Synthesis of spiro carbon linked deoxy disaccharides

Article abstract of DOI:10.1016/S0957-4166(02)00466-4

Synthesis of the isomers of deoxy spiro carbon linked disaccharides has been reported. But-3-yn-1-ol has been utilised as a four carbon conjunctive reagent for the C-C bond formation and was later stereoselectively converted into cis and trans olefins for

Full text of DOI:10.1016/S0957-4166(02)00466-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1599–1607
Synthesis of spiro carbon linked deoxy disaccharides†
G. V. M. Sharma,a,* J. Janardhan Reddy,a M. H. V. Ramana Raob and Nicolas Galloisb,‡
aD-211, Discovery Laboratory, Organic Chemistry Division-III, Indian Institute of Chemical Technology,
Hyderabad 500 007, India
bNMR Group, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 8 April 2002; accepted 29 July 2002
Abstract—Synthesis of the isomers of deoxy spiro carbon linked disaccharides has been reported. But-3-yn-1-ol has been utilised
as a four carbon conjunctive reagent for the CꢀC bond formation and was later stereoselectively converted into cis and trans
olefins for further elaboration into the deoxy sugar moiety through cis dihydroxylation. © 2002 Elsevier Science Ltd. All rights
reserved.
1. Introduction
‘spiro’ carbon linked deoxy disaccharides 1, 2, 3 and 4.
Since the newly constructed sugar moiety is a deoxy
sugar, deoxy disaccharides 1–4 are named as ‘spiro’
carbon linked deoxy disaccharides.
Carbohydrates were earlier recognised as suitable chiral
starting materials for the synthesis of a plethora of
non-carbohydrate compounds and as chiral auxil-
iaries.1,2 Because of their important role in complex
biological processes, over the years bioactive glycosub-
stances have received a great deal of attention in chem-
ical, medical and pharmaceutical research.3–6 Though
several synthesis of glycosyl mimics,7 such as C-gly-
cosides, C-saccharides etc., are reported, much work
has not been done on the synthesis of spiro C-disaccha-
rides, in which the sugars are attached through a ‘spiro’
carbon atom. Recently we have demonstrated the use
of furan for the first synthesis8 of spiro carbon linked
disaccharides. Our continued interest in the use of
carbohydrate-derived chiral templates for the synthesis
of various bioactive compounds9 as well as new glyco-
substances,10 prompted us to report the synthesis of the
2. Results and discussion
Our earlier studies in this direction have extensively
utilised methodologies for CꢀC bond formation
between an ‘enantiopure’ precursor and a homologa-
tive, manipulable reactant, from which the new sugar is
derived ‘de novo’. Thus, the retrosynthetic analysis of
1–4 (Scheme 1) indicated that the olefinic alcohol 5
could be an appropriate homochiral intermediate for
the stereoselective construction of the new sugar, while
5 could be made from propargylic carbinol 6. Further,
the synthesis of 6 could be envisaged from ‘enantio-
pure’ ketone 7, which could be derived from
D-xylose.
* Corresponding author. E-mail: esmvee@iict.ap.nic.in
† IICT Communication No. 020123.
‡ On a study deputation for the partial fulfillment of the Master Degree from Inorganique Moleculaire, University de Rennes 1, Cedex, France.
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00466-4

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G. V. M. Sharma et al. / Tetrahedron: Asymmetry 13 (2002) 1599–1607
Scheme 1.
Accordingly, addition of lithium anion generated from
between H7 and H9, H6 and H8a in 1. The relative
orientation of two sugar rings was confirmed by charac-
teristic NOEs, like H2ꢀH7, H2ꢀH9. The presence of
NOE between Me (A)ꢀH1 and Me (A)ꢀH2 as well as
Me (B)ꢀH4 indicates that the five-membered ring con-
taining cyclic acetal is in equilibrium between two
envelope conformations. The sugar ring conformation
in 2 is also consistent with the vicinal couplings as the
characteristic NOE H6ꢀH8a, supporting a chair form.
The cross peak in the NOESY spectrum between H2
and H7 supports the relative orientation of the two
sugar rings.
A to ketone 7 (Scheme 2), afforded the 3-C-homo-
propargyl- -allose derivative 6 (50%) [h]D=+11.8 (c 1.0
D
CHCl3). Because of steric hindrance of the 1,2-O-iso-
propylidene group, the attack of homopropargyl group
is from the b-face to give 6 as an exclusive product. The
acetylenic group in 6 was subjected to reduction under
two different reaction conditions to obtain stereoselec-
tively both the cis and trans olefinic compounds. Thus,
on reaction with LAH in THF, 6 gave the trans olefin
1
8 (77%), whose H NMR spectrum amply indicated the
disappearance of the TBDMS group. Similarly, oxida-
tive deprotection of 6 with DDQ in aq. CH2Cl2 gave
alcohol 9 (72%), which on further partial hydrogena-
tion with Lindlar’s catalyst afforded 10 (80%) [h]D=
+5.8 (c 0.38, CHCl3).
The cis olefin 10 (Scheme 4) was subjected to oxidation
with IBX in DMSO to afford the lactol 17 (70%), which
on acetylation (Ac2O, Et3N) in CH2Cl2 gave a separable
mixture of anomers 18a (30%) [h]D=−12.7 (c 1.5,
CHCl3) and 18b (60%) [h]D=+44.2 (c 1.01, CHCl3)
(1:2), respectively. cis-Hydroxylation (OsO4–NMO) of
olefins 18a and 18b in acetone–water (3:1) afforded
diols 19a (80%) and 19b (85%), respectively, with com-
plete diastereoselectivity albeit at a very slow rate with
only 60 and 75% conversion even after 20 days. Finally,
acetylation (Ac2O, Et3N) of the diols 19a and 19b in
CH2Cl2 furnished the spiro saccharides 4 and 3 in 98
and 94%, respectively, whose structures were unam-
biguously confirmed by spectral analysis.
Treatment of alcohol 8 with TBDMSCl and imidazole
in CH2Cl2 (Scheme 3) afforded 11 (80%), which on cis
hydroxylation11 using OsO4–NMO in acetone–water
(3:1) furnished the diols 12a (70%) and 12b (23%) in 3:1
ratio. Acetylation with Ac2O and Et3N in CH2Cl2, 12a
gave the diacetate 13a in 80% yield, while isomer 12b
gave triacetate 13b in 50% yield. The diacetate 13a on
deprotection of PMB group with DDQ, gave alcohol 14
in 75% yield, [h]D=−17.6 (c 1.0 CHCl3). Further oxida-
tion of the primary alcohol 14 with IBX in DMSO gave
the lactol 15 (50%) along with enal 16 (20%) as a
separable mixture (3:1) of isomers. Lactol 15 on reac-
tion with Ac2O and Et3N in CH2Cl2 gave a separable
mixture of anomers 1 (74%) and 2 (4.6%) in 16:1 ratios.
Unlike 1 and 2, in spiro saccharides 3 and 4, the
six-membered ring exists in distorted boat configuration
since the bulky acetate groups are occupying axial
3
positions. This is evident from the J couplings, J8a,9
=
Extensive NMR studies were carried out for the struc-
tural characterisation of 1 and 2 (Fig. 1). The six-mem-
bered ring in 1 and 2 exists in the energetically favoured
chair form with all the bulky acetates in equatorial
positions, except at C9 in 2. This is supported by the
vicinal coupling constants (3J) and NOE effects
2.9, J8b,9=6.9, J7,8a=6.9, J7,8b=3.9, J6,7=3.4 Hz for 3
and about 4 Hz vicinal couplings in the six-membered
ring for 4. Further support for this and the relative
orientation of the two rings at the spiro carbon comes
from the NOE data (Fig. 2). In 3 H6ꢀH8a, H2ꢀH9,
Scheme 2. Reagents and conditions: (a) HCꢁCCH2CH2OPMB (A), n-BuLi, THF; (b) LAH, THF; (c) DDQ, CH2Cl2:H2O (19:1);
(d) H2, Pd/CaCO3, n-hexane, quinoline.

G. V. M. Sharma et al. / Tetrahedron: Asymmetry 13 (2002) 1599–1607
1601
Scheme 3. Reagents and conditions: (a) TBDMSCl, imidazole, CH2Cl2; (b) OsO4–NMO, acetone:water (3:1); (c) Ac2O, Et3N,
DMAP, CH2Cl2; (d) DDQ, CH2Cl2:H2O (19:1); (e) IBX, DMSO.
Figure 1.
H2ꢀH6, H5ꢀH6, H5%ꢀH6 NOEs are consistent with the
proposed structure, whereas in 4 NOE between H4 and
H9 supports the structure. The conformation of the
five-membered ring with the isopropylidene ring is sim-
ilar to 1 and 2.
the chiral ketone 5 and but-3-yn-1-ol. The homopropar-
gyl alcohol is utilised as a four carbon conjunctive
reagent for developing stereoselectively into the new
sugar moiety, while the stereochemical outcome of the
formation of the spiro junction is defined by the 1,2-O-
isopropylidene group and the chirality being transferred
from the sugar synthon during the introduction of the
diol system on the cis and trans olefins to give the new
sugar systems in 1–4.
Thus, in conclusion, a simple, efficient and enantiose-
lective synthesis of the spiro carbon linked deoxy disac-
charides 1, 2, 3 and 4 has been achieved starting from

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G. V. M. Sharma et al. / Tetrahedron: Asymmetry 13 (2002) 1599–1607
Scheme 4. Reagents and conditions: (a) IBX, DMSO; (b) Ac2O, Et3N, DMAP, CH2Cl2; (c) OsO4–NMO, acetone: water (3:1).
Figure 2.
3. Experimental
H-5%, OCH3), 3.80–3.95 (m, 2H, H-4, 5), 4.42 (d, 1H,
J1,2 3.8 Hz, H-2),4.46 (AB q, 2H, OCH2), 5.74 (d, 1H
J1,2 3.8 Hz, H-1), 6.83 (d, 2H, J 8.4 Hz, Ar-H), 7.2 (d,
2H, J 8.4 Hz, Ar-H); 13C NMR (CDCl3, 50 MHz): l
−5.51, −5.32, 18.27, 20.15, 25.87 (3C), 26.65, 29.66,
55.25, 63.03, 67.76, 72.62, 75.58, 77.74, 81.18, 84.14,
85.72, 104.23, 113.34, 113.85 (2C), 113.95, 129.06,
130.0, 159.06; FABMS (m/z, %): 515 (M++23, 6), 492
(M+, 3), 491 (M+−1, 7), 121 (100), 73 (33). Anal. calcd
for C26H40O7Si (492): C, 63.38; H, 8.18. Found: C,
63.29; H, 8.12%.
3.1. 5-tert-Butyldimethylsilyloxymethyl-6-[4-(4-methoxy-
benzyloxy)-1-butynyl]-2,2-dimethyl-(3aR,5R,6R,6aR)-
perhydrofuro[2,3-d][1,3]dioxol-6-ol, 6
To a stirred solution of 1-(p-methoxybenzyl-but-3-yn-1-
ol (1.13 g, 5.95 mmol) in dry THF (10 mL), was added
n-BuLi (4.57 mL, 5.95 mmol, 1.3 molar solution in
hexane) dropwise at −78°C. After 30 min, a solution of
ketone 7 (1.5 g, 4.96 mmol) in dry THF (10 mL) was
added dropwise at the same temperature and the reac-
tion mixture warmed to room temperature over a
period of 1 h. The reaction mixture was treated with
saturated aqueous NH4Cl solution (10 mL), diluted
with water (20 mL) and extracted with ethyl acetate
(2×50 mL). The organic layer was washed with water
(20 mL), brine (10 mL), dried (Na2SO4) and concen-
trated to the crude, which was purified by column
chromatography (silica gel, 1:12 ethyl acetate–
petroleum ether) to afford 6 as a syrup (1.4 g, 50%).
[h]D=+11.8 (c 1.0, CHCl3); IR (neat): 750, 850, 1000,
1060, 1100, 1260, 1350, 1480, 1600, 2240, 2840, 2900,
3.2. 5-Hydroxymethyl-6-[4-(4-methoxybenzyloxy)-(E)-1-
butenyl]-2,2-dimethyl-3aR,5R,6R,6aR)-perhydrofuro[2,3-
d][1,3]dioxol-6-ol, 8
To a cooled (0°C) suspension of LiAlH4 (0.084 g, 2.23
mmol) in dry THF (10 mL), was added a solution of 6
(0.5 g, 1.01 mmol) in dry THF (5 mL) dropwise at the
same temperature and stirred for 12 h at room temper-
ature. The reaction mixture was quenched with satu-
rated aqueous Na2SO4 solution (10 mL), diluted with
ethyl acetate (20 mL), filtered through Celite and
washed with ethyl acetate (2×10 mL). The combined
organic layers were dried (Na2SO4), ethyl acetate evap-
orated and the obtained residue was purified by column
chromatography (silica gel, 1:3 ethyl acetate–petroleum
3400 cm−1; H NMR (CDCl3, 200 MHz): l 0.06 (s, 6H,
2 Si CH3), 0.88 (s, 9H, C(CH3)3), 1.35, 1.56 (2s, 6H, 2
CH3), 2.49 (t, 2H, J 7.5 Hz, H-8, 8%), 2.92 (br. s, 1H,
OH), 3.5 (t, 2H, J 7.5 Hz, H-9, 9%), 3.78–3.80 (m, 4H,
1

G. V. M. Sharma et al. / Tetrahedron: Asymmetry 13 (2002) 1599–1607
1603
ether) to afford 8 as a syrup (0.30 g, 77%). [h]D=+20.2
(c 1.0, CHCl3); IR (neat): 750, 1000, 1050, 1280, 1400,
J6,7 10.6 Hz, H-6), 5.60–5.75 (m, 1H, H-7), 5.75 (d, 1H,
J1,2 4.8 Hz, H-1); 13C NMR (CDCl3, 50 MHz): l −5.42,
−5.24, 18.28, 25.87 (3C), 26.56, 26.64, 31.67, 61.25,
62.09, 80.42, 83.24, 84.27, 103.84, 112.89, 127.77,
132.01; FABMS (m/z, %): 397 (M++23, 18), 199 (12),
89 (26), 73 (100). Anal. calcd for C18H34O6Si (374): C,
57.72; H, 9.15. Found: C, 57.64; H, 9.09%.
1
1500, 1600, 2850, 2900, 3400 cm−1; H NMR (CDCl3,
200 MHz): l 1.34, 1.57 (2s, 6H, 2 CH3), 2.33 (m, 2H,
H-8 8%), 2.88, 2.96 (2s, 2H, 2 OH), 3.45 (t, 2H, J 6.4 Hz,
H-9, 9%), 3.60 (d, 2H, J 5.5 Hz, H-5, 5%), 3.78 (s, 3H,
OCH3), 3.89 (t, 1H, J 5.5 Hz, H-4), 4.15 (d, 1H, J1,2 4.1
Hz, H-2), 4.51 (s, 2H, OCH2), 5.42 (br. d, 1H, J6,7 16.0
Hz, H-6), 5.78 (d, 1H, J1,2 4.1, Hz, H-1), 5.99 (dt, 1H,
J 16.1, 5.9 Hz, H-7), 6.84 (d, 2H, J 9.2 Hz, Ar-H), 7.20
(d, 2H, J 9.2 Hz, Ar-H); FABMS (m/z, %): 403 (M++
23, 12), 341 (25), 147 (40), 73 (100), 55 (38). Anal. calcd
for C20H28O7 (380): C, 63.14; H, 7.42. Found: C, 63.09;
H, 7.31%.
3.5. 5-tert-Butyldimethylsilyloxymethyl-6-[4-(4-methoxy-
benzyloxy)-(E)-1-butenyl]-2,2-dimethyl-(3aR,5R,
6R,6aR)-perhydrofuro[2,3-d][1,3]dioxol-6-ol, 11
To a stirred solution of 8 (0.3 g, 0.789 mmol) and
imidazole (0.107 g, 1.57 mmol) in dichloromethane (5
mL) was added TBDMSCl (0.118g, 0.789 mmol) in
portions at 0°C. After 12 h it was diluted with water (20
mL) and extracted with dichloromethane (2×20 mL).
The combined organic layers were washed with water
(20 mL), brine (10 mL), dried (Na2SO4) and concen-
trated. The crude was purified by column chromatogra-
phy (silica gel, 1:20 ethyl acetate–petroleum ether) to
afford 11 as a syrup (0.312 g, 80%). [h]D=+17.55 (c 1.0,
CHCl3); IR (neat): 800, 1050, 1100, 1250, 1500, 1625,
1700, 2850, 2950, 3400 cm−; 1 1H NMR (CDCl3, 400
MHz): l 0.08, 1.10 (2s, 6H, 2 Si CH3), 0.88, 0.92 (2s,
9H, C(CH3)3), 1.34, 1.56 (2s, 6H, 2 CH3), 2.36 (m, 2H,
H-8, 8%), 3.47 (t, 2H, J 6.7 Hz, H-9, 9%), 3.55–3.68 (m,
2H, H-5, 5%), 3.77 (s, 3H, OCH3), 3.90 (t, 1H, J 4.8 Hz,
H-4), 4.14 (d, 1H, J1,2 5.7 Hz, H-2), 4.46 (s, 2H, -CH2),
5.40 (br. d, 1H, J6,7 16.2 Hz, H-6), 5.71 (d, 1H, J1,2 5.7
Hz, H-1), 5.85–5.95 (dt, 1H, J 8.6, 16.2 Hz, H-7), 6.82
(d, 2H, J 8.5 Hz, Ar-H), 7.20 (d, 2H, J 8.6 Hz, Ar-H);
13C NMR (CDCl3, 50 MHz): l −5.57, −5.41, 18.10,
25.75 (2C), 26.44 (2C), 29.49, 32.75, 55.06, 62.20, 64.44,
69.12, 72.37, 79.22, 82.80, 83.73, 103.76, 112.55, 113.66
(2C), 127.98, 128.34, 129.02, 130.34, 159.06; FABMS
(m/z, %): 517 (M++23, 21), 493 (M+−1, 8), 403 (24), 121
(100), 69 (44). Anal. calcd for C26H42O7Si (494): C,
63.13; H, 8.56. Found: C, 63.01; H, 8.42%.
3.3. 4-[6-Hydroxy-5-tert-butyldimethylsilyloxymethyl-
2,2-dimethyl-(3aR,5R,6R,6aR)perhydrofuro[2,3-d]-
[1,3]dioxol-6-yl]-3-butyn-1-ol, 9
To a stirred solution of 6 (1.590 g, 3.23 mmol) in
dichloromethane–water (20 mL, 19:1) was added DDQ
(0.88 g, 3.87 mmol) at 0°C and the reaction mixture
stirred for 1 h at room temperature. The reaction
mixture was quenched with saturated aqueous
NaHCO3 solution (5 mL) and extracted with
dichloromethane (2×50 mL). The combined organic
layers were washed with water (10 mL), brine (10 mL),
dried (Na2SO4), concentrated and the residue was
purified by column chromatography (silica gel, 3:7 ethyl
acetate–petroleum ether) to afford alcohol 9 as a
gummy syrup (0.865 g, 72%). [h]D=+11.65 (c 3.54,
CHCl3); IR (neat): 750, 850, 1025, 1100, 1250, 1350,
1480, 1600, 2250, 2880, 2950, 3450 cm−1; 1H NMR
(CDCl3, 200 MHz): l 0.12 (s, 6H, 2 Si CH3), 0.94 (s,
9H, C(CH3)3), 1.39, 1.60 (2s, 6H, 2 CH3), 2.51 (t, 2H, J
7.2 Hz, H-8, 8%), 3.15 (br. s, 2H, OH), 3.74 (t, 2H, J 7.2
Hz, H-9, 9%), 3.94 (m, 3H, H-4, 5, 5%), 4.51 (d, 1H, J1,2
4.8 Hz, H-2), 5.81 (d, 1H, J1,2 4.8 Hz, H-1); FABMS
(m/z, %): 395 (M++23, 10), 297 (64), 165 (100), 149 (75).
Anal. calcd for C18H32O6Si (372): C, 58.03; H, 8.66.
Found: C, 57.99; H, 8.49%.
3.6. Hydroxylation of 11
3.4. 4-[6-Hydroxy-5-tert-butyldimethylsilyloxymethyl-
2,2-dimethyl-(3aR,5R,6R,6aR)-perhydrofuro[2,3-d]-
[1,3]dioxol-6-yl]-(Z)-3-buten-1-ol, 10
To a stirred solution of 11 (0.2 g, 0.404 mmol) in
acetone–water (10 mL, 3:1) were added sequentially
N-methyl morpholine N-oxide (0.093 g, 0.808 mmol)
and OsO4 (four drops) at room temperature. After
completion of reaction (2 days, monitored by TLC),
reaction mixture was quenched by saturated aqueous
NaHSO3 solution (3 mL) and acetone evaporated on
rotary evaporator. The reaction mixture was diluted
with water (15 mL) and extracted with ethyl acetate
(2×15 mL). The combined organic layers were washed
with water (10 mL), brine (10 mL), dried (Na2SO4),
concentrated and purified by column chromatography
(silica gel, 1:5 ethyl acetate–petroleum ether) to afford
12a (0.150 g, 70%) and 12b (0.050 g, 23%) as syrups in
3:1 ratio.
To a stirred solution of alcohol 9 (0.300 g, 0.806 mmol)
in hexane (5 mL) were added Pd–CaCO3 (0.010 g)
followed by quinoline (0.010 g, 0.0806 mmol) and
stirred for 4 h at room temperature. The reaction
mixture was filtered and washed with ethyl acetate
(2×20 mL). The combined organic extracts were washed
with brine (10 mL), dried (Na2SO4), evaporated and the
residue purified by column chromatography (silica gel,
1:7 ethyl acetate–petroleum ether) to afford 10 as a
solid (0.240 g, 80%). Mp=80–85°C; [h]D=+5.8 (c
0.385, CHCl3); IR (KBR): 720, 750, 820, 900, 1050,
1180, 1240, 1280, 1400, 1450, 1600, 2800, 2840, 2920,
3200, 3390 cm−; 1 1H NMR (CDCl3, 200 MHz): l 0.08
(s, 6H, 2 Si CH3), 0.89 (s, 9H, C(CH3)3), 1.35, 1.60 (2s,
6H, 2 CH3), 2.23 (br. s, 1H, OH), 2.43–2.84 (m, 2H,
H-8, 8%), 3.24 (br. s, 1H, OH), 3.55–3.94 (m, 5H, H-4, 5,
5%, 9, 9%), 4.25 (d, 1H, J1,2 4.8 Hz, H-2), 5.40 (br. d, 1H,
First eluted was 1-[6-hydroxy-5-tert-butyldimethylsilyl-
oxymethyl-2,2-dimethyl-(3aR,5R,6R,6aR)-perhydrofuro-
[2,3-d][1,3]dioxol-6-yl]-4-(4-methoxybenzyloxy)-(1R,2S)-
butane-1,2-diol, 12a: [h]D=+15.9 (c 1.0, CHCl3); IR
(neat): 750, 850, 1020, 1100, 1260, 1320, 1440, 1600,

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G. V. M. Sharma et al. / Tetrahedron: Asymmetry 13 (2002) 1599–1607
2840, 2920, 3400, 3520cm−1;1HNMR(CDCl3, 200MHz):
l 0.10 (s, 6H, 2 Si CH3), 0.90 (s, 9H, C(CH3)3), 1.37, 1.54
(2s, 6H, 2 CH3), 1.65–1.84 (m, 1H, H-8), 1.88–2.12 (m,
1H, H-8%), 2.96 (s, 1H, OH), 3.54–3.70 (m, 2H, H-9, 9%),
3.70–3.81 (m, 5H, H-5, 5%, OCH3), 3.88 (d, 1H, J6,7 10.3
Hz, H-6), 3.95–4.08 (m, 1H, H-7), 4.11–4.30 (m, 1H, H-4),
4.44 (s, 2H, OCH2-), 5.11 (d, 1H, J1,2 3.8 Hz, H-2), 5.78
(d, 1H, J1,2 3.8 Hz, H-1), 6.82 (d, 2H, J 10.3 Hz, Ar-H),
7.22 (d, 2H, J 10.3 Hz, Ar-H); FABMS (m/z, %): 551
(M++23, 68), 493 (7), 121 (100), 69 (19), 57 (33).
3.8. 1-[5-Hydroxymethyl-2,2-dimethyl-6-methylcarbonyl-
oxy-(3aR,5R,6S,6aR)-perhydrofuro[2,3-d][1,3]dioxol-6-
yl]-4-(4-methoxybenzyloxy)-2-methylcarbonyloxy-
(1S,2R)-butyl acetate, 13b
A solution of the diol 12b (0.150 g, 0.284 mmol) and
triethylamine (0.2 mL, 1.42 mmol), in dichloromethane
(5 mL) was treated with acetic anhydride (0.08 mL, 0.85
mmol) in the presence of catalytic DMAP at 0°C. After
1 h, worked up as described for 13a, purified by column
chromatography (silica gel, 1:19 ethyl acetate–petroleum
ether) to afford 13b (0.08 g) in 50% yield as a syrup.
[h]D=+41.4 (c 1.0, CHCl3); IR (neat): 750, 820, 1040,
1090, 1200, 1240, 1350, 1450, 1740, 2800, 2900 cm−1; 1H
NMR (CDCl3, 200 MHz): l 0.07, 0.10 (2s, 6H, 2 Si CH3),
0.90(s, 9H, C(CH3)3), 1.29, 1.46(2s, 6H, 2CH3), 1.52–1.90
(m, 2H, H-8, 8%), 2.04, 2.05, 2.10 (3s, 9H, 3 OAc), 3.36
(t, 2H, J 5.5 Hz, H-9, 9%), 3.78 (s, 3H, OCH3), 3.93–4.20
(m, 3H, H-4, 5, 5%), 4.34 (s, 2H, OCH2-), 4.98 (d, 1H, J1,2
4.5 Hz, H-2), 5.19–5.34 (m, 1H, H-7), 5.50–5.60 (m, 1H,
H-6), 5.72 (d, 1H, J1,2 4.5 Hz, H-1), 6.82 (d, 2H, J 9.4
Hz, Ar-H), 7.20 (d, 2H, J 9.4 Hz, Ar-H).
Second eluted was 1-[6-hydroxy-5-tert-butyldimethylsily-
loxymethyl - 2,2 - dimethyl - (3aR,5R,6R,6aR) - perhydro-
furo[2,3-d][1,3]dioxol-6-yl]-4-(4-methoxybenzyloxy)-(1S,2
R)-butane-1,2-diol, 12b: [h]D=+10.35 (c 1.0, CHCl3); IR
(neat): 720, 840, 1040, 1100, 1250, 1350, 1400, 1600, 2800,
1
2900, 3400, 3520 cm−1; H NMR (CDCl3, 200 MHz): l
0.06 (s, 6H, 2 Si CH3), 0.86 (s, 9H, C(CH3)3), 1.34, 1.56
(2s, 6H, 2 CH3), 1.94–2.16 (m, 2H, H-8, 8%), 3.44 (br. s,
1H, H-5), 3.5-3.61 (m, 3H, H-5%, 9, 9%), 3.78 (s, 3H, OCH3),
3.81 (dd, 1H, J6,7 4.1, J7,8 11.3 Hz, H-7), 3.97 (d, 1H, J6,7
4.1 Hz, H-6), 4.14 (dd, 1H, J4,5 4.1 Hz, J4,5% 10.3 Hz, H-4),
4.42 (s, 2H, OCH2-), 4.45 (d, 1H, J1,2 5.1 Hz, H-2), 5.74
(d, 1H, J1,2 5.1 Hz, H-1), 6.82 (d, 2H, J 8.2 Hz, Ar-H),
7.20 (d, 2H, J 8.2 Hz, Ar-H); FABMS (m/z, %): 551
(M++23, 62), 459 (15), 121 (100), 73 (52), 69 (44), 57 (74).
3.9. 4-Hydroxy-1-[6-5-tert-butyldimethylsilyloxymethyl-
2,2-dimethyl-(3aR,5R,6S,6aR)-perhydrofuro[2,3-
d][1,3]dioxol-6-yl]-2-methylcarbonyloxy-(1R,2S)-butyl
acetate, 14
3.7. 1-[6-Hydroxy-5-tert-butyldimethylsilyloxymethyl-
2,2-dimethyl-(3aR,5R,6S,6aR)-perhydrofuro[2,3-
d][1,3]dioxol-6-yl]-4-(4-methoxybenzyloxy)-2-methylcar-
bonyloxy-(1R,2S)-butyl acetate, 13a
To a stirred solution of 13a (0.110 g, 0.179 mmol) in
dichloromethane-water (5 mL, 19:1), was added DDQ
(0.049 g, 0.215 mmol), reaction mixture stirred for 1 h.
The reaction mixture was quenched with saturated
aqueous NaHCO3 solution (5 mL) and extracted with
dichloromethane (2×20 mL). The combined organic
layers were washed with water (10 mL), brine (10 mL),
dried (Na2SO4), concentrated and the residue was purified
by column chromatography (silica gel, 1:5 ethyl acetate–
petroleum ether) to afford 14 as a syrup (0.066 g, 75%).
[h]D=−17.6 (c 1.0, CHCl3); IR (neat): 720, 850, 1020,
1100, 1240, 1340, 1750, 2850, 2920, 3400, 3520 cm−1; 1H
NMR (CDCl3, 200 MHz): l 0.09 (s, 6H, 2 Si CH3), 0.91
(s, 9H, C(CH3)3), 1.39, 1.58 (2s, 6H, 2 CH3), 1.70–1.89
(m, 2H, H-8, 8%), 2.11, 2.14 (2s, 6H, 3 OAc), 2.90 (s, 1H,
OH), 3.45 (ddd, 1H, J8,9 4.3, J8%,9 10.0, J9,9% 11.0 Hz, H-9),
3.66 (dt, 1H, J8,9% 4.8, J8%,9% 4.8, J9,9% 11.0 Hz, H-9%), 3.80
(d, 2H, J4,5 5.3 Hz, H-5, 5%), 3.91 (t, 1H, J 5.3 Hz, H-4),
4.87 (d, 1H, J1,2 4.0 Hz, H-2), 5.22 (d, 1H, J6,7 3.3 Hz,
H-6), 5.64 (dt, 1H, J6,7 3.3, J7,8 3.3, J7,8% 9.6 Hz, H-7), 5.72
(d, 1H, J1,2 4.0 Hz, H-1); FABMS (m/z, %): 515 (M++23,
28), 147 (34), 117 (100), 107 (38), 95 (56), 89 (96). Anal.
calcd for C22H40O10Si (492): C, 53.64; H, 8.18. Found:
C, 53.57; H, 8.07%.
A solution of the diol 12a (0.140 g, 0.265 mmol) and
triethylamine (0.18 mL, 1.325 mmol), in dichloromethane
(5 mL) was treated with acetic anhydride (0.05 mL, 0.53
mmol) in presence of catalytic DMAP at 0°C. After 1 h,
the mixture was neutralised with saturated aqueous
NaHCO3 solution (5 mL) and extracted with
dichloromethane (2×10 mL). Combined organic layers
were washed with water (10 mL), brine (10 mL), dried
(Na2SO4), concentrated and the residue was purified by
column chromatography (silica gel, 1:12 ethyl acetate–
petroleum ether) to afford 13a as a syrup (0.13 g, 80%).
[h]D=−14.2 (c 1.0, CHCl3); IR (neat): 720, 840, 1020,
1150, 1240, 1340, 1450, 1750, 2850, 2920, 3400 cm−1; 1H
NMR (CDCl3, 200 MHz): l 0.08 (2s, 6H, 2 Si CH3), 0.90
(s, 9H, C(CH3)3), 1.39, 1.57 (2s, 6H, 2 CH3), 1.65–1.93
(m, 2H, H-8, 8%), 2.10, 2.80 (2s, 6H, 2 OAc), 2.88 (s, 1H,
OH), 3.31–3.49 (m, 2H, H-5, 5%), 3.60 (t, 2H, J 8.7 Hz,
H-9, 9%), 3.79 (s, 3H, OCH3), 3.97 (t, 1H, J 7.8 Hz, H-4),
4.37 (s, 2H, OCH2-) 4.81 (d, 1H, J1,2 4.6 Hz, H-2), 5.15
(d, 1H, J6,7 3.6 Hz, H-6), 5.44–5.58 (m, 1H, H-7), 5.72
(d, 1H, J1,2 4.6 Hz, H-1), 6.83 (d, 2H, J 8.2 Hz, Ar-H),
7.21 (d, 2H, J 8.2 Hz, Ar-H); 13C NMR (CDCl3, 50 MHz):
l −5.59, −5.43, 18.11, 20.56, 20.76, 25.56, 25.77 (2C),
26.39, 26.50, 29.51, 32.22, 55.08, 61.52, 66.00, 69.59,
71.65, 72.51, 76.38, 78.75, 80.07, 84.33, 105.03, 112.32,
113.65, 129.17, 130.34, 159.09, 169.20, 169.83; FABMS
(m/z, %): 582 (M++1−OCH3, 16), 241 (32), 176 (37), 165
(46), 154 (100). Anal. calcd for C30H48O11Si (612): C,
58.80; H, 7.90. Found: C, 58.78; H, 7.79%.
3.10. Conversion of 14 to 1 and 2
A stirred solution of 14 (0.040 g, 0.08 mmol) in DMSO
(3 mL) was treated with iodoxy benzoic acid (IBX,
0.027 g, 0.097 mmol) at room temperature for 1 h. The
reaction mixture was quenched with saturated aqueous
NaHCO3 solution (5 mL) and extracted with ethyl

G. V. M. Sharma et al. / Tetrahedron: Asymmetry 13 (2002) 1599–1607
1605
acetate (2×10 mL). The combined organic layers were
washed with water (10 mL), brine (10 mL), dried
(Na2SO4), concentrated and the residue was purified by
column chromatography (silica gel, 1:5 ethyl acetate–
petroleum ether) to afford separable mixture of 15
(0.020 g, 50%) and 16 (0.007 g, 20%) as a syrup.
J6,7 9.5 Hz, H-6), 5.40 (br. d, 1H, J8a,9 2.8, J8e,9 0.9 Hz,
H-9), 5.56 (ddd, 1H, J6,7 9.5, J7,8a 11.9, J7,8e 5.2 Hz,
H-7), 5.70 (d, 1H, J1,2 3.8 Hz, H-1); FABMS (m/z, %):
552 (M++23−3, 01), 325 (9), 281 (25), 207 (45), 173 (42),
165 (59), 153 (100). Anal. calcd for C24H40O11Si (532):
C, 54.12; H, 7.57. Found: C, 54.09; H, 7.46%.
First eluted was 3-formyl-1-[6-hydroxy 5-tert-butyl-
dimethylsilyloxymethyl-2,2-dimethyl-(3aR,5R,6R,6aR)-
perhydrofuro[2,3-d][1,3]dioxol-6-yl]-(1R,2E)-2-propenyl
acetate, 16: [h]D=17.51 (c 1.0, CHCl3); IR (neat): 720,
800, 1050, 1120, 1240, 1290, 1300, 1500, 1600, 1750,
Second eluted was 5-tert-butyldimethylsilyloxymethyl-
2,2-dimethyl-3%,4%-di(methyl carbonyloxy)-(3%S,3aR,4%R,
5R,6%S,6%S,6aR) - spiro[perhydrofuro[2,3 - d][1,3]dioxole-
6,2%-(3%H,4%H,5%H,6%H-pyran)]-6-yl acetate, 1: mp=120–
125°C; [h]D=18.71 (c 1.3, CHCl3); IR (KBR): 840,
1050, 1240, 1300, 1360, 1740, 2840, 2920 cm−1; 1H
NMR (CDCl3, 500 MHz): l 0.06, 0.07 (2s, 6H, 2
SiCH3), 0.90 (s, 9H, C(CH3)3), 1.38 (s, 3H, CH3(A)),
1.56 (s, 3H, CH3(B)), 1.78 (ddd, 1H, J7,8a 11.5, J8a,9
10.1, J8a,8e 12.0 Hz, H-8a), 2.01, 2.02, 2.10 (3s, 9H, 3
OAc), 2.37 (ddd, 1H, J7,8e 5.3, J8e,9 2.4 Hz, H-8e), 2.78
(m, 2H, H-5,5%), 4.16 (t, 1H, J4,5 6.2, J4,5% 6.2 Hz, H-4),
4.70 (d, 1H, J1,2 3.9 Hz, H-2), 5.12 (d, 1H, J6,7 9.6 Hz,
H-6), 5.24 (ddd, 1H, J6,7 9.6, J7,8a 11.5, J7,8e 5.3 Hz,
H-7), 5.77 (d, 1H, J1,2 3.9 Hz H-1), 6.02 (dd, 1H, J8a,9
10.1, J8e,9 2.4 Hz, H-9), 13C NMR (CDCl3, 50 MHz): l
−5.41, −5.25, 18.31, 20.76, 20.90, 25.89, 26.61, 26.85,
29.30, 29.66, 34.94, 61.41, 68.78, 69.25, 76.18, 78.45,
81.19, 81.96, 89.42, 105.77, 113.02, 168.24, 169.04,
170.10. FABMS (m/z, %): 555 (M++23, 51), 295 (52),
255 (67), 185 (91), 163 (99), 153 (100), 147 (69). HRMS:
calcd for C24H40O11NaSi: 555.223761. Observed:
555.225681.
1
1800, 3390, 3400 cm−1; H NMR (CDCl3, 200 MHz): l
0.06, 0.08 (2s, 6H, 2 Si CH3), 0.90 (s, 9H, C(CH3)3),
1.38, 1.58 (2s, 6H, 2 CH3), 2.10 (s, 3H, OAc), 2.95 (s,
1H, OH), 3.74 (d, 2H, J4,5 6.5 Hz, H-5, 5%), 3.97 (t, 1H,
J 6.5 Hz, H-4), 4.29 (d, 1H, J1,2 4.3 Hz, H-2), 5.74 (d,
1H, J1,2 4.3 Hz, H-1), 5.80 (d, 1H, J6,7 7.6 Hz, H-6),
6.10 (dd, 1H, J7,8 16.2 J8,9 7.6 Hz, H-8), 7.00 (dd, 1H,
J6,7 7.6, J7,8 16.2 Hz, H-7) 9.58 (d, 1H, J8,9 7.6 Hz, H-9).
Second eluted was 6%-hydroxy- 5-tert-butyldimethylsilyl-
oxymethyl-2,2-dimethyl-3%-methylcarbonyloxy-(3%S,
3aR,4%R,5R,6%S,6aR)-spiro[perhydrofuro[2,3-d][1,3]-
dioxole-6,2%-(3%H,4%H,5%H,6%H-pyran)]-4-yl acetate, 15:
IR (neat): 680, 750, 800, 1020, 1080, 1220, 1340, 1750,
1
3390, 3460 cm−1; H NMR (CDCl3, 200 MHz):l 0.09
(s, 6H, 2 Si CH3), 0.9 (s, 9H, C(CH3)3), 1.38, 1.58 (2s,
6H, 2 CH3), 1.65–1.84 (m, 1H, H-8%), 2.04 (s, 6H, 3
OAc), 2.19–2.4 (m, 1H, H-8), 3.26 (br. d, 1H, OH),
3.67–3.82 (m, 2H, H-5, 5%), 4.02 (dd, 1H, J4,5 8.6, J4,5%
3.8 Hz, H-4), 4.82 (d, 1H, J1,2 3.8 Hz, H-2), 5.06 (br. d,
1H, J6,7 10.3 Hz, H-6), 5.39 (br. d, 1H, H-9), 5.44–5.62
(m, 1H, H-7), 5.67 (d, 1H, J1,2 3.8 Hz, H-1); 13C NMR
(CDCl3, 50 MHz): l −5.48, −5.29, 18.31, 20.20, 25.90,
26.69, 55.29, 63.05, 67.82, 72.67, 75.66, 77.21, 77.78,
81.19, 84.19, 104.29, 113.39, 113.89, 129.28, 130.08,
159.34, 170.88; FABMS (m/z, %): 513 (M++23, 5), 313
(36), 191 (55), 171 (62), 159 (81) 154 (100).
3.11. Conversion of 10 to 18a and 18b
To a solution of alcohol 10 (0.200 g, 0.534 mmol) in
DMSO (5 mL) was added IBX (0.180 g, 0.641 mmol),
and stirred for 5 h at room temperature. It was worked
up as described for 15, purified by column chromatog-
raphy (silica gel, 1:9 ethyl acetate–petroleum ether) to
afford 5-tert-butyldimethylsilyloxymethyl-2,2-dimethyl-
(3aR,5R,6%R,6aR) - piro[perhydrofuro[2,3 - d][1,3]dioxole-
6,2%-(5%H,6%H-pyran)]-6%-ol, 17 as a solid (0.14 g, 70%).
Mp=120–125°C; [h]D=+8.6 (c 0.75, CHCl3); IR
(KBR): 680, 750, 820, 1050, 1080, 1250, 1350, 1450,
1600, 1700, 3390, 3450 cm−; 1 1H NMR (CDCl3, 200
MHz): l 0.08 (s, 6H, 2 SiCH3), 0.80 (s, 9H, C(CH3)3),
1.30, 1.36 (2s, 6H, 2 CH3), 2.05–2.52 (m, 2H, H-8, 8%),
3.18 (br. s, 1H, OH), 3.61–3.87 (m, 2H, H-5, 5%),
3.96–4.16 (m, 1H, H-4), 4.40 (d, 1H, J1,2 4.6 Hz, H-2),
5.51 (d, 1H, J8,9 4.6 Hz, H-9), 5.58 (br. d, 1H, J6,7 11.5
Hz, H-6), 5.73–5.81 (m, 1H, H-1), 5.81–5.96 (m, 1H,
H-7); FABMS (m/z, %): 395 (M++23, 10), 297 (58), 215
(60), 69 (66), 55 (100).
The above mixture of lactols 15 (0.100 g, 0.204 mmol)
and triethylamine (0.07 mL, 0.510 mmol), in
dichloromethane (10 mL) was treated with acetic anhy-
dride (0.02 mL, 0.204 mmol) in presence of catalytic
DMAP at 0°C. After 1 h, it was worked up as described
for 13 and the residue was purified by column chro-
matography (silica gel, 1:20 ethyl acetate–petroleum
ether) to afford a separable mixture of 1 (0.080 g, 74%)
and 2 (0.005 g, 4.6%) in a 16:1 ratio as syrup.
First eluted was 5-tert-butyldimethylsilyloxymethyl-2,2-
dimethyl - 3%,4% - di(methylcarbonyloxy) - (3%S,3aR,4%R,5R,
6%S,6%R,6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,2%-
(3%H,4%H,5%H,6%H-pyran)]-6-yl acetate, 2: [h]D=−6.1 (c
0.25, CHCl3); IR (neat): 820, 1100, 1240, 1300, 1350,
A mixture of the lactols 17 (0.120 g, 0.322 mmol) and
1
1750, 2850, 2900 cm−1; H NMR (CDCl3, 500 MHz): l
triethylamine
(0.134
mL,
0.966
mmol),
in
0.07, 0.08 (2s, 6H, 2 Si CH3), 0.89 (s, 9H, C(CH3)), 1.38
(s, 3H, CH3(A)), 1.57 (s, 3H, CH3(B)), 1.73 (dt, 1H,
J8a,9 2.8, J7,8a 11.9, J8a,8e 11.9 Hz, H-8a), 2.01, 2.02 (2s,
9H, 3 OAc), 2.27 (ddd, 1H, J7,8e 5.2, J8e,9 0.9 Hz, H-8e),
3.76 (dd, 1H, J4,5% 4.3, J5,5% 11.4 Hz, H-5%), 3.83 (dd, 1H,
J4,5 7.6, J5,5% 11.4 Hz, H-5), 4.09 (dd, 1H, J4,5 7.6, J4,5%
4.3 Hz, H-4), 4.83 (d, 1H, J1,2 3.8 Hz, H-2), 5.10 (d, 1H,
dichloromethane (5 mL) was treated with acetic anhy-
dride (0.03 mL, 0.322 mmol) in the presence of catalytic
DMAP at 0°C. After 1 h, it was worked up as described
for 13 and the residue purified by column chromatogra-
phy (silica gel, 1:14 ethyl acetate–petroleum ether) to
afford a separable anomeric mixture of acetates 18a
(0.040 g, 30%) and 18b (0.080 g, 60%) in a 1:2 ratio.

1606
G. V. M. Sharma et al. / Tetrahedron: Asymmetry 13 (2002) 1599–1607
First eluted was 5-tert-butyldimethylsilyloxymethyl-2,2-
dimethyl - (3aR,5R,6%R,6%R,6aR) - spiro[perhydrofuro[2,3-
d][1,3]dioxole-6,2%-(5%H,6%H-pyran)]-6-yl acetate, 18a:
mp=100–105°C; [h]D=−12.7 (c 1.5, CHCl3); IR (KBR):
700, 820, 880, 1080, 1100, 1240, 1350, 1760, 2800, 2840,
3.13. 3%,4%-Dihydroxy5-t-butyldimethylsilyloxyymethyl-
2,2-dimethyl(3%R,3aR,4%R,5R,6%S,6%R,6aR)-spiro[perhy-
drofuro[2,3-d][1,3]dioxole-6,2%-(3%H,4%H,5%H,6%H-pyran)]-6
-yl acetate, 19b
1
2920 cm−1; H NMR (CDCl3, 200 MHz): l 0.05 (s, 6H,
To a stirred solution of olefin 18b (0.160 g, 0.386 mmol)
in acetone–water (10 mL, 3:1) were added sequentially
N-methyl morpholine N-oxide (0.090 g, 0.772 mmol) and
OsO4 (four drops) at room temperature. After 20 days,
it was worked up as described for 12 and purified by
column chromatography (silica gel, 1:3 ethyl acetate–
petroleum ether) to afford diol 19b as a solid (0.110 g,
85%). The conversion of reaction was after 20 days 75%
only and 0.040 g of starting material was recovered.
Mp=165–170°C; [h]D=71.60 (c 0.55, CHCl3); IR
(KBR): 720, 840, 1020, 1100, 1200, 1250, 1320, 1400,
1720, 2800, 2920, 3400, 3520 cm−1; 1H NMR (CDCl3, 200
MHz): l 0.08 (s, 6H, 2 Si CH3), 0.92 (s, 9H, C(CH3)3),
1.40, 1.51 (2s, 6H, 2 CH3), 1.92 (ddd, 1H, J7,8 5.0, J8,9
10.2, J8,8% 15.2 Hz, H-8) 2.11 (s, 3H, 1 OAc), 2.28 (dt, 1H,
J7,8% 3.8, J8%,9 3.8, J8,8% 15.2 Hz, H-8%), 3.65 (d, 1H, J6, 7
5.1 Hz, H-6), 3.88–4.01 (m, 2H, H-5%, 7), 4.10 (dd, 1H,
J4,5 4.6, J5,5% 15.2 Hz, H-5), 4.32 (dd, 1H, J4,5 4.6, J4,5% 8.1
Hz, H-4), 5.39 (d, 1H, J1,2 5.1 Hz, H-2), 5.78 (d, 1H, J1,2
5.1 Hz, H-1), 6.26 (dd, 1H, J8,9 10.2, J8%,9 3.8 Hz, H-9);
13C NMR (CDCl3, 50 MHz): l −5.44, −5.34, 25.92, 27.00
(7C), 29.79, 35.67, 59.71, 68.10, 68.31, 78.80, 81.73, 89.92,
96.25, 105.13; FABMS (m/z, %): 471 (M++23, 100), 391
(44), 331 (70), 181 (72), 171 (74).
2 Si CH3), 0.87 (s, 9H, C(CH3)3), 1.31, 1.56 (2s, 6H, 2
CH3), 2.04 (s, 3H, OAc), 2.06–2.20 (m, 1H, H-8%),
2.48–2.67 (m, 1H, H-8), 3.58–3.73 (m, 2H, H-5, 5%), 4.10
(t, 1H, J 4.6 Hz, H-4), 4.25 (d, 1H, J1,2 3.7 Hz, H-2), 5.64
(br. d, 1H, J6,7 11.5 Hz, H-6), 5.74 (d, 1H, J1,2 3.7 Hz,
H-1), 5.83–5.96 (m, 1H, H-7), 6.36 (t, 1H, J 4.6 Hz, H-9);
13C NMR (CDCl3, 50 MHz): l −5.45, −5.30, 18.21, 21.20,
25.80 (2C), 26.51, 26.68, 28.24, 29.58, 61.89, 78.66, 81.06,
83.69, 88.98, 103.85, 112.49, 122.67, 124.01, 169.28;
FABMS (m/z, %): 415 (M++1, 10), 281 (78), 221 (100),
207 (98). Anal. calcd for C20H34O7Si (414): C, 57.94; H,
8.27. Found: C, 57.88; H, 8.17%.
Second eluted was 5-tert-butyldimethylsilyloxymethyl-
2,2-dimethyl-(3aR,5R,6%S,6%R,6aR)-spiro[perhydrofuro-
[2,3-d][1,3]dioxole-6,2%-(5%H,6%H-pyran)]-6-yl
acetate,
18b: mp=95–97°C; [h]D=44.20 (c 1.01, CHCl3); IR
(KBR): 780, 820, 1020, 1100, 1250,1340, 1440, 1730,
2850, 2920, 2960 cm−; 1 1H NMR (CDCl3, 200 MHz): l
0.09 (s, 6H, 2 Si CH3), 0.91 (s, 9H, C(CH3)3), 1.36, 1.60
(2s, 6H, 2 CH3), 2.12 (s, 3H, OAc), 2.25–2.50 (m, 2H,
H-8, 8%), 3.63 (dd, 1H, J5,5% 11.4, J4,5% 7.1 Hz, H-5%), 3.85
(dd, 1H, J5,5% 11.4, J4,5 2.4 Hz, H-5), 4.13 (dd, 1H, J4,5%
9.5, J4, 52.4 Hz, H-4), 4.28 (d, 1H, J1,2 4.3 Hz, H-2), 5.66
(br. d, 1H, J6,7 9.5 Hz, H-6), 5.74 (d, 1H, J1,2 4.3 Hz, H-1),
5.90 (dt, 1H, J7,8 4.8, J7,8% 4.8, J6,7 9.5 Hz, H-7), 6.15 (dd,
1H, J8,9 4.2, J8%,9 5.1 Hz, H-9); 13C NMR (CDCl3, 50
MHz): l −5.31, −5.16, 14.05, 18.29, 21.25, 25.89, 26.44,
26.79, 29.28, 29.51, 29.66, 61.93, 81.83, 83.17, 90.49,
103.58, 113.28, 123.79, 125.29, 169.07; FABMS (m/z, %):
415 (M++1, 10), 281 (78), 221 (100), 207 (98). Anal. calcd
for C20H34O7Si (414): C, 57.94; H, 8.27. Found: C, 57.85;
H, 8.19%.
3.14. 5-tert-Butyldimethylsilyloxymethyl-2,2-dimethyl-
3%,4%-di(methylcarbonyloxy)-(3%R,3aR,4%R,5R,6%S,6%S,
6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,2%-
(3%H,4%H,5%H,6%H-pyran)]-6-yl acetate, 3
A mixture of the diol 19b (0.090 g, 0.200 mmol) and
triethylamine
(0.166
mL,
1.200
mmol),
in
dichloromethane (5 mL) was treated with acetic anhy-
dride (0.037 mL, 0.400 mmol) in the presence of catalytic
DMAP at 0°C. After 1 h, it was worked up as described
for 13 and the residue was purified by column chro-
matography (silica gel, 1:20 ethyl acetate–petroleum
ether) to afford 3 (0.100 g) in 94% yield as a gummy
syrup. [h]D=40.69 (c 1.15, CHCl3); IR (neat): 750, 840,
1000, 1050, 1090, 1210, 1240, 1350, 1440, 1460, 1750,
3.12. 3%,4%-Dihydroxy-5-tert-butyldimethylsilyloxy-
methyl-2,2-dimethyl-(3%S,3aR,4%S,5R,6%R,6%R,6aR)-
spiro[perhydrofuro[2,3-d][1,3]dioxole-6,2%-
(3%H,4%H,5%H,6%H-pyran)]-6-yl acetate, 19a
To a stirred solution of olefin 18a (0.080 g, 0.193 mmol)
in acetone–water (5 mL, 3:1) were added sequentially
N-methyl morpholine N-oxide (0.045 g, 0.386 mmol) and
OsO4 (two drops) at room temperature. After 20 days,
it was worked up described for 12 and purified by column
chromatography (silica gel, 1:3.3 ethyl acetate–petroleum
ether) to afford diol 19a as a solid (0.043 g, 80%). The
conversion of the reaction was 60% and starting material
0.030 g recovered. Mp=125–130°C; [h]D=−22.3 (c 1.5,
CHCl3); IR (KBR): 680, 1020, 1150, 1220, 1350, 1420,
1
2800, 2900 cm−1; H NMR (CDCl3, 500 MHz): l 0.06,
0.07(2s, 6H, 2 SiCH3), 0.90 (s, 9H, C(CH3)3), 1.36 (1S,
3H, CH3(A)), 1.54 (s, 3H, CH3(B)), 1.95 (ddd, 1H, J7,8b
3.9, J8b,9 6.9, J8a,8b 13.7 Hz, H-8b), (2s, 9H, 3 OAc), 2.23
(ddd, 1H, J7,8a 6.9, J8a,9 2.9, J8a,8b 13.7 Hz, H-8a), 3.79
(dd, 1H, J4,5% 4.4, J5, 5%11.3 Hz, H-5%), 3.89 (dd, 1H, J4,5
4.9, J5,5% 11.3 Hz, H-5), 4.26 (t, 1H, J4,5 4.9, J4,5% 4.4 Hz,
H-4), 4.87 (d, 1H, J1,2 4.4 Hz, H-2), 5.32 (d, 1H, J 6,7 3.4
Hz, H-6), 5.46 (dt, 1H, J6,7 3.4, J7,8a 6.9, J7,8b 3.9 Hz H-7),
5.79 (d, 1H, J1,2 4.4 Hz, H-1), 6.32 (dd, 1H, J8a,9 2.9, J8b,9
6.9 Hz, H-9); 13C NMR (CDCl3, 50 MHz): l −5.53,
−5.43, 18.21, 20.64, 20.88, 21.07, 25.81(2C), 26.79, 27.29,
29.62, 32.10, 61.58, 66.58, 66.68, 80.68, 82.58, 83.04,
89.91, 104.98, 113.34, 168.42, 169.22, 169.57; FABMS
(m/z, %): 555 (M++23, 6), 415 (52), 255 (65), 185 (82),
163 (78), 147 (100). Anal. calcd for C24H40O11Si (532):
C, 54.12; H, 7.57. Found: C, 54.09; H, 7.49%.
1
1680, 2840, 2900, 3380 cm−1; H NMR (CDCl3, 200
MHz): l 0.10 (s, 6H, 2 Si CH3), 0.82 (s, 9H, C(CH3)3),
1.30, 1.48 (2s, 6H, 2 CH3), 2.02 (s, 3H, 1 OAc), 2.06–2.15
(m, 2H, H-8, 8%), 3.52 (d, 1H, J6,7 5.1 Hz, H-6), 3.75–4.06
(m, 3H, H-5, 5%, 7), 4.24 (dd, 1H, J4,5 5.1, J4,5% 8.2 Hz,
H-4), 5.32 (d, 1H, J1,2 4.1 Hz, H-2), 5.71 (d, 1H, J1,2 4.1
Hz, H-1), 6.10 (d, 1H, J8,9 5.1 Hz, H-9); FABMS (m/z,
%): 471 (M++23, 5), 401 (74), 281 (67), 221 (75), 207 (100).

G. V. M. Sharma et al. / Tetrahedron: Asymmetry 13 (2002) 1599–1607
1607
3.15. 5-tert-Butyldimethylsilyloxymethyl-2,2-dimethyl-
3%,4%-di(methylcarbonyloxy)-(3%S,3aR,4%S,5R,6%R,6%S,
6aR)-spiro[perhydrofuro[2,3-d][1,3]dioxole-6,2%-
(3%H,4%H,5%H,6%H-pyran)]-6-yl acetate, 4
financial support. This work was supported by a grant-
in-aid project (CSIR Young Scientist Award to Dr.
G.V.M. Sharma).
A mixture of diol 19a (0.030 g, 0.066 mmol) and
triethylamine (0.055 mL, 0.396 mmol), in dichloro-
methane (5 mL) was treated with acetic anhydride
(0.012 mL, 0.132 mmol) in the presence of catalytic
DMAP at 0°C. After 1 h, it was worked up as described
for 13 and the residue was purified by column chro-
matography (silica gel, 1:20 ethyl acetate–petroleum
ether) to afford 4 (0.035 g) in 98% yield as a solid.
Mp=120–125°C; [h]D=−25.95 (c 1.2, CHCl3); IR
(KBR): 720, 820, 1020, 1150, 1210, 1350, 1440, 1480,
References
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Tetrahedron: Asymmetry 2000, 11, 2643.
1
1780, 2820, 2900 cm−1; H NMR (CDCl3, 500 MHz): l
0.06, 0.07 (2s, 6H, 2 SiCH3), 0.88 (s, 9H, C(CH3)3), 1.36
(s, 3H, CH3 (A)), 1.54 (s, 3H, CH3(B)), 2.06, 2.07, 2.12
(3s, 9H, 3 OAc), 2.10 (m, 1H, 8b), 2.21 (ddd, 1H, J7,8a
4.3, J8a,9 2.4, J8a,8b 14.8 Hz, H-8a), 3.69 (dd, 1H, J4,5b 5.3,
J5a,5b 11.0 Hz, H-5b), 3.77 (dd, 1H, J4,5a 6.2, J5a,5b 11.0
Hz, H-5a), 4.19 (t, 1H, J4,5a 6.2, J4,5b 5.3 Hz, H-4), 5.04
(d, 1H, J6,7 3.8 Hz, H-6), 5.21 (d, 1H, J1,2 3.8 Hz, H-2),
5.36 (ddd, 1H, J6,7 3.8, J7,8a 4.3, J7,8b 3.9 Hz, H-7), 5.73
(d, 1H, J1,2 3.8 Hz, H-1), 6.18 (dd, 1H, J8a,9 2.4, J8b,9 4.3
Hz, H-9); 13C NMR (CDCl3, 50 MHz): l −5.68, −5.54,
18.10, 20.55, 20.85, 21.15, 25.69, 26.73, 26.84, 29.48,
30.84, 31.72, 61.16, 65.83, 65.96, 79.91, 80.96, 81.57,
88.03, 104.85, 111.95, 168.82(2C), 169.58. FABMS (m/z,
%): 555 (M++23, 30), 517 (9), 415 (68), 255 (50), 185 (30),
136 (40), 117 (100). HRMS: calcd for C23H37O11Si:
517.210516. Observed: 517.209264.
Acknowledgements
11. (a) Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron Lett.
1983, 24, 3943; (b) Cha, J. K.; Christ, W. J.; Kishi, Y.
Tetrahedron 1984, 40, 2247.
We thank Dr. A. C. Kunwar for useful discussions. J.J.R.
and M.H.V.R.R. are thankful to CSIR, New Delhi for