Synthesis of polyhydroxylated carbo-bicyclic compounds from sugar allyltins

Article abstract of DOI:10.1016/j.tetasy.2013.09.018

A highly functionalized polyhydroxylated dienoaldehyde, readily obtained from a d-glucose allyltin, served as a convenient precursor for a variety of configurationally different carbo-bicyclic polyols available in a free (deprotected) form. The activity of the free polyols against glycosidases was also tested.

Full text of DOI:10.1016/j.tetasy.2013.09.018

Tetrahedron: Asymmetry 24 (2013) 1402–1411
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of polyhydroxylated carbo-bicyclic compounds
from sugar allyltins
⇑
Marta Magdycz, Sławomir Jarosz
Institute of Organic Chemistry, 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 30 July 2013
Accepted 18 September 2013
Available online 29 October 2013
A highly functionalized polyhydroxylated dienoaldehyde, readily obtained from a
D-glucose allyltin,
served as a convenient precursor for a variety of configurationally different carbo-bicyclic polyols avail-
able in a free (deprotected) form. The activity of the free polyols against glycosidases was also tested.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
Bu3Sn
O
Sugar chirons1 are particularly useful in the synthesis of poly-
hydroxylated carbo- and hetero cyclic derivatives. These com-
pounds can be regarded as sugar mimics;2 because of their
similarity to ‘normal’ sugars, they efficiently block specific
enzymes.3 The synthesis and application of bicyclic derivatives
are also a subject of interest.4
Previously we have proposed a general, convenient methodol-
ogy for the preparation of enantiomerically pure carbo-bicyclic
systems, such as 1, from sugar allyltins.5 These organometallics
undergo a controlled fragmentation to dienoaldehydes 2 with an
E-geometry across the internal double bond, regardless of the
E- or Z-configuration of the starting allyltin.6 Such dienoaldehydes
are converted into hydrindane or decalin derivatives 3 or 4 respec-
tively (see Fig. 1). We have already reported on the stereoselective
functionalization of a bicyclic skeleton of intermediate 4, which
provided a number of bicyclic derivatives containing oxygen, nitro-
gen, phosphorus, or sulfur functionalities (see Fig. 2).7
H
BnO
BnO
O
BnO
OMe
OBn
OBn
2
BnO
1
OBn
H
OBn
OBn
H
H
BnO
CO2Me
H
H
O
O
OBn
BnO
4
O
3
Figure 1. Synthesis of polyhydroxylated bicyclic compounds from
gurated allyltin 1.
D-gluco-confi-
C5–C50 bond. We have reported that the introduction of two
hydroxyl groups (via cis- or trans-di-hydroxylation) at the C2-C3
positions, as well as the azide, is possible.5,7,8 However, the prob-
lem of the cleavage of the exo-carbon–carbon bond still remains
unsolved (Fig. 3).
Although the direct oxidation of the allylic position in 3 and 4
was not possible, we could perform this transformation indirectly.
Opening of the oxirane ring in 8 (a and b) with selenium species
followed by oxidative work-up afforded olefins 7 and 9 respec-
tively; the latter were then converted into fully hydroxylated
derivatives.7
Herein we report a concise approach to fully functionalized
bicyclic derivatives with a hydrindane skeleton.
The most convenient route to cleave the C5–C50-bond in a
highly stereoselective manner is, undoubtedly, the Baeyer–Villiger
oxidation of ketone 120, which can be prepared from the parent
ester in a few synthetic steps (route a). The introduction of a
keto-function in the cyclization step (route b) would significantly
reduce the number of synthetic steps (Fig. 4).
2. Results and discussion
The conversion of the hydrindane scaffold of 12 into an all-
hydroxylated derivative requires functionalization of the double
bond, oxidation of the allylic position, and finally cleavage of the
2.1. Synthesis of bicyclo[4.3.0]nonenes with a ketone pendant
at the C5 position
⇑
The reaction of dienoaldehyde 2 with phosphonate 13 under
mild PTC conditions9 afforded triene 14, which underwent
Corresponding author. Tel.: +48 22 343 23 22; fax: +48 226326681.
E-mail address: slawomir.jarosz@icho.edu.pl (S. Jarosz).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.09.018

M. Magdycz, S. Jarosz / Tetrahedron: Asymmetry 24 (2013) 1402–1411
1403
O
4
O
O
(a)
EtO
+
P
2
EtO
BnO
BnO
OBn
OBn
OH
OBn
O
H
H
13
OBn
OBn
H
HO
OBn
OBn
14
16
OBn
O
H
H
H
H
H
O
1
5
6
6
+
BnO
5
BnO
H
H
9
H
H
7
O
ratio
15 : 16 = 1:1
OBn
OBn
BnO
BnO
HO
15
H
HO
from α-
NOE: H1-H5, H6-H9
NOE: H5-H7, H1-H7, H1-H9
8
from β-
Scheme 1. Reagents: (a) K2CO3, 18-crown-6, toluene rt.
H
7
H
epoxide
epoxide
9
E-geometry across the newly formed double bond in the interme-
diate triene 14.
Nu
HO
The trans-junction between both rings in 15 and 16 can be
explained by assuming the (preferred) endo-transition state of
the Diels–Alder reaction (Fig. 5).
HO
Nu
H
H
Nu = OR, N3,
SCN (
PPh2
SH),
H
H
11
10
Me(O)C
Me(O)C
OBn
OBn
Figure 2. Synthesis of highly functionalized decalins.
16
15
OBn
endo
OBn
OBn
BnO
functionalization
indirect oxidation
endo
of the double bond
of the allylic position
Figure 5. The exo-transition states leading to bicycle 15 and 16.
2
4
5
???
4
B
5
B
1
BnO
CO2Me
5'
2.2. Functionalization of the double bond in cycloadduct 15
???
A
9
O
12'
OBn
Two methods, cis- and trans-di-hydroxylation were used to
functionalize the double bond in the cycloadducts. Catalytic osmy-
lation of olefin 15 provided two stereoisomeric diols 17 and 18 in
96% yield and in a 1:1.3 ratio. Epoxidation of 15 afforded an insep-
arable mixture of both epoxides 20, which were converted by basic
BnO
12
insertion of the
hydroxyl group
Figure 3. Functionalization of the hydrindane skeleton.
hydrolysis into
a single stereoisomeric diol 19. This trans-
di-hydroxylation could be carried out more effectively in a one
pot two-step process, consisting of oxidation of the double bond
with 30% hydrogen peroxide in formic acid followed by opening of
the oxirane ring, without isolation of the epoxide (see Scheme 2).
The configurations of all three stereoisomers were proven by
the NOESY NMR spectra; the most important correlations are
shown in Scheme 2.
The next step in the functionalization of the skeleton of 15 con-
sisted of the cleavage of the exo-C5-C50 bond. This was carried out
by a Baeyer–Villiger oxidation, which is known to proceed with the
retention of the configuration.10 The reaction of diols 17–19 under
standard conditions (MCPBA, Na2HPO4),11 although not very
efficient, allowed us to obtain the corresponding acetates 21–23
in rather moderate yields. A much better yield was obtained when
stronger peracids were used; thus derivative 24, upon treatment
with TFAA/H2O2, provided 55% of the corresponding acetate 25
(Scheme 3).
O
BnO
CO2Me
two steps
BnO
BnO
route a
OBn
BnO
OBn
one or
proposed
route b
two steps
three
steps
or four
O
one
step
BnO
BnO
BnO
O
BnO
OBn
OBn
Figure 4. Route to bicyclic derivatives with the C-acetate pendant.
In the NOESY spectra of 21–23, the interaction between the H1
and H5 resonances was observed, which proved that the configura-
tion at the C5 center remained—as expected—unchanged.
spontaneous cyclization to give two stereoisomeric bicyclic
derivatives 15 and 16 in equal amounts (Scheme 1).
The structure of both stereoisomers was determined from the
NOESY spectra; the most important interactions are shown in
Scheme 1. The trans-relationship between the H-5 and H-6 protons
in both adducts 15 and 16 unequivocally confirmed the (expected)
2.3. Functionalization of the double bond in cycloadduct 16
The same sequence of reactions was carried out on second
stereoisomeric adduct 16; this time, the opposite stereoselectivity

1404
M. Magdycz, S. Jarosz / Tetrahedron: Asymmetry 24 (2013) 1402–1411
OH
OH
OH
2
2
HO
(a)
HO
H
HO
H
16
H
H
O
H
O
1
5
6
H
O
1
5
6
+
BnO
BnO
BnO
9
9
5'
H
H
7
H
7
OBn
OBn
OBn
BnO
BnO
O
BnO
26
17
18
(b)
OH
(a)
HO
H
H
H
O
H
BnO
H
(c)
(b) (c)
O
BnO
15
H
OBn
O
BnO
OBn
27
BnO
19
OH
OH
HO
HO
H
H
O
(c)
H
H
(d)
H
H
+
H
BnO
BnO
H
20
H
O
O
ratio
28 : 29 = 1.2 :1
OBn
BnO
17
18
19
NOE: : H2-H6, : H1-H2, : H3-H6, H1-H2
OBn
BnO
29
28
Scheme 2. Reagents: (a) OsO4 (cat.), NMO, THF/t-BuOH/H2O (v/v: 10/1/0.1);
(b) HCO2H, 30% H2O2; (c) MeOH, 10% NaOH (d) MCPBA.
NOESY: 26: H2-H6, 27: H2-H6, 28: H1-H2, 29: H1-H3
Scheme 4. Reagents: (a) OsO4 (cat.), NMO, THF/t-BuOH/H2O (v/v: 10/1/0.1);
(b) MCPBA, NaHCO3; (c) (1) HCO2H 30% H2O2; (2) MeOH, 10% NaOHaq
.
18
19
OH
17
HO
H
26 and 29
(a)
(a)
(a)
(a)
(a)
BnO
OAc
H
OH
no product
OH
OBn
OH
28
BnO
30
HO
H
HO
H
HO
NOESY: H1-H5
5
1
7
H
OBn
BnO
OAc
BnO
OAc
OBn
9
BnO
OAc
H
BnO
H
H
H
(c)
BnO
(b)
OBn
OBn
BnO
OBn
BnO
OBn
H
BnO
22
21
BnO
OAc
23
H
BnO
H
O
OBn
BnO
OBn
OBn
32
26
BnO
31
BnO
BnO
H
NOESY: H1-H5
(c)
(b)
H
19
Scheme 5. Reagents: (a) MCPBA, NaH2PO4; (b) BnCl, NaOH; (c) TFAA, 50% H2O2.
BnO
OAc
BnO
H
H
O
OBn
OBn
BnO
BnO
25
2.4. Attempts to functionalize the C4 position of the bicyclic
adducts
24
Scheme 3. Reagents: (a) MCPBA, Na2HPO4; (b) BnCl, NaOH; (c) TFAA, 50% H2O2.
Although the direct allylic oxidation in adducts of type 3 or 4
(see Fig. 1) is not possible,12 it can be performed indirectly, that
is, by the formation of an epoxide followed by opening of the three
membered ring with a selenium nucleophile and oxidative work-
up according to Sharpless procedure.8a,13
However, opening of the oxirane ring in b-epoxide 27 with a
selenium anion was unsuccessful. Attempts to introduce unsatura-
tion at the C4–C5 position via elimination of a molecule of water
from 34 did not give any positive results. Mesylate 33 was com-
pletely resistant toward basic elimination, although it underwent
facile SN2 displacement with the acetate ion to afford isomer
36-Ac. On the other hand, xanthate 35 was only converted at high
temperature to the ‘wrong’ olefin 37, which had the double bond
between the C5 and C6 atoms (Fig. 6).
was noted. Osmylation of the double bond in 16 provided a single
stereoisomeric diol 26, while a one-pot trans-dihydroxylation gave
two isomers 28 and 29 in a 1.2:1 ratio. Alternatively, epoxidation of
olefin 16 provided a single oxirane 27. The configurations of diols
26, 28, and 29 as well as epoxide 27 were determined by the
NOESY spectra; the most important interactions are shown in
Scheme 4.
Cleavage of the C5–C50 bond via A Baeyer–Villiger reaction in
the diols arising from cycloadduct 16 was much more difficult
than those that originated from 15 (i.e., 17–19; Scheme 3).
Although diol 28 reacted as expected to provide acetate 30 in
moderate yield, the other stereoisomers 26 and 29 did not under-
go this process. Oxidation of diol 26, however, could be
performed ‘indirectly’ by protection of the free hydroxyls as
benzyl ethers to 31 followed by a cleavage of the C5–C50-bond
with TFAA/H2O2 (Scheme 5).
Unsaturation at the C4–C5 position could be introduced, how-
ever, in another stereoisomeric structure derived from 15 as shown
in Scheme 6.
Several of the prepared compounds were deprotected; deriva-
tives: 41a, 42a, and 43a were tested for the IR activity against four

M. Magdycz, S. Jarosz / Tetrahedron: Asymmetry 24 (2013) 1402–1411
1405
OBn
3. Conclusion
OBn
BnO
H
OBn
3
4
We have presented a convenient route to a number of stereoiso-
meric, highly oxygenated derivatives with hydrindane skeleton.
These compounds could be efficiently deprotected, however, none
of these ‘free’ derivatives showed any significant activity against
glycosidases.
3
1
5
3
5
5
BnO
OH
6
H
8
OCSSMe
OMs
35
OBn
BnO
33
34
OBn
OBn
OBn
4. Experimental
BnO
BnO
H
BnO
H
H
4.1. General methods
5
BnO
6
BnO
BnO
OAc
H
H
NMR spectra were recorded in CDCl3 (unless otherwise stated)
with a Varian AM-600 (600 MHz 1H, 150 MHz 13C) at room temper-
ature. Chemical shifts (d) are reported in ppm relative to Me4Si (d
0.00) for 1H and residual chloroform (d 77.00) for 13C. All significant
resonances were assigned by COSY (1H–1H), HSQC (1H–13C), and
HMBC (1H–13C) correlations. Reagents were purchased from
Sigma–Aldrich, Alfa Aesar or ABCR, and used without further
purification. Commercial THF, CH2Cl2, and MeOH were dried over
freshly activated (24 h at 250 °C) 3 Å molecular sieves for at least
three days. Hexanes (65–80 °C fraction from petroleum) and EtOAc
were purified by distillation. Other solvents were used without
further purification. Thin-layer chromatography was carried out
on silica gel 60 F254 (Merck). Mass spectra were recorded with an
ESI/MS Mariner (PerSeptive Biosystem) mass spectrometer. Optical
rotations were measured with a Jasco P 1020 polarimeter (sodium
light) in chloroform (c = 1) at room temperature. The organic
solutions were dried over MgSO4.
OBn
BnO
OBn
36-Ac
OBn
37
BnO
BnO
38
NOESY: H5-H6
Figure 6. Attempts to functionalize the allylic position in 34.
OBn
OBn
3
BnO
5
3
OAc
OBn
H
(a)
for 25b
(R = Ms)
5
39
BnO
BnO
BnO
OR
H
OBn
H
BnO
R = Ac (25)
R = H (25a)
R = Ms (25b)
H
OBn
BnO
40
4.2. Synthesis of derivatives of bicyclo[4.3.0]nonene
Scheme 6. Reagents: (a) CsOAc, DMF.
A mixture of (2R,3S,4R)-tri-O-benzyl-octa-5(E),7-diene-1-al14
2
enzymes: a- and b-glucosidase, a-mannosidase, and a-fucosidase.
(4.1 g, 9.25 mmol), phosphonate 13 (2.0 g, 10.2 mmol), K2CO3
(3.8 g, 27.8 mmol), and 18-crown-6 (30 mg) in toluene (100 mL)
was stirred at rt for 24 h (TLC monitoring in hexane–ethyl acetate,
3:1). Water (30 mL) was then added, the organic phase was sepa-
rated, and the aqueous phase extracted with ethyl acetate
(25 mL). Combined organic solutions were washed with water
and brine, dried, and concentrated. Crystallization of the residue
from methanol afforded pure 16 (1.87 g); the mother liquors were
concentrated and the product 15 was isolated by column chroma-
tography (hexane–ethyl acetate, 12:1) as a colorless oil (1.95 g);
overall yield was 86%.
The results are presented in Table 1; No significant activity was
noted. (Fig. 7)
Table 1
Inhibition of the enzymes by bicyclic polyols (in %)
Compound
c (mmol/l)
41a
42a
43a
17.2
15.3
26.9
10.1
39.7
13.9
12.6
3.5
22.8
19.6
17.8
3.3
0
11.7
34.6
a-Glucosidase
b-Glucosidase
a
a
-Mannosidase
-Fucosidase
4.3. (1R),5S,6S,7S,8S,9R)-7,8,9-Tri-O-benzyl-5-methylcarbonyl-
bicyclo[4,3,0]non-2-ene 15
OH
OH
HO
H
HO
H
½
a rDt
ꢀ
¼ þ43:8 (c 1, CHCl3); 1H NMR d: 5.97 (dd, J = 1.4, 9.8 Hz, 1H,
RO
OH
21
22
H-2), 5.62 (m, 1H, H-3), 4.63 (m, 4H, 4 ꢁ OCH2Ph), 4.50 (d,
J = 11.5 Hz, 1H, OCH2Ph), 4.34 (d, J = 11.5 Hz, 1H, OCH2Ph), 3.96
(m, 2H, H-7 and H-8), 3.64 (dd, J = 3.9, 10.5 Hz, 1H, H-9), 3.12 (dt,
J = 6.3, 11.2 Hz, 1H, H-5), 2.73 (m, 1H, H-1), 2.42 (m, 1H, H-4a),
2.12 (s, 3H, H-11), 2.06 (m, 1H, H-4b), 1.98 (m, 1H, H-6); 13C
NMR d: 211.0 (C-10), 128.2 (C-2), 126.2 (C-3), 89.9, 81.2 (C-7 and
C-8), 88.6 (C-9), 72.3, 71.7, 70.8 (3 ꢁ OCH2Ph), 46.9 (C-5), 43.5
(C-6), 43.3 (C-1), 29.6 (C-4), 29.2 (C-11). HRMS (m/z) calcd for
RO
OH
H
H
OR
RO
OR
RO
42. R = Bn
42a. R = H
41. R = Bn
41a. R = H
OH
OH
HO
HO
H
C
C
32H34O4Na (M+Na+) 505.2349, found 505.2343. Anal. Calcd for
32H34O4: C, 79.64; H, 7.10. Found: C, 79.43; H: 7.05.
30
H
RO
OH
23
H
RO
OH
H
OR
RO
4.4. (1S,5R,6R,7S,8S,9R)-7,8,9-tri-O-benzyl-5-methylcarbonyl-
bicyclo[4,3,0]non-2-ene 16
OR
RO
44.
R = Bn
44a. R = H
43. R = Bn
43a. R = H
Mp = 127 °C; ½a rDt
ꢀ
¼ þ13:6 (c 1, CHCl3); 1H NMR d: 5.85 (m, 1H,
H-2), 5.75 (m, 1H, H-3), 4.32–4.70 (m, 6H, 6 ꢁ OCH2Ph), 3,93 (d, 1H,
Figure 7. De-protected highly oxygenated hydrindanes.

1406
M. Magdycz, S. Jarosz / Tetrahedron: Asymmetry 24 (2013) 1402–1411
J = 3.3 Hz, H-8), 3.82 (m, 1H, H-9), 3.70 (dd, 1H, J = 3.3, 9.7 Hz, 1H,
H-7), 2.75 (m, 1H, H-5), 2.64 (m, 1H, H-6), 2.47 and 2.31 (2 ꢁ m,
2H, H-4), 2.40 (m, 1H, H-1), 2.12 (s, 3H, H-11); 13C NMR d: 211.2
(C-10), 127.6 (C-3), 125.8 (C-2), 89.4 (C-8), 88.5 (C-7), 80.7 (C-9),
72.2, 71.8, 71.0 (3 ꢁ OCH2Ph), 53.7 (C-5), 44.5 (C-6), 43.5 (C-1),
partitioned between methylene chloride (20 mL) and water
(20 mL), and the organic phase was separated, washed with
water (20 mL) and brine (20 mL), dried, and concentrated. The
crude product was purified by column chromatography
(hexane–ethyl acetate, 6:1) to afford an inseparable mixture of
both stereoisomeric oxiranes.
28.5 (C-4), 27.6 (C-11). HRMS (m/z) calcd for
C32H34O4Na
(M+Na+) 505.2339, found 505.2349. Anal. Calcd for C32H34O4: C,
79.64; H, 7.10. Found: C, 79.36; H: 7.22.
4.9. (1R,5S,6S,7S,8S,9R)-7,8,9-Tri-O-benzyl-5-methylcarbonyl-
2,3-epoxy-bicyclo [4.3.0]nonane 20
4.5. The cis-dihydroxylation of bicyclo[4.3.0]nonene 15
1H NMR (C6D6) d: 3.99–4.63 (m, 13.3H), 3.29 (d, J = 3.9 Hz, 1H),
3.10 (d, J = 2.7 Hz, 0.35H), 2.71(m, 2H), 2.61 (m, 0.7H), 2.41 (m,
2.7H), 2.31 (m, 2H), 2.01 (m, 0.7H), 1.69 (s, 3H, H-11), 1.66 (s,
1H, H-11’), 1.60 (m, 1.7H).
To a solution of olefin 15 (0.85 g, 1.7 mmol) in THF (10 mL),
t-butanol (1 mL), and water (0.1 mL), N-methylmorpholine-N-
oxide (0.39 g, 2.1 mmol) was added followed by OsO4 (0.1 mL of
a 1% solution in t-butyl alcohol), and the mixture was stirred at
rt until disappearance of the starting material (ca. 24 h; TLC mon-
itoring in hexane–ethyl acetate, 1:1). Methanol (5 mL) was then
added followed by saturated sodium thiosulfate (10 mL), and the
mixture was stirred for 30 min. Next, it was filtered through Celite
and partitioned between water (20 mL) and ethyl acetate (30 mL).
The organic phase was separated and the aqueous phase extracted
with EtOAc (2 ꢁ 50 mL). The combined organic solutions were
washed with water and brine, dried, concentrated, and the
products were isolated by column chromatography (methylene
chloride–isopropanol, 97:3) to afford 17 (365 mg, 0.71 mmol,
41%) and 18 (482 mg, 0.93 mmol, 55%) as colorless oils.
4.10. The trans-dihydroxylation of bicyclo[4.3.0]nonene 15
To a solution of the olefin 15 (750 mg, 1.5 mmol) in formic acid
(25 mL), a 30% solution of H2O2 (0.45 mL) was added and the mix-
ture was stirred at rt until disappearance of the starting material
(30 min.). Formic acid was removed in vacuo, the residue was
dissolved in methanol (30 mL) containing 10% aq. NaOH (10 mL),
and the mixture was stirred until TLC (hexane–ethyl acetate, 1:1)
showed the formation of a new product. It was then partitioned
between methylene chloride (40 mL) and water (25 mL), the
organic phase was separated, and the aqueous phase extracted
with CH2Cl2 (2 ꢁ 30 mL). The combined organic solutions were
washed with water and brine, dried, concentrated, and the product
was purified by column chromatography (hexane–ethyl acetate,
1:1) to afford diol 19 (699 mg, 1.4 mmol, 90%) as a colorless oil.
4.6. (1R,2S,3R,5S,6S,7S,8R,9R)-7,8,9-Tri-O-benzyl-5-methyl-carbonyl-
2,3-dihydroxybicyclo[4.3.0]nonane 17
½
a rDt
ꢀ
¼ ꢂ29:5 (c 1, CHCl3); 1H NMR (C6D6) d: 4.61 (d,
J = 11.7 Hz, 1H, OCH2Ph), 4.48 (d, J = 11.7 Hz, 1H, OCH2Ph),
4.45 (m, 2H, 2 ꢁ OCH2Ph), 4.18 (m, 2H, 2 ꢁ OCH2Ph), 4.07 (d,
J = 5.0 Hz, 1H, H-9), 3.94 (d, J = 4.1 Hz, 1H, H-8), 3.86 (d,
J = 4.1 Hz, 1H, H-7), 3.84 (m, 1H, H-3), 3.34 (m, 1H, H-5), 3.24
(m, 1H, H-2), 2.61 (m, 1H, H-1), 2.04 (dt, J = 13.9, 3.5 Hz, 1H,
H-4a), 1.87 (ddd, J = 5.0, 10.8, 13.6 Hz, 1H, H-6),), 1.75 (s, 3H,
H-11), 0.96 (m, 1H, H-4b); 13C NMR (C6D6) d: 209.8 (C-10),
90.1 (C-7), 89.7 (C-8), 81.7 (C-9), 76.4 (C-2), 72.2, 71.8, 71.2
(3 ꢁ OCH2Ph), 68.5 (C-3), 43.8 (C-5), 43.2 (C-1, C-6), 33.4
(C-4), 28.4 (C-11). HRMS (m/z) calcd for C32H36O6Na (M+Na+)
539.2400, found 539.2404. Anal. Calcd for C32H36O6: C, 74.40;
H, 7.02. Found: C, 74.43; H: 7.17.
4.11. (1R,2R,3R,5S,6S,7S,8R,9R)-7,8,9-Tri-O-benzyl-5-methyl-
carbonyl-2,3-dihydroxybicyclo[4.3.0]nonane 19
½
a rDt
ꢀ
¼ ꢂ2:3 (c 1, CHCl3); 1H NMR (C6D6) d: 4.63 (2H, 2 ꢁ
OCH2Ph), 4.42 (2H, 2 ꢁ OCH2Ph), 3.86 (m, 1H, H-2), 4.28 (d,
J = 11.7 Hz, 1H, OCH2Ph), 4.24 (dd, J = 3.9 and 10.0 Hz, 1H, H-9),
4.14 (d, J = 11.7 Hz, 1H, OCH2Ph), 4.06 (d, J = 5.2 Hz, 1H, H-7),
4.02 (d, J = 3.9 Hz, 1H, H-8), 3.68 (s, 1H, H-3), 3.26 (m, 1H, H-5),
2.69 (m, 1H, H-1), 2.47 (m, 1H, H-6), 1.78 (s, 3H, H-11), 1.66 (m,
2H, H-4); 13C NMR (C6D6) d: 210.8 (C-10), 89.4 (C-8), 85.3 (C-9),
81.9 (C-7), 72.5, 71.8, 71.1 (3 ꢁ OCH2Ph), 70.3 (C-3), 68.6 (C-2),
44.9 (C-5), 43.7 (C-1), 38.6 (C-6), 30.6 (C-4), 28.3 (C-11). HRMS
(m/z) calcd for C32H36O6Na (M+Na+) 539.2404, found 539.2393.
Anal. Calcd for C32H36O6: C, 74.40; H, 7.02. Found: C, 74.25;
H: 6.96.
4.7. (1R,2R,3S,5S,6S,7S,8R,9R)-7,8,9-Tri-O-benzyl-5-methyl-
carbonyl-2,3-dihydroxybicyclo[4.3.0]nonane 18
Mp = 118 °C; ½a rDt
ꢀ
¼ ꢂ15:6 (c 1, CHCl3); 1H NMR (C6D6) d: 4.63
4.12. Baeyer–Villiger oxidation of compounds 17, 18, 19, and 24;
general procedure
(m, 2H, OCH2Ph), 4.45 (d, J = 11.8 Hz, 1H, OCH2Ph), 4.39 (d,
J = 11.4 Hz, 1H, OCH2Ph), 4.29 (d, J = 11.8 Hz, 1H, OCH2Ph), 4.25
(m, 1H, H-9), 4.08 (d, J = 11.4 Hz, 1H, OCH2Ph), 4.01 (m, 3H, H-2,
H-7 and H-8), 3.23 (m, 1H, H-3), 2.57 (dt, Jd = 4.3, 11.3 Hz, 1H,
H-5), 2.50 (m, 1H, H-6), 2.09 (m, 1H, H-1), 1.71 (s, 3H, H-11),
1.48 (m, 2H, H-4); 13C NMR (C6D6) d: 208.5 (C-10), 89.7 and 81.5
(C-7 and C-8), 84.8 (C-9), 72.6, 71.7, 71.1 (3 ꢁ OCH2Ph), 72.0
(C-3), 68.4 (C-2), 48.1 (C-1), 47.6 (C-5), 38.2 (C-6), 31.2 (C-4),
28.1 (C-11). HRMS (m/z) calcd for C32H36O6Na (M+Na+) 539.2404,
found 539.2420. Anal. Calcd for C32H36O6: C, 74.40; H, 7.02. Found:
C, 74.31, H; 7.04.
To
a solution of the corresponding ketone (1 mmol) in
methylene chloride (30 mL), Na2HPO4 (213 mg, 1.5 mmol), and
m-chloroperbenzoic acid (55% purity; 466 mg, 1.5 mmol) were
added, the mixture was stirred at rt for 7 days, and then parti-
tioned between water and CH2Cl2. The organic phase was
separated and the aqueous phase extracted with CH2Cl2 (30 mL).
The combined organic solutions were washed with water and
brine, dried, concentrated, and the products were isolated by
column chromatography (hexane–ethyl acetate, 10:9).
4.8. Epoxidation of olefin 15
4.13. (1R,2S,3R,5S,6S,7S,8R,9R)-7,8,9-Tri-O-benzyl-5-O-acetyl-2,
3-dihydroxy-bicyclo[4.3.0]nonane 21
To a solution of olefin 15 (102 mg, 0,21 mmol) in methylene
chloride (10 mL), m-chloroperbenzoic acid (135 mg, 0.42 mmol)
was added and the mixture was stirred at rt for 30 min.
(TLC monitoring in hexane–ethyl acetate, 3:1). Next, it was
Obtained from 17 (103 mg, 0.19 mmol); yield: 24% (0.05 mmol,
26 mg). ½a rDt
ꢀ
¼ ꢂ46:9 (c 1, CHCl3); 1H NMR d: 5.39 (dt, J = 4.7,
10.8 Hz, 1H, H-5), 4.37–4.59 (m, 6H, 6 ꢁ OCH2Ph), 4.01 (m, 1H,

M. Magdycz, S. Jarosz / Tetrahedron: Asymmetry 24 (2013) 1402–1411
1407
H-2), 3.88 (m, 2H, H-7 and H-8), 3.75 (d, J = 4.4 Hz, 1H, H-9), 3.60
(m, 1H, H-3), 2.55 (m, 2H, H-1 and H-4a), 1.94 (s, 3H,
H-11), 1.27 (m, 1H, H-4b); 13C NMR d: 169.9 (C-10), 90.2, 88.1
(C-7 and C-8), 78.4 (C-9), 76.0 (C-3), 72.1, 71.8, 70.9 (3 ꢁ OCH2Ph),
69.5 (C-2), 67.2 (C-5), 45.9 (C-6), 42.5 (C-1), 35.3 (C-4), 21.2 (C-11).
HRMS (m/z) calcd for C32H36O7Na (M+Na+) 555.2359, found 555.2364.
13.4 Hz, 1H, H-4b); 13C NMR (C6D6) d: 209.5 (C-10), 89.7 (C-8),
85.0 (C-9), 82.1 (C-7), 74.2 (C-3), 74.0 (C-2), 72.4, 72.2, 71.8, 71.2,
71.0 (5 ꢁ OCH2Ph), 45.1 (C-5), 44.2 (C-1), 39.6 (C-6), 28.7 (C-4),
28.2 (C-11). HRMS (m/z) calcd for C46H48O6Na (M+Na+) 719.3343,
found 719.3342. Anal. Calcd for C46H48O6: C, 79.28; H, 6.94. Found:
C, 79.28; H. 6.73.
To a solution of 24 (105 mg, 0.2 mmol) in methylene chloride
(15 mL), Na2HPO4 (60 mg, 0.4 mmol) and trifluoroacetic anhydride
(0.1 mL, 0.4 mmol) were added followed by 50% aq. H2O2 (0.08 mL,
0.4 mmol). The mixture was stirred at room temperature for 24 h
(TLC monitoring in hexane–ethyl acetate, 3:1) and partitioned
between water (20 mL) and methylene chloride (15 mL). The
organic phase was separated, washed with water (10 mL) and
brine (10 mL), dried, concentrated, and product 25 was isolated
by column chromatography (hexane–ethyl acetate, 12:1);
yield 59 mg (0.09 mmol, 55%).
4.14. (1R,2R,3S,5S,6S,7S,8R,9R)-7,8,9-Tri-O-benzyl-5-O-acetyl-2,
3-dihydroxy-bicyclo[4.3.0]nonane 22
Obtained from 18 (462 mg, 0,86 mmol); yield: 34% (0.29 mmol,
162 mg). ½a rDt
ꢀ
¼ ꢂ51:3; 1H NMR d: 5.01 (dt, J = 4.5, 10.9 Hz, 1H,
H-5), 4.52–4.61 (m, 4H, 4 ꢁ OCH2Ph), 4.46 (d, J = 11.8 Hz, 1H,
OCH2Ph), 4.36 (d, J = 12.2 Hz, 1H, OCH2Ph), 4.03 (m, 2H, H-2 and
H-7), 3.90 (d, J = 3.4 Hz, 1H, H-8), 3.73 (d, J = 4.3 Hz, 1H, H-9),
3.68 (m, 1H, H-3), 2.16 (m, 2H, H-4a and H-6), 2.09 (m, 1H, H-1),
1.92 (s, 3H, H-11), 1.58 (q, J = 11.5 Hz, 1H, H-4b); 13C NMR d:
170.3 (C-10), 88.5 (C-8), 84.1 (C-7), 78.1 (C-9), 72.2, 71.5, 70.5
(3 ꢁ OCH2Ph), 70.3 (C-3), 67.9 (C-5), 67.4 (C-2), 45.6 (C-1), 40.8
(C-6), 33.6 (C-4), 21.2 (C-11). HRMS (m/z) calcd for C32H36O7Na
(M+Na+) 555.2359, found 555.2355.
4.18. (1S,2R,3R,5R,6R,7S,8S,9R)-2,3,7,8,9-Penta-O-benzyl-5-O-
acetyl-bicyclo [4.3.0] nonane 25
½
a rDt
ꢀ
¼ ꢂ36:5 (c 1, CHCl3); 1H NMR (C6D6) d: 5.87 (dt, J = 4.4,
11.0 Hz, 1H, H-5), 4.63 (d, J = 12.0 Hz, 1H, OCH2Ph), 4.51 (m, 3H,
3 ꢁ OCH2Ph), 4.44 (d, J = 11.6 Hz, 1H, OCH2Ph), 4.39 (dd, J = 3.2,
9.7 Hz, 1H, H-9), 4.31 (m, 3H, 3 ꢁ OCH2Ph), 4.23 (d, J = 11.7 Hz,
1H, OCH2Ph), 4.14 (d, J = 12.0 Hz, 1H, OCH2Ph), 4.09 (d, J = 3.4 Hz,
1H, H-8), 4.01 (d, J = 4.5 Hz, 1H, H-7), 3.88 (t, J = 2.9 Hz, 1H, H-2),
3.73 (q, J = 2.9 Hz, 1H, H-3) 3.15 ddd, J = 2.7, 9.7, 13.9 Hz, 1H,
H-1), 2.64 (dt, J = 13.2, 3.8 Hz, 1H, H-4a), 2.55 (ddd, J = 4.5, 11.0,
13.9 Hz, 1H, H-6), 1.73 (m, 4H, H-4b and H-11); 13C NMR (C6D6)
d: 169.7 (C-10), 89.2 (C-8), 85.1 (C-9), 79.2 (C-7), 74.9 (C-2), 74.1
(C-3), 72.3, 72.1, 71.7, 70.8, 70.6 (5 ꢁ OCH2Ph), 68.5 (C-5), 44.3
(C-1), 43.1 (C-6), 30.4 (C-4), 21.1 (C-11). HRMS (m/z) calcd for
4.15. (1R,2R,3R,5S,6S,7S,8R,9R)-7,8,9-Tri-O-benzyl-5-O-acetyl-2,
3-dihydroxy-bicyclo[4.3.0]nonane 23
Obtained from 19 (110 mg, 0.21 mmol); yield: 28% (0.06 mmol,
32 mg). ½a rDt
ꢀ
¼ ꢂ32:3 (c 1, CHCl3); 1H NMR (C6D6) d: 5.77 (dt, J = 4.5
and 11.2 Hz, 1H, H-5), 4.68 (s, 2H, 2 ꢁ OCH2Ph), 4.48 (d, J = 12.4 Hz,
1H, OCH2Ph), 4.42 (d, J = 11.7 Hz, 1H, OCH2Ph), 4.39 (dd, J = 3.3,
9.7 Hz, 1H, C-9), 4.34 (d, J = 11.7 Hz, 1H, OCH2Ph), 4.28 (d,
J = 12.4 Hz, 1H, OCH2Ph), 4.08 (d, J = 3.3 Hz, 1H, H-8), 4.03 (s, 1H,
H-2), 3.95 (d, J = 4.5 Hz, 1H, H-7), 3.90 (m, 1H, H-3), 3.00 (m, 1H,
H-1), 2.46 (m, 1H, H-6), 2.36 (m, 1H, H-4a), 1.85 (m, 1H, H-4b),
1.64 (s, 3H, H-11); 13C NMR (C6D6) d: 170.5 (C-10), 88.9 (C-8),
85.5 (C-9), 79.3 (C-7), 72.3, 71.6, 70.5 (3 ꢁ OCH2Ph), 72.1 (C-3),
68.9 (C-5), 68.0 (C-2), 44.0 (C-1), 42.1 (C-6), 33.3 (C-4), 21.1
(C-11). HRMS (m/z) calcd for C32H36O7Na (M+Na+) 555.2359, found
555.2354.
C
C
46H48O7Na (M+Na+) 735.3292, found 735.3308. Anal. Calcd for
46H48O7: C, 77.50; H, 6.79. Found: C, 77.51; H, 6.56.
4.19. The cis-dihydroxylation of olefin 16
Catalytic osmylation of 16 (1.36 g, 2,8 mmol), performed analo-
gously to the oxidation of 15, afforded diol 26, which was isolated
by column chromatography (hexane–ethyl acetate, 1:1) as a color-
less oil (1.27 g, 2.46 mmol, 88%).
4.16. Preparation of protected derivative 25
Diol 19 (332 mg, 0.64 mmol), benzyl chloride (1.9 ml, 1.58 mmol),
and Bu4NBr (80 mg, 0.32 mmol) were dissolved in THF (15 mL)
to which 50% aq. NaOH (15 mL) was added, and the mixture was
vigorously stirred for 24 h at rt (until the disappearance of the
starting material; TLC monitoring in hexane–ethyl acetate, 4:1).
Next it was partitioned between water (20 mL) and ether (30 mL),
the organic phase was separated, and the aqueous phase extracted
with ether (2 ꢁ 20 mL). The combined organic solutions were
washed with water (20 mL) and brine (20 mL), dried, concentrated,
and the product was purified by column chromatography
(hexane–ethyl acetate, 12:1) to afford compound 24 (223 mg,
0.32 mmol, 50%) as an oil.
4.20. (1S,2R,3S,5R,6R,7S,8R,9R)-7,8,9-Tri-O-benzyl-5-methyl-
carbonyl-2,3-dihydroxybicyclo[4.3.0]none 26
1H NMR d: 4.70 (d, J = 11.9 Hz, 1H, OCH2Ph), 4.51 m, 2H,
2 ꢁ OCH2Ph), 4.45 d, J = 11.6 Hz, 1H, OCH2Ph), 4.39 (m, 2H,
2 ꢁ OCH2Ph), 4.07 (m, 1H, H-3), 3.95 (dd, J = 3.0, 10.6 Hz, 1H, H-2),
3.87 (m, 2H, H-8 and H-9), 3.74 (m, 1H, H-7), 2.71 (m, J = 3.6,
12.2 Hz, 1H, H-5), 2.19 (m, 1H, H-6), 2.06 (s, 3H, H-11), 2.01 (m,
1H, H-1), 1.94 (m, J = 3.6, 14.2 Hz, 1H, H-4a), 1.62 (ddd, J = 14.2,
12.2, 2.4, 1H, H-4b); 13C NMR d: 211.2 (C-10), 89.6 (C-7), 88.2 and
79.2 (C-8 and C-9), 71.8, 71.7, 71.0 (3 ꢁ OCH2Ph), 69.6 (C-2), 69.3
(C-3), 49.2 (C-5), 45.9 (C-6), 44.2 (C-1), 33.8 (C-4), 29.1 (C-11). HRMS
(m/z) calcd for C32H36O6Na (M+Na+) 539.2404, found 539.2388.
4.17. (1S,2R,3R,5R,6R,7S,8S,9R)-2,3,7,8,9-Penta-O-benzyl-5-methyl-
carbonyl-bicyclo[4.3.0]nonane 24
4.21. Epoxidation of olefin 16
½
a rDt
ꢀ
¼ ꢂ2:3 (c 1, CHCl3); 1H NMR (C6D6) d: 4.67 (d, J = 12.0 Hz,
Treatment of 16 (103 mg, 0,21 mmol) with MCPBA, as described
for the epoxidation of 15, afforded 27 (87 mg, 0.18 mmol, 84%).
1H, OCH2Ph), 4.52 (m, 3H, 3 ꢁ OCH2Ph), 4.37 (dd, J = 3.8, 9.9 Hz,
1H, H-9), 4.32 (d, J = 11.6 Hz, 1H, OCH2Ph), 4.27 (m, 2H, 2 ꢁ
OCH2Ph), 4.22 (m, 3H, 3 ꢁ OCH2Ph), 4.19 (d, J = 5.1 Hz, 1H, H-7),
4.12 (d, J = 3.8 Hz, 1H, H-8), 3.93 (t, J = 2.8 Hz, 1H, H-2), 3.65 (q,
J = 2.8, 1H, H-3), 3.36 (m, 1H, H-5), 2.93 (ddd, J = 2.4, 9.7, 13.9 Hz,
1H, H-1), 2.70 (ddd, J = 5.1, 10.9, 13.9 Hz, 1H, H-6), 1.85 (dt,
J = 13.4. 3.3 Hz, 1H, H-4a), 1.79 (s, 3H, H-11), 1.69 (dt, J = 2.6,
4.22. (1S,2R,3S,5R,6R,7S,8S,9R)-7,8,9-Tri-O-benzyl-5-methylocar-
bonyl-2,3-epoxy bicyclo[4,3,0]nonane 27
½
a rDt
ꢀ
¼ ꢂ12:5 (c 1, CHCl3); 1H NMR (C6D6) d: 4.50 (d, J = 11.64,
1H, OCH2Ph), 4.44 (m, 1H, OCH2Ph), 4.35 (d, J = 12.9, 1H, OCH2Ph),

1408
M. Magdycz, S. Jarosz / Tetrahedron: Asymmetry 24 (2013) 1402–1411
4.15(dd, J = 11.9 and 16.2, 2H, 2 ꢁ OCH2Ph), 3.84 (d, J = 3.4, 1H, H8),
3.64 (d, J = 4.7, 1H, H-7), 3.58 (dd, J = 3.4, 9.7, 1H, H-9), 3.36 (d,
J = 3.9, 1H, H-2), 2.87 (s, 1H, H-3), 2.33 (dt, J = 4.7, 11.3, 1H, H-5),
2.25 (m, 1H, H-1), 1.89 (m, 1H, H-4a), 1.83 (dd, J = 4.7, 13.4, 1H,
H-6), 1.77 (s, 3H, H-11), 1.70 (m, 1H, H-4b); 13C NMR (C6D6) d:
208.1 (C-10), 88.7 (C-8), 87.8 (C-9), 81.0 (C-7), 72.2, 71.6, 71.0
(3 ꢁ OCH2Ph), 52.6 (C-3), 51.9 (C-2), 49.5 (C-5), 44.7 (C-6), 44.5
(C-1), 28.8 (C-11), 27.7 (C-4).HRMS (m/z) calcd for C32H34O5Na
(M+Na+) 521.4376, found 521.4370.
4.27. (1S,2R,3S,5R,6R,7S,8R,9R)-2,3,7,8,9-Penta-O-benzyl-5-methyl-
carbonyl-bicyclo[4.3.0]nonane (31)
Diol 26 (367 mg, 0.71 mmol) was di-benzylated according to
the procedure used for the preparation of 24 from 19; yield of
31: 250 mg (0.36 mmol, 50%). 1H NMR d: 4.32–4.69 (m,
10H,10 ꢁ OCH2Ph), 4.03 (d, J = 4.2 Hz, 1H, H-2), 3.86 (m, 1H, H3),
3.78 (m, 1H, H-7), 3.76 (m, 1H, H-9), 2.72 (dt, J = 3.3 Hz, 12.2, 1H,
H-5), 2.41 (m, 1H, H-1), 2.01 (dt, J = 14.3, 3.3 Hz, 1H, H-6), 2.06
(3H, H-11), 2.27 (m, 1H, H-4a), 1.46 (m, 1H, H-4b); 13C NMR d:
211.3 (C-10), 89.8 (C-9), 87.9 (C-8), 80.0 (C-2), 78.2 (C-7), 72.6
(C-3), 71.8, 71.6, 71.4, 71.0, 70.9 (5 ꢁ OCH2Ph), 49.6 (C-5), 46.4
(C-6), 43.7 (C-1), 31.5 (C-4), 29.0 (C-11). HRMS (m/z) calcd for
4.23. The trans-dihydroxylation of bicyclo[4.3.0]nonene 16
This reaction was carried out starting from 16 (1.0 g, 2 mmol)
analogously to the trans-dihydroxylation of 15. The products 28
(436 mg, 0.84 mmol, 42%) and 29 (368 mg, 0.71 mmol, 36%) were
isolated by column chromatography (methylene chloride–
methanol, 97:3) as colorless oils.
C
46H48O6Na (M+Na+) 719.3343, found 719.3348.
4.28. (1S,2R,3S,5R,6R,7S,8R,9R)-2,3,7,8,9-Penta-O-benzyl-5-O-
acetyl-bicyclo [4.3.0]nonane 32
4.24. (1S,2S,3S,5R,6R,7S,8R,9R)-7,8,9-Tri-O-benzyl-5-methyl-
carbonyl-2,3-dihydroxybicyclo[4.3.0]nonane 28
Treatment of 31 (250 mg, 0.36 mmol) with TFAA/50% H2O2 (as
described for 24) afforded 32 (149 mg, 0.21 mmol, 58%).
½
a rDt
ꢀ
¼ þ46:5 (c 1, CHCl3); 1H NMR (C6D6) d: 5.59 (dt, J = 4.4,
½
a rDt
ꢀ
¼ þ32:9 (c 1, CHCl3); 1H NMR (C6D6) d: 4.52 (d, J = 11.4 Hz,
10.9 Hz, 1H, H-5), 4.55 (d, J = 11.4 Hz, 1H, OCH2Ph), 4.49 (m, 3H,
3 ꢁ OCH2Ph), 4.41 (d, J = 12.4 Hz, 1H, OCH2Ph), 4.36 (d,
J = 11.8 Hz, 1H, OCH2Ph), 4.31 (d, J = 11.8 Hz, 1H, OCH2Ph), 4.26
(d, J = 11.8 Hz, 1H, OCH2Ph), 4.21 (m, 2H, H-7 and OCH2Ph), 4.09
(d, J = 11.8, 1H, OCH2Ph), 4.05 (d, J = 4.2, 1H, H-9), 3.93
(d, J = 2.9 Hz, 1H, H-8), 3.68 (m, 1H, H-3), 3.65 (dd, J = 2.5,
10.7 Hz, 1H, H-2), 2.83 (ddd, J = 4.43, 10.7, 13.7 Hz, 1H, H-1),
2.48 (m, 1H, H-6), 2.22 (m, 1H, H-4a), 1.67 (s, 3H, H-11), 1.22
(m, 1H, H-4b); 13C NMR (C6D6) d: 170.1 (C-5), 90.7 (C-7), 88.8
(C-8), 80.6 (C-9), 78.8 (C-2), 73.5 (C-3), 71.7 (C-5), 72.4, 71.8,
71.6, 71.1, 70.9 (5 ꢁ OCH2Ph), 48.7 (C-6), 43.4 (C-1), 35.1 (C-4),
21.1 (C-11). HRMS (m/z) calcd for C46H48O7Na (M+Na+) 735.3292,
found 735.3314. Anal. Calcd for C46H48O7: C, 77.50; H, 6.79. Found:
C, 77.23; H, 7.09.
1H, OCH2Ph), 4.43 (d, J = 11.4 Hz, 1H, OCH2Ph), 4.32 (m, 3H,
3 ꢁ OCH2Ph), 4.20 (m, 2H, H-2 and OCH2Ph), 3.91 (m, 1H, H-3),
3.83 (m, 2H, H-8 and H-9), 3.78 (dd, J = 9.3, 3.8 Hz, 1H, H-7), 2.94
(m, 1H, H-6), 2.81 (m, 1H, H-5), 2.19 (m, 2H, H-1 and H-4a), 1.97
(s, 3H, H-11), 1.45 (m, 1H, H-4b); 13C NMR d: 209.8 (C-10), 90.4
(C-7), 88.5 and 88.2 (C-8 and C-9), 72.5, 71.6, 70.9 (3 ꢁ OCH2Ph),
71.0 (C-2), 69.3 (C-3), 52.2 (C-5), 41.6 (C-1), 40.9 (C-6), 30.6
(C-4), 27.3 (C-11). HRMS (m/z) calcd for C32H36O6Na (M+Na+)
539.2404, found 539.2404. Anal. Calcd for C32H36O6: C, 74.40; H,
7.02. Found: C, 74.34; H, 7.17.
4.25. (1S,2R,3S,5R,6R,7S,8R,9R)-7,8,9-Tri-O-benzyl-5-methyl-
carbonyl-2,3-dihydroxybicyclo[4.3.0]nonane 29
½
a rDt
ꢀ
¼ þ14:8 (c 1, CHCl3); 1H NMR d: 4.69 (d, J = 12, 1H Hz,
4.29. Hydrolysis of the acetates in the Baeyer–Villiger products;
general procedure
OCH2Ph), 4.54 (d, J = 12 Hz, 1H, OCH2Ph), 4.48 (d, J = 11.4 Hz,
1H, OCH2Ph), 4.24 (d, J = 11.4 Hz, 1H, OCH2Ph), 4.36 (m, 2H,
2 ꢁ OCH2Ph), 3.89 (m, 2H, H-8 and H-9), 3.75 (ꢃt, J = 9.5 Hz, 1H,
H-2), 3.65 (m, 1H, H-7), 3.47 (m, 1H, H-3), 2.33 (m, 2H, H-5
and H-6), 2.06 (s, 3H, H-11), 1.96 (m, 1H, H-4a), 1.63 (m, 2H,
H-1 and H-4b); 13C NMR d: 209.9 (C-10), 89.1 (C-7), 89.0 and
78.6 (C-8 and C-9), 74.8 (C-3), 73.0 (C-2), 72.1, 71.7, 71.3
(3 ꢁ OCH2Ph), 53.7 and 46.1 (C-5 and C-6), 48.8 (C-1), 35.2
(C-4), 27.8 (C-11). HRMS (m/z) calcd for C32H36O6Na (M+Na+)
539.2404, found 539.2408.
To a solution of the corresponding acetate (1 mmoL) in metha-
nol (20 mL) a 10% solution of NaOH aq. (5 mL) was added, and the
mixture was stirred at rt until the disappearance of the starting
material (ca. 1 h; TLC monitoring in methylene chloride–methanol,
30:1). The mixture was concentrated to ca. 1/3 volume and parti-
tioned between methylene chloride (30 mL) and water (15 mL).
The organic phase was separated and the aqueous phase extracted
with CH2Cl2 (10 mL). The combined organic solutions were washed
with water (10 mL), dried, concentrated, and the product was iso-
lated by column chromatography (CH2Cl2–methanol, 30:1).
4.26. (1S,2S,3S,5R,6R,7S,8R,9R)-7,8,9-Tri-O-benzyl-5-O-acetyl-2,
3-dihydroxy-bicyclo[4.3.0]nonane 30
4.30. (1R,2S,3R,5S,6S,7S,8R,9R)-7,8,9-Tri-O-benzyl-2,3,5-trihydroxy-
bicyclo[4.3.0] nonane 41
This compound was obtained from 28 (435 mg, 0.83 mmol)
according to the general procedure for the Baeyer–Villiger oxida-
tion (with MCPBA); yield: 28% (0.23 mmol, 115 mg). ½a Drt
ꢀ ¼ þ23:2
Obtained from 21 (107 mg, 0.21 mmol); yield: 90% (0.19 mmol,
87 mg). ½a rDt
ꢀ
¼ ꢂ30:7 (c 1, CHCl3); 1H NMR d: 4.72 (d, J = 12.1, 1H,
(c 1, CHCl3); 1H NMR (C6D6) d: 5.54 (m, 1H, H-5), 4.30 (m, 3H,
3 ꢁ OCH2Ph), 4.20 (m, 2H, H-7 and OCH2Ph), 4.12 (m, 1H, H-2),
4.03 (d, J = 11.9 Hz, 1H, OCH2Ph), 3.94 (m, 1H, H-3), 3.86 (d,
J = 3.1 Hz, 1H, H-8), 3.8 (d, J = 4.9 Hz, 1H, H-9), 3.94 (m, 1H, H-6),
2.35 (ddd, J = 1.8, 4.9, 14.1 Hz), 2.24 (m, 1H, H-4a), 1.87 (m, 1H,
H-4b), 1.68 (s, 3H, H-11); 13C NMR (C6D6) d: 170.4 (C-10),
90.7 (C-7), 88.6 (C-8), 84.8 (C-9), 72.7 (C-5), 72.4, 71.6, 70.7
(3 ꢁ OCH2Ph), 70.9 (C-3), 70.6 (C-2), 44.0 (C-6), 41.4 (C-1), 34.2
(C-4), 21.09 (C-11). HRMS (m/z) calcd for C32H36O7Na (M+Na+)
555.2359, found 555.2344. Anal. Calcd for C32H36O7: C, 72.16; H,
6.81. Found: C, 71.94; H, 6.91.
OCH2Ph), 4.48–4.63 (m, 4H, 4 ꢁ OCH2Ph), 4.38 (d, J = 11.4 Hz, 1H,
OCH2Ph), 4.32 (dt, J = 4.6, 10.7 Hz, 1H, H-5), 3.99 (m, 1H, H-3),
3.90 (m, 2H, H-7 and H-8), 3.87 (dd, J = 3.8 and 9.8 Hz, 1H, H-9),
3.57 (dd, J = 2.9, 10.4 Hz, 1H, H-2), 2.44 (m, 1H, H-1), 2.27 (m,
1H, H-4a), 1.53 (m, 1H, H-6), 1.36 (m, 1H, H-4b); 13C NMR d:
90.1 (C-9), 89.3, 79.2 (C-7 and C-8), 76.2 (C-2), 72.1, 71.9, 71.3
(3 ꢁ OCH2Ph), 69.7 (C-3), 63.9 (C-5), 48.8 (C-6), 42.4 (C-1), 38.8
(C-4). HRMS (m/z) calcd for C30H34O6Na (M+Na+) 513.2253, found
513.2250. Anal. Calcd for C30H34O6: C, 73.45; H, 6.99. Found.: C,
73.53; H: 7.10.

M. Magdycz, S. Jarosz / Tetrahedron: Asymmetry 24 (2013) 1402–1411
1409
4.31. (1R,2R,3S,5S,6S,7S,8R,9R)-7,8,9-Tri-O-benzyl-2,3,5-trihydroxy-
bicyclo[4.3.0] nonane 42
d: 3.53–3.88 (m, 6H, H-2, H-3, H-5, H-7, H-8, H-9), 1.87 (m, 1H,
H-4a), 1.65 (m, 2H, H-1 and H-6), 1.46 (m, 1H, H-4b); 13C NMR
(D2O) d: 86.9, 77.3, 74.8, 70.4, 66.8, 65.3 (C-2, C-3, C-5, C-7, C-8,
C-9), 46.1, 43.4 (C-1 and C-6), 36.2 (C-4). HRMS (m/z) calcd for
C9H16O6Na (M+Na+) 243.0845, found 243.0839.
Obtained from 22 (149 mg, 0.28 mmol); yield: 70% (0.20 mmol,
96 mg). ½a rDt
ꢀ
¼ ꢂ33:1 (c 1, CHCl3); 1H NMR d: 4.46–4.67 (m, 6H,
6 ꢁ OCH2Ph), 4.38 (d, J = 11.4 Hz, 1H, OCH2Ph), 4.02 (m, 2H, H-2
and H-7), 3.88–3.94 (m, 3H, H-5, H-8, H-9), 3.64 (m, 1H, H-3),
1.92–2.04 (m, 3H, H-1, H-6, H-4a), 1.56 (m, 1H, H-4b); 13C NMR
(150 MHz) d: 89.4, 78.9, 65.6 (C-5, C-8 and C-9), 83.9 (C-7), 72.2,
71.6, 70.8 (3 ꢁ OCH2Ph), 70.8 (C-3), 67.6 (C-2), 45.6, 44.1 (C-1,
C-6), 37.4 (C-4). HRMS (m/z) calcd. for C30H34O6Na (M+Na+)
513.2253, found 513.2255.
4.37. (1R,2R,3R,5S,6S,7S,8R,9R)-2,3,5,7,8,9-Hexahydroxybicyclo-
[4.3.0]nonane 43a
Debenzylation of 43 (80 mg, 0.16 mmol) afforded free deriva-
tive 43a (33 mg; 92%). ½a Drt
ꢀ
¼ ꢂ2:4 (c 1, CHCl3); 1H NMR (D2O) d:
3.88–3.92 (m, 3H, H-3, H-5, H-7), 3.71–3.77 (m, 3H, H-2, H-8,
H-9), 2.01 (m, 1H, H-1), 1.88 (m, 1H, H-4a), 1.67 (m, 1H, H-6),
1.53 (m, 1H, H-4b); 13C NMR (D2O) d: 86.9, 86.5, 77.7, 75.3, 71.2,
66.8, 64.3 (C-2, C-3, C-5, C-7, C-8, C-9), 44.0 (C-1), 43.9 (C-6),
35.5 (C-4). HRMS (m/z) calcd for C9H16O6Na (M+Na+) 243.0845,
found 243.0842.
4.32. (1R,2R,3R,5S,6S,7S,8R,9R)-7,8,9-Tri-O-benzyl-2,3,5-trihydroxy-
bicyclo [4.3.0]nonane 43
Obtained from 23 (117 mg, 0.21 mmol); yield: 80% (0.17 mmol,
86 mg). ½a rDt
ꢀ
¼ ꢂ13:1 (c 1, CHCl3); 1H NMR d: 4.69 (d, J = 12.1 Hz,
1H, OCH2Ph), 4.63 (d, J = 11.9 Hz, 1H, OCH2Ph), 4.52 (m, 3H,
3 ꢁ OCH2Ph), 4.46 (d, J = 11.6, 1H, OCH2Ph), 4.19 (dt, J = 4.5,
10.9 Hz, 1H, H-3), 4.52 (m, 3H, H-7, H-8, H-9), 3.83 (m, 1H, H-5),
2.42 (m, 1H, H-6), 1.96 (m, 1H, H-4a), 1.84 (m, 1H, H-1), 1.64 (m,
1H, H-4b); 13C NMR d: 89.2, 84.2, 79.3 (C-7, C-8 and C-9), 72.1,
71.7, 70.9 (C-2, 3 ꢁ OCH2Ph), 68.1 (C-5), 64.6 (C-3), 44.7 (C-1),
43.3 (C-6), 36.3 (C-4). HRMS (m/z) calcd for C30H34O6Na (M+Na+)
513.2253, found 513.2252.
4.38. (1S,2S,3S,5R,6R,7S,8R,9R)-2,3,5,7,8,9-Hexahydroxybicyclo-
[4.3.0]nonane 44a
Debenzylation of 44 (69 mg, 0.20 mmol) afforded free deriva-
tive 44a (30 mg; 95%). ½a Drt
ꢀ
¼ þ14:8 (c 1, CHCl3); 1H NMR (D2O)
d: 3.66–3.99 (m, 6H, H-2, H-3, H-5, H-7, H-8, H-9), 2.01 (m, 1H,
H-1), 1.83 (m, 2H, H-6 and H-4a), 1.58 (m, 1H, H-4b); 13C NMR
(D2O) d: 86.5, 82.6, 78.5, 70.9, 70.7, 70.1 (C-6, C-2, C-3, C-5, C-7,
C-8, C-9), 46.2 (C-1), 40.2 (C-6), 36.0 (C-4). HRMS (m/z) calcd for
C9H16O6Na (M+Na+) 243.0845, found 243.0843.
4.33. (1S,2S,3S,5R,6R,7S,8R,9R)-7,8,9-Tri-O-benzyl-2,3,5-trihydro-
xybicyclo[4.3.0] nonane 44
4.39. (1S,2R,3S,5S,6R,7S,8R,9R)-2,3,7,8,9-Penta-O-benzyl-5-hydroxy-
bicyclo[4.3.0] nonane 36
Obtained from 30 (110 mg, 0.21 mmol); yield: 91% (0.19 mmol,
92 mg). ½a rDt
ꢀ
¼ þ19:9 (c 1, CHCl3); 1H NMR d: 4.48–4.74 (m, 6H,
6 ꢁ OCH2Ph), 4.08 (d, J = 5.1 Hz, 1H, H-7), 4.05 (m, 1H, H-2), 4.01
(m,1H, H-3), 3.93 (d, J = 3.6, 1H, H-8), 3.87 (m, 2H, H-5 and H-9),
2.44 (m, 1H, H-6), 2.08 (ddd, J = 1.8, 4.9, 14.0 Hz, 1H, H-1), 1.95
(m, 1H, H-4a), 1.82 (m, 1H, H-4b); 13C NMR d: 90.2 (C-9), 88.4
(C-8), 84.7 (C-8), 72.1, 71.9, 70.9 (3 ꢁ OCH2Ph), 71.1 (C-3 and
C-5), 70.3 (C-2), 44.9 (C-6), 40.3 (C-1), 36.2 (C-4). HRMS (m/z) calcd
for C30H34O6Na (M+Na+) 513.2253, found 513.2250. Anal. Calcd for
Compound 36-Ac (33 mg, 0.05 mmol) was converted, according
to the general procedure for hydrolysis, into 36 isolated (29 mg,
92%) by column chromatography (hexane–ethyl acetate, 5:1).
½
a rDt
ꢀ
¼ þ45:6 (c 1, CHCl3); 1H NMR (C6D6) d: 4.74 (m, 2H, 2 ꢁ
OCH2Ph), 4.55 (m, 3H, H-7 and 2 ꢁ OCH2Ph), 4.50 (d, J = 12.0, 1H,
OCH2Ph), 4.40 (m, 2H, 2 ꢁ OCH2Ph), 4.35 (m, 3H, 3 ꢁ OCH2Ph),
4.24 (m, 2H, H-5 and H-9), 4.14 (d, J = 3.5 Hz, 1H, H-8), 3.76 (d,
J = 10.1 Hz, 1H, OH), 3.72, (m, 1H, H-3), 3.64 (dd, J = 2.6, 10.9 Hz,
1H, H-2), 2.87 (ddd, J = 4.8, 11.1, 13.8 Hz, 1H, H-1), 2.33 (ddd,
J = 2.4, 9.4, 13.8 Hz, 1H, H-6), 2.11 (dt, J = 14.9, 3.1 Hz, 1H, H-4a),
0.97 (m, 1H, H-4b); 13C NMR (C6D6) d: 88.6 (C-8), 85.9 (C-7),
81.3 (C-9), 79.1 (C-2), 75.5 (C-3), 72.9, 72.4, 71.2, 70.8, 70.6
(5 ꢁ OCH2Ph), 65.7 (C-5), 50.2 (C-6), 39.0 (C-1), 34.6 (C-4). LR-MS
(m/z) for C44H46O6Na (M+Na+) 693.4. Anal. calcd for C44H46O6:
C, 78.78; H, 6.91. Found: C, 78.83; H, 6.99.
C30H34O6: C, 73.45; H, 6.99. Found: C, 73.18; H, 6.99.
4.34. Removal of the benzyl groups from partially protected
derivatives. Preparation of bicyclic hexa-ols
To
a solution of the corresponding benzylated derivative
(0.2 mmol), 10% Pd/C was added (ꢃ60 mg) and the heterogeneous
mixture was placed in an autoclave under H2 pressure (20 bar).
After 3 h, the autoclave was decompressed and the mixture was fil-
tered through Celite and concentrated.
4.40. (1S,2R,3R,5R,6R,7S,8S,9R)-2,3,7,8,9-Penta-O-benzylo-5-
4.35. (1R,2S,3R,5S,6S,7S,8R,9R)-2,3,5,7,8,9-Hexahydroxybicyclo-
hydroxy-bicyclo [4.3.0]nonane 25a
[4.3.0]nonane 41a
Compound 25 (62 mg, 0.05 mmol) hydrolyzed according to the
Debenzylation of 41 (80 mg, 0.16 mmol) afforded free deriva-
general procedure afforded 25a (45 mg, 75%) as an oil. ½a Drt
ꢀ ¼ ꢂ18:0
tive 41a (32 mg; 90%). ½a Drt
ꢀ
¼ ꢂ51:8 (c 1, CHCl3); 1H NMR (D2O)
(c 1, CHCl3); 1H NMR (C6D6) d: 4.61 (d, J = 12.0 Hz, 1H, OCH2Ph),
4.49 (d, J = 12.0 Hz, 1H, OCH2Ph), 4.41 (m, 3H, H-5 and 2 ꢁ
OCH2Ph), 4.31 (dd, J = 3.6, 9.9 Hz, 1H, H-9), 4.24 (m, 3H,
3 ꢁ OCH2Ph), 4.15 (m, 2H, 2 ꢁ OCH2Ph), 4.08 (d, J = 3.6 Hz,
1H, H-8), 4.03 (d, J = 4.8 Hz, 1H, H-7), 3.82 (m, 1H, H-2), 3.63 (m,
1H, H-3), 2.90 (ddd, J = 2.6, 9.9, 13.8 Hz, 1H, H-1), 2.14 (ddd,
J = 4.8, 10.3, 13.8 Hz, 1H, H-6), 2.07 (dt, J = 13.5, 3.8 Hz, 1H, H-4a),
1.62 (m, 1H, H-4b); 13C NMR (C6D6) d: 89.9 (C-7), 84.7 (C-9), 79.9
(C-8), 75.4 (C-3), 73.5 (C-2), 72.0, 71.7, 71.4, 70.8, 70.6 (5 ꢁ OCH2Ph),
64.7 (C-5), 46.0 (C-6), 43.9 (C-1), 34.6 (C-4). HRMS (m/z) calcd for
d: 3.53–3.92 (m, 6H, H-2, H-3, H-5, H-7, H-8, H-9), 1.98-2.07 (m,
2H, H-4a and H-1 or H-6) and 1.37–1.47(m, 2H, H-4b and H-1 or
H-6); 13C NMR (D2O) d: 86.6, 83.1, 75.6, 75.1, 71,0, 63,8 (C-2, C-3,
C-5, C-7, C-8, C-9), 49.3, 43.8 (C-1 and C-6), 39.4 (C-4). HRMS
(m/z) calcd for C9H16O6Na (M+Na+) 243.0845, found 243.0842.
4.36. (1R,2R,3S,5S,6S,7S,8R,9R)-2,3,5,7,8,9-Hexahydroxybicyclo-
[4.3.0]nonane 42a
Debenzylation of 42 (96 mg, 0.20 mmol) afforded free deriva-
C
C
44H46O6Na (M+Na+) 693.3186, found 693.3187. Anal. calcd for
44H46O6: C, 78.78; H, 6.91. Found: C, 78.88; H, 6.69.
tive 42a (37 mg; 86%). ½a Drt
ꢀ
¼ ꢂ34:3 (c 1, CHCl3); 1H NMR (D2O)

1410
M. Magdycz, S. Jarosz / Tetrahedron: Asymmetry 24 (2013) 1402–1411
4.41. (1S,2R,3R,5R,6R,7S,8S,9R)-2,3,7,8,9-Penta-O-benzyl-5-O-
mesyl-bicyclo [4.3.0]nonane 25b
81.01 (C-7 andC-9), 78.88 (C-2), 73.12 (C-3), 71.98, 71.74, 71.66,
71.21, 70.50 (5 ꢁ OCH2Ph), 67.49 (C-5), 47.76 (C-6), 40.11 (C-1),
31.32 (C-4), 20.82 (C(O)CH3). HRMS (m/z) calcd for C46H48O7Na
(M+Na+) 735.3292, found 735.3292. Anal. calcd for C46H48O7: C,
77.50; H, 6.99. Found: C, 77.29; H; 6.93.
To a cooled (0 °C) solution of alcohol 25a (43 mg, 0.07 mmol)
and triethylamine (0.01 mL, 0.15 mmol) in methylene chloride
(10 mL), mesyl chloride (0.02 mL, 0.15 mmol) was added and the
mixture was stirred for 2 h (TLC monitoring in hexane–ethyl ace-
tate, 3:1). The mixture was then partitioned between water
(30 mL) and methylene chloride (20 mL). The organic phase was
separated, washed with water (15 mL), dried, concentrated, and
the product (45 mg, 0.06 mmol, 92%) was isolated by column chro-
4.44. (1S,2R,3S,7S,8R,9R)-2,3,7,8,9-Penta-O-benzyl-bicyclo[4.3.0]-
non-5,6-ene 37
To a solution of alcohol 34 (84 mg, 0.13 mmol) in THF (5 mL),
sodium hydride (50% dispersion in mineral oil, 7 mg, 0.15 mmol)
was added and the mixture was stirred at rt for 20 min. Carbon
disulfide (0.05 mL, 0.65 mmol) was added and—after another
20 min, methyl iodide (0.04 mL, 0.65 mmol), and the mixture was
stirred for 3 h at rt (TLC monitoring in hexane–ethyl acetate,
3:1). Next, it was partitioned between water (10 mL) and ethyl ace-
tate (10 mL), the organic phase was separated, and the aqueous
phase extracted with ethyl acetate (10 mL). The combined organic
solutions were washed with water and brine (5 mL each), dried,
and concentrated. Crude xanthate 35 was heated at 200 °C for
1 h (TLC monitoring in hexane–ethyl acetate, 3:1). After cooling
to rt, the crude product was purified by column chromatography
(hexane–ethyl acetate, 11:1) to afford olefin 37 (10 mg, 0.02 mmol,
12%) as an oil. 1H NMR (C6D6) d: 5.79 (m, 1H, H-5), 4.56 (m, 3H,
3 ꢁ OCH2Ph), 4.46 (m, 4H, 4 ꢁ OCH2Ph), 4.32 (m, 4H, 3 ꢁ OCH2Ph
and 1H), 4.21 (d, J = 5.6 Hz, 1H), 4.02 (m, 2H), 3.92 (s, 1H), 3.83
(m, 1H), 2.31 (m, 1H, H-4a), 1.92 (m, 1H, H-4b); 13C NMR (C6D6)
d: 117.12 (C-5),86.90, 85.77, 81.82, 77.49, 72,74 (C-2, C-3, C-7,
C-8, C-9), 71.87, 71.78, 71.43, 71.32, 70.83 (5 ꢁ OCH2Ph), 44.21
(C-1), 31.13 (C-4). LR-MS (m/z) for C44H45O5Na (M+Na+) 675.3.
matography (hexane–ethyl acetate, 10:1) as an oil. ½a Drt
ꢀ ¼ ꢂ7:4 (c 1,
CHCl3); 1H NMR d: 5.51 (dt, J = 4.5, 10.9 Hz, 1H, H-5), 4.54 (m, 2H,
2 ꢁ OCH2Ph), 4.45 (dd, J 8.8, 11.7 Hz, 2H, 2 ꢁ OCH2Ph), 4.44 (d,
J = 12.1 Hz, 1H, OCH2Ph), 4.36 (m, 2H, 2 ꢁ OCH2Ph), 4.33 (m, 4H,
H-9, 3 ꢁ OCH2Ph), 4.17 (dd, J = 4.3, 11.7 Hz, 2H, 2 ꢁ OCH2Ph), 4.08
(d, J = 12.0 Hz, 1H, OCH2Ph), 4.03 (m, 2H, H-7 and H-8), 3.79 (m,
1H, H-2), 3.64 (m, 1H, H-3), 3.07 (ddd, J = 2.6, 9.6, 13.8 Hz, 1H,
H-1), 2.68 (dt, J = 13.4, 3.8 Hz, 1H, H-4a), 2.57 (ddd, J = 4.5, 10.6,
13.8 Hz, 1H, H-6), 2.31 (s, 3H, -OMs), 1.94 (m, 1H); 13C NMR d:
88.0, 80.3 (C-7, C-8), 85.0 (C-9), 76.7 (C-5), 75.0 (C-3), 73.5 (C-2),
72.3, 72.2, 71.7, 70.9, 70.8 (5 ꢁ OCH2Ph), 44.7 (C-1), 43.7 (C-6),
37.7 (OMs), 32.3 (C-4); HRMS (m/z) calcd for C45H48O8SNa
(M+Na+) 771.2958, found 771.2965. Anal. calcd for C45H48O8S: C,
72.17; H, 6.46. Found: C, 72.29; H. 6.43.
4.42. (1S,2R,3S,5R,6R,7S,8R,9R)-2,3,7,8,9-Penta-O-benzyl-5-O-
mesyl-bicyclo[4.3.0] nonane 33
Alcohol 34 (100 mg, 0.15 mmol), converted into 33 (90 mg,
0.12 mmol, 81%) analogously to 25, was purified by column chro-
matography (toluene–methanol, 19:1). ½a Drt
ꢀ
¼ þ47:8 (c 1, CHCl3);
4.45. (1S,2R,3R,6R,7S,8S,9R)-2,3,7,8,9-Penta-O-benzylbicyclo[4.3.0]-
non-4,5-ene 40
1H NMR (C6D6) d: 5.08 (dt, J = 4.4, 10.9 Hz, 1H, H-5), 4.56 (m, 1H,
OCH2Ph), 4.50 (m, 2H, 2 ꢁ OCH2Ph), 4.44 (d, J = 12.1 Hz, 1H,
OCH2Ph), 4.36 (m, 2H, 2 ꢁ OCH2Ph), 4.30 (d, J = 11.7 Hz, 1H, OCH2Ph),
4.21 (d, J = 11.7 Hz, OCH2Ph), 4.12 (d, J = 4.2 Hz, 1H), 4.03 (dd,
J = 2.6, 8.8 Hz, 1H), 3.95 (d, J = 2.6 Hz, 1H), 3.65 (m, 1H), 3.60 (dd,
J = 2.6, 10.9 Hz, 1H), 2.78 (m, 1H), 2.63 (m, 2H), 2.21 (s, 3H,
-OMs), 1.27 (m, 1H); 13C NMR (C6D6) d: 89.9, 87.6, 80.0,79.7,
77.8, 73.1 (C-2, C-3, C-5, C-7, C-8, C-9), 71.8, 71.4, 71.3, 70.8, 70.6
(5 ꢁ OCH2Ph), 47.9, 43.5 (C-1, C-6), 37.2 (-OMs), 36.2 (C-4). HRMS
To a solution of compound 25b (33 mg, 0.04 mmol) in DMF
(10 mL), CsOAc (14 mg, 0.08 mmol) was added and the mixture
was stirred and heated at reflux for 48 h (TLC monitoring in hex-
ane–ethyl acetate, 3:1). After cooling, it was partitioned between
water (20 mL) and ether (30 mL), the organic phase was separated,
and the aqueous phase extracted with ether (2 ꢁ 20 mL). The com-
bined organic solutions were washed with water and brine (10 mL
each), dried, concentrated, and the crude product was purified by
column chromatography (hexane–ethyl acetate, 3:1) to afford 40
(14 mg, 45%) as an oil. 1H NMR (C6D6) d: 6.19 (d, J = 10.2, 1H),
5.88 (m, 1H), 4.65 (d, J = 12.1 Hz, 1H), 4.55 (d, J = 12.1 Hz, 1H),
4.43 (m, 3H), 4.33 (m, 6H), 4.17 (s, 1H), 4.15 (d, J = 3.7 Hz, 1H),
3.95 (m, 1H), 3.81 (d, J = 4.8 Hz), 3.05 (ddd, J = 2.1, 10.1, 12.7 Hz,
1H), 2.88 (m, 1H); 13C NMR (C6D6) d: 131.39, 126.77 (C-4 and
C-5), 91.10, 84.38, 81.74, 75.18, 73.50 (C-2, C-3, C-7, C-8, C-9),
72.19, 71.83, 71.65, 71.34, 70.98 (5 ꢁ OCH2Ph), 44.23, 38.76 (C-1
and C-6). HRMS (m/z) calcd for C44H44O5Na (M+Na+) 675.3086,
found 675.3082.
(m/z) calcd for
C
45H48O8SNa (M+Na+): 771.2962, found
771.2965.Anal. calcd for C45H48O8S: C, 72.17; H, 6.46; S, 4.28.
Found: C, 72.06; H, 6.32; S, 4.47.
4.43. (1S,2R,3S,5S,6R,7S,8R,9R)-2,3,7,8,9-Penta-O-benzyl-5-O-
acetyl-bicyclo[4.3.0] nonane 36-Ac
A solution of mesylate 33 (50 mg, 0.07 mmol) and cesium ace-
tate (14 mg, 0.08 mmol) in DMF (10 mL) was stirred at rt for 48 h
(TLC monitoring in hexane–ethyl acetate, 3:1), and then parti-
tioned between water (20 mL) and ether (30 mL). The organic
phase was separated and the aqueous phase extracted with ether
(2 ꢁ 10 mL). The combined organic solutions were washed with
water and brine (5 mL each), dried, concentrated, and the crude
product was isolated by column chromatography (hexane–ethyl
acetate, 9:1) to afford 36-Ac (35 mg, 0.05 mmol, 65%) as an oil.
Acknowledgements
The support from Grant: POIG.01.01.02-14-102/09 (part-
financed by the European Union within the European Regional
Development Fund) is acknowledged.
½
a rDt
ꢀ
¼ þ7:8 (c 1, CHCl3); 1H NMR (C6D6) d: 5.33 (m, 1H, H-5),
4.67 (d, J = 12.3, 1H, OCH2Ph), 4.57 (m, 2H, 2 ꢁ OCH2Ph), 4.50 (d,
J = 11.6 Hz, 1H, OCH2Ph), 4.39 (m, 4H, 4 ꢁ OCH2Ph), 4.32 (d,
J = 11.9 Hz, 1H, OCH2Ph), 4.24 (d, J = 11.9 Hz, 1H, OCH2Ph), 4.18
(m, 2H, H-7, H-9), 4.11 (d, J = 3.2 Hz, 1H, H-8), 3.66 (dd, J1 = 3.2,
11.0 Hz, 1H, H-2), 3.62 (m, 1H, H-3), 3.05 (ddd, J = 4.5, 10.7,
13.7 Hz, 1H, H-1), 2.59 (dt, J = 15.8, 2.9 Hz, 1H, H-4a), 2.40 (ddd,
J = 2.9, 9.7, 13.7 Hz, 1H, H-6), 1.55 (s, 3H, C(O)CH3), 0.92 (m, 1H,
H-4b); 13C NMR (C6D6) d: 170.36 (C(O)CH3), 89.29 (C-8), 84.64,
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