New stable anomeric hydroperoxides derived from 2-deoxysugars; Enantioselective epoxidation of 2-methyl-1,4-naphthoquinone

Article abstract of DOI:10.1016/j.tetasy.2005.04.009

3,5-Di- or 3,4,6-tri-O-substituted-2-deoxysugars or their glycosides can be oxidized with hydrogen peroxide in the presence of an acid catalyst to the corresponding anomeric hydroperoxides, which are relatively stable, can be separated into pure anomers b

Full text of DOI:10.1016/j.tetasy.2005.04.009

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 1975–1981
New stable anomeric hydroperoxides derived
from 2-deoxysugars; enantioselective epoxidation
of 2-methyl-1,4-naphthoquinone
a
Wioletta Kosnik, Andrew V. Stachulski and Marek Chmielewski
b
a,
*
´
aInstitute of Organic Chemistry of the Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
bRobert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
Received 9 March 2005; accepted 11 April 2005
Available online 23 May 2005
Abstract—3,5-Di- or 3,4,6-tri-O-substituted-2-deoxysugars or their glycosides can be oxidized with hydrogen peroxide in the pres-
ence of an acid catalyst to the corresponding anomeric hydroperoxides, which are relatively stable, can be separated into pure ano-
mers by column chromatography and stored in a refrigerator without visible decomposition. The hydroperoxides thus obtained were
used for the enantioselective epoxidation of 2-methyl-1,4-naphthoquinone with ees in the range 28–47%.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
CH2OR
O
R
CH2OR
OOH
Some time ago we reported the oxidation of 2,3-unsatu-
rated hexopyranosides and 2-C-methylene glycosides
with hydrogen peroxide in the presence of a molybde-
num trioxide catalyst to give the corresponding ano-
meric hydroperoxides 1–10.1–4 Hydroperoxides 1–10
are relatively stable, can be purified on a silica gel col-
umn and stored in a refrigerator without visible decom-
position. Hydroperoxides 5–10 can be used for the
enantioselective oxidation of prochiral alcohols and sul-
fides in the presence of Ti(O-i-Pr)4 with ees ranging from
about 10% to 50%.3–5
O
O
RO
OOH
OOH
RO
4: R = Ac
7: R = Bn
3: R = Ac
6: R = Bn
1: R = CO2Bu
2: R = CH2OAc
CH2OBn
CH2OR
CH2OBn
RO
O
BnO
O
OBn
O
OBn
OOH
BnO
OOH
OOH
The catalytic asymmetric epoxidation of allylic alcohols
by Sharpless6 and of Z-alkenes by Jacobsen7 are among
the leading achievements of contemporary organic syn-
thesis. In comparison to that, hydroperoxides 3–10 do
not offer visible advantages. They are more expensive,
provide significantly lower asymmetric induction, un-
dergo self-oxidation and cannot be regenerated by sub-
sequent reoxidation since the hemiacetals obtained from
them are unstable and rearrange to a,b-unsaturated
aldehydes.8
5: R = Ac
8: R = Bn
9
10
Considerable, if less spectacular, progress has been re-
ported in the epoxidation of electrophilic olefins. The re-
sults of Wynberg,9 Enders,10 Shibasaki,11 Jackson,12
Lygo,13 Adam,14 Julia-Colonna,15 Roberts16 and others17
are especially noteworthy. Enantioselective oxidation of
a,b-unsaturated carbonyl compounds by enantiomeri-
cally pure hydroperoxides in the presence of bases has
hardly been studied, with only a few hydroperoxides
being used.14,18–20 The crucial role of the base in these
reactions has been noticed by Adam et al.14,19 In the case
of the epoxidation of chalcones using 1-phenylethyl
*
Corresponding author. Tel.: +48 22 6318788; fax: +48 22 6326681;
e-mail: chmiel@icho.edu.pl
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.04.009

´
W. Kosnik et al. / Tetrahedron: Asymmetry 16 (2005) 1975–1981
1976
hydroperoxide, the replacement of KOH by DBU
changes the direction of asymmetric induction.
Z
, B
-
CH2OPiv
O
CH2OPiv
O
CH2OPiv
OOH
CH2OBn
CH2OBn
PivO
O
BnO
BnO
O
O
OBn
OBn
OOH
PivO
OOH
PivO
OOH
OH
13
12
11
RO
22
18
OCH2
O
+
OOH
O
O
t-Bu2Si
H2O2, H
CH
3
Scheme 1.
OOH
16
14: R=Ac
15: R=Piv
exclusively, or almost exclusively a single anomer and
would offer a possible reuse of the reagent. It should
be stressed that the particular proportion of a,b-ano-
mers of a sugar hemiacetal does not necessary deter-
mine, after oxidation, similar proportion of anomeric
hydroperoxides since the hydroperoxide group exhibits
a much stronger anomeric effect than the hydroxyl.2
The possibility of the regeneration of the hemiacetal
and its reoxidation to the hydroperoxide would enhance
significantly the economy of the process (Scheme 1).
Taylor et al.18,20 have used anomeric hydroperoxides 8
and 11–16 related to compounds 3–10 for the epoxida-
tion of quinones. In the best case, an ee of 82% was ob-
tained.20 Compounds 8 and 11–16 were synthesized by a
modification of the method of Fehlhaber, Snatzke and
Vlahov.21
CH2OBn
CH2OBn
BnO
2. Results and discussion
O
O
OBn
OBn
OOH
Oxidation of sugars 19 and 20, which are known to exist
as single anomers, failed. Hydrogen peroxide (50%) in
the presence of molybdenum trioxide or sulfuric
acid18,20,21 did not convert either sugar into the corre-
sponding anomeric hydroperoxide. On the other hand,
oxidation of the readily available 2-deoxysugars or
methyl glycosides 21–28 with 50% hydrogen peroxide
in dioxane in the presence of sulfuric acid over 18 h–
6 days provided the derived hydroperoxides 18 and
29–41 in 48–75% yields. In the case of 21 a mixture of
anomers 29:30 in a ratio of about 2.1:1 was obtained;
in the case of 22, the ratio of 18:32 amounted to 16:1;
in the case of 23, the ratio of 31:33 amounted to 8:1;
compound 24 gave one hydroperoxide 34 only.
BnO
OOH
17
18
O
O
BnOH2C
OH
O
O
BnO
O O
CH2OBn
OH
BnO
20
19
Epoxidation of electrophilic olefins with anomeric
hydroperoxides derived from 2,3-unsaturated sugars 1–
16 in the presence of a base in principle does not remove
the drawbacks of the reagents mentioned above, particu-
larly, the lack of possibility of regeneration of the
hydroperoxide after oxidation.
Glycosides 25–27 were separated by chromatography
into pure a- and b-anomers and used for anomeric oxida-
tion separately, or as mixtures of both anomers. As was
to be expected, in each case, the same ratio of anomeric
hydroperoxides was obtained. Glycosides 25 and 26
afforded mixtures of hydroperoxides 35:38 and 36:39 in
a similar ratio for both of about 1.6:1 whereas 27 afford-
ed 37 and 40 in a ratio of about 1.2:1. In all cases, the a-
anomers dominated. Except for hydroperoxides 18:32
and 31:33, other mixtures of anomers were separated
by chromatography. Glycoside 28 was obtained as a mix-
ture of D-manno and D-gluco epimers in a ratio of about
3:2, respectively, which without separation was subjected
to oxidation providing an even more complex mixture of
hydroperoxides 41 (a-manno:a-gluco:b-gluco:b-manno
as 8.7:5.8:1.2:1, respectively) that was not investigated
further. Configurations at the anomeric centre of hydro-
A few years ago we reported on the synthesis of hydro-
peroxides 17 and 18 by direct oxidation of tri-O-benzyl-
D-glucal and tri-O-benzyl-D-galactal, respectively, with
the molybdenum trioxide–hydrogen peroxide mixture.4
Compound 18 has been evaluated by Adam et al.19 in
asymmetric oxidation of a,b-unsaturated carbonyl com-
pounds, giving preparatively useful ees.
The syntheses of 17 and 18 showed that the stability of
hydroperoxides does not depend on an allylic acetal
fragment and consequently has prompted us to search
for other hydroperoxides of that kind. The particular
target of our investigation was to find a sugar, which
after oxidation of the anomeric centre would provide

´
W. Kosnik et al. / Tetrahedron: Asymmetry 16 (2005) 1975–1981
1977
peroxides 18, 29–31 and 35–41 were easily proved by 1H
NMR spectra. In the case of anomers 32 and 33, their
presence in the product was anticipated on the basis of
characteristic downfield signals of their hydroperoxide
protons. Except for acetates 35 and 38, which can be sep-
arated by flash chromatography but cannot be stored,
the other anomeric hydroperoxides 36, 37, 39 and 40
are relatively stable and can be kept in the refrigerator
without visible decomposition.
CH2OR
CH2OBn
O
ROH2C
O
RO
BnO
OOH
O
OBn
H3C
OR
OOH
OOH
OR
32: R=Bn
33: R=Piv
34
35: R=Ac
36: R=Bn
37: R=Piv
CH2OBn
Cl
ROH2C
OOH
O
O
O
O
CH2OBn
O
CH2OBn
CH2OR
P
OBn
BnO
OOH
RO
O
O
N
N
H
OBn
OR
H3C
OBn
OH
BnO
OR
CH3
HOO
BnO
OCH3
OH
38: R=Ac
39: R=Bn
40: R=Piv
41
42
X
24
22:R=Bn
23: R=Piv
21
CH2OBn
O
It is noteworthy that O-benzylated hydroperoxides
display higher ees than related O-pivaloyl derivatives.
As anticipated, the configuration of the anomeric car-
bon atom, to which the hydroxyperoxide group is
bound, helps decide the direction of the asymmetric
induction: compare the results found for the pairs of
anomers 29/30, 36/39 and 37/40.
ROH2C
O
OCH3
OBn
OCH3
CH3
BnO
OR
25:R=Ac
26: R=Bn
27; R=Piv
28: R=Bn
O
O
O
DBU
The easy synthesis of stable hydroperoxides from 2-
deoxy- and from 2,3-unsaturated sugars, but not from
fully hydroxylated sugars 19 and 20, demonstrates that
the crucial issue in the formation of anomeric hydroper-
oxides is the readiness of the sugar to expel alkoxyl or
hydroxyl from the anomeric centre under mild acidic
conditions and form a glycosyl cation to which hydro-
gen peroxide can add. 2-Deoxy- and 2,3-unsaturated-
sugars are known to undergo hydrolysis easily.8,22 The
ring oxygen stabilizes the hydroperoxide; interaction be-
tween both groups is manifested by the strong anomeric
effect.2 A similar stability has been reported for related
acetal hydroperoxides 42.23
O
HPO, Toluene
O
44
43
Scheme 2. HPO = hydroperoxide.
3. Conclusion
In summary, we have demonstrated that 2-deoxysugars
and their glycosides can be oxidized using hydrogen
peroxide in the presence of acids to form anomeric
hydroperoxides. Like hydroperoxides derived from
2,3-unsaturated hexopyranoses,1–4,18,20 compounds 18
and 29–41 are relatively stable and can be purified or
separated into anomers on a silica gel column and can
be stored in a refrigerator without visible decomposi-
tion. The sugars can be isolated from the final reaction
mixture, after asymmetric epoxidation of electrophilic
olefins, as hemiacetals, which can be reoxidized to the
corresponding hydroperoxides.
CH2OBn
CH2OBn
OOH
CH2OPiv
PivO
O
O
O
OBn
OBn
OPiv
OOH
BnO
BnO
OOH
29
30
31
Epoxidations with the anomeric hydroperoxides 18,
29–31, 34, 36, 37, 39 and 40 as chiral oxidants were
performed on 2-methyl-1,4-naphthoquinone 43 under
standard conditions used by Taylor et al.18 (Scheme
2). The results obtained are summarized in Table 1.
Asymmetric inductions are in the range of those re-
ported for 2,3-unsaturated anomeric hydroperoxides by
Taylor et al.18,20 and for compound 18 by Adam et al.19
4. Experimental
Melting points were determined on a Koefler hot-stage
apparatus. NMR spectra were recorded using Brucker
Avance 500 and Varian Mercury 400 instruments. IR
spectra were recorded on a Perkin–Elmer FTIR
Spectrum 200 spectrophotometer. Mass spectra were
recorded using AMD-604 Inectra GmbH and

´
W. Kosnik et al. / Tetrahedron: Asymmetry 16 (2005) 1975–1981
1978
Table 1. Asymmetric oxidation of quinone 43 with enantiomerically pure hydroperoxides 18, 29–31, 34, 36, 37, 39, 40 at 20 ꢁC
Hydroperoxide
Proportion of HPOa:43
Time (h)
Yield (%)
eeb (%)
Absolute configuration
of epoxide 44
18
18
29
30
31
34
36
37
39
40
1.2
2.0
1.2
1.2
2.0
2.0
1.0
1.0
1.0
1.0
18
20
26
26
22
22.5
25
30
25
30
80
89
83
79
72
90
76
63
73
67
42.3
42.3
44.9
33.2
28.8
46.9
29.9
38.5
47.3
29.3
(2R,3R)
(2R,3R)
(2R,3R)
(2S,3S)
(2R,3R)
(2R,3R)
(2R,3R)
(2R,3R)
(2S,3S)
(2S,3S)
a HPO = hydroperoxide.
b Determined by HPLC on Daicel Chiralpak AD-H column.
HPLC–MS with Mariner and API 356 detectors. Opti-
cal rotations were measured using a JASCO P 3010
polarimeter at 22 3 ꢁC. Chiral HPLC was performed
on a Daicel Chiralpak AD-H column, to measure the
ee of 2-methyl-2,3-epoxy-1,4-naphthoquinone. Column
chromatography was performed using E. Merck Kiesel-
gel (230–400 mesh).
(Piv); HR-MS/ESI calcd for C16H28O6Na (M+Na)+
339.1778. Found: 339.1783. Anal. Calcd for C16H28O6:
C, 60.74; H, 8.92. Found: C, 60.61; H, 8.74.
4.3. Methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-methyl-a-D-
talohexopyranoside 24
Methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-methylene-a-D-
lyxohexopyranoside obtained following known proce-
dure29 was hydrogenated according to the procedure
described by Hansen and Tagmose.30 Yield 92%;
[a]D = +35.0 (c 0.62, CHCl3); IR (film): m 2909, 1078,
3,4,6-Tri-O-protected sugars 21–23 were obtained from
corresponding glycals using the procedure of Takahashi
and Vasella.24 Methyl 2-deoxy-D-erythropentofurano-
sides were obtained by a standard method;25 their acet-
ylation and separation26 provided 25a and 25b;
benzylation and separation27 gave 26a and 26b; pivaloyl-
ation and separation28 afforded 27a and 27b.
1
697 cmÀ1; H NMR (500 MHz, CDCl3): d 4.64 (br s,
1H, H-1), 4.97–4.44 (m, 6H, 3Bn), 3.96 (dt, 1H, J 6.2,
6.4, 1.3 Hz, H-5), 3.86–3.83 (m, 2H, H-4, H-3), 3.68
(dd, 1H, J 9.6, 6.2 Hz, H-6a), 3.65 (dd, 1H, J 9.6,
6.4 Hz, H-6b), 3.34 (s, 3H, CH3O), 2.27 (m, 1H, H-2),
1.26 (d, 3H, J 7.4 Hz, CH3); 13C NMR (125 MHz,
CDCl3): d 103.92 (C-1), 76.38 (C-4), 74.74 (C-3), 74.13
(Bn), 73.48 (Bn), 70.20 (Bn), 69.80 (C-5), 69.77 (C-6),
54.82 (CH3O), 36.37 (C-2), 12.57 (CH3); HR-MS/ESI
calcd for C29H34O5Na (M+Na)+ 485.2298. Found:
485.2297. Anal. Calcd for C29H34O5: C, 75.30; H, 7.41.
Found: C, 75.24; H, 7.45.
4.1. Methyl 2-deoxy-3,5-di-O-pivaloyl-a-D-erythropento-
furanoside 27a
Yield 85%; [a]D = +55.1 (c 0.52 CHCl3); IR (film): m
1
2974, 1733 (C@O) cmÀ1; H NMR (500 MHz, CDCl3):
d 5.09 (dd, 1H, J 5.3, 0.9 Hz, H-1), 5.03 (ddd, 1H, J
8.1, 2.1, 3.7 Hz, H-3), 4.30–4.26 (m, 1H, H-4), 4.23–
4.18 (m, 2H, H-5a, H-5b), 3.36 (s, 3H, CH3O), 2.37
(ddd, 1H, J 14.5, 5.3, 8.1 Hz, H-2a), 1.97 (ddd, 1H, J
14.5, 0.9, 2.1 Hz, H-2b), 1.21 (s, 9H, Piv), 1.20 (s, 9H,
Piv); 13C NMR (125 MHz, CDCl3): d 178.42 (Piv),
178.06 (Piv), 104.83 (C-1), 80.89 (C-3), 73.99 (C-4),
63.86 (C-5), 54.78 (CH3O), 39.09 (C-2), 38.81 (Piv),
38.54 (Piv), 27.08 (Piv), 27.01 (Piv); HR-MS/ESI calcd
for C16H28O6Na (M+Na)+ 339.1778. Found: 339.1791.
Anal. Calcd for C16H28O6: C, 60.74; H, 8.92. Found:
C, 60.80; H, 8.94.
4.4. Methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-methyl-a-D-
manno and a-D-glucohexopyranosides 28
Methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-methyl-a-D-manno
and a-D-glucohexopyranosides 28 were obtained from
methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-methylene-a-D-
arabinohexopyranoside as a mixture of two epimers in a
ratio of about 1:1, by the procedure described above.25,26
4.2. Methyl 2-deoxy-3,5-di-O-pivaloyl-b-D-erythropento-
furanoside 27b
Compound 28a-manno: Yield 55%; 1H NMR
(500 MHz, CDCl3): selected signals taken for the mix-
ture: d 4.65 (d, 1H, J 1.4 Hz, H-1), 2.43 (qdd, 1H, J
1.4, 5.3, 7.3 Hz, H-2), 1.12 (d, 3H, J 7.3 Hz, CH3).
Yield 85%; [a]D = À44.0 (c 0.4 CHCl3); IR (film): m 2974,
1733 (C@O) cmÀ1; 1H NMR (500 MHz, CDCl3): d 5.21
(ddd, 1H, J 7.2, 4.6, 2.5 Hz, H-3), 5.14 (dd, 1H, J 2.4,
5.5 Hz, H-1), 4.23–4.15 (m, 3H, H-4, H-5a, H-5b),
3.34 (s, 3H, CH3O), 2.40 (ddd, 1H, J 14.1, 2.4, 7.2 Hz,
H-2a), 2.09 (ddd, 1H, J 14.1, 5.5, 4.6 Hz, H-2b), 1.23
(s, 9H, Piv), 1.22 (s, 9H, Piv); 13C NMR (125 MHz,
CDCl3): d 178.16 (Piv), 177.96 (Piv), 105.61 (C-1),
81.85 (C-3), 74.86 (C-4), 64.84 (C-5), 55.11 (CH3O),
39.19 (C-2), 38.79 (Piv), 38.54 (Piv), 27.15 (Piv), 27.00
1
Compound 28a-gluco: Yield 35%; H NMR (500 MHz,
CDCl3) selected signals taken for the mixture: d 4.61 (d,
1H, J 3.3 Hz, H-1), 1.97 (m 1H, H-2), 1.12 (d, 3H, J
6.8 Hz, CH3).
HR-MS/ESI taken for the mixture 28, calcd for
C29H34O5Na (M+Na)+ 485.2298. Found: 485.2290.

´
W. Kosnik et al. / Tetrahedron: Asymmetry 16 (2005) 1975–1981
1979
4.5. Synthesis of hydroperoxides; general procedure
4.7, 12.4 Hz, H-2a), 2.03 (m, 1H, J 13.4, 4.7, 1.2 Hz,
H-2b); 13C NMR (125 MHz, CDCl3): d 102.11(C-1),
74.27 (Bn), 73.95 (C-5), 73.67 (Bn), 72.76 (C-4), 70.90
(C-3), 70.47 (Bn), 70.09 (C-6), 28.23 (C-2); HR-MS/
LSIMS-NBA calcd for C27H31O6 (M+H)+ 451.21206.
Found: 451.21298. Anal. Calcd for C27H30O6: C,
71.98; H, 6.71. Found: C, 71.89; H, 6.68. Compound
Methyl glycosides 23–30 (0.25 mM) were dissolved in
1,4-dioxane (1 mL) and 50% H2O2 (3 mL) and treated
with concd H2SO4 (50 lL). The reaction was stirred at
room temp until disappearance of the substrate was
complete (TLC). Subsequently the mixture was treated
with CH2Cl2 (50 mL) and the organic layer separated.
Water solution was extracted with CH2Cl2 and the ex-
tracts combined, washed with water, dried and evapo-
rated at room temperature. The crude product was
purified or the products separated on a silica gel column
using hexane–ethyl acetate 7.5:2.5 v/v as an eluent to af-
ford hydroperoxides 18, 29/30, 32, 34, 35/38, 36/39, 37/
40, 41 in 50–90% overall yield.
1
32: H NMR (500 MHz, CDCl3): 9.31 (s, 1H, OOH).
4.9. 2-Deoxy-3,4,6-tri-O-pivaloyl-a-D-lyxohexopyranosyl
hydroperoxide 31
Yield 70%; [a]D = +79.8 (c 0.35, CHCl3); IR (film): m
1
3395 (O–H), 2974, 1737 (C@O), 1155 cmÀ1; H NMR
(500 MHz, CDCl3): d 8.95 (s, 1H, OOH), 5.47 (d, 1H,
J 4.6 Hz, H-1), 5.37 (br d, 1H, J 2.9 Hz, H-4), 5.12
(ddd, 1H, J 12.7, 5.1, 2.9 Hz, H-3), 4.35 (br t, 1H, H-
5), 4.20 (dd, 1H, J 11.1, 6.7 Hz, H-6a), 4.03 (dd, 1H, J
11.1, 7.1 Hz, H-6b), 2.12 (dt, 1H, J 13.4, 12.7, 4.6 Hz,
H-2a), 1.97 (dd, 1H, J 13.4, 5.1 Hz, H-2b), 1.25 (s, 9H,
Piv), 1.20 (s, 9H, Piv), 1.19 (s, 9H, Piv); 13C NMR
(125 MHz, CDCl3): d 178.21 (Piv), 177.37 (Piv), 176.89
(Piv), 101.23 (C-1), 67.73 (C-4), 65.81 (C-3), 65.54 (C-5),
61.76 (C-6), 39.12 (Piv), 38.78 (Piv), 38.67 (Piv), 27.67
(C-2), 27.21 (Piv), 27.09 (Piv), 27.01 (Piv); HR-MS/ESI
calcd for C21H36O9Na (M+Na)+ 455.2252. Found:
455.2259. Anal. Calcd for C21H36O9: C, 58.32; H, 8.39.
Found: C, 56.48; H, 8.55. Compound 33: 1H NMR
(500 MHz, CDCl3): 9.36 (s, 1H, OOH).
4.6. 3,4,6-Tri-O-benzyl-2-deoxy-a-D-arabinohexopyranos-
yl hydroperoxide 29
Yield 45%; [a]D = +66.7 (c 0.5, CHCl3); IR (film): m
1
3317.3 (OO–H) cmÀ1; H NMR (500 MHz, CDCl3): d
9.22 (s, 1H, OOH), 5.35 (dd, 1H, J 1.5, 4.7 Hz, H-1),
4.87–4.50 (m, 6H, 3 · Bn), 3.89 (ddd, 1H, J 9.9, 2.1,
5.1 Hz, H-5), 3.78 (ddd, 1H, J 5.1, 11.5, 8.6 Hz, H-3),
3.77 (dd, 1H, J 10.5, 2.1 Hz, H-6a), 3.70 (dd, 1H, J
10.5, 5.1 Hz, H-6b), 3.51 (dd, 1H, J 9.9, 8.6 Hz, H-4),
2.26 (ddd, 1H, J 13.8, 1.5, 5.1 Hz, H-2a), 1.78 (ddd,
1H, J 13.8, 4.7, 11.5 Hz, H-2b); 13C NMR (125 MHz,
CDCl3): d 101.50 (C-1), 77.95 (C-5), 76.72 (C-3), 74.85
(Bn), 73.62 (Bn), 71.83 (Bn), 71.58 (C-4), 69.23 (C-6),
32.49 (C-2); HR-MS/LSIMS-NBA calcd for C27H30-
O6Na (M+Na)+ 473.19401. Found: 473.19489. Anal.
Calcd for C27H30O6: C, 71.98; H, 6.71. Found: C,
72.00; H, 6.86.
4.10. 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-a-D-talohexo-
pyranosyl hydroperoxide 34
Yield 48%; [a]D = +2.1 (c 1.19, CHCl3); IR (film): m 3326
(O–H), 2874, 1061, 698 cmÀ1 1H NMR (500 MHz,
;
4.7. 3,4,6-Tri-O-benzyl-2-deoxy-b-D-arabinohexopyranosyl
hydroperoxide 30
CDCl3): d 9.46 (s, 1H, OOH), 5.19 (br s, 1H, H-1),
4.93–4.44 (m, 6H, 3 · Bn), 4.06 (ddd, 1H, J 7.1, 4.8,
1.8 Hz, H-5), 3.78 (br s, 1H, H-4), 3.76 (dd, 1H, J 9.9,
7.1 Hz, H-6a), 3.65 (dd, 1H, J 5.5, 3.0 Hz, H-3), 3.59
(dd, 1H, J 9.9, 4.8 Hz, H-6b), 2.31 (m, 1H, H-2), 1.29
(d, 3H, J 7.4 Hz, CH3); 13C NMR (125 MHz, CDCl3):
d 106.74 (C-1), 75.85 (C-4), 74.51 (C-3), 74.03 (Bn),
73.70 (Bn), 71.05 (C-5), 70.38 (Bn), 70.28 (C-6), 33.79
(C-2), 12.63 (CH3); 13C NMR (125 MHz, CDCl3): d
106.74 (C-1), 75.85 (C-4), 74.51 (C-3), 74.03 (Bn),
73.70 (Bn), 71.05 (C-5), 70.38 (Bn), 70.28 (C-6), 33.79
(C-2), 12.63 (CH3); HR-MS/ESI calcd for C28H32O6Na
(M+Na)+ 487.2091. Found: 487.2063. Anal. Calcd
for C28H32O6: C, 72.39; H, 6.94. Found: C, 72.31; H,
6.96.
Yield 21%; [a]D = +7.2 (c 0.5, CHCl3); IR (film): m
3352.4 (O-H), 2869.2, 1085.9, 698.3 cmÀ1 1H NMR
;
(500 MHz, CDCl3): d 9.64 (s, 1H, OOH), 5.02 (dd,
1H, J 2.8, 8.7 Hz, H-1), 4.83–4.51 (m, 6H, 3 · Bn),
3.81 (dd, 1H, J 10.6, 4.7 Hz, H-6a), 3.69 (dd, 1H, J
10.6, 1.7 Hz, H-6b), 3.72–3.58 (m, 3H, H-5, H-3, H-4),
2.30 (ddd, 1H, J 12.9, 2.8, 5.4 Hz, H-2a), 1.61 (ddd,
1H, J 12.9, 8.7, 10.1 Hz, H-2b); 13C NMR (125 MHz,
CDCl3): d 102.19 (C-1), 78.15 (C-5), 77.00 (C-3), 74.64
(C-4), 74.60 (Bn), 73.45 (Bn), 71.58 (Bn), 69.15 (C-6),
32.29 (C-2); HR-MS/LSIMS-NBA calcd for C27H30-
O6Na (M+Na)+ 473.19401. Found: 473.19349. Anal.
Calcd for C27H30O6: C, 71.98; H, 6.71. Found: C,
71.69; H, 6.85.
4.11. 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-a-D-gluco-,
b-D-gluco-, a-D-manno- and b-D-mannohexopyranosyl
hydroperoxide 41
4.8. 3,4,6-Tri-O-benzyl-2-deoxy-a-D-lyxohexopyranosyl
hydroperoxide 18
Compound was obtained from 28 according to general
procedure. H NMR (500 MHz, CDCl3) taken for the
1
Yield 75%; [a]D = +32.3 (c 1, CHCl3); IR (film): m 3341.2
(O-H), 2873.3, 1092.9, 698.3 cmÀ1; 1H NMR (500 MHz,
CDCl3): d 9.08 (s, 1H, OOH), 5.41 (d, 1H, J 4.7 Hz,
H-1), 4.92–4.42 (m, 6H, 3 · Bn), 3.97 (m, 1H, H-5),
3.85 (br s, 1H, H-4), 3.72 (ddd, 1H, J 12.4, 4.7,
2.5 Hz, H-3), 3.65 (dd, 1H, J 9.6, 6.6 Hz, H-6a), 3.51
(dd, 1H, J 9.6, 5.6 Hz, H-6b), 2.29 (ddd, 1H, J 13.4,
mixture: a-D-gluco-, (21%) d 9.09 (s, 1H, OOH), 5.18
(d, 1H, J 4.2 Hz, H-1), 2.03 (m, 1H, RJ 36.4 Hz, H-2),
1.10 (d, 1H, J 7.0 Hz, CH3); a-D-manno-, (32%) d 9.22
(s, 1H, OOH), 5.14 (d, 1H, J 1.9 Hz, H-1), 2.03 (m,
1H, RJ 30.0 Hz, H-2), 1.10 (d, 1H, J 7.2 Hz, CH3);
b-D-manno- (3.5%) d 9.52 (s, 1H, OOH), 5.00 (d, 1H,

´
W. Kosnik et al. / Tetrahedron: Asymmetry 16 (2005) 1975–1981
1980
J 2.5 Hz, H-1), 2.49 (m, 1H, RJ 27.0 Hz, H-2), 1.11
(d, 1H, J 6.7 Hz, CH3); b-D-gluco-, (4.5%) d 9.49 (s,
1H, OOH), 4.72 (d, 1H, J 7.8 Hz, H-1), 2.49 (m, 1H,
RJ 36.4 Hz, H-2), 1.11 (d, 1H, J 7.0 Hz, CH3); HR-
MS/ESI taken for the mixture 41 calcd for C28H32O6Na
(M+Na)+ 487.2091. Found: 487.2093.
4.15. 3,5-Di-O-benzyl-2-deoxy-b-D-erythropentofuranosyl
hydroperoxide 39
Yield 27%; [a]D À9.8 (c 0.60, CHCl3); IR (film): m 3369
(O–H), 2866, 1089, 698 cmÀ1 1H NMR (500 MHz,
;
CDCl3): d 9.16 (s, 1H, OOH), 5.61 (br d, 1H, J
5.8 Hz, H-1), 4.61–4.44 (m, 4H, 2 · Bn), 4.30 (m, 1H,
J 5.0, 6.7, 7.2 Hz, H-3), 4.20 (m, 1H, J 4.5, 4.2,
5.0 Hz, H-4), 3.71 (dd, 1H, J 10.3, 4.5 Hz, H-5a), 3.57
(dd, 1H, J 10.3, 4.2 Hz, H-5b), 2.37 (ddd, 1H, J 13.9,
1.3, 7.2 Hz, H-2a), 2.16 (dt, 1H, J 13.9, 5.8, 6.7 Hz, H-
2b); 13C NMR (125 MHz, CDCl3): d 107.44 (C-1),
83.16 (C-4), 78.32 (C-3), 73.46 (Bn), 72.04 (Bn), 70.24
(C-5), 36.70 (C-2); HR-MS/ESI calcd for C19H22O5Na
(M+Na)+ 353.1359. Found: 353.1348. Anal. Calcd for
C19H22O5: C, 69.07; H, 6.71. Found: C, 69.41; H, 6.86.
4.12. 2-Deoxy-3,5-di-O-acetyl-a-D-erythropentofuranosyl
hydroperoxide 35
Yield 34%; IR (film): m 3362 (O–H), 1741 (C@O),
1238 cmÀ1 1H NMR (500 MHz, CDCl3): d 8.88 (s,
.
1H, OOH), 5.67 (dd, 1H, J 6.5, 0.9 Hz, H-1), 5.03
(ddd, 1H, J 7.8, 2.7, 3.4 Hz, H-3), 4.37 (m, 1H, H-4),
4.33 (dd, 1H, J 11.8, 3.5 Hz, H-5a), 4.17 (dd, 1H, J
11.7, 4.6 Hz, H-5b), 2.49 (ddd, 1H, J 14.7, 6.5, 7.8 Hz,
H-2a), 2.09 (s, 3H, Ac), 2.08 (s, 3H, Ac) 1.99 (br d,
1H, J 15.0 Hz, H-2b); 13C NMR (125 MHz, CDCl3): d
170.71 (Ac), 170.60 (Ac), 107.67 (C-1), 81.38 (C-3),
73.34 (C-4), 63.62 (C-5), 35.95 (C-2), 20.88 (Ac), 20.74
(Ac); HR-MS/ESI calcd for C9H14O7Na (M+Na)+
257.0632. Found: 257.0624. Compound 35 did not give
consistent elemental analysis and since contaminations
were found in its NMR spectrum, [a]D was not
provided.
4.16. 2-Deoxy-3,5-di-O-pivaloyl-a-D-erythropentofurano-
syl hydroperoxide 37
Yield 44%; [a]D 95.4 (c 0.73, CHCl3); IR (film): m 3388
(O–H), 2973, 1730 (C@O), 1157 cmÀ1
;
1H NMR
(500 MHz, CDCl3): d 8.69 (s, 1H, OOH), 5.67 (dd,
1H, J 6.3, 1.3 Hz, H-1), 5.05 (ddd, 1H, J 7.7, 2.1,
3.3 Hz, H-3), 4.35 (q, 1H, J 3.6, 3.9, 3.3 Hz, H-4), 4.29
(dd, 1H, J 11.9, 3.6 Hz, H-5a), 4.19 (dd, 1H, J 11.9,
3.9 Hz, H-5b), 2.48 (ddd, 1H, J 15.3, 6.3, 7.7 Hz, H-
2a), 1.97 (dt, 1H, J 15.3, 1.3, 2.1 Hz, H-2b), 1.21 (s,
9H, Piv), 1.20 (s, 9H, Piv); 13C NMR (125 MHz,
CDCl3): d 178.24 (Piv), 178.00 (Piv), 107.82 (C-1),
81.99 (C-3), 73.40 (C-4), 63.62 (C-5), 38.81 (Piv), 38.56
(Piv), 36.18 (C-2), 27.17 (Piv), 26.93 (Piv); HR-MS/ESI
calcd for C15H26O7Na (M+Na)+ 341.1571. Found:
341.1575. Anal. Calcd for C15H26O7: C, 56.59; H, 8.23.
Found: C, 56.85; H, 8.32.
4.13. 2-Deoxy-3,5-di-O-acetyl-b-D-erythropentofuranosyl
hydroperoxide 38
Yield 21%; IR (film): m 3361 (O–H), 1739 (C@O) cmÀ1
;
1H NMR (500 MHz, CDCl3): d 10.05 (s, 1H, OOH),
5.63 (dd, 1H, J 1.7, 6.1 Hz, H-1), 5.09 (ddd, 1H,
J 7.9, 5.6, 3.2 Hz, H-3), 4.71 (dd, 1H, J 11.5, 8.7 Hz,
H-5a), 4.26–4.19 (m, 2H, H-4, H-5b), 2.41 (ddd, 1H, J
14.7, 1.7, 7.9 Hz, H-2a), 2.21 (dt, 1H, J 14.7, 6.1,
5.7 Hz, H-2b), 2.14 (s, 3H, Ac), 2.06 (s, 3H, Ac); 13C
NMR (125 MHz, CDCl3): d 172.55 (Ac), 170.72 (Ac),
108.04 (C-1), 83.96 (C-3), 74.08 (C-4), 65.44 (C-5),
35.88 (C-2), 21.19 (Ac), 20.80 (Ac); DEPT 135
(125 MHz, CDCl3): d 108.04 (C-1), 83.96 (C-3), 74.08
(C-4), 65.44 (C-5), 35.88 (C-2), 21.19 (Ac), 20.80 (Ac);
HR-MS/ESI calcd for C9H14O7Na (M+Na)+ 257.0632.
Found: 257.0639. Compound 38 did not give consistent
elemental analysis and since contaminations were found
in its NMR spectrum, [a]D was not provided.
4.17. 2-Deoxy-3,5-di-O-pivaloyl-b-D-erythropentofurano-
syl hydroperoxide 40
Yield 36%; [a]D = À97.0 (c 0.81, CHCl3); IR (film): m
1
3369 (O–H), 2973, 1731 (C@O), 1154 cmÀ1; H NMR
(500 MHz, CDCl3): d 10.32 (s, 1H, OOH), 5.63 (d, 1H,
J 1.2, 6.1 Hz, H-1), 5.05 (ddd, 1H, J 7.9, 5.8, 3.3 Hz,
H-3), 4.81 (dd, 1H, J 12.1, 9.9 Hz, H-5a), 4.20–4.15
(m, 2H, H-4, H-5b), 2.43 (ddd, 1H, J 14.6, 1.2, 7.9 Hz,
H-2a), 2.20 (dt, 1H, J 14.6, 6.1, 7.9 Hz, H-2b), 1.24 (s,
9H, Piv), 1.20 (s, 9H, Piv); 13C NMR (125 MHz,
CDCl3): d 180.35 (Piv), 178.49 (Piv), 108.07 (C-1),
84.36 (C-3), 73.94 (C-4), 65.62 (C-5), 39.19 (Piv), 38.57
(Piv), 35.95 (C-2), 27.13 (Piv), 27.01 (Piv); HR-MS/ESI
calcd for C15H26O7Na (M+Na)+ 341.1571. Found:
341.1581. Anal. Calcd for C15H26O7: C, 56.59; H, 8.23.
Found: C, 56.81; H, 8.02.
4.14. 3,5-Di-O-benzyl-2-deoxy-a-D-erythropentofuranosyl
hydroperoxide 36
Yield 42%; [a]D 66.2 (c 0.74, CHCl3); IR (film): m 3328
(O–H), 2863, 1095, 698 cmÀ1 1H NMR (500 MHz,
;
CDCl3): d 8.94 (s, 1H, OOH), 5.61 (dd, 1H, J 6.5,
2.1 Hz, H-1), 4.57–4.42 (m, 4H, 2 · Bn), 4.33 (m, 1H,
J 4.4, 3.8, 4.5 Hz, H-4), 4.01 (ddd, 1H, J 7.7, 3.2,
4.4 Hz, H-3), 3.58 (dd, 1H, J 10.6, 3.8 Hz, H-5a),
3.42 (dd, 1H, J 10.6, 4.5 Hz, H-5b), 2.32 (ddd, 1H, J
14.6, 6.5, 7.7 Hz, H-2a), 1.96 (ddd, 1H, J 14.6, 2.1,
4.18. Epoxidation of 43; general procedure18,20
Hydroperoxide 18, 29–31, 34, 36, 37, 39 or 40
(0.103 mM) in toluene (20 mL) was treated with DBU
(16 lL, 0.103 mM). After 10 min at room temperature
the mixture was treated with quinone 43 (molar equiva-
lents, see Table 1) in toluene (10 mL). The progress of
the reaction was monitored by TLC. After the disap-
pearance of quinone, the mixture was washed with
3.2 Hz, H-2b); 13C NMR (125 MHz, CDCl3):
d
107.77 (C-1), 82.85 (C-4), 78.16 (C-3), 73.56 (Bn),
71.67 (Bn), 69.94 (C-5), 35.68 (C-2); HR-MS/ESI calcd
for C19H22O5Na (M+Na)+ 353.1359. Found: 353.1365.
Anal. Calcd for C19H22O5: C, 69.07; H, 6.71. Found:
C, 69.15; H, 6.85.

´
W. Kosnik et al. / Tetrahedron: Asymmetry 16 (2005) 1975–1981
1981
15. Julia, S.; Guixer, J.; Masana, J.; Rocas, J.; Colonna, S.;
Annuziata, R.; Molinari, H. J. Chem. Soc., Perkin Trans.
1 1982, 1317–1324.
water. The water layer was extracted with CH2Cl2
(3 · 15 mL). Organic layers were combined and filtered
through silica gel to afford epoxide 44. Ees were assigned
by chiral HPLC (see above).
16. (a) Adger, B. M.; Barkley, J. V.; Bergeron, S.; Cappi, M.
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Acknowledgements
This work was supported by the State Committee for
Scientific Research Grant No. 3 T09A 024 28.
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