Synthesis of highly oxygenated bicyclo[4.3.0]nonanes from sugar allyltins: model transformations of the adduct derived from the d-mannose

Article abstract of DOI:10.1016/j.tetasy.2008.04.014

Sugar allyltin, a derivative of the d-mannose, was converted in a few well-defined steps into the bicyclic precursor of fully oxygenated hydrindane. Selective transformations of this precursor into the bicyclic derivatives containing the azido functionali

Full text of DOI:10.1016/j.tetasy.2008.04.014

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 1127–1133
Synthesis of highly oxygenated bicyclo[4.3.0]nonanes from sugar
allyltins: model transformations of the adduct derived from the
D-mannose
*
´
Sławomir Jarosz, Anna Błonska and Piotr Cmoch
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warszawa, Poland
Received 26 March 2008; accepted 10 April 2008
Available online 13 May 2008
Abstract—Sugar allyltin, a derivative of the D-mannose, was converted in a few well-defined steps into the bicyclic precursor of fully
oxygenated hydrindane. Selective transformations of this precursor into the bicyclic derivatives containing the azido functionality are
presented. The previously assigned structure of the bicyclic skeleton is also corrected.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
SnBu3
ZnCl2
OH
O
Bu3Sn
Polyhydroxylated carbocyclic compounds are regarded as
sugar mimics.1 Different approaches are used to prepare
such targets, involving mostly transformations of simple
5
5
O
O
BnO
BnO
OMe
O
5
sugars (such as Ferrier-II rearrangement,2 Sinay ‘molecular
¨
2
D-gluco-
OBn
1
D-manno-
D-galacto-
scissors’,3 RCM cyclization of sugar olefins4 and others1).
Much less is known, however, about the synthesis and
properties of the bicyclic analogues, although the backbone
is present in some natural products. For example, a highly
oxygenated decalin skeleton can be found in the structure
of macrolide antibiotics such as nargenicin A, the synthesis
of which in enantiomerically pure form was realized by
Roush.5
140 °C
5
O
O
P
O
5
OMe
OMe
BnO
Ph3P=CHCOR
BnO
BnO
4
3
RCHO
OBn
At the end of 1980s, Herczegh presented a route to poly-
hydroxylated bicyclic derivatives, which was based upon
the standard transformations of simple monosaccharides.6
A convenient route to the racemic, fully oxygenated bicy-
clo[4.3.0]nonanes and bicyclo[4.4.0]decanes was elaborated
by Mehta and Ramesh, who found that such derivatives
possess interesting anti-glucosidase activity.7
OBn
OBn
hydrindane
skeleton
COR
6
R
O
decalin
skeleton
5
OBn
trans from 3
cis only
Over the past decade, we have presented a general ap-
proach to enantiomerically pure polyhydroxylated carbobi-
cyclic compounds, based on the selective transformations
of allyltin derivatives of simple monosaccharides; the idea
cis from
4
Figure 1. Convenient routes to highly oxygenated carbobicyclic deriva-
tives. from sugar allyltins (Ref. 8).
*
is outlined in Figure 1. The synthesis is initiated from the
corresponding dienoaldehydes 3 or 4 (obtained by a
Corresponding author. Tel.: +48 22 343 23 22; fax: +48 22 632 66 81;
e-mail: sljar@icho.edu.pl
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.04.014

1128
S. Jarosz et al. / Tetrahedron: Asymmetry 19 (2008) 1127–1133
controlled fragmentation of the primary 1 or secondary 2
sugar allyltins), which are conveniently converted into the
bicyclic precursors 5 and 6.8
SnBu3
CO2Me
O
H
5
5
O
BnO
BnO
BnO
BnO
5
BnO
BnO
OMe
Appropriate functionalization of the allylic system in these
precursors should afford the fully oxygenated derivatives
including the analogues containing other than oxygen het-
eroatoms. The model study performed on precursors 7 and
8, derived from the D-gluco-configurated sugar allyltin 1,
allowed us to obtain configurationally different products
resulting from the oxidation of the double bond.8,9 We also
succeeded in the functionalization of the allylic position in
these precursors,10 although standard methods such as
LDA-catalyzed isomerization of the corresponding epox-
ides failed11 (Fig. 2).
OBn
OBn
10
OBn
11
9
D-manno
H
1
5
6
H
S
BnO
Me
R
CO2
9
H
BnO
CO2Me
7
H
S
OBn
BnO
OBn
12
BnO
correct structure
13
previously assigned structure
not correct
OBn
H
H
1
5
H
OBn
OBn
OBn
6
BnO
9
7
BnO
CO2Me
H
H
OBn
BnO
H
OBn
BnO
R
O
14
8
7
Figure 3. The assignment of the configuration of the main product of the
cyclization of triene 11.
Figure 2. Decalin (7) and hydrindane (8) precursors obtained from the D-
gluco-configurated sugar allyltin 1.
Table 1. The 1H and 13C NMR chemical shifts for 14 in CDCl3 solution at
303 K
Herein we report the functionalization of the hydrinadane
skeleton of the precursor obtained from the D-manno-con-
figurated sugar allyltin 9.
1H/13C resonances Chemical shift (ppm.)
H1/C1
2.92 (m)/43.1
H2/C2
H3/C3
5.89 (dd) [1.6, 10.0 Hz]/126.2
5.66 (m)/127.7
2. Results and discussion
H4a,H4e/C4
H5/C5
2.02 (m), 2.30 (m)/29.9
2.34 (m)/34.1
3.27 (dd) [6.2, 9.1 Hz], 3.40 (dd) [3.9, 9.1 Hz]/73.2
1.78 (ddd) [3.3, 11.1, 14.2 Hz]/44.3
4.04 (t)/77.6
2.1. Determination of the configuration of the IMDA product
of 11
H50,H500/C50
H6/C6
H7/C7
In 1997, we reported on the selective intramolecular Diels–
Alder (IMDA) reaction of trienes originated from sugar
allyltins, derived from three simple monosaccharides: D-
glucose, D-mannose, and D-galactose.12 The (1S,5R,6R)-
configuration was assigned to the main stereoisomer of
the Diels–Alder cyclization of triene 11 (12: originated
from the D-manno-allyltin 9). However, subsequent studies
on the functionalization of this bicyclic adduct indicated
that the assignment based on the NOE (6%) between the
H-6 and H-9 protons was not correct. The diagnostic sig-
nals of the H-9 and H-7 protons were observed almost at
the same field (d 3.72 and 3.75) and the NOE effect was as-
signed incorrectly to the H-9 and not to H-7.12
H8/C8
H9/C9
–OCH2Ph at C50
–OCH2Ph at C7
–OCH2Ph at C8
–OCH2Ph at C9
3.96 (dd) [2.1, 4.6 Hz]/90.3
3.99 (dd) [2.1, 6.7 Hz]/83.0
4.36 (d), 4.44 (d) [12.1 Hz]/73.0
4.40 (d), 4.80 (d) [11.6 Hz]/73.7
4.57 (dd)/72.2
4.53 (s)/71.5
the 2D gradient-selected HSQC and HMBC experiments
and are collected in Table 1. Knowing the assignments of
1
the H NMR signals (Table 1), five protons (H1, H2, H3,
one of H4, and H6) were chosen and irradiated in the
NOE differential experiment.
A comprehensive NMR study performed on derivative 14
(prepared from the main adduct of the IMDA reaction of
11 by standard methods) indicated that the (1R,5S,6S)-
configuration should be assigned to the main product of
cyclization of triene 11, that is, compound 13 (not 12)
was formed in this intramolecular Diels–Alder reaction
(Fig. 3).
The strongest NOE effects observed in the NOE differential
spectra were for H1, H2, and H6 protons, which is pre-
sented in Figure 4. Irradiation of the hydrogen H2 led to
the observation of the NOE at H1 (4.0%), H9 (1.1%),
and H3 (7.0%). Irradiation of the H1 proton resulted in
the following NOE effects: H9 (9.0%) and H2 (4.0%),
whereas after saturation of the H6 proton, the NOE effects
were observable only at H7 (3.5%) and H8 (3.5%). Analysis
of the above-mentioned NOE effects observed for 14, con-
firmed the trans-configuration of H1 and H6 protons as
presented in Figure 4.
The assignment of the relative configuration of the protons
in 14 was carried out by the analysis of different NMR
experiments taken in CDCl3. The correct 1H and 13C
NMR chemical shift assignments were possible based on

S. Jarosz et al. / Tetrahedron: Asymmetry 19 (2008) 1127–1133
1129
1.1%
4.0%
9.0%
H
4.0%
H
H
H
H
7.0%
BnO
BnO
H
H
H
H
H
BnO
BnO
H
H
BnO
BnO
H
BnO
H
H
9
1
CH2OBn
3.5%
6
H
H
BnO
H
BnO
H
H
3.5%
CH2OBn
H
CH2OBn
Figure 4. The 1H NMR NOE effects for 14.
Further confirmation of the relative stereochemistry of the
bicyclic scaffold came from the spectra of the products of
its transformations, that is, compounds 17–21 (Fig. 5). In
all the spectra, the respective NOE cross peaks between
H1–H9, H1–H5, and H6–H7 (and/or H8) were observed.
epoxide. Consequently the main product 15 was assigned
as (2R,3S)-configuration.
Opening of the epoxide ring in 15 with sodium azide under
standard conditions (THF, aq EtOH, NaN3) provided
three products. Two of them, 17 and 18, proved to be the
corresponding azides. The third product isolated from this
reaction turned to be the trans-diol to which structure 19
was assigned; it was identical in all respect to the main ste-
reoisomer formed in the reaction of 15 with water under
acidic conditions.
NOESY
RO
H
RO
H
H
H
H
H
H
1
RO
RO
9
6
5
H
H
H
OR
15, 16
RO
RO
OR
17-21
The structure of the main stereoisomeric azide 17 was
established on the basis of the NMR experiments per-
formed on its acetate 17-Ac (see Fig. 6).
Figure 5. The NOESY correlations in the bicyclic scaffold.
1
The signal resonating at the lowest field in the H NMR
2.2. Functionalization of the bicyclic skeleton in 14
spectrum of 17-Ac (d 4.98 ppm) correlated to two high field
H-4 protons (d 1.81 and 1.63 ppm) and to the signal at d
71.39 ppm in the 13C NMR spectrum, which strongly indi-
cated at the presence of the acetoxyl group at the C-3 posi-
tion. Therefore, the opening of the three-membered ring
had to occur at the C-2 position, thus yielding compound
17. This was proved further by the occurence of the cross
peak between the H1 and H2 in the NOESY spectrum,
which indicated the cis-arrangement of these protons. Con-
sequently the alternative derivative resulting from the
opening of the three-membered ring at the C-3 position
had the structure depicted by formula 18.
Functionalization of the bicyclic skeleton leading to the
fully oxygenated derivatives can be performed by the oxi-
dation of the C-4 position followed by the oxidation of
the C2–C3 double bond. Since the direct allylic oxidation
in such complex derivatives proved not to be possible, this
goal can be realized by the transformation of the corre-
sponding epoxides (prepared from the parent olefin) either
by their conversion into the allylic alcohols (via opening of
the three-membered ring with the selenide anion followed
by oxidative work-upà), or by opening of the three-mem-
bered ring with a suitable nucleophile and further transfor-
mation of the product(s). Herein we report the synthesis
and functionalization of the carbobicyclic skeleton 14
derived from the D-mannose, which should open a con-
venient route to bicyclic derivatives with the amino func-
tionalities (Scheme 1).
Opening of the three-membered ring in the second epoxide
16 was highly regioselective and afforded only one azido-
alcohol to which structure 21 was assigned on the basis
of the NMR data. The signal of the carbon atom connected
to the azido function (d 61.09 ppm) correlated to the pro-
ton resonance occurring at d 3.84, which displayed the
cross peaks to both H-4 (d 1.73 ppm) in the COSY spec-
trum. Therefore, the opening of the oxirane ring occurred
at the C-3 position. This was further confirmed by the cross
peak in the NOESY spectrum between the H1 and H2 pro-
tons in 21 (see Fig. 6).
Standard epoxidation of olefin 14 with m-chloroperbenzoic
acid afforded two epoxides 15 and 16 in 88% yield and in a
5:4 ratio. The configuration of these products was assigned
from the advanced NMR experiments. The NOE cross
peaks between the H1 and H2 in the spectrum of the minor
epoxide 16 indicated a cis-arrangement of these two pro-
tons, thus confirming the (2S,3R)-configuration of this
The opening of the oxirane ring in either in 15 or 16 with
the oxygen nucleophile provides two distereoisomeric
trans-diols 19 and 20. Reaction of the main epoxide 15 with
water catalyzed by acid provided both trans-diols 19 and 20
in a 2:1 ratio. Reaction of the minor epoxide 16 under the
same conditions furnished only one diol 19. The structure
of 19 and 20 was assigned from the NMR spectra of these
diols. In the NOESY spectrum of 19, the cross peak
Similar to 14, the bicyclic compound derived from the D-gluco-configu-
rated allyltin did not undergo such an oxidation under a variety of
conditions (see Ref. 11).
à This strategy was successfully applied to the functionalization of
configurationally different carbobicycles derived from sugar allyltins;
see Ref. 10.

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S. Jarosz et al. / Tetrahedron: Asymmetry 19 (2008) 1127–1133
OH
O
BnO
BnO
BnO
H
BnO
BnO
H
H
1
OH
+
9
BnO
ii.
5
6
N3
H
BnO
+
BnO
H
BnO
BnO
BnO
N3
H
19 (14%)
OBn
15 (49%)
17 (22%)
18(14%)
BnO
BnO
H
OH
BnO
BnO
OH
i.
H
iii.
14
OH
+
H
BnO
BnO
H
BnO
BnO
HO
NOESY
19 (61%)
20 (28%)
H
H
BnO
BnO
N3
BnO
BnO
H
ii.
O
19 (65%)
BnO
H
OBn
H
BnO
BnO
HO
21 (67%)
16 (39%)
iii.
Scheme 1. Reagents and conditions: (i) MCPBA, CH2Cl2, rt, 2 h; (ii) THF, aqueous EtOH, NaN3, reflux, 20 h; (iii) aqueous acetone, HClO4 (cat.), 0 °C,
30 min.
NOESY
OAc
NOESY
N3
NOESY
OH
BnO
BnO
BnO
BnO
BnO
H
H1
H
H
H
H
9
BnO
3
5
4
H
BnO
H
BnO
BnO
H
BnO
BnO
BnO
HO
N3
HO
19
17-Ac
21
C-3 δ = 61.09 ppm. correlation
to H-3 (3.84 ppm);
C-2 δ = 60.34 ppm. correlation
to H-2 (3.84 ppm);
H3 δ = 3.84 ppm; COSY to
both H4 (1.73 ppm)
H3 δ = 4.98 ppm; COSY to
both H4 (1.81, 1.63 ppm)
Figure 6. Assignment of the configuration of the products resulting from the opening of the oxirane ring.
between the H-1 and H-2 protons could be seen, while in
the isomeric diol 20, such a correlation is not possible.
We have observed such a correlation between the H1 and
H2 protons in the product resulting from the opening of
epoxide 16 with water; thus the structure 19 can be safely
assigned to this isomer.
bicyclic derivative with the (1R,5S,6S)-configuration. The
functionalization of the double bond was realized by epox-
idation followed by the opening of the three-membered
ring either with oxygen or nitrogen nucleophiles.
4. Experimental
4.1. General
Opening of the epoxide ring in 16 was highly selective and
gave products azido-alcohol 21 or diol 19, the stereochem-
istry of which could be predicted by the well-known Furst-
¨
Plattner rule of the trans diaxial opening of the three-mem-
bered ring in cyclohexane derivatives.13 We were, however,
surprised that significant amounts of the trans-diequatorial
products 18 and 20 were formed in the reaction of epoxide
15 with nucleophiles. We believe that this is due to the ste-
ric factors, since the C-2 position from ‘the bottom part’ is
shielded by the neighboring five-membered ring.
The NMR spectra were recorded in CDCl3 at 303 K with a
Bruker DRX Avance 500 spectrometer equipped with a
TBI 50SB H-C/BB-D-05 Z-G probehead, operating at
500.133 and 125.773 MHz for 1H and 13C, respectively
(internal Me4Si). The assignment of the 1H and 13C
NMR signals was made using the results of the 2D meth-
1
ods including COSY, H–13C gradient-selected heteronu-
clear single quantum correlation (HSQC), heteronuclear
multi bond correlation (HMBC), and DEPT. The relative
configurations of the protons were determined based on
NOESY and/or NOE differential experiments. The 1H-
and 13C-aromatic resonances occurring at the typical d val-
ues were omitted for simplicity. Mass spectra were
3. Conclusion
The intramolecular Diels–Alder reaction of triene 11 de-
rived form the D-mannose provided, as the major product,

S. Jarosz et al. / Tetrahedron: Asymmetry 19 (2008) 1127–1133
1131
recorded with an ESI/MS Mariner (PerSeptive Biosystem)
mass spectrometer. Optical rotations were measured with a
Digital Jasco polarimeter DIP-360 (k = 589 nm) for solu-
tions in CHCl3 (c 1) at room temperature. Column chro-
matography was performed on silica gel (Merck, 70–230
or 230–400 mesh). Methylene chloride was distilled from
CaH2 and THF from potassium prior to use. Organic solu-
tions were dried over anhydrous magnesium sulfate.
J5,6 10.9, H-6); 13C NMR: d 89.90 (C-8), 82.62 (C-9),
76.48 (C-7), 73.61, 72.91, 72.32, 71.46 (4 ꢀ OCH2Ph),
71.88 (CH2OBn), 53.43 (C-3), 52.77 (C-2), 43.15 (C-6),
42.94 (C-1), 31.43 (C-5), 28.61 (C-4). NOESY (diagnostic):
H-1/H-9, H-6/H-7, and/or H-8.
4.5. (1S,2S,3R,5R,6R,7R,8R,9R)-7,8,9-Tri-O-benzyl-2,3-
epoxy-5-benzyloxymethyl-bicyclo[4.3.0]nonane 16
4.2. (1R,5R,6R,7R,8R,9R)-7,8,9-Tri-O-benzyl-5-benzyl-
oxymethyl-bicyclo[4.3.0]non-2-ene 14
[a]D = +35.3 (c 1, CHCl3); HRMS m/z: 599.2773 [C38H40-
1
O5Na (M+Na+) requires 599.27680]; H NMR: d 4.27–
4.87 (8H, 4 ꢀ OCH2Ph), 4.14 (dd, J8,9 2.8, J1,9 7.1, H-9),
3.91–3.94 (2H, m, H-7 and H-8), 3.7 (d, J2,3 4.1, H-2),
3.26 (dd J 4.2, Jgem 9.0, one of CH2OBn), 3.11 (dd, J 6.8,
one of CH2OBn), 3.08 (dd, J3,4eq 4.7, H-3), 2.67 (dd, J1.6
12.9, H-1), 2.14 (m, Heq-4), 2.00 (m, H-5), 1.86 (m, H-6),
1.78 (dd, J4,5 10.6 Jgem 15.6, Hax-4); 13C NMR: d 83.11
(C-9), 90.49 and 77.46 (C-7 and C-8), 73.61, 72.98, 72.85,
72.30, 71.75 (4 ꢀ OCH2Ph and CH2OBn), 52.65 (C-2),
50.25 (C-3), 43.99 (C-1), 39.07 (C-6), 32.98 (C-5), 27.30
(C-4). NOESY (diagnostic): H-1/H-2, H-1/H-9, H-3/Heq-
4, H-6/H-7, and/or H-8.
To a stirred suspension of LiAlH4 (1.5 equiv, 3.62 mmol,
137.4 mg) in dry THF (10 mL) under an argon atmosphere,
a solution of ester 1313 (1.2 g, 2.41 mmol) in THF (5 mL)
was added dropwise at 0 °C. After 20 min, the cooling bath
was removed and stirring was continued at rt for another
2 h. The excess of hydride was decomposed by the careful
addition of water and the mixture was partitioned between
5% H2SO4 (10 mL) and ethyl acetate (15 mL). The organic
layer was separated, washed with water, dried, and concen-
trated to afford the crude alcohol (963 mg, 85%), which was
used in the next step without further purification.
To a vigorously stirred solution of this alcohol (456 mg,
0.97 mmol) in CH2Cl2 (30 mL), THF (10 mL), and aque-
ous 50% NaOHaq (20 mL), benzyl chloride (10 equiv,
9.70 mmol, 1.11 mL) was added, followed by tetrabutyl-
ammonium bromide (1 equiv, 0.97 mmol, 312 mg). After
48 h of vigorous stirring, the mixture was partitioned
between water (30 mL) and CH2Cl2 (40 mL), the organic
phase was separated, washed with water until neutrality
and the aqueous one was extracted twice with CH2Cl2.
Combined organic layers were dried, and concentrated,
and the product was purified by column chromatography
(hexane–ethyl acetate, 98:2) to afford 14 as an amorphous
solid (418 mg, 77%). [a]D = +46.2; HRMS m/z: 583.28072
[C38H40O4Na (M+Na+) requires 583.28188]. The NMR
data are presented in Table 1.
4.6. Reaction of epoxide 15 with sodium azide
To a solution of epoxide 15 (105 mg, 0.182 mmol) in THF
(3.5 mL), ethanol (10 mL), and water (3 mL), NaN3
(1.25 mmol, 81 mg) and NH4Cl (1.55 mmol, 83 mg) were
added, and the mixture was boiled under reflux for 20 h.
It was then cooled to rt, diluted with AcOEt (10 mL),
washed with water (10 mL), and brine, dried, concentrated,
and the products were isolated by column chromatography
(hexane–ethyl acetate, 92:8, 84:16, and then 60:40) to afford
18 (16 mg, 14%), 17 (25 mg, 22%), and diol 19 (15 mg,
14%).
4.7. Reaction of epoxide 16 with sodium azide
To a solution of epoxide 16 (62 mg, 0.108 mmol) in THF
(2 mL), ethanol (4 mL), and water (0.5 mL), NaN3
(1.3 equiv, 0.140 mmol, 9 mg), and NH4Cl (1.5 equiv,
0.170 mmol, 9 mg) were added, and the mixture was boiled
under reflux for 20 h. Then it was cooled to rt, diluted with
AcOEt (10 mL), washed with water (4 mL), and brine,
dried, concentrated, and the product 21 (45 mg, 67%) was
isolated by column chromatography (hexane–ethyl acetate,
96:4).
4.3. Epoxidation of compound 14
To a solution of olefin 14 (1 g, 1.78 mmol) in CH2Cl2
(30 mL), MCPBA (55%, 1.3 equiv, 730 mg) was added
and the mixture was stirred for 2 h at room temperature.
Then it was diluted with CH2Cl2 (15 mL), washed with
2% aq NaOH, water, and brine. The organic phase was
dried, and concentrated, and the products were isolated
by column chromatography (hexane–ethyl acetate, 96:4
and then 9:1). Isolated first was epoxide 15 (503 mg,
49%) and then 16 (402 mg, 39%).
4.8. Reaction of epoxide 15 with water
4.4. (1S,2R,3S,5R,6R,7R,8R,9R)-7,8,9-Tri-O-benzyl-2,3-
epoxy-5-benzyloxymethyl-bicyclo[4.3.0]nonane 15
To a cooled to 0 °C solution of 15 (70 mg, 121.4 lmol) in
acetone (10 mL) and water (0.5 mL), HClO4 (3 drops of
a 35% solution in water) was added, and the mixture was
stirred for 30 min at 0 °C. Then it was quenched with aque-
ous Na2CO3 and the mixture was partitioned between
water (10 mL) and AcOEt (15 mL). The organic phase
was separated, dried, concentrated, and the products were
isolated by column chromatography (hexane–ethyl acetate,
84:16 and 36:24) to afford 19 (44 mg, 61%) and 20 (20 mg,
28%).
[a]D = +43.9 (c 1, CHCl3); HRMS m/z: 599.27527 [C38H40-
1
O5Na (M+Na+) requires 599.27680]; H NMR: d 4.29–
4.80 (8H, 4 ꢀ OCH2Ph), 4.11 (dd, J8,9 1.8, J1,9 7.0, H-9),
3.92 (m, H-8), 3.91 (m, H-7), 3.46 (d, J2,3 3.9, H-2), 3.27
(2H, ꢁd, CH2OBn), 3.18 (m, H-3), 2.42 (dd, J1,6 13.9,
H-1), 2.24 (dd, J4,5 4.8, Jgem 15.0, Heq-4), 1.89 (m, H-5),
1.74 (ddd, J3,4 2.5, J4,5 11.4, Hax-4), 1.54 (ddd,J6,7 3.0,

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S. Jarosz et al. / Tetrahedron: Asymmetry 19 (2008) 1127–1133
4.9. Reaction of epoxide 16 with water
(C-5), 31.40 (C-4). NOESY (diagnostic): H-1/H-2, H-1/
H-5, H-1/H-9, H-6/H-7, H-6/H-8.
Reaction of epoxide 16 (40 mg, 0.07 mmol) under the same
conditions as described in Section 4.8. afforded diol 19 in
65% yield.
4.10.4. (1S,2R,3R,5R,6R,7R,8R,9R)-2,3-Di-hydroxy-7,8,9-
tri-O-benzyl-5-benzyloxymethyl-bicyclo[4.3.0]nonane
20.
[a]D = +33.8 (c 1, CHCl3); HRMS m/z: 617.28769
1
[C38H42O6Na (M+Na+) requires 617.28736]. H NMR: d
4.10. Characteristics of the products of the ring opening
reactions of epoxides 15 and 16
4.44–4.76 (8H, 4 ꢀ OCH2Ph), 4.12 (dd, J8,9 3.0, J1,9 7.5,
H-9), 3.99 (ꢁt, H-7), 3.91 (ꢁt, H-8), 3.60 (ꢁt, H-2), 3.54
(ddd, J3,4eq 4.4, J2,3 8.7, J3,4ax 12.6, H-3), 3.29 (dd, J 4.4,
Jgem 9.1, one of CH2OBn), 3.19 (dd, J 5.9, one of
CH2OBn), 2.24 (ddd, J1,2 10.4, J1,6 13.2, H-1), 2.10 (ddd,
J3,4eq = J4eq,5 4.3, Jgem 12.7, Heq-4), 2.02 (m, H-5), 1.63
(ddd, J6,7 3.2, J5,6 10.9, H-6), 1.30 (m, Hax-4); 13C NMR:
d 90.17 (C-8), 81.91 (C-9), 70.01 (C-7), 74.78 and 74.72
(C-2 and C-3), 73.57, 73.10, 72.25, 71.50 (4 ꢀ OCH2Ph),
72.47 (CH2OBn), 47.59 (C-1), 45.45 (C-6), 35.91 (C-4),
34.56 (C-5).
4.10.1. (1S,2S,3S,5R,6R,7R,8R,9R)-2-Azido-2-deoxy-3-hydr-
oxy-7,8,9-tri-O-benzyl-5-benzyloxymethyl-bicyclo[4.3.0]non-
ane 17. [a]D = +6.5 (c 1, CHCl3); HRMS m/z: 642.29110
[C38H41N3O5Na (M+Na+) requires 642.29384].
This compound was characterized further as the acetate:
1H NMR: d 4.98 (dd, J2,3 3.0, J3,4 6.3, H-3), 4.35–4.75
(8H, 4 ꢀ OCH2Ph), 4.18 (dd, J8,9 5.2, J1,9 9.3, H-9), 3.98
(ꢁt, H-7), 3.88 (dd, J7,8 3.6, H-8), 3.84 (ꢁt, H-2), 3.25
(dd, J 4.3, Jgem 9.1, one of CH2OBn), 3.14 (dd, J 6.1, one
of CH2OBn), 2.60 (ddd, J1,2 2.3, J1,6 13.1, H-1), 2.10 (m,
H-5), 2.04 (3H, s, CH3CO), 1.92 (ddd, J6,7 3.0, J5,6 8.8,
H-6), 1.81 (m, one of H-4), 1.63 (ddd, J4,5 12.6, Jgem
15.0, one of H-4); 13C NMR: d 169.97 (CH3CO), 91.04
(C-8), 82.51 (C-9), 76.52 (C-7), 73.41, 73.16, 72.53, 72.37
(4 ꢀ OCH2Ph and CH2OBn), 71.39 (C-3), 60.34 (C-2),
40.84 (C-1), 40.34 (C-6), 32.87 (C-5), 28.85 (C-4), 21.33
(CH3CO); IR m cmꢂ1 (film): 2114 (strong, –N@N@N).
NOESY (diagnostic): H-1/H-2, H-1/H-5, H-1/H-9, H-6/
H-7, H-6/H-8.
NOESY (diagnostic): H-1/H-3, H-1/H-9, H-2/Hax-4, H-2/
H-6, H-3/Heq-4, H-3/H-5, H-6/Hax-4, H-6/H-7, H-6/H-8.
4.10.5. (1S,2S,3S,5R,6R,7R,8R,9R)-3-Azido-3-deoxy-2-hydr-
oxy-7,8,9-tri-O-benzyl-5-benzyloxymethyl-bicyclo[4,3,0]-
nonane 21. [a]D = ꢂ7.4 (c 1, CHCl3); HRMS m/z:
642.29403 [C38H41N3O5Na (M+Na+) requires 642.29384].
1H NMR: d 4.28–4.67 (8H, 4 ꢀ OCH2Ph), 4.17 (dd, J8,9
3.6, J1,9 8.2, H-9), 4.06 (m, H-2), 3.96 (ꢁt, H-7), 3.78 (ꢁt,
H-8), 3.73 (m, H-3), 3.22 (dd, J 4.4, Jgem 9.2, one of
CH2OBn), 3.14 (dd, J 5.7, one of CH2OBn), 2.46 (ddd,
J1,2 1.4, J1,6 13.6, H-1), 2.07 (m, H-5), 1.95 (m, H-6), 1.73
(2H, m, both H-4); 13C NMR: d 90.25 (C-8), 85.60 (C-9),
76.66 (C-7), 73.55, 73.02, 72.27, 72.07 (4 ꢀ OCH2Ph),
72.67 (CH2OBn), 68.54 (C-2), 61.09 (C-3), 41.40 (C-1),
39.74 (C-6), 32.26 (C-5), 28.00(C-4). NOESY (diagnostic):
H-1/H-2, H-1/H-5, H-1/H-9, H-6/H-7, H-6/H-8.
4.10.2.
(1S,2R,3R,5R,6R,7R,8R,9R)-3-Azido-3-deoxy-2-
hydroxy-7,8,9-tri-O-benzyl-5-benzyloxymethyl-bicyclo[4.3.0]-
nonane 18. [a]D = +23.7 (c 1, CHCl3); HRMS m/z:
642.291460
[C38H41N3O5Na
(M+Na+)
requires
642.29384]. 1H NMR: d 4.33–4.78 (8H, 4 ꢀ OCH2Ph),
4.12 (dd, J8,9 2.8, J1,9 7.2, H-9), 3.95 (ꢁt, H-7), 3.90 (ꢁt,
H-8), 3.66 (ꢁt, H-2), 3.32 (ddd, J3,4eq 4.7, J2,3 9.3, J3,4ax
13.9, H-3), 3.28 (dd, J 4.0, Jgem 9.1, one of CH2OBn),
3.15 (dd, J 6.1, one of CH2OBn), 2.25 (ddd, J1,2 10.6, J1,6
17.9 H-1), 2.14 (m, one of H-4), 2.01 (m, H-5), 1.60 (m,
H-6), 1.32 (m, one of H-4); 13C NMR: d 89.87 (C-8),
81.77 (C-9), 76.87 (C-7), 73.65, 73.15, 72.29, 71.92, and
71.68 (4 ꢀ OCH2Ph and CH2OBn), 73.03 (C-2), 65.91 (C-
3), 48.36 (C-1), 44.72 (C-6), 34.93 (C-5), 33.67 (C-4); IR m
cmꢂ1 (film): 2100 (strong, –N@N@N). NOESY (diagnos-
tic): H-1/H-3, H-1/H-5, H-1/H-9, H-2/H-6, H-3/H-5, H-
6/H-7.
Acknowledgment
This work was financed by the Grant No. PBZ-KBN-126/
T09/07 from the Ministry of Science and Higher
Education.
References
1. Selected recent reviews and papers: Arjona, A.; Gomez, A.
M.; Lopez, J. C.; Plumet, J. Chem. Rev. 2007, 107, 1919;
Long, M.; Ziegler, Th. Eur. J. Org. Chem. 2007, 768; Zhou,
J.; Wang, G.; Zhang, L.-H.; Ye, X.-S. Curr. Org. Chem. 2006,
10, 625; Podeschwa, M. A. L.; Plettenburg, O.; Altenbach,
H.-J. Eur. J. Org. Chem. 2005, 3101, and 3116; Freeman, S.;
Hudlicky, T. Bioorg. Med. Chem. Lett. 2004, 14, 1209, and
references cited therein.
4.10.3. (1S,2S,3S,5R,6R,7R,8R,9R)-2,3-Di-hydroxy-7,8,9-
tri-O-benzyl-5-benzyloxymethyl-bicyclo[4.3.0]nonane
19.
[a]D = ꢂ1.3 (c 1, CHCl3); HRMS m/z: 617.28444
1
[C38H42O6Na (M+Na+) requires 617.28736]. H NMR: d
4.38–4.75 (8H, 4 ꢀ OCH2Ph), 4.26 (dd, J8,9 3.8, J1,9 8.3,
H-9), 4.12 (ꢁt, H-2), 4.05 (ꢁt, H-7), 3.92 (dd, J1,2 2.9,
J3,4 6.0, H-3), 3.86 (ꢁt, H-8), 3.32 (dd, J 4.7, Jgem 9.1,
one of CH2OBn), 3.24 (dd, J 6.0, one of CH2OBn), 2.65
(ddd, J1,2 2.0, J1,6 13.7, H-1), 2.25 (m, H-5), 2.00 (ddd,
J6,7 3.0, J5,6 10.9, H-6), 1.71–1.74 (2H, m, both H-4); 13C
NMR: d 90.52 (C-8), 85.80 (C-9), 76.91 (C-7), 73.47,
73.30, 73.04, 72.19, 72.01 (4 ꢀ OCH2Ph and CH2OBn),
70.39 (C-2), 69.59 (C-3), 41.14 (C-1), 40.13 (C-6), 31.63
2. Ferrier, R. J.; Middleton, S. Chem. Rev. 1993, 93, 2779.
3. Sollogub, M.; Millet, J.-M.; Sinay, P. Angew. Chem., Int. Ed.
¨
2000, 39, 362.
4. Jorgensen, M.; Hadwiger, P.; Madsen, R.; Stutz, A. E.;
¨
Wrodnigg, T. M. Curr. Org. Chem. 2000, 4, 565; microreview:
Madsen, R. Eur. J. Org. Chem. 2007, 399.
5. Roush, W. R.; Koyama, K.; Curtin, M. L.; Moriarty, K. J. J.
Am. Chem. Soc. 1996, 118, 7502.

S. Jarosz et al. / Tetrahedron: Asymmetry 19 (2008) 1127–1133
1133
´
6. Herczegh, P.; Zsely, M.; Szilagy, L.; Bajza, I.; Kovacs, A.;
Batta, G.; Bognar, R. In Cycloaddition Reactions in Carbo-
hydrate Chemistry; Guliano R. M. Ed.; ACS Symposium
Series; 1992; Vol. 494, p 112.
7. Mehta, G.; Ramesh, S. S. Can. J. Chem. 2005, 83, 581;
Mehta, G.; Ramesh, S. S. Tetrahedron Lett. 2001, 42, 1987;
Mehta, G.; Ramesh, S. S. Chem. Commun. 2000, 2429.
8. Microreview: Jarosz, S.; Gaweł, A. Eur. J. Org. Chem. 2005,
3415.
9. Jarosz, S.; Skora, S. Tetrahedron: Asymmetry 2001, 12, 1651.
´
10. Jarosz, S.; Nowogrodzki, M. J. Carbohydr. Chem. 2006, 25,
139.
11. Jarosz, S.; Boryczko, B.; Cmoch, P.; Gomez, A. M.; Lopez,
C. Tetrahedron: Asymmetry 2005, 16, 513.
12. Jarosz, S.; Kozłowska, E.; Jezewski, A. Tetrahedron 1997, 53,
_
10775.
13. Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic
Compounds; Wiley-Interscience: New Yoork, 1994, p 730.