An Efficient Method for the Synthesis of 2,3-Unsaturated Glycopyranosides Catalyzed by Bismuth Trichloride in Ferrier Rearrangement

Article abstract of DOI:10.1055/s-2002-23551

The reaction of tri-O-acetyl-D-glucal and tri-O-benzyl-D-glucal with various alcohols and thiols to afford the corresponding glycopyranosides in excellent yields by bismuth trichloride in acetonitrile at ambient temperature has been demonstrated.

Full text of DOI:10.1055/s-2002-23551

598
SHORT PAPER
An Efficient Method for the Synthesis of 2,3-Unsaturated Glycopyranosides
Catalyzed by Bismuth Trichloride in Ferrier Rearrangement1
S
ynthesis of 2,3-U
.
nsaturated G
R
lycopyranosidesaghavendra Swamy, Y. Venkateswarlu*
Organic Chemistry Division-1, Indian Institute Of Chemical Technology, Hyderabad, 500 007 India
Fax +91(40)7160512; E-mail: luchem@iict.ap.nic.in
Received 10 November 2001; revised 6 February 2002
first examined the reaction of tri-O-acetyl-D-glucal with
Abstract: The reaction of tri-O-acetyl-D-glucal and tri-O-benzyl-
D-glucal with various alcohols and thiols to afford the correspond-
ing glycopyranosides in excellent yields by bismuth trichloride in
acetonitrile at ambient temperature has been demonstrated.
benzyl alcohol in the presence of bismuth trichloride in
acetonitrile at ambient temperature affording the corre-
sponding 2,3-unsaturated glycopyranoside in 94% yield
as the -anomer (Table, entry d). This success encouraged
us to extend the generality of the reaction. The glycosida-
tion of tri-O-acetyl glucals with primary, secondary, ben-
zyl, allyl and propargyl alcohols and thiophenol
proceeded smoothly (Table). Extension of this reaction to
other glycosyl acceptors such as N-BOC protected threo-
nine furnished the - and -anomers in 60:40 ratio (Table
entry j). These compounds are potential precursors for the
synthesis of glycopeptide building blocks. This also indi-
cates that BOC-protected amino acids are suitable sub-
strates for this reaction conditions. Furthermore we
extended the reaction to tri-O-benzoyl-D-glucal with ethyl
alcohol, which gave good result.
Key words: Ferrier rearrangement, carbohydrates, bismuth trichlo-
ride, unsaturated glycopyranosides
Alkyl and aryl 2,3-unsaturated glycosides and pseudogly-
cals are versatile chiral intermediates2 in the synthesis of
glucopeptides,3 modified carbohydrates,4 nucleosides5
and biologically active natural products. 2-Deoxy and 2,3-
dideoxy sugars derived from 2,3-unsaturated glycosides
are important building blocks in many bioactive mole-
cules such as antibiotics.6 Lewis acid catalyzed allylic re-
arrangement of glycols is well known as Ferrier
rearrangement7 and is a widely employed reaction to ob-
tain 2,3-unsaturated glycosides. A variety of reagents are
used to effect this transformation, which include strong
acids such as BF3 OEt2,8 and SnCl4.9 Other reagents such
as acidic montmorillonite K-10,10 DDQ,11 NIS,12 lithium
13
tetrafluroborate, InCl3 and triflates like Sc(OTf)3,14
Yb(OTf)315 are also known to bring about the Ferrier rear-
rangement under different conditions. However, many of
these procedures suffer from disadvantages like strong
oxidizing conditions, high acidity, longer reaction times,
unsatisfactory yields, low stereoselectivity and use of a
large amount of reagent or catalyst. For instance, in some
cases 1.6 equivalents of NIS or varied amount of
BF3 OEt2 are needed to effect the transformation. Fur-
thermore, the metal triflates required for the transforma-
tion are highly expensive.
Scheme
In conclusion the present procedure for the 2,3-unsaturat-
ed glycosides has the advantages of mild reaction condi-
tions, high stereoselectivity, reduced reaction time,
inexpensive catalyst, high yields of products and simple
experimental workup procedure. BiCl3-catalyzed Ferrier
glycosylation has been developed to produce structurally
diverse O- and S-glucopyranosides and will be an impor-
tant addition to the present existing methodologies.
8
In view of the current thrust on catalytic processes there is
a merit in developing a truly catalytic method to prepare
2,3-unsaturated glycopyranosides from alcohols and thi-
ols using inexpensive and non-polluting reagent. Herein,
we wish to report the bismuth trichloride-catalyzed gly-
cosylation with alcohols and thiols. The reaction proceeds
efficiently at ambient temperature and the products are
obtained in excellent yields (Scheme). Furthermore, other
functionalities such as BOC, allyl and propargyl are com-
patible under the reaction conditions. The reaction condi-
tions are very mild and no byproducts are observed. We
2,3-Unsaturated Glycosides from Alcohols and Thiols; General
Procedure
A solution of glucal (1 mmol) and an alcohol (1.1 mmol) in MeCN
(10 mL) was treated with BiCl3 (5 mol%) and stirred for an appro-
priate time (Table) at r.t. The solvent was removed under reduced
pressure, H2O was added, and the mixture was extracted with
EtOAc. The organic layer was washed with brine, dried (Na2SO4)
and concentrated to give the crude product, which was purified on
a silica gel column to provide pure the 2,3-unsaturated glycosides in
high yields (Table).
Synthesis 2002, No. 5, 08 04 2002. Article Identifier:
1437-210X,E;2002,0,05,0598,0600,ftx,en;Z12201SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

SHORT PAPER
Synthesis of 2,3-Unsaturated Glycopyranosides
599
Table BiCl3-Catalyzed Glycosidation of Alcohols and Thiols
Entry
a
Acceptor
Unsaturated
Glycoside
Time (h)
1
Yield
(%)a
Anomeric Ratio
( / )b
CH3CH2OH
967
10:1
b
c
CH3CH2OH
1
1
95
9:1
CH3(CH2)2CH2OH
967
11:1
d
PhCH2OH
1
9416
10:1
e
f
1.5
1.5
9614
9:1
9617
10:1
g
h
1.5
1.5
9518
11:1
10:1
9519
i
2
90
8:2
j
2
91
6:4
k
PhSH
1.5
9520
10:1
a Isolated yield as pure anomeric mixtures after purification. The literature references are given for known glycosides.
b The anomeric ratio was determined on the basis of the integration ratios of the anomeric hydrogens in the 1H NMR spectra at 200MHz.
Synthesis 2002, No. 5, 598–600 ISSN 0039-7881 © Thieme Stuttgart · New York

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N. Raghavendra Swamy, Y. Venkateswarlu
SHORT PAPER
Ethyl 4,6-Di-O-benzoyl-2,3-dideoxy- -D-erythro-hex-2-enopyr-
anoside (Entry b)
Reference
1H NMR (CDCl3, 200 MHz): = 1.22 (t, 3 H, J = 5.5 Hz), 3.57–
3.68 (m, 1 H, OCH2), 3.8–3.92 (m, 1 H, OCH2), 4.40–4.60 (m, 3 H,
H-5,6,6 ), 5.07 (d, 1 H, J = 4 Hz H-1), 5.65 (m, 1 H, H-4), 5.83 (d,
1 H J2,3 = 10.9 Hz, H-2), 6.01 (d, 1 H, J3,4 = 1.5 Hz, J3,2 = 11.1 Hz,
H-3),7.40–7.61 (m, 6 Harom), 7.94–8.13 (m, 4 Harom).
(1) IICT Communication No. 01/09/07.
(2) (a) Fraser-Reid, B. Acc. Chem. Res. 1985, 18, 347.
(b) Ferrier, R. J. Adv. Carbohydr. Chem. Biochem. 1969, 24,
199.
(3) (a) Winterfeld, G. A. Ph.D. Dissertation; University of
Konstanz: Germany, 2000. (b) Durgan, B. J.; Jackson, R. F.
W. Synlett 1996, 859.
Anal. Calcd for C22H24O6: C, 68.5; H, 6.3. Found: C, 68.7; H, 6.3.
(4) Schmidt, R. R.; Angerbauer, R. Angew.Chem., Int. Ed. Engl.
1977, 16, 783; Angew. Chem. 1977, 89, 822.
(5) (a) Schmidt, R. R.; Angebauer, R. Carbohydr. Res. 1979, 72,
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Peredes, L. M. R. Carbohydr. Res. 1998, 181, 308.
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Chemistry and Biochemistry; Academic Press: New York,
1980, 761.
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Liebigs Ann. Chem. 1991, 509.
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Konoshita, M. J. Chem. Soc.,Chem.Commun. 1993, 704.
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2000, 41, 1271.
Cholesteryl 4,6-Di-O-acetyl-2,3-dideoxy- -D-erythro-hex-2-
enopyranoside (Entry i)
Mp 115–117 °C; [ ]D25 +75 (c = 1, CHCl3).
1H NMR (CDCl3, 200 MHz): = 5.8 (d, J = 2.5 Hz, 2 H, H-2 ,3 ),
5.35 (m, 1 H, H-6), 5.23 (d, J = 6 Hz, H-4 ), 5.05 (br s, 1 H, H-1 ),
4.19 (br s, 2 H, H-6 ,6 ), 4.05 (m, 1 H, H-5 ), 3.45 (m, 1 H, H-3),
2.25 (m, 2 H), 2.0 (s, 6 H), 0.92 (s, 3 H), 0.85 (d, J = 6.5 Hz), 0.8 (d,
J = 6.5 Hz, 6 H, H-26,27), 0.71 (s,3 H, H-19).
Anal. Calcd for C38H58O6: C, 74.2; H, 9.8; Found : C, 74.0; H, 9.75.
Methyl N-(tert-Butoxycarbonyl)threonine 4,6-Di-O-acetyl-2,3-
dideoxy- -D-erythro-hex-2-enopyranoside (Entry j)
[ ]D25 +42.39 (c = 1, CHCl3).
1H NMR (CDCl3, 200 MHz): = 1.31 (d, J = 6.3 Hz, 3 H CH3),1.42
[s, 9 H,C(CH3)3], 2.08 (s, 6 H, OCOCH3), 3.78 (s, 3 H, CO2CH3),
4.08–3.80 (m, 5 H, H-5,6,6 , -CH, -CH), 4.95 (br s, 1 H, H-1),
5.15 (d, JNH = 9.8 Hz, 1 H, NH), 5.26 (dd, J3,4 = 1.1 Hz, J4,5 = 9.8
Hz, 1 H, H-4), 5.65 (br s, 1 H, H-2), 5.84 (br s, 1 H, H-3).
Acknowledgment
(14) Yadav, J. S.; Reddy, B. V. S.; Murthy, C. V. S. R.; Kumar,
G. M. Synlett 2000, 1450.
(15) Takhi, M.; Abdel-Rahman, Adel A.-H.; Schmidt, R. R.
Synlett 2001, 427.
(16) Dearg, S. B.; Steven, V. L.; Sadie, V.; Mervyn, T.
Tetrahedron 1991, 47, 1329.
We are thankful to the Director, IICT and Dr. J. S. Yadav for their
constant encouragement and CSIR New Delhi for providing a fel-
lowship to NRS.
(17) Frappa, I.; Sinou, D. Synth. Commun. 1995, 25, 2941.
(18) Lesueur, C.; Nouguier, R.; Bertrand, M. P.; Hoffmann, P.;
De Mesmeker, E. Terahedron 1994, 50, 5369.
(19) Moufid, N.; Chapleur, Y.; Mayon, P. J. Chem. Soc., Perkin
Trans.1 1992, 999.
(20) Valverde, S.; Garcia-Ochoa, S. J. Carbohydr. Chem. 1989,
8, 553.
Synthesis 2002, No. 5, 598–600 ISSN 0039-7881 © Thieme Stuttgart · New York