Pd(II)-mediated synthesis of 2-deoxy- and rare-C-glycosides

Article abstract of DOI:10.1016/S0957-4166(01)00098-2

The synthesis of 2-deoxy-C-glycosides and rare-C-saccharides from the γ,δ-olefinic alcohols is described. In the presence of Pd(II) reagents these olefinic alcohols undergo an efficient intramolecular oxidative cyclisation to afford the target molecules.

Full text of DOI:10.1016/S0957-4166(01)00098-2

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 539–544
Pd(II)-mediated synthesis of 2-deoxy- and rare-C-glycosides†
G. V. M. Sharma,* A. Subhash Chander and Palakodety Radha Krishna
Discovery Laboratory D-211, Organic Chemistry Division III, Indian Institute of Chemical Technology,
Hyderabad 500 007, India
Received 13 October 2000; accepted 6 February 2001
Abstract—The synthesis of 2-deoxy-C-glycosides and rare-C-saccharides from the g,d-olefinic alcohols is described. In the
presence of Pd(II) reagents these olefinic alcohols undergo an efficient intramolecular oxidative cyclisation to afford the target
molecules. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Bio-active carbohydrates play a prominent role in sev-
eral life processes. The synthesis of glycosyl mimics,1
where the acid labile O-glycosidic bond is replaced by a
C-glycosidic bond, has attracted attention in the recent
past. A variety of C-glycosides, 2-deoxy-C-glycosides
and rare-C-glycosides are common structural elements
in several natural products, especially antibiotics with
2.1. Synthesis of 2-deoxy-C-methyl glycoside 1
The requisite olefinic alcohols for the synthesis of 2-
deoxy-C-glycosides were prepared from 2,3-O-iso-
propylidene-(R)-glyceraldehyde. Accordingly,
4
on
reaction with allyl bromide (Scheme 1) in the presence
of zinc in THF12 gave carbinol 5. On reaction of 5 with
benzyl bromide in the presence of sodium hydride the
benzyl ether 6 formed cleanly. On hydrolysis with 60%
aq. AcOH formation of the diol 7 was effected in 75%
yield. Benzoylation of 7 with benzoyl chloride in the
presence of pyridine in CH2Cl2 gave the mono-benzoate
8 along with minor amounts of di-benzoate.
antitumor
activity
such
as
daunorubicin,2
calicheamycin3 and olivomycin A,4 and a number of
compounds of the aureolic acid family. The synthesis of
monosaccharides, which find widespread application as
intermediates in natural product synthesis,5 is therefore
challenging to synthetic organic chemists.
In continuation of our interest on the synthesis of rare
The olefinic alcohol 8 on reaction with PdCl2–CuCl–O2
underwent oxidative cyclisation13,14 and gave the 2-
deoxy hemiketal 9 in 86% yield, which on reductive
deoxygenation with triethylsilane15 in the presence of
boron trifluoride monoetherate, furnished the 2-deoxy-
C-methyl glycoside 1 as an inseparable mixture of a-
and b-isomers in a 1:1 ratio in 70% yield.
saccharides6, C-glycosides7,8
,
C-saccharides9,10 and
pseudo saccharides,11 and the prominent place occupied
by the 2-deoxy and rare-C-saccharides, herein we
describe the Pd(II)-mediated synthesis of these com-
pounds from olefinic alcohols by an oxidative cyclisa-
tion protocol.
O
O
O
O
BzO
BzO
CH3
BnO
OBn
1
OBn
OBn
2
3
* Corresponding author. E-mail: esmvee@iict.ap.nic.in
†
IICT Communication No. 4643.
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00098-2

540
G. V. M. Sharma et al. / Tetrahedron: Asymmetry 12 (2001) 539–544
Br
OR'
O
O
1. Zn,
RO
O
O
3. 60% aq. AcOH
aq. NH4Cl, THF
2. BnBr, NaH, DMF
CHO
4. BzCl, Py, CH2Cl2
4
OBn
OR
7 R = R' = H
5 R = H
8 R = Bz, R' = H
8a R = R' =Bz
6 R = Bn
O
O
BzO
BzO
OH
CH3
6. Et3SiH, BF3.Et2O
5. PdCl2 - CuCl - O2
dry CH3CN, 00C
CH3CN:H2O (7:1)
OBn
OBn
9
1 α / β = 1:1
Scheme 1.
2.2. Synthesis of 2-deoxy-C-vinyl glycoside 2
of the sugar. The main strategy was to convert the 5,
6-diol of DAG into an olefin, where use of the C-(2)
hydroxyl group as an internal nucleophile for oxidative
cyclisation would result in an unusual C-methyl
glycoside.
Carbinol 5 was subjected to ozonolysis in CH2Cl2 at
−78°C to give the corresponding aldehyde 10 (Scheme
2), which on Wittig olefination with ethyl
triphenylphosphorane gave olefin 11. On reaction with
benzyl bromide and sodium hydride 12 was formed in
78% yield, which on hydrolysis with 60% aq. AcOH
gave diol 13 in 70% yield. Reaction of 13 with benzoyl
chloride in the presence of pyridine in CH2Cl2 gave the
mono-benzoate 14 along with traces of di-benzoate.
Oxidative cyclisation of the olefinic alcohol 14 with
Pd(OAc)2–NaOAc–O2 in DMSO then gave the 2-
deoxy-C-vinyl glycoside 2 as a 1:1 ratio of inseparable
a- and b-isomers in a 65% yield.
Olefin 15, prepared (Scheme 3) through a known proce-
dure,16,17 was subjected to hydrolysis with 60% aq.
AcOH in the presence of conc. H2SO4 (catalytic) to
afford the diol 16. Reduction of 16 with sodium boro-
hydride in ethanol followed by further reaction of triol
with acetone CuSO4 gave 17 in 47% overall yield. The
alcohol 17 was then reacted with benzyl bromide in the
presence of sodium hydride to afford 18 in 85% yield.
Hydrolysis of 18 with 60% aq. AcOH at room tempera-
ture gave the diol 19, which finally on PdCl2–CuCl–O2-
mediated oxidative cyclisation afforded the 1,6-anhydro
2.3. Synthesis of the rare-C-methyl glycoside 3
rare-C-glycoside 3 (L-xylo derivative) in 70% yield.
The rare saccharide synthesis was initiated from ‘diacet-
one glucose’ (DAG), where unlike the case of earlier
allylic alcohols, the olefin was incorporated at the C-(5)
Thus, in summary the protocol presented is a mild and
efficient method for the synthesis of 2-deoxy-C-methyl
O
O
1. O3, CH2Cl2, -780C
4. 60% aq. AcOH
X
5
2. Ph3P+C2H5Br-
n-BuLi, THF
5. BzCl, Py, CH2Cl2
OR
3. BnBr, NaH, DMF
10 X = O, R = H
11 X = CHCH3, R = H
14 X = CHCH3, R = Bn
O
BzO
OH
RO
6. Pd(OAc)2 - NaOAc - O2
DMSO
OBn
OBn
13 R = H
2 α / β = 1:1
14 R = Bz
Scheme 2.

G. V. M. Sharma et al. / Tetrahedron: Asymmetry 12 (2001) 539–544
541
OBn
O
O
OH
OBn
1. 60% aq. AcOH
2. NaBH4, EtOH
O
OBn
O
H+
OR
3. CH3COCH3
CuSO4, H+
O
O
OH
15
4. BnBr, NaH, DMF
16
17 R = H
18 R = Bn
O
O
OBn
BnO
5. 60% aq. AcOH
6. PdCl2-CuCl-O2
CH3CN:H2O (7:1)
OH
OBn
OH
OBn
19
3
Scheme 3.
glycoside 1, 2-deoxy-C-vinyl glycoside 2 and rare-C-
methyl glycoside 3 using the Pd(II)-mediated oxidative
cyclisation of g,d-olefinic alcohols by an internal oxy-
gen nucleophile. The Markownikoff addition product,
the hemiketal, was efficiently converted into 2-deoxy-C-
methyl glycoside by reductive deoxygenation. The util-
ity of the present methodology and the C-glycosides
synthesised could find wide use in the synthesis of new
glyco substances.
CH3), 2.20–2.52 (m, 2H, H-3,3%), 3.30–3.62 (m, 1H,
H-4), 3.83–4.26 (m, 3H, H-5,6,6%), 4.58–4.70 (m, 2H,
-OCH2Ph), 5.00–5.20 (m, 2H, H-1,1%), 5.76–6.01 (m,
1H, H-2), 7.21–7.40 (m, 5H, -OCH2Ph); EIMS (m/z,
%): 247 (17), 171 (56), 155 (100), 91 (78). Anal. calcd
for C16H22O3: C, 73.25; H, 8.45. Found: C, 73.19; H,
8.41%.
3.2. 3-Benzyloxy-(2R,3S)-5-hexene-1,2-diol 7
A solution of 6 (0.9 g, 3.43 mmol) in 60% aq. acetic
acid (10 mL) was stirred at room temperature for 12 h.
The reaction mixture was neutralised with excess solid
NaHCO3 (8 g) and the compound was extracted into
ethyl acetate (3×15 mL). The combined ethyl acetate
layers were washed with water (15 mL), brine (15 mL)
and dried (Na2SO4). Evaporation of solvent and purifi-
cation of the residue by column chromatography (60–
120 mesh silica gel, ethyl acetate: petroleum ether 1:4)
gave 7 as a syrup (0.57 g 75%). [h]D=+3.95 (c 1.92,
3. Experimental
Solvents were dried over standard drying agents and
freshly distilled prior to use. 1H (200 MHz, 500
MHz) and 13C NMR (50 MHz, 125 MHz) spectra
were recorded in deuteriochloroform solution with
tetramethylsilane as an internal reference on Varian
Gemini-200 MHz and INOVA-500 MHz spectrometers,
and coupling constants (J) are given in Hz. Optical
rotations were measured with a Jasco DIP-370 instru-
ment and [h]D values are in units of 10−1 deg cm2 g−1.
Organic solutions were dried over anhydrous Na2SO4
and concentrated below 40°C in vacuo. The nomencla-
ture used in the experimental section was adopted from
ACD/Name version 1.0b, ACD Inc., Toronto, Canada.
1
CHCl3); IR (neat): 1080, 2936, 3400 cm−1; H NMR
(200 MHz, CDCl3): l 2.08–2.65 (m, 3H, H-3,3% -OH),
3.45–3.72 (m, 4H, H-4,5,6,6%), 4.40–4.74 (m, 2H,
-OCH2Ph), 5.02–5.20 (m, 2H, H-1,1%), 5.70–5.98 (m,
1H, H-2), 7.20–7.40 (m, 5H, -OCH2Ph); EIMS (m/z,
%): 222 (M+, 3), 205 (19), 131 (100), 107 (58). Anal.
calcd for C13H18O3: C, 70.25; H, 8.16. Found: C, 70.17;
H, 8.09%.
3.1. 4-[1-Benzyloxy-(1S)-3-butenyl]-2,2-dimethyl-(4R)-
1,3-dioxolane 6
3.3. Benzoylation of diol 7
To a stirred solution of 5 (1.0 g, 5.81 mmol) in dry
DMF (3 mL), sodium hydride (60% dispersion in oil,
0.53 g, 11.62 mmol,) was added at 0°C and stirred for
30 min. Benzyl bromide (0.68 mL, 5.81 mmol) was
added and further stirred for 3 h at room temperature.
The reaction was quenched by adding aq. NH4Cl solu-
tion (10 mL) and the compound was extracted into
ether (2×15 mL). The combined ether layers were
washed with water (20 mL), brine (20 mL) and dried
(Na2SO4). Evaporation of the solvent and purification
of the residue by column chromatography (60–120
mesh silica gel, ethyl acetate: petroleum ether 1:9) gave
6 as a syrup (0.99 g, 65%). [h]D=+16.9 (c 2.88, CHCl3);
1H NMR (200 MHz, CDCl3): l 1.34, 1.55 (2s, 6H,
To a stirred solution of 7 (1.2 g, 5.40 mmol) and
pyridine (0.87 mL, 10.81 mmol) in CH2Cl2 (10 mL),
was added dropwise benzoyl chloride (0.75 mL, 5.40
mmol) in CH2Cl2 (2 mL) at 0°C. The reaction mixture
was stirred for 3 h at 0°C then diluted with cold water
(20 mL) and extracted into CH2Cl2 (2×20 mL) and the
combined CH2Cl2 layers were washed with 5% cold aq.
HCl solution (25 mL), aq. NaHCO3 solution (20 mL),
water (20 mL), brine (20 mL) and dried (Na2SO4).
Evaporation of the solvent and purification of the
residue by column chromatography (60–120 mesh silica
gel, ethyl acetate: petroleum ether 1:4) gave 8 and 8a
(total 1.37 g 75%) in two bands.

542
G. V. M. Sharma et al. / Tetrahedron: Asymmetry 12 (2001) 539–544
First eluted was 1-[1-[1,2-di(phenylcarbonyloxy)-(1R)-
ethyl]-(1S)-3-butenyloxymethyl] benzene 8a as a syrup
H-1), 4.16–4.70 (m, 6H, H-3,4,5,5%,-OCH2Ph), 7.18–7.33
(m, 5H, -OCH2Ph), 7.37–7.60 (m, 3H, Ph), 7.98–8.10
(m, 2H, Ph); FABMS (m/z, %): 311 (21), 309 (43), 105
(100), 91 (87). Anal. calcd for C20H22O4: C, 73.60; H,
6.79. Found: C, 73.56; H, 6.72%.
1
(0.23 g, 10%). H NMR (200 MHz, CDCl3): l 2.35–
2.60 (m, 2H, H-3,3%), 3.80–3.92 (m, 1H, H-4), 4.60–4.80
(m, 4H, H-6,6%, -OCH2Ph), 5.05–5.20 (m, 2H, H-1,1%),
5.50–5.65 (m, 1H, H-5), 5.76–5.98 (m, 1H, H-2), 7.20–
7.40 (m, 5H, -OCH2Ph), 7.42–7.64 (m, 6H, Ph), 7.90–
8.10 (m, 4H, Ph); FABMS (m/z, %): 430 (M+, 9), 220
(100), 210 (43), 107 (67).
3.6. 1-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-(1S,3E)-3-
penten-1-ol 11
A stirred solution of 5 (2.0 g, 11.62 mmol) in dry
CH2Cl2 (20 mL), was bubbled with ozone continuously
for 15 min (until the colour of the reaction mixture
changed to blue) at −78°C and triphenylphosphine (3.3
g, 12.79 mmol) was added and stirred for 5 min. The
reaction mixture was warmed to room temperature and
evaporated under reduced pressure to give the crude
aldehyde 10.
Second eluted was 1-[1-[1-hydroxy-2-phenylcarbony-
loxy-(1R)-ethyl]-(1S)-3-butenyloxy methyl]benzene 8 as
1
a syrup (1.14 g, 65%). [h]D=+12.4 (c 1.50, CHCl3); H
NMR (200 MHz, CDCl3): l 2.42–2.57 (m, 2H, H-3,3%),
3.50–3.65 (m, 1H, H-4), 3.86–4.02 (m, 1H, H-5), 4.32–
4.76 (m, 4H, H-6,6%-OCH2Ph), 5.05–5.25 (m, 2H, H-
1,1%), 5.71–6.01 (m, 1H, H-2), 7.20–7.34 (m, 5H,
-OCH2Ph), 7.36–7.60 (m, 3H, Ph), 7.94–8.05 (m, 2H,
Ph); FABMS (m/z, %): 327 (M++1, 19), 219 (15), 105
(72), 91 (100), 55 (45). Anal. calcd for C20H22O4: C,
73.60; H, 6.79. Found: C, 73.55; H, 6.71%.
To a stirred suspension of ethyl triphenylphosphonium
bromide (5.1 g, 11.79 mmol) in dry THF (50 mL),
potassium tert-butoxide (1.5 g, 13.79 mmol) in dry
THF (10 mL) was added at room temperature over 10
min under nitrogen atmosphere. After 30 min a solu-
tion of the above aldehyde 10 in dry THF (10 mL) was
added dropwise at room temperature and stirred for
further 18h. The reaction mixture was quenched by
adding aq. NH4Cl solution (20 mL) and extracted into
ether (2×25 mL). The combined ether layers were
washed with water (20 mL), brine (20 mL) and dried
(Na2SO4). Evaporation of solvent and purification of
residue by column chromatography (60–120 mesh silica
gel, ethyl acetate: petroleum ether 1:9) gave 11 as a
syrup (1.03 g, 48% overall yield from 5). [h]D=+ 13.4 (c
1.08, CHCl3); 1H NMR (200 MHz, CDCl3): l 1.34,
1.40 (2s, 6H, CH3), 1.56–1.73 (m, 3H, CH3), 2.17–2.30
(m, 2H, H-4,4%), 3.60–3.78 (m, 1H, H-7), 3.82–4.05 (m,
3H, H-5,6,7%), 5.32–5.74 (m, 2H, H-2,3); EIMS (m/z,
%): 171 (17), 169 (29), 43 (100).
3.4. 3-Benzyloxy-5-hydroxy-5-methyl-2-phenylcarbonyl-
oxymethyl-(2R,3S)-tetrahydrofuran 9
To a stirred solution of 8 (0.2 g, 0.61 mmol), pallad-
ium(II) chloride (0.01 g, 0.06 mmol) and copper(I)
chloride (0.06 g, 0.61 mmol) in aq. acetonitrile (3 mL,
1:7), oxygen gas was bubbled continuously for 2 h. The
reaction mixture was filtered through a silicagel bed
with ether eluent. Evaporation of solvent and purifica-
tion of residue by column chromatography (60–120
mesh silica gel, ethyl acetate: petroleum ether 1:9) gave
9 (0.18 g, 86%) as an inseparable mixture of isomers. 1H
NMR (200 MHz, CDCl3): l 1.50–1.60 (m, 3H, CH3),
1.90–2.08 (m, 2H, H-2,2%), 3.85–4.00 (m, 1H, H-3),
4.04–4.20 (m, 1H, H-4), 4.23–4.75 (m, 4H, H-5,5%,-
OCH2Ph), 7.20–7.35 (m, 5H, -OCH2Ph), 7.40–7.62 (m,
3H, Ph), 7.93–8.12 (m, 2H, Ph); FABMS (m/z, %): 327
(19), 325 (81), 105 (57), 91 (100), 55 (71). Anal. calcd
for C20H22O5: C, 70.16; H, 6.48. Found: C, 70.11; H,
6.41%.
3.7. 4-[1-Benzyloxy-(1S,3E)-3-pentenyl]-2,2-dimethyl-
(4R)-1,3-dioxolane 12
To a stirred solution of 11 (1.5 g, 8.06 mmol) in dry
DMF (3 mL), was added sodium hydride (0.77 g, 16.12
mmol, 60% suspension), followed by benzyl bromide
(1.14 mL, 9.67 mmol). The reaction was worked up and
purified as described for 6, to give 12 as a syrup (1.74 g
3.5. 3-Benzyloxy-5-methyl-2-phenylcarbonyloxymethyl-
(2R,3S)-tetrahydrofuran 1
To a stirred solution of 9 (0.1 g, 0.29 mmol) and
triethylsilane (0.09 mL, 0.58 mmol) in dry acetonitrile
(3 mL), boron trifluoride etherate (0.036 mL, 0.29
mmol) was added under nitrogen atmosphere at 0°C
and stirred for 15 min. The reaction mixture was
diluted with aq. K2CO3 solution (2 mL), brought to
room temperature and stirred for further 1 h. The
mixture was extracted into ether (2×10 mL) and the
combined ether extracts were washed with water (10
mL), brine (10 mL) and dried (Na2SO4). Evaporation
of solvent and purification of residue by column chro-
matography (60–120 mesh silica gel, ethyl acetate:
petroleum ether 1:9) gave 1 (0.066 g) in 70% yield as an
inseparable mixture of isomers (1:1). [h]D=+7.7 (c 1.42,
CHCl3); IR (neat): 700, 1100, 1280, 1728, 2944 cm−1; 1H
NMR (200 MHz, CDCl3): l 1.30 (d, 3H, J 6.8 Hz,
CH3), 2.08–2.32 (m, 2H, H-2,2%), 3.98–4.08 (m, 1H,
1
78%). [h]D=+5.6 (c 1.04, CHCl3); H NMR (200 MHz,
CDCl3): l 1.30–1.45 (m, 6H, CH3), 1.60–1.72 (m, 3H,
CH3), 2.20–2.42 (m, 2H, H-4,4%), 3.42–3.60 (m, 1H,
H-7), 3.80–3.92 (m, 1H, H-7%), 3.96–4.10 (m, 2H, H-
5,6), 4.48–4.72 (m, 2H, -OCH2Ph), 5.40–5.66 (m, 2H,
H-2,3), 7.20–7.42 (m, 5H, -OCH2Ph); EIMS (m/z, %):
261 (27), 233 (43), 185 (100), 91 (78). Anal. calcd for
C17H24O3: C, 73.88; H, 8.75. Found: C, 73.80; H,
8.69%.
3.8. 3-Benzyloxy-(2R,3S,5E)-5-heptene-1,2-diol 13
Compound 12 (1.7 g, 6.15 mmol) was taken in 60% aq.
acetic acid (10 mL) and stirred for 12 h at room
temperature, worked up and purified as described for 7,
to give 13 as a syrup (1.01 g, 70%). [h]D=+17.8 (c 1.40,

G. V. M. Sharma et al. / Tetrahedron: Asymmetry 12 (2001) 539–544
543
1
CHCl3); H NMR (200 MHz, CDCl3): l 1.55–1.70 (m,
3H, CH3), 2.22–2.50 (m, 2H, H-4,4%), 2.92–3.30 (br. s,
2H, -OH), 3.40–3.72 (m, 4H, H-5,6,7,7%), 4.40–4.70 (m,
2H, -OCH2Ph), 5.32–5.64 (m, 2H, H-2,3), 7.18–7.36 (m,
5H, -OCH2Ph); EIMS (m/z, %): 221 (9), 219 (14), 129
(53), 91 (100). Anal. calcd for C14H20O3: C, 71.16; H,
8.53. Found: C, 71.08; H, 8.46%.
3.12. 1-Benzyloxy[2,2-dimethyl-(4S)-1,3-dioxolan-4-yl]-
methyl-(1R)-2-propenyl alcohol 17
To a solution of 16 (2.2 g, 9.32 mmol) in ethanol (15
mL) sodium borohydride (0.69 g, 18.64 mmol) was
added in portions and stirred for 2 h at room tempera-
ture. Solvent was evaporated under reduced pressure
and the crude triol was subjected to the next reaction.
3.9. 1-[1-[1-Hydroxy-2-phenylcarbonyloxy-(1R)-ethyl]-
(1S,3E)-3-pentenyloxymethyl]benzene 14
To a solution of the above triol and dry CuSO4 (5.0 g)
in acetone (20 mL), conc. H2SO4 (catalytic) was added
and stirred for 12 h at room temperature. The reaction
mixture was filtered off, neutralised with solid NaHCO3
(5.0 g) and extracted into ethyl acetate (2×20 mL). The
combined ethyl acetate layers were washed with water
(20 mL), brine (20 mL) and dried (Na2SO4). Evapora-
tion of solvent and purification of residue by column
chromatography (60–120 mesh silica gel, ethyl acetate:
petroleum ether 1:9) gave 17 as a syrup (1.21 g, 47%
To a stirred solution of 13 (0.65 g, 2.75 mmol) and
pyridine (0.44 mL, 5.50 mmol) in dry CH2Cl2 (10 mL),
benzoyl chloride (0.32 mL, 2.75 mmol) in dry CH2Cl2
(2 mL) was added drop wise at 0°C, worked up and
purified as described for 8, to give 14 (0.7 g) in 76%
yield as a syrup. [h]D=+21.95 (c 1.16, CHCl3); 1H
NMR (200 MHz, CDCl3): l 1.62–1.72 (m, 3H, CH3),
2.36–2.60 (m, 2H, H-4,4%), 3.50–3.68 (m, 1H, H-5),
3.85–4.05 (m, 1H, H-6), 4.32–4.78 (m, 4H, H-7,7%–
OCH2Ph), 5.40–5.70 (m, 2H, H-2,3), 7.20–7.35 (m, 5H,
-OCH2Ph), 7.45–7.54 (m, 3H, -CO2Ph), 8.00 (d, 2H,
-CO2Ph); FABMS (m/z, %): 340 (M+, 5), 323 (32), 249
(43), 235 (100), 105 (87). Anal. calcd for C21H24O4: C,
74.09; H, 7.11. Found: C, 74.03; H, 7.05%.
1
yield from 16). [h]D=−3.8 (c 1.0, CHCl3); H NMR
(200 MHz, CDCl3): l 1.34, 1.40 (2s, 6H, CH3), 2.35 (br.
d, 1H, -OH), 3.37 (dd, 1H, J3,4 6.0, J4,5 4.0 Hz, H-4),
3.74 (t, 1H, J5,6 8.0, J6,6% 8.0 Hz, H-6), 3.94–4.10 (m, 2H,
H-5,6%), 4.28 (dd, 1H, J3,4 6.0, J2,3 16.0 Hz, H-3), 4.62,
4.80 (2d, 2H, -OCH2Ph), 5.17 (d, 1H, J 10.0 Hz, H-1),
5.32 (d, 1H, J 16.0 Hz, H-1%), 5.78–5.95 (m, 1H, H-2),
7.20–7.36 (m, 5H, -OCH2Ph); EIMS (m/z, %): 263 (31),
261 (25), 187 (100), 107 (54). Anal. calcd for C16H22O4:
C, 69.04; H, 7.97. Found: C, 68.99; H, 7.93%.
3.10. 3-Benzyloxy-2-phenylcarbonyloxymethyl-5-vinyl-
(2R,3S)-tetrahydrofuran 2
To a stirred solution of 14 (0.1 g, 0.28 mmol), palladium-
(II) acetate (0.01 g, 0.002 mmol) and NaOAc (0.046 g,
0.56 mmol) in dry DMSO (3 mL), oxygen was bubbled
for 12 h at 50°C. The reaction mixture was brought to
room temperature, diluted with water (20 mL) and
extracted into ether (2×15 mL). The combined ether
layers were washed with water (15 mL), brine (20 mL)
and dried (Na2SO4). Evaporation of solvent and purifi-
cation of residue by column chromatography (60–120
mesh silica gel, ethyl acetate: petroleum ether 1:9), gave
2 (0.06 g) in 65% yield as an inseparable mixture
3.13. 3,4-Dibenzyloxy-4-[2,2-dimethyl-(4S)-1,3-dioxolan-
4-yl]-(3R)-1-butene 18
To a stirred solution of 17 (1.0 g, 3.59 mmol) in DMF
(3 mL), NaH (60% suspension in mineral oil, 0.33 g,
7.19 mmol,) followed by benzyl bromide (0.42 mL, 3.59
mmol) were added, worked up and purified as
described for 6, to give 18 as a syrup (1.12 g, 85%).
[h]D=−25.66 (c 0.40, CHCl3); 1H NMR (200 MHz,
CDCl3): l 1.35, 1.40 (2s, 6H, CH3), 3.41 (t, 1H, J4,5 5.4,
J5,6 6.3 Hz, H-5), 3.65 (t, 1H, J5,6 6.3, J6,6% 9.0 Hz, H-6),
3.80 (t, 1H, J5,6% 6.3, J6,6% 9.0 Hz, H-6%), 3.94 (t, 1H, J3,4
4.5, J4,5 5.4 Hz, H-4), 4.22 (dd, 1H, J2,3 13.6, J3,4 4.5
Hz, H-3), 4.57 (s, 2H, -OCH2Ph), 4.78 (s, 2H, -
OCH2Ph), 5.30 (s, 1H, H-1), 5.36 (d, 1H, J 8.0 Hz,
H-1%), 5.81–5.61 (m, 1H, H-2), 7.22–7.40 (m, 10H,
-OCH2Ph); FABMS (m/z, %): 368 (M+, 7), 353 (27),
187 (56), 181 (100), 91 (74). Anal. calcd for C23H28O4:
C, 74.97; H, 7.66. Found: C, 74.93; H, 7.61%.
1
(a/b=1:1) as a syrup. [h]D=+23.2 (c 2.01, CHCl3); H
NMR (200 MHz, CDCl3): l 1.70–2.00 (m, 1H H-4),
2.16–2.50 (m, 1H, H-4%), 4.04–4.16 (m, 1H, H-5), 4.22–
4.42 (m, 2H, H-3,6), 4.42–4.72 (m, 4H, H-7,7%,
-OCH2Ph), 5.08–5.22 (m, 1H, H-1), 5.22–5.38 (m, 1H,
H-1%), 5.74–6.08 (m, 1H, H-2), 7.20–7.34 (m, 5H,
-OCH2Ph), 7.45–7.56 (m, 3H, -CO2Ph), 8.00 (d, 2H,
-CO2Ph); FABMS (m/z, %): 338 (M+, 3), 324 (21), 231
(65), 105 (100), 91 (73). Anal. calcd for C21H22O4: C,
74.54; H, 6.55. Found: C, 74.47; H, 6.46%.
3.14. 3,4-Dibenzyloxy-(2S,3S,4R)-5-hexene-1,2-diol 19
3.11. 4-Benzyloxy-5-vinyl-(3R,4S,5R)-tetrahydro-2,3-
furandiol 16
A solution of 18 (1.0 g, 2.71 mmol) in 60% aqueous
acetic acid (5 mL) was stirred for 12 h at room temper-
ature, worked up and purified as described for 7, to
give 19 (0.55 g, 62%) as a syrup. [h]D=−4.45 (c 1.24,
A solution of 15 (5.0 g, 18.11 mmol) in 60% aq. AcOH
(50 mL) containing conc. H2SO4 (catalytic) was stirred
for 48 h at room temperature, worked up and purified
as described for 7, to give 16 (2.47 g) in 58% yield as a
1
CHCl3); H NMR (200 MHz, CDCl3): l 2.62 (br. s,
2H, -OH), 3.40–3.51 (m, 3H, H-5,6,6%), 3.62–3.72 (m,
1H, H-4), 4.06 (t, 1H, J2,3 8.0, J3,4 5.5 Hz, H-3), 4.32 (d,
1H, -OCH(H)Ph), 4.56 (t, 2H, -OCH2Ph), 4.80 (d, 1H,
-OCH(H)Ph), 5.30 (s, 1H, H-1), 5.38 (d, 1H, J 7.8 Hz,
H-1%), 5.72–5.92 (m, 1H, H-2), 7.14–7.31 (m, 10H,
-OCH2Ph); FABMS (m/z, %): 328 (M+, 6), 311 (32),
1
syrup. H NMR (200 MHz, CDCl3): l 3.50 (br. s, 1H,
-OH), 3.80–3.92 (m, 1H, H-3), 4.42–4.70 (m, 4H, H-2,4,
-OCH2Ph), 5.08–5.45 (m, 3H, H-1, 6,6%), 5.80–6.10 (m,
1H, H-5), 7.20–7.40 (m, 5H, -OCH2Ph); EIMS (m/z,
%): 219 (22), 145 (100), 107 (47), 91 (76).

544
G. V. M. Sharma et al. / Tetrahedron: Asymmetry 12 (2001) 539–544
181 (67), 147 (100), 91 (55). Anal. calcd for C20H24O4:
C, 73.15; H, 7.37. Found: C, 73.16; H, 7.28%.
2. Anthracycline Antibiotics; EI Khadem, H. S. Ed.; Aca-
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6. Sharma, G. V. M.; Ramanaiah, K. C. V.; Krishnudu, K.
Tetrahedron: Asymmetry 1994, 5, 1905–1908.
7. Sharma, G. V. M.; Chander, A. S.; Krishnudu, K.;
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8. Sharma, G. V. M.; Chander, A. S.; Krishnudu, K.;
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hedron Lett. 1997, 38, 6929–6932.
3.15. 5,6-Dibenzyloxy-1-methyl-(1S,4S,5R,6S)-2,7-
dioxabicyclo[2.2.1]heptane 3
To a stirred solution of 19 (0.1 g, 0.30 mmol), palladiu-
m(II) chloride (0.005 g, 0.03 mmol) and copper(I) chlo-
ride (0.03 g, 0.30 mmol) in aq. acetonitrile (3mL, 1:7),
oxygen gas was bubbled continuously for 48 h at room
temperature, worked up and purified as described for 9,
to give 3 (0.069 g) in 70% yield as a syrup. [h]D=+30.3
1
(c 0.95, CHCl3); H NMR (200 MHz, CDCl3): l 1.51
(s, 3H, CH3), 3.38–3.46 (m, 2H, H-5,5%), 3.84 (br. d, 1H,
J2,3 4.5 Hz, H-3), 4.00 (d, 1H, J2,3 4.5 Hz, H-2), 4.40 (s,
2H, -OCH2Ph), 4.44–4.52 (m, 3H, H-4, -OCH2Ph),
7.17–7.32 (m, 10H, -OCH2Ph); FABMS (m/z, %): 309
(24), 257 (23), 181 (100), 143 (56). Anal. calcd for
C20H22O4: C, 73.60; H, 6.79. Found: C, 73.53; H,
6.71%.
10. Sharma, G. V. M.; Reddy, V. G.; Krishna, P. R. Tetra-
hedron Lett. 1999, 40, 1783–1786.
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Tetrahedron: Asymmetry 2000, 11, 2643–2646.
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1079–1100.
Acknowledgements
One of the authors, A. Subhash Chander would like to
thank UGC, New Delhi, for financial support.
14. Frederikson, M.; Grigg, R. Org. Prep. Proc. Int. 1997, 29,
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