, (75 L) rt; C.0.25 mmol substrate in toluene (1 mL), H2O2
solution in ether (ca. 2 M, 2 mL), concd H2SO4 (75 L), rt; (D) conditions C, 0 to 5 °C.
LichroCARTÒ 250-4, eluent: hexane–isopropanol 99.5:0.5, 1 mL/min (1
,1b);
95:5, 1 mL/min. (2 ,2b).
l
l
l
b
a
a

2466
B. Szechner et al. / Carbohydrate Research 345 (2010) 2464–2468
CH2OBn
BnO
O
OBn
O
O
BnO
O
16
OBn
CH2OBn
Figure 1. Crystal structure of compound 16. Thermal ellipsoids shown at 30% probability level.
Figure 2. X-ray structure of 1
a
. Thermal ellipsoids shown at 30% probability level.
Figure 3. X-ray structure of 2b. Thermal ellipsoids shown at 30% probability level.
with satd NaHCO3 solution (10 mL) and water (3 Â 15 mL). After
drying (Na2SO4), solvents were removed and the residue was
flash-chromatographed (hexanes–ethyl acetate 9:1) affording an
inseparable mixture (ca. 85:15) of 8 and 9 (Rf 0.18, 1.34 g, 88.6%).
1H NMR (500 MHz, CDCl3) d 7.34–7.21 and 7.19–7.16 (m, 15H,
aromatic); 5.27 (br d, 1H, J 2.6 Hz, H-1); 4.69–4.62 (m, 3H), 4.87,
4.51 and 4.47 (3d, 3H, CH2Ph); 4.04 (ddd, 1H, J 9.8, 8.9, 3.4 Hz, H-
3); 3.94 (ddd, 1H, J 9.9, 3.4, 2.1 Hz, H-5); 3.80 (dd, 1H, J 10.4,
3.7 Hz, H-6a); 3.64–3.60 (m, 2H, H-6b, H-4); 2.11 (ddd, 1H, J
12.5, 4.9, 1.3 Hz, H-2e); 1.72 (dt, 1H, J 12.7, J 3.7 Hz, H-2a), 1.21
(s, 9H, t-Bu).
3.2.2. tert-Butyl 3,4,6-tri-O-benzyl-
and tert-butyl 3,4,6-tri-O-benzyl-b-
3,4,6-Tri-O-benzyl- -galactal (5) (2.08 g, 5 mmol) in dry dichlo-
romethane (25 mL) was reacted with tert-butanol (1.11 g,
15 mmol) and triphenylphosphine hydrobromide (TPHB, 86 mg,
0.25 mmol). After 3 h the reaction mixture was worked-up as in
the preceding experiment. The crude product was flash-chromato-
graphed; elution with 5% ethyl acetate in hexanes afforded as a
first fraction product 10 (Rf 0.21, 1.52 g, 62.4% yield), which was
a
D
-
D
-lyxo-hexopyranoside (10)
-lyxo-hexopyranoside (11)
D
crystallised from hexanes, mp 62.5–64 °C, [a] +57.4 (c 1, CHCl3).
D
13C NMR (125 MHz, CDCl3) d 138.9, 138.7, 138.3, 128.39, 128.33,
128.29, 128.26, 127.96, 127.82, 127.65, 127.59, 127.52, 127.49,
127.43, 92.0, 78.6, 77.9, 75.0, 74.5, 73.4, 71.7, 70.3, 69.1, 37.0, 28.6.
In the 1H NMR spectrum only a few signals for compound 9
were clearly separated: 3.74 (dd, 1H, J 10.7, 1.8 Hz, H-6); 2.21
(ddd, 1H, J 12.5, 5.0, 1.9 Hz, H-2); 1.27 (s, t-Bu).
1H NMR (500 MHz, CDCl3) d 7.36–7.20 (m, 15 H, aromatic); 5.28
(br d, 1H, J 3.0 Hz, H-1); 4.92, 4.48, 4.42 (3d, 3H, CH2Ph) and 4.63–
4.57 (m, 3H, CH2Ph); 4.08 (br t, 1H, J 6.9 Hz, H-5); 3.99 (ddd, 1H, J
12.0, 4.2, 2.4 Hz, H-3); 3.63 (dd, 1H, J 9.2, 7.7 Hz, H-6a); 3.50 (dd,
1H, J 9.2, 5.7 Hz, H-6b); 2.33 (dt, 1H, J 12.1, 3.9 Hz, H-2a); 1.82
(ddt, 1H, J 12.1, 4.3, 1.4 Hz, H-2e); 1.21 (s, 9H, t-Bu).
IR (CHCl3) 2978, 1454, 1366, 1092, 995, 699 cmÀ1
HRMS Calcd for
31H38O5Na (M+Na+) 513.26115. Found:
513.26199.
.
13C NMR (125 MHz, CDCl3) d 139.1, 138.7, 138.3, 128.3, 128.11,
128.09, 127.7, 127.6, 127.4, 127.3, 92.4, 75.1, 74.3, 74.2, 73.4, 73.3,
70.4, 69.5, 69.3, 32.8, 28.6.
C

B. Szechner et al. / Carbohydrate Research 345 (2010) 2464–2468
2467
IR (CHCl3) 2978, 1454, 1367, 1091, 699 cmÀ1
Calcd for C31H38O5: C, 75.89; H, 7.81. Found: C, 75.88; H, 7.92.
Further elution of the column gave b-anomer 11 (Rf 0.17, 0.37 g,
.
Further elution of the column gave b-anomer 13 (Rf 0.13,
240 mg, 23.3%), [
a
]
D
À 46.8 (c 1, CH2Cl2).
1H NMR (500 MHz, C6D6) d 7.33–7.07 (m, 15H, aromatic); 4.97
(dd, 1H, J 10.4, 2.0 Hz, H-1); 4.91, 4.60, 4.51, 4.44, 4.37 and 4.28
(6d, 6H, CH2Ph); 3.78–3.73 (m, 2H, H-3, H-4); 3.64 (t, 1H, J
9.0 Hz, H-6a); 3.44 (m, 2H, H-6b, H-5); 3.32 (s, 3H, OCH3); 2.14
(ddd, 1H, J 12.2, 5.1, 2.0 Hz, H-2e); 1.64 (q, 1H, J ꢀ 11.4 Hz, H-
2a); 1.46 and 1.36 (2s, 6H, 2 Â CH3).
15.1%) as an oil. [
a
]
À28.0 (c 1.8, CHCl3).
D
1H NMR (500 MHz, C6D6) d 7.37–7.06 (m, 15H, aromatic); 5.05,
4.61 (2d, 21H) and 4.36–4.27 (m, 4H, CH2Ph); 4.52 (dd, 1H, J 9.6,
2.0 Hz, H-1); 3.81 (dd, 1H, J 9.0, 7.3 Hz, H-6a); 3.75 (br s, 1H, H-
4); 3.66 (dd, 1H, J 9.0, 5.6 Hz, H-6b); 3.38 (br t, 1H, H-5); 3.31
(ddd, 1H, J 12.2, 4.2, 2.7 Hz, H-3); 2.47 (dt, 1H, J 12.2, 9.7 Hz, H-
2a); 1.96 (dm, 1H, H-2e); 1.24 (s, 9H, t-Bu).
13C NMR (125 MHz, C6D6) d 139.4, 139.2, 139.1, 128.52, 128.49,
128.40, 128.3, 128.2, 128.1, 127.91, 127.87, 127.70, 127.67, 127.6,
105.3, 101.5, 96.4, 79.8, 78.2, 75.8, 74.9, 73.6, 71.2, 69.7, 49.1,
33.7, 23.4, 23.0.
13C NMR (125 MHz, CDCl3) d 139.8, 139.2, 139.0, 128.6, 128.5,
128.4, 128.3, 128.2, 128.11, 128.06, 128.0, 127.9, 127.7, 127.6,
127.4, 95.4, 78.4, 74.73, 74.70, 74.0, 73.5, 72.9, 70.1, 70.0, 34.5,
29.0.
IR (CCl4) 3032, 2868, 1454, 1364, 1211, 1088 cmÀ1
.
HRMS Calcd for C31H38O7Na (M+Na+) 545.25098. Found:
545.25063.
IR (CHCl3) 2870, 1454, 1366, 1099, 1069, 698 cmÀ1
HRMS Calcd for
513.25892.
.
C
31H38O5Na (M+Na+) 513.26115. Found:
3.3.2. 3,4,6-tri-O-Benzyl-
methoxy-1-methyl)ethyl peroxide (15)
To a solution of 3,4,6-tri-O-benzyl- -lyxo-hexopyranosyl hydro-
a- (14) and b-D-lyxo-hexopyranosyl (1-
D
3.3. Oxidation
peroxide (2, 842 mg, 1.87 mmol) in dry dichloromethane (20 mL)
2-methoxypropene (150 mg, 2.08 mmol) and PPTS (31.2 mg,
0.12 mmol) were added. After 3 h the reaction mixture was diluted
with ether (50 mL) and washed with satd NaHCO3 (10 mL) solution
and finally with water (3 Â 10 mL). After drying (Na2SO4) and
evaporation of solvents the residue was flash-chromatographed.
Elution with 20% of ethyl acetate in hexanes gave a first fraction
Method A. According to Taylor and co-workers.9 To a solution of
substrate (0.25 mmol) in dioxane (3–4 mL). 50% H2O2 (3 mL) was
added followed by concd sulfuric acid (75 lL). When tlc showed
the disappearance of the starting material, the reaction mixture
was diluted with dichloromethane (50 mL) and washed with water
(5 Â 20 mL). After drying (Na2SO4) and removal of solvents the res-
idue was flash-chromatographed.
Method B. Substrate (0.25 mmol, t-butyl glycoside or free sugar)
was dissolved in Milas solution (15 mL) and to this solution con-
a
-anomer 14 (Rf 0.34, 668 mg, 68.9%), [
a] + 82.7 (c 1.1, CH2Cl2).
D
1H NMR (500 MHz, C6D6) d 7.39–7.05 (m, 15H, aromatic); 5.55
(br d, 1H, J 4.3 Hz, H-1); 5.01, 4.61, 4.35. 4.29, 4.20 and 4.15 (6d,
6H, CH2Ph); 4.41 (dd, 1H, J 7.9, 5.5 Hz, H-5); 3.99 (br s, 1H, H-4);
3.96 (t, 1H, J 8.6 Hz, H-6a); 3.79–3.74 (m, 2H, H-6b, H-3); 3.21 (s,
3H, OCH3); 2.40 (dt, 1H, J 12.7, 4.6 Hz, H-2e); 1.97 (br dd, 1H, J
13.0, 4.6 Hz, H-2a); 1.33 and 1.30 (2s, 6H, 2CH3).
centrated H2SO4 (75 lL) was added. The reaction mixture was stir-
red at room temperature and monitored by tlc. After 1–2 days the
reaction mixture was worked-up as in the preceding experiment.
Method C. To a solution of substrate (0.25 mmol) in toluene
(2 mL) was added a solution of H2O2 in diethyl ether (2 mL) and
13C NMR (125 MHz, C6D6) d 139.8, 139.1, 139.0, 128.50, 128.49,
128.4, 128.3, 128.2, 128.1, 128.0, 127.7, 127.58, 127.52, 105.1,
100.8, 74.93, 74.88, 73.7, 73.5, 71.1, 70.4, 69.5, 49.1, 29.2, 23.1, 23.0.
concd sulfuric acid (75 lL). After 1 h tlc showed the reaction was
complete. It was diluted with diethyl ether (50 mL) and washed
with water until neutral. After drying (Na2SO4) and evaporation
of solvents the residue was flash-chromatographed affording pure
product.
IR (CCl4) 3067, 2944, 1454. 1368, 1210, 1115, 1097, 1068 cmÀ1
.
HRMS Calcd for
545.25079.
Further elution of the column gave b-anomer 15 (Rf 0.23, 84 mg,
8.6% yield), [
C
31H38O7Na (M+Na+) 545.25098. Found:
a]
À56.6 (c 1.3, CH2Cl2).
D
1H NMR (500 MHz, C6D6) d 7.34–7.05 (m, 15H, aromatic); 4.98,
4.59, 4.29, 4.24, 4.21 and 4.16 (6d, 6H, CH2Ph); 4.95 (dd, 1H, J 10.4,
2.1 Hz, H-1); 3.85 (dd, 1H, J 8.9, J 7.8 Hz, H-5); 3.75 (br s, 1H, H-4);
3.69 (dd, 1H, J 9.0, 5.3 Hz, H-6a); 3.29 (s, 3H, OCH3); 3.19 (dd, 1H, J
12.0, 4.3, 2.6 Hz, H-3); 3.27 (q, 1H, J ꢀ 11.4 Hz. H-2a); 1.95 (dm, 1H,
J 11.7 Hz, H-2e); 1.41 and 1.35 (2 Â s, 6H, 2 Â CH3).
3.3.1. 3,4,6-Tri-O-benzyl-a- (12) and b-D-arabino-hexopyranosyl
(1-methoxy-1-methyl)ethyl peroxide (13)
To a solution of hydroperoxide 1 (775 mg, 1.72 mmol) in dichlo-
romethane (20 mL), 2-methoxypropene (144 mg, 2 mmol) and
pyridinium p-toluenesulfonate (PPTS, 30 mg, 0.12 mmol) were
added and the reaction mixture was stirred at rt. After 3 h the reac-
tion mixture was diluted with ether (100 mL) and washed with
satd NaHCO3 (10 mL) and water (5 Â 10 mL). After drying (Na2SO4)
the solvents were removed and the residue was flash-chromato-
13C NMR (125 MHz, C6D6) d 139.7, 139.0, 138.9, 128.6, 128.5,
128.4, 128.3, 128.1, 127.9, 127.75, 127.70, 127.5, 127.4, 105.2,
102.3, 78.3, 74.8, 74.3, 73.6, 72.7, 70.3, 69.4, 49.1, 29.9, 23.3, 23.1.
IR (CCl4) 3032, 2867, 1363, 1098, 1063 cmÀ1
HRMS Calcd for
545.25333.
.
graphed. Eluting with 10% acetone in hexanes gave
(Rf 0.16, 450 mg, 43.7%), [ +108.0 (c 1.1, CH2Cl2).
a -anomer 12
C
31H38O7Na (M+Na+) 545.25098. Found:
a]
D
1H NMR (500 MHz, C6D6) d 7.33–7.06 (m, 15H, aromatic); 5.48
(br d, 1H, J 3.9 Hz, H-1); 5.06, 4.70, 4.51 and 4.41 (4 Â d, 4H,
CH2Ph); 4.34–4.31 (m, 2H, H-3, H-4); 4.28 (dm, 1H, J 9.7 Hz, H-
5); 3.97–3.85 (m, 3H, H-6a, CH2Ph); 3.78 (dd, 1H, J 10.8, 1.6 Hz,
H-6b); 3.21 (s, 3H, OCH3), 2.16 (ddd, 1H, J 13.4, 4.9, 1.0 Hz, H-
2e); 1.62 (ddd, 1H, J 13.4, 11.6, 4.6 Hz, H-2a); 1.33 and 1.32
(2 Â s, 6H, 2 Â CH3).
3.3.3. 2,4,6-Tri-O-benzyl-a-D-arabino-hexopyranosyl
hydroperoxide (1
a)
Diluted sulfuric acid (20% w/w, 0.5 mL) was added to a solution of
peroxide 12 (450 mg, 0.86 mmol) in acetone (20 mL) and the reac-
tion mixture was stirred at rt for 1 h when tlc showed the disappear-
ance of starting material. Most of the acetone was evaporated at rt
and the residue was dissolved in dichloromethane (50 mL) and
washed with water until neutral. Drying (Na2SO4) and removing
the solvent gave a crude product. Flash-chromatography in hexanes–
13C NMR(125 MHz, C6D6) d 139.6, 139.4, 139.3, 128.5, 128.44,
128.40, 128.3, 128.1, 127,9, 127.8, 127.7, 127.55, 127.52, 127.50,
105.1, 100.3, 78.6, 77.7, 75.0, 73.5, 72.5, 71.6, 69.6, 49.1, 33.5,
23.2, 22.9.
IR (CCl4) 3032, 2942, 1454, 1368, 1210, 1100 cmÀ1
HRMS Calcd for
545.25172.
.
ethyl acetate 7:3 afforded pure 1
acetate–hexanes. Mp 100.5–102 °C, [
Calcd for C27H30O6: C, 71.98; H, 6.71. Found: C, 71.99; H, 6.66.
a
which was crystallised from ethyl
C
31H38O7Na (M+Na+) 545.25096. Found:
a]D +90 (c 0.5, CHCl3), Rf 0.23.

2468
B. Szechner et al. / Carbohydrate Research 345 (2010) 2464–2468
3.3.4. 2,4,6-Tri-O-benzyl-b-
(2b)
D-lyxo-hexopyranosyl hydroperoxide
References
1. (a) Mieczkowski, J.; Jurczak, J.; Chmielewski, M.; Zamojski, A. Carbohydr. Res.
1977, 56, 180–182; (b) Chmielewski, M.; Jurczak, J.; Maciejewski, S. Carbohydr.
Res. 1987, 165, 111–115; (c) Hamann, H.-J.; Höft, E.; Mostowicz, D.; Mishnev,
A.; Urban´ czyk-Lipkowska, Z.; Chmielewski, M. Tetrahedron 1997, 53, 185–192;
(d) Mostowicz, D. M.; Jurczak, M.; Hamann, H.-J.; Höft, E.; Chmielewski, M. Eur.
J. Org. Chem. 1998, 2617–2621.
2. Kos´nik, W.; Stachulski, A.; Chmielewski, M. Tetrahedron: Asymmetry 2005, 16,
1975–1981. Corrigendum: Tetrahedron: Asymmetry 2006, 17, 313.
3. Kos´nik, W.; Bocian, W.; Kozerski, L.; Tvaroška, I.; Chmielewski, M. Chem. Eur. J.
2008, 14, 6087–6097.
To a solution of peroxide 15 (84 mg, 0.18 mmol) in acetone
(5 mL) PPTS (5 mg, 0.02 mmol) was added. After 30 min the ace-
tone was evaporated at rt and the residue was diluted with dichlo-
romethane (30 mL), washed with water (5 Â 10 mL) and dried
(Na2SO4). After removing the solvents the crude product was
flash-chromatographed in hexanes–ethyl acetate (7:3) to afford
peroxide 16 (Rf 0.5, 8 mg) and hydroperoxide 2b (Rf 0.25, 54 mg,
74.5% yield) which was crystallised from ethyl acetate–hexanes.
4. Chmielewski, M.; Fokt, I.; Grodner, J.; Grynkiewicz, G.; Szeja, W. J. Carbohydr.
Chem. 1989, 8, 735–741.
Mp 118.5–120 °C, [
a
]
À25.1 (c 0.5, CHCl3).
D
1H NMR (500 MHz, CDCl3) d 9.31 (br s, 1H, OOH); 7.36–7.25 (m,
15H, aromatic), 4.98 (dd, 1H, J 8.3, 3.9 Hz, H-1); 4.88, 4.61, 4.60,
4.57, 4.49 and 4.45 (6d, 6H, CH2Ph); 3.83 (br s, 1H, H-4); 3.80
(dd, 1H, J 8.4, 5.6 Hz, H-6a); 3.68–3.60 (m, 3H, H-6b, H-3, H-5);
2.08–1.99 (m, 2H, H-2a, H-2b).
5. Takahashi, Y.; Vasella, A. Helv. Chim. Acta 1992, 75, 1563–1571.
6. Bolitt, V.; Mioskowski, C. J. Org. Chem. 1990, 55. 5812–5613.
7. Pachamuthu, K.; Vankar, Y. D. J. Org. Chem. 2001, 66, 7511–7513.
8. Fehlhaber, H.-W.; Snatzke, G.; Vlahov, I. Liebigs Ann. Chem. 1987, 637–
638.
9. Bundu, A.; Berry, N. G.; Gill, C. D.; Dwyer, C. L.; Stachulski, A. V.; Taylor, R. J. K.;
Whithall, J. Tetrahedron: Asymmetry 2005, 16, 283–293.
10. Ma˛kosza, M.; Surowiec, M. OPPI Briefs 2003, 35, 412–414.
11. Milas, N. A.; Sussman, S. J. Am. Chem. Soc. 1936, 58, 1302–1304.
12. Dussault, P. H.; Woller, K. R. J. Am. Chem. Soc. 1997, 119, 3824–
3825.
13C NMR (125 MHz, CDCl3) d 138.5, 138.0, 137.8, 128.5, 128.4,
128.2, 128.1, 128.0, 127.9, 127.7, 127.6, 127.4, 102.8, 76.3, 73.9,
73.6, 73.5, 72.1, 70.6, 69.1, 29.2.
IR (KBr) 3291, 2921, 2868, 1454, 1119, 1039, 729 cmÀ1
.
´
13. Kosnik, W.; Grzeszczyk, B.; Chmielewski, M. Synlett 2007, 2837–2840.
Calcd for C27H30O6: C, 71.98; H, 6.71. Found: C, 71.93; H, 6.64.
14. The Crystallographic Information Files (CIF’s), containing details of data
collection and structure refinement have been deposited with the Cambridge
Crystallographic Data Centre under following numbers: CCDC 782150, CCDC
Acknowledgement
782149 and CCDC 782148 for compounds 1
under following numbers: CCDC 782150, CCDC 782149, and CCDC 782148 for
compounds 1 , 2b and 16, respectively.
a, 2b and 16, respectively. Centre
a
This publication was financed by the European Union within
European Regional Development Fund, Project POIG.01.01.02.-
14–102/09.
15. Kos´nik, W.; Bocian, W.; Chmielewski, M.; Tvaroška, I. Carbohydr. Res. 2008, 343,
1463–1472.