Sugar allyltins in the synthesis of carbohydrate mimics. Study on the cis-hydroxylation of the bicyclo[4.3.0]nonenes derived from d-mannose

Article abstract of DOI:10.1016/j.tetasy.2009.11.008

Sugar allyltin derivatives were applied in the synthesis of highly oxygenated hydrindane system. The transformation of organometallic derived from d-mannose into two diastereoisomeric bicyclo[4.3.0]nonenes with the trans geometry between both the rings wa

Full text of DOI:10.1016/j.tetasy.2009.11.008

Tetrahedron: Asymmetry 20 (2009) 2728–2732
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Sugar allyltins in the synthesis of carbohydrate mimics. Study
on the cis-hydroxylation of the bicyclo[4.3.0]nonenes derived from D-mannose
*
´
Anna Błonska, Piotr Cmoch, Sławomir Jarosz
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, 01-224 Warszawa, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Sugar allyltin derivatives were applied in the synthesis of highly oxygenated hydrindane system. The
transformation of organometallic derived from D-mannose into two diastereoisomeric bicyclo[4.3.0]non-
enes with the trans geometry between both the rings was realized in a few well-defined steps. The func-
tionalization of these synthons provided a wide range of polyhydroxylated hydrindane derivatives. The
stereochemical aspects of these processes are discussed.
Received 5 October 2009
Accepted 13 November 2009
Available online 7 December 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
The transformation of these precursors into fully hydroxylated
decalins and perhydroindanes requires the oxidation of the allylic
Polyhydroxylated derivatives of cyclopentane and cyclohexane
possess a broad range of biological activity.1 These extremely
important compounds are available via a number of methods
including Ferrier-II rearrangement,2 Sinaÿ ‘molecular scissors’,3
RCM cyclization of sugar olefins,4 and many others.1
Much less is known about the synthesis and biological proper-
ties of the bicyclic system, although such a backbone is present
in selected natural products. For example, a highly oxygenated
decalin skeleton can be found in the structure of macrolide antibi-
otics such as nargenicin A, the synthesis of which in enantiomeri-
cally pure form was realized by Roush in 1996.5 Herczegh
presented a route to polyhydroxylated bicyclic derivatives based
on standard transformations of simple monosaccharides.6 A conve-
nient route to fully oxygenated bicyclo[4.3.0]nonanes and bicy-
clo[4.4.0]decanes was elaborated by Mehta and Ramesh, who
also found that such derivatives possess interesting anti-glucosi-
dase activity.7
position, oxidation of the double bond, and oxidative cleavage of
the exo C–C bond (Fig. 1). Herein we report a study directed to
the synthesis of carbobicyclic sugar mimics from D-mannose.
OH
O
SnBu3
5
BnO
BnO
OMe
O
5
OBn
1
ZnCl2
oxidation
sugar
mimics
Ph3P=CHCOR
O
5
deprotection
COR
Over the past few years, we have described a convenient method-
ologyforthepreparationof polyhydroxylatedenantiomericallypure
bicyclic systems from sugar allyltins, which was based on a con-
trolled fragmentation of organometallics 1 into dienoaldehydes 2.
Proper functionalization of highly reactive intermediates 2 pro-
vided either bicyclo[4.3.0]nonene or bicyclo[4.4.0]decene deriva-
BnO
oxidative
cleavage
2
3
OBn
hydrindane skeleton (trans)
OBn
tives
3
or 5, respectively (Fig. 1).8 Starting from different
-glucose, -mannose, -galactose, pre-
OBn
OBn
RCHO
PTC
O
O
monosaccharides such as:
D
D
D
OMe
cursors 3 and 5 with different configurations are available.
P
OMe
R
O
5
4
BnO
* Corresponding author. Fax: +48 22 632 66 81.
E-mail address: sljar@icho.edu.pl (S. Jarosz).
decalin skeleton (cis)
These bicyclic compounds may be used also for the preparation of mono-
carbocyclic derivatives, via a cleavage of either ring in 3 or 5 (see Refs. 8,9).
Figure 1. Convenient routes to precursors of highly oxygenated carbobicyclic
derivatives from sugar allyltins (Ref. 8).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.11.008

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A. Błonska et al. / Tetrahedron: Asymmetry 20 (2009) 2728–2732
SnBu3
OMe
2. Results and discussion
Controlled fragmentation of the mannose-derived allyltin 6
gave dienoaldehyde 7, which upon reaction with Ph3P@CHCO2Me
and subsequent cyclization, provided two stereoisomeric adducts
8 and 9 in a 9:1 ratio. The ester function was then reduced and
the free hydroxyl groups were protected as benzyl ethers furnish-
ing compounds 1010 and 11 (Fig. 2).
O
O
BnO
BnO
OBn
OBn
OBn
OBn
7
6
The trans-configuration at the ring-junction in the minor isomer
11 was the same as in the primary adduct 9;8,10 and this was addi-
tionally confirmed by advanced NMR experiments performed on
11. The important NOE correlations were observed between H1–
H5 and H1–H8. The H7 and H9 overlapped (see Section 4) and
hence no diagnostic information could be extracted from the corre-
lation with H6. However, no correlation was observed between H6
and H8, which strongly suggested that those two protons are trans
to each other.à The configuration of 11 was further supported by the
NMR data recorded for its dihydroxylated derivatives (for the diag-
nostic NOE values see Scheme 1).
We have reported that the trans-diols (and also azidoalcohols)
are available by epoxidation of the double bond followed by open-
ing of the oxirane ring (Fig. 3).10
Herein, alternative functionalization of these highly versatile
synthons, providing various stereoisomeric polyhydroxylated com-
pounds is reported.
Osmylation of olefins 10 and 11 proceeded smoothly and affor-
ded the corresponding cis-diols; the results are shown in Scheme 1.
The oxidation of olefin 10 proceeded with relatively good stereose-
lectivity (ca. 4:1), while the same reaction performed for 11 pro-
vided both diols in almost equal amounts. The configuration of
all diols was assigned using the results of 1D selective 1H NOESY
experiments as well as 2D NOESY correlations performed for the
corresponding diacetates (14-Ac to 17-Ac).
ref . 8
H
H
1
BnO
R
5
H
OBn
BnO
R
6
9
H
+
BnO
OBn
BnO
main isomer
8.
9. R = CO2Me
11 R = CH2OBn
R = CO2Me
10 R = CH2OBn
Figure 2. Bicyclo[4.3.0]nonenes derived from D-mannose.
Per-acetylation of the triols afforded the diacetate 21; no tri-
acetyl derivative was formed under the standard conditions. The
configuration of compound 21 was proven using NOE effects ob-
served for the following pairs of protons: H1–H2, H1–H5, H4–H6,
H6–H7, H6–H8, and H1–H9.
Again, the preferred attack of osmium tetraoxide occurred from
the less hindered side of the molecule also being the side opposite
to the hydroxyl group present in the molecule, which is consistent
with Kishi’s rule.14
Double cis-hydroxylation of the main stereoisomer 10 provided
two diols 14 and 15, the configurations of which were assigned
from the NOESY spectra of their diacetates. The cross peaks in
the NOESY spectrum of the diacetate 14-Ac between H1–H9, H1–
H5, H2–H6, and H6–H8 unambiguously pointed to the structure
14; therefore the structure of the minor isomer should be drawn
as 15. It was also supported by the NOESY spectrum of diacetate
15-Ac in which the correlation between H1–H2, H1–H9, and H3–
H5 were the most diagnostic.
Attack of the osmium tetraoxide from the less hindered side of
the molecule explains the predominant formation of diol 14.
Osmylation of the minor stereoisomeric olefin 11 gave 16 (diag-
nostic NOE cross peaks observed for 16-Ac: H1–H2, H1–H3, and
H3–H5) and 17 (NOE correlations: H2–H6 and H2–H9).
The conversion of the precursors such as 10 and 11 into fully
hydroxylated derivatives lies in the oxidation of the allylic posi-
tion; which has a problem. Direct oxidation of the allylic position
in such compounds proved to be impossible,11 although, it can be
achieved using an indirect methodology, which is based on well-
established selenium chemistry.12,13
This methodology was used for the functionalization of the
allylic position in olefin 10. Thus, opening of the oxirane ring in
epoxide 13 (obtained from olefin 10) with a selenide anion
followed by oxidative work-up provided allylic alcohol 18, whose
structure was fully confirmed by NMR experiments (the diagnos-
tic NOE interactions are shown in Scheme 2). Osmylation of
this olefin under standard conditions furnished two stereoiso-
meric triols with good selectivity (ca. 5:1) and in good yield
(Scheme 2).
3. Conclusion
The
D-manno-configurated allyltin derivative was converted
into the corresponding dienoaldehyde which served as a starting
material for the preparation of complex bicyclic compounds.
Osmylation of the double bond provided the corresponding stereo-
isomeric diols. A more advanced functionalization was realized by
the indirect oxidation of the allylic position followed by cis-di-
hydroxylation of the newly formed olefinic bond. Several diaste-
reoisomeric polyhydroxylated derivatives of enantiomerically pure
hydrindane were obtained by the methodology presented herein.
4. Experimental
4.1. General
The NMR spectra of all compounds were measured in CDCl3 solu-
tions (unless otherwise stated) with the following spectrometers:
Bruker DRX 500 (at temperature 303 K) equipped with a TBI 500SB
HC/BB-D-05 Z-G probehead and Varian-NMR-vnmrs600 (at temper-
ature 298 K) equipped with a PFG Auto XID (1H/15N–31P 5 mm)
indirect probehead. For several samples, benzene-d6 was chosen to
get a best 1H NMR signal separation needed for determination of
the configuration. Standard experimental conditions and standard
Bruker and Varian programs were used.
To assign the structures, the following 1D and 2D experiments
were employed: 1H selective TOCSY, COSY, 1H–13
C gradient
selected HSQC and HMBC with adiabatic pulses optimized for
1J(C–H) = 146 Hz and nJ(C–H) = 8 Hz, respectively. Relative configu-
rations were determined using the results of the 1D selective 1H
NOESY experiment using standard Varian (CHEMPACK 4.1) sequence
à
In the cis arrangement between these two protons, the NOESY cross-peaks should
be observed as in 18 (Scheme 2).

´
A. Błonska et al. / Tetrahedron: Asymmetry 20 (2009) 2728–2732
2730
BnO
BnO
H
BnO
H
OAc
BnO
BnO
H
AcO
1
9
6
i.
BnO
OAc
5
BnO
H
BnO
OBn
H
BnO
OBn
H
OAc
10
OBn
14. R = H (75%)
14-Ac R = Ac
15. R = H (18%)
15-Ac R = Ac
ii.
ii.
OBn
BnO
OBn
OBn
OR
OBn
OBn
BnO
BnO
i.
OBn
OR
OR
BnO
OR
BnO
BnO
11 : NOE : H1-H5; H1-H8
17. R = H (33%)
17-Ac R =Ac
16. R = H (43%)
16-Ac R = Ac
ii.
ii.
NOE data :
14-Ac : H1-H9; H1-H5; H2-H6; H6-H7; H6-H8
15-Ac : H1-H2; H1-H5; H1-H9; H2-H9; H3-H5; H6-H7; H6-H8
16-Ac : H1-H2; H1-H3; H1-H5; H1-H7; H2-H3; H5-H7; H6-H9
17-Ac : H1-H5; H2-H6; H2-H9; H5-H7; H6-H9
Scheme 1. Reagents: (i) OsO4, NMO, THF/tBuOH/H2O; (ii) Ac2O, Et3N, CH2Cl2, DMAP.
and 2D NOESY experiment. The 1H and 13C NMR spectral data are
O
BnO
BnO
H
given relative to the TMS signal at 0.0 ppm. Concentration of all
solutions used for NMR measurements was about 20–30 mg in
0.6 cm3 of solvent. The 1H and 13C NMR signals of benzyl groups
occurring at the typical d values were omitted for simplicity.
Mass spectra were 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 solutions
in CHCl3 (c = 1) at room temperature. Column chromatography was
performed on silica gel (Merck, 70–230 or 230–400 mesh); HPLC
analyses were conducted with a Shimadzu Preparative Liquid
Chromatograph LC-8A equipped with UV detector SPD-6A. Organic
solutions were dried over anhydrous magnesium sulfate. THF was
distilled from potassium prior to use and ethanol was distilled
from magnesium and stored over molecular sieve 4 Å and under
an argon atmosphere. Compound 10 was prepared as described
previously.10
preferred attack
BnO
H
OBn
12
ref . 10
Nu (H2O, NaN3)
exclusive attack
10
H
BnO
H
BnO
O
13
BnO
H
OBn
Figure 3. Synthesis of trans aminoalcohols and diols from epoxides derived from
10.
H
H
2
BnO
H
H
4.2. (1S,5S,6S,7R,8R,9R)-7,8,9-Tri-O-benzyl-5-benzyloxymethyl-
bicyclo[4.3.0]non-2-ene 11
9
BnO
BnO
H
BnO
1
i.
5
H
BnO
6
O
HO
To
a stirred suspension of LiAlH4 (1.5 equiv, 3.62 mmol,
H
OBn
137.4 mg) in dry THF (10 mL), a solution of ester 9 (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 continued at
rt for 2 h. The excess hydride was decomposed by the careful addi-
tion of water and the mixture was partitioned between saturated
aqueous NaHCO3 (10 mL) and ethyl acetate (15 mL). The organic
layer was separated, washed with water, dried, and concentrated
to afford a crude alcohol (963 mg, 85%), which was used in the next
step without further purification.
BnO
13
H
OBn
18
ii.
BnO
BnO
H
BnO
BnO
H
OR
OR
OH
+
BnO
HO
OBn
BnO
HO
OBn
H
H
OH
To
a vigorously stirred solution of this alcohol (516 mg,
19 R = H (58%)
21 R = Ac
20 (12%)
1.1 mmol) in CH2Cl2 (30 mL), 50% NaOHaq (20 mL), and benzyl
chloride (10 equiv, 11.0 mmol, 1.3 mL) were added, followed by
tetrabutylammonium bromide (1 equiv, 1.1 mmol, 354 mg). After
48 h of vigorous stirring, the mixture was partitioned between
water (30 mL) and CH2Cl2 (40 mL); the organic phase was sepa-
rated, washed with water until neutrality, and the aqueous one
was extracted twice with CH2Cl2. The combined organic layers
iii.
NOE in 18 : H1-H2; H1-H5; H1-H9; H6-H7; H6-H8
NOE in 21 : H1-H2; H1-H5; H1-H9; H4-H6; H6-H7; H6-H8
Scheme 2. Reagents: (i) (1) PhSe–SePh, NaBH4; (2) H2O2; (ii) NMO, OsO4 (cat.), THF,
tert-butanol, water; (iii) Ac2O, Py.

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A. Błonska et al. / Tetrahedron: Asymmetry 20 (2009) 2728–2732
were dried, concentrated, and the product was purified by column
chromatography (hexane–ethyl acetate, 98:2) to afford 11 as an
amorphous solid (430 mg, 70%).
[a]
D = +55.6; 1H NMR d: 5.48 (m, H-3), 5.03 (dd, J2,3 3.0, J1,2 11.7,
H-2), 4.31–4.78 (8H, 4 Â OCH2Ph), 4.02 (m, H-7), 3.93 (dd, J8,9 1.5,
J1,9 6.2, H-9), 3.90 (dd, J7,8 4.8, H-8), 3.26 (dd, J 4.1, Jgem 9.1, one
of CH2OBn), 3.15 (dd, J 6.0, one of CH2OBn), 2.75 (ddd, J1,6 13.4,
H-1), 2.26 (m, H-5), 2.05 (3H, s, CH3), 1.99 (m, one of H-4), 1.89
(3H, s, CH3), 1.71 (ddd, J6,7 3.8, J5,6 11.4, H-6), 1.50 (m, one of H-
4); 13C NMR d: 170.40, 170.16 (2 Â CH3CO), 138.93, 138.38,
138.08, 138.02 (4 Â Cipso), 88.29 (C-8), 81.31 (C-9), 77.53 (C-7),
73.71, 73.08, 72.24, 72.10, 71.29 (4 Â OCH2Ph and CH2OBn),
71.53 (C-2), 69.18 (C-3), 45.10 (C-6), 41.65 (C-1), 32.78 (C-4),
31.21 (C-5), 21.13 and 20.90 (2 Â CH3). NOE: H1–H9, H1–H5,
H2–H3, H2–H6, H6–H7, H6–H8, H7–H8.
HRMS m/z: 583.28072 [C38H40O4Na (M+Na+) requires
583.28188]; [a]
D = +62.9; 1H NMR d: 5.91 (dd, J1,2 2.1, J2,3 10.0, H-
2), 5.67 (m, H-3), 4.33–4.69 (8H, 4 Â OCH2Ph), 3.99 (dd, J 2.9, 6.8,
H-8), 3.86 (dd, J 4.5, Jgem 9.3, one of CH2OBn), 3.70–3.74 (2H, m,
H-7 and H-9), 3.33 (ꢀt, J 9.3, one of CH2OBn), 2.48 (m, one of H-
4), 2.13 (m, H-1), 2.05 (m, H-5), 1.87 (m, one of H-4), 1.82 (m, H-
6); 13C NMR d: 138.77, 138.28, 138.16, 138.15 (4 Â Cipso), 127.39–
128.47 (Ar, C-3), 126.97 (C-2), 87.23 and 80.68 (C-7, C-9), 81.60
(C-8), 73.92 (CH2OBn), 73.00, 72.17, 72.02, 71.59 (4 Â OCH2Ph),
45.04 (C-6), 44.19 (C-1), 39.69 (C-5), 31.50 (C-4). NOE: H1–H2,
H1–H5, H1–H8, H2–H3.
4.4.2. (1S,2S,3R,5R,6R,7R,8R,9R)-2,3-Di-hydroxy-7,8,9-tri-O-
benzyl-5-benzyloxymethyl-bicyclo[4.3.0]nonane 15 (18%)
This product was characterized as the diacetate 15-Ac: HRMS
m/z: 701.31159 [C42H46O8Na (M+Na+) requires 701.30849];
4.3. (1R,2R,5R,6R,7R,8R,9R)-2-Hydroxy-7,8,9-tri-O-benzyl-5-
benzyloxymethyl-bicyclo[4.3.0]non-3-ene 18
[a]
D = +10.3; 1H NMR d: 5.28–5.22 (2H, m, H-2, H-3), 4.40–4.90
To a solution of diphenyldiselenide (70 mg, 0.23 mmol) in anhy-
drous ethanol (6 mL), sodium borohydride was added in portions
(17 mg, 0.46 mmol) and the mixture was stirred for 1 h until the
yellow color disappeared. Then a solution of the epoxide 1310
(130 mg, 0.23 mmol) in THF (2 mL) was added and the mixture
was heated at reflux for 5 h. After cooling to 5 °C (ice bath) hydro-
gen peroxide (30% in water, 0.75 mL) was added, the mixture was
stirred for 24 h at rt, and quenched with saturated sodium carbon-
ate (6 mL). Water (20 mL) was added, and the product was ex-
tracted with diethyl ether (3 Â 15 mL). The organic phase was
washed with brine, dried, concentrated, and the product was iso-
lated by HPLC (hexane–ethyl acetate, 84:16) to give allylic alcohol
18 (48 mg; 37%) as an oil. HRMS m/z: 599.27974 [C38H40O5Na
(8H, 4 Â OCH2Ph), 3.93–3.97 (3H, H-7, H-8, H-9), 3.52 (dd, J 7.7,
Jgem 9.1, one of CH2OBn), 3.33 (dd, J 5.9, one of CH2OBn), 2.43 (m,
H-6), 2.30 (m, H-1), 2.20 (m, H-5), 2.08 (m, one of H-4), 2.02 (3H,
s, CH3), 2.00 (3H, s, CH3), 1.72 (m, one of H-4); 13C NMR d:
170.27, 170.17 (2 Â CH3CO), 138.70, 138.44, 138.42, 138.37
(4 Â Cipso), 87.54, 87.22, 82.07 (C-7, C-8, C-9), 74.13 (CH2OBn),
73.43, 72.93, 72.49, 71.98 (4 Â OCH2Ph), 72.70 (C-2), 79.17 (C-3),
41.80 (C-1), 39.30 (C-6), 32.26 (C-5), 29.19 (C-4), 21.17 and 21.07
(2 Â CH3).
1H NMR (C6D6) d: 1H NMR d: 5.66 (dd, J2,3 3.1, J1,2 9.0, H-2), 5.52
(m, H-3), 4.30–4.79 (8H, 4 Â OCH2Ph), 4.18 (ꢀt, H-9), 3.90 (ꢀt,
J7,8 ꢀ J8,9 4.6, H-8), 3.71 (ꢀt, J6,7 ꢀ J7,8 4.4, H-7), 3.44 (dd, J 7.0, Jgem
9.0, one of CH2OBn), 3.31 (dd, J 5.9, one of CH2OBn), 2.50 (ddd, J1,9
4.2, J1,2 ꢀ J1,6 ꢀ 8.9, H-1), 2.44 (m, H-6), 2.27 (m, H-5), 2.04 (ddd,
J3,4eq 4.1, J4eq,5 10.0, Jgem 14.2, Heq-4), 1.81 (dd, J3,4ax 7.0, Hax-4),
1.77 (3H, s, CH3), 1.70 (3H, s, CH3); 13C NMR (C6D6) d: 169.73,
169.51 (2 Â CH3CO), 139.28, 139.27, 139.21, 139.08 (4 Â Cipso),
87.62 (C-9), 87.13 (C-8), 82.42 (C-7), 74.27 (CH2OBn), 73.49,
73.04, 72.67, 72.20 (4 Â OCH2Ph), 72.70 (C-2), 69.17 (C-3), 42.95
(C-1), 39.55 (C-6), 32.95 (C-5), 29.53 (C-4), 20.81 and 20.78
(2 Â CH3); NOE: H1–H2, H1–H5, H1–H9, H2–H3, H2–H9, H3–H5,
H6–H7, H6–H8, H7–H8.
(M+Na+) requires 599.2768]; [
a
]
D = À29.6; 1H NMR d: 5.91 (ddd,
J2,3 5.2, J3,5 2.5, J3,4 9.9, H-3), 5.83 (dd, J4,5 1.8, H-4), 4.47–4.79
(8H, 4 Â OCH2Ph), 4.48 (m, H-2), 4.43 (dd, J8,9 5.8, J1,9 9.7, H-9),
4.15 (ꢀt, H-7), 3.96 (dd, J7,8 3.5, H-8), 3.40 (2H, m, CH2OBn), 2.77
(m, H-5), 2.38 (ddd, J1,2 2.9, J1,6 13.2, H-1), 2.17 (ddd, J6,7 2.8, J5,6
10.5, H-6); 13C NMR d: 139.04, 138.42, 137.97, 137.83 (4 Â Cipso),
132.57 (C-4), 128.85 (C-3), 90.93 (C-8), 84.65 (C-9), 76.55 (C-7),
72.23–73.34 (4 Â OCH2Ph), 64.59 (C-2), 43.40 (C-1), 38.44 (C-6),
38.05 (C-5). NOE: H1–H9, H1–H2, H1–H5, H2–H3, H3–H4, H4–
H5, H6–H7, H6–H8, H7–H8.
ꢁ The reaction of 11 was conducted for 40 h and afforded two
products 16 and 17 which were separated by HPLC (hexane–
ethyl acetate, 7:3).
4.4. cis-Di-hydroxylations: general procedure
The corresponding olefin 10, 11, or 18 (0.50 mmol) was dis-
solved in THF (5 mL), tert-butanol (0.5 mL), and water (0.05 mL)
to which N-methyl morpholine N-oxide (1.2 equiv, 0.60 mmol,
70 mg) and osmium tetraoxide (0.25 mL of a ca. 2% solution in
tert-BuOH) were added. The mixture was stirred at rt until the dis-
appearance of the starting material (TLC monitoring in hexane–
ethyl acetate, 2:1). Methanol (15 mL) was added followed by satu-
rated aq NaHSO3 solution. The mixture was stirred for 0.5 h, and
then partitioned between water (20 mL) and ethyl acetate
(50 mL). The organic phase was separated, washed with water
(50 mL), brine (20 mL), dried, concentrated, and the crude products
were isolated by column chromatography or HPLC.
4.4.3. (1R,2R,3S,5S,6S,7R,8R,9R)-2,3-Di-hydroxy-7,8,9-tri-O-
benzyl-5-benzyloxymethyl-bicyclo[4.3.0]nonane 16 (43%)
HRMS m/z: 617.28785 [C38H42O6Na (M+Na+) requires
617.28736]. This product was characterized further as the diace-
tate 16-Ac: [a]
D = +21.1; 1H NMR d: 5.62 (m, H-2), 4.86 (ddd, J2,3
2.9, J3,4eq 4.8, J3,4ax 12.3, H-3), 4.31–4.63 (8H, 4 Â OCH2Ph), 3.93
(dd, J8,9 2.7, J7,8 6.5, H-8), 3.88 (dd, J 3.9, Jgem 9.5, one of CH2OBn),
3.67 (dd, J1,9 8.8, H-9), 3.61 (dd, J6,7 10.3, H-7), 3.29 (ꢀt, J 9.3, one
of CH2OBn), 2.13 (ddd, J4eq,5 4.0, Jgem 12.8, Heq-4), 2.04 (m, H-6),
1.76 (m, H-5), 1.63 (m, H-1), 1.51 (m, Hax-4); 13C NMR d: 170.48,
170.11 (2 Â CH3CO), 138.54, 137.92, 137.86, 137.73 (4 Â Cipso),
82.22 (C-9), 81.23, 81.22 (C-7 and C-8) 71.72–73.06 (4 Â OCH2Ph
and CH2OBn), 72.11 (C-3), 67.97 (C-2), 46.90 (C-1), 40.62 (C-5),
40.34 (C-6), 29.93 (C-4), 20.93, 20.88 (2 Â CH3). NOE: H1–H2,
H1–H3, H1–H5, H1–H7, H2–H3, H5–H7, H6–H9, H7–H8.
ꢁ The reaction of 10 was conducted for 40 h and afforded two
products 14 and 15 which were separated by column chroma-
tography (hexane–ethyl acetate, 4:1).
4.4.1. (1S,2R,3S,5R,6R,7R,8R,9R)-2,3-Di-hydroxy-7,8,9-tri-O-
benzyl-5-benzyloxymethyl-bicyclo[4.3.0]nonane 14 (75%)
This product was characterized as the diacetate 14-Ac: HRMS
m/z: 701.30602 [C42H46O8Na (M+Na+) requires 701.30849];
4.4.4. (1R,2S,3R,5S,6S,7R,8R,9R)-2,3-Di-hydroxy-7,8,9-tri-O-
benzyl-5-benzyloxymethyl-bicyclo[4.3.0]nonane 17 (33%)
HRMS m/z: 617.28775 [C38H42O6Na (M+Na+) requires
617.28736].

´
A. Błonska et al. / Tetrahedron: Asymmetry 20 (2009) 2728–2732
2732
This product was characterized further as the diacetate 17-Ac:
[a]
D = +22.2; 1H NMR d: 5.39 (m, H-3), 4.92 (dd, J2,3 3.1, J1,2 11.4,
H-2), 4.36–4.64 (8H, 4 Â OCH2Ph), 3.90 (dd, J8,9 1.9, J7,8 5.9, H-8),
3.89 (dd, J 3.8, Jgem 9.3, one of CH2OBn), 3.82 (dd, J1,9 7.9, H-9),
3.74 (dd, J6,7 10.5, H-7), 3.28 (ꢀt, J 9.1, one of CH2OBn), 2.24 (m,
Heq-4), 2.06 (3H, s, CH3), 2.03 (m, H-1), 1.97 (m, H-5), 1.91 (3H, s,
72.37, 71.91 (4 Â OCH2Ph), 70.78 (C-3), 69.50 (C-4), 68.61 (C-2),
67.07 (CH2OBn), 41.66 (C-1), 38.11 (C-6), 36.95 (C-5), 21.04,
20.84 (2 Â CH3). NOE: H1–H2, H1–H5, H1–H9, H2–H3, H3–H4,
H4–H6, H6–H7, H6–H8, H7–H8.
Acknowledgment
CH3), 1.85 (m, H-6), 1.38 (ddd, J3,4ax 2.6, J4ax,5 12.0, Jgem 14.8, Hax
-
4); 13C NMR d: 170.58, 170.18 (2 Â CH3CO), 138.52, 138.07,
137.97, 137.89 (4 Â Cipso), 86.22 (C-9), 81.83 (C-7), 80.45 (C-8),
75.05 (C-2), 71.70–73.09 (4 Â OCH2Ph and CH2OBn), 69.27 (C-3),
45.05 (C-6), 43.33 (C-1), 37.18 (C-5), 34.12 (C-4), 21.20, 21.02
(2 Â CH3). NOE: H2–H3, H2–Hax4, H2–H6, H2–H-9, Hax4–H6,
Heq4–H-, H6–H9, H6–CH2OBn, H7–H-8.
This work was financed by the Ministry of Science and Higher
Education, Grant No. N N204 092635.
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ꢁ The reaction of allylic alcohol 18 (58 mg, 0.1 mmol) was con-
ducted for 18 h and afforded an unseparable mixture of both iso-
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21; 1H NMR (600 MHz) d: 5.33 (dd, J3,4 3.1, J4,5 11.4, H-4), 5.28
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