Synthesis of vinyl α-D-glucopyranosides from mixed acetal glycosides

Full text of DOI:10.1081/CAR-100102545

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SYNTHESIS OF VINYL α-D-GLUCOPYRANOSIDES FROM
MIXED ACETAL GLYCOSIDES
Jocelyn Edathil a , Joan Nguyen a , Kevin Hughes a , Walter J. Boyko a & Robert M
Giuliano b
a Department of Chemistry , Villanova University , Villanova, PA, 19085, U.S.A.
b Department of Chemistry , Villanova University , Villanova, PA, 19085, U.S.A.
Published online: 11 Dec 2006.
To cite this article: Jocelyn Edathil , Joan Nguyen , Kevin Hughes , Walter J. Boyko & Robert M Giuliano (2001) SYNTHESIS
OF VINYL α-D-GLUCOPYRANOSIDES FROM MIXED ACETAL GLYCOSIDES , Journal of Carbohydrate Chemistry, 20:1, 81-85,
DOI: 10.1081/CAR-100102545
To link to this article: http://dx.doi.org/10.1081/CAR-100102545
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J. CARBOHYDRATE CHEMISTRY, 20(1), 81–85 (2001)
COMMUNICATION
SYNTHESIS OF VINYL ꢀ-D-GLUCOPYRANOSIDES
FROM MIXED ACETAL GLYCOSIDES1
Jocelyn Edathil, Joan Nguyen, Kevin Hughes, Walter J. Boyko,
and Robert M. Giuliano*
Department of Chemistry, Villanova University, Villanova, PA 19085
Vinyl D-glucopyranosides are useful intermediates in a wide variety of appli-
cations in synthetic carbohydrate chemistry. They have been utilized as chiral aux-
iliaries in the inverse-electron-demand cycloaddition with isoquinolinium salts,
giving homochiral tetralins (Bradsher cycloaddition),2 and as precursors to enan-
tiomerically pure cyclobutanols by [2ꢁ2] cycloaddition with ketenes.3 Vinyl gly-
cosides that are unsaturated at C2-C3 undergo thermal Claisen rearrangement to
give C-3 branched glycal derivatives.4 Isopropenyl5 and butenyl glycosides have
been used as glycosyl donors in oligosaccharide synthesis.6 Vinyl glycosides and
mixed acetal glycosides have been studied as substrates for glycosidases.7,8 In
more recent studies, vinylated sugars, in which the vinyl group is attached to non-
anomeric hydroxyl groups, have been utilized in the synthesis of cyclooctanoic
mimetics of carbohydrates,9 as precursors to C-glycosides,10 and as intermediates
in the synthesis of ꢂ-mannosides by intramolecular tethering and delivery.11
Vinyl glycosides are most often synthesized from glucopyranosides with an
unblocked anomeric hydroxyl group by transvinylation with mercuric acetate12 or
from glycosyl halides by nucleophilic displacement with bis(acylmethyl)mercury
reagents.13
Elimination reactions of 2-(phenylselenyl)ethyl glycosides14 and 2-
(trimethylammonium)-ethyl glycosides,12 and photolysis of 4-oxopentyl glyco-
sides by Norrish Type II reactions also give vinyl glycosides.15 Our studies of het-
ero-Diels-Alder reactions in carbohydrate synthesis required access to vinyl
D-glucopyranosides. A mercury-free preparation of vinyl ethers derived from chi-
ral alcohols has been reported,16 in which treatment of mixed acetals with
trimethylsilyl trifluoromethane sulfonate and an amine (Gassman method)17 gave
good yields of vinyl ethers. We were intrigued by the possibility of synthesizing
vinyl glycosides by the Gassman method, since the required monosaccharides that
81
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EDATHIL ET AL.
are unblocked at the anomeric center are readily available with both ether and es-
ter protecting groups on the remaining hydroxyl groups. Treatment of these start-
ing materials with vinyl ethers in the presence of an acid catalyst would provide the
mixed acetal glycosides needed for the elimination reaction.18 Mixed acetal gly-
cosides are also available by the reaction of TMS glycosides and dialkyl acetals in
the presence of TMS-triflate.19 Herein, we describe the synthesis of vinyl and iso-
propenyl ꢀ-D-glucopyranosides by the Gassman method.
Both 2,3,4,6-tetra-O-benzyl-D-glucopyranoside and its corresponding tetra-
O-acetyl derivative,20 1a and 1b, were treated with ethyl vinyl ether in
dichloromethane in the presence of PPTS to give the mixed acetal ꢀ-D-glucopyra-
nosides 2a7 and 2b8 in 85-90% yields as a 1:1 mixture of diastereomers that were
not separated. The major products (ꢀ9:1) were the ꢀ-anomers in each case. Re-
duction of the quantity of acid catalyst and the use of no more than five equivalents
of vinyl ether gave clean product that could be used directly in the elimination step
(see Experimental).
Treatment of the benzyl-protected mixed acetal glycoside (2b) with
trimethylsilyl trifluoromethanesulfonate and triethylamine gave the vinyl ꢀ-D-glu-
copyranoside 312 in 68% yield after purification by flash chromatography. Prod-
ucts resulting from ring-opening, glycals formed by elimination of the anomeric
substituent, or the TMS glycoside 4 that would result from an alternative elimina-
tion were not detected. The regioselectivity observed is consistent with that re-
ported by Dujardin, Rossignol, and Brown,16 and it is assumed to result from com-
plexation of the trimethylsilyl cation with the ethoxy group oxygen of the mixed
acetal, rather than the oxygen at C-1.

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VINYL ꢀ-D-GLUCOPYRANOSIDES
83
The synthesis of isopropenyl 2,3,4,6-tetra-O-benzyl-ꢀ-D-glucopyranoside by
the Gassman method was also successful. Treatment of the mixed acetal glycoside
5 (prepared from 1b using 2-methoxypropene) gave a product mixture containing
a 2:1 ratio of isopropenyl glycoside 65 to TMS glycoside 48, from which 6 was iso-
lated in 54% yield.
The preparation of acetate ester-protected vinyl glycosides from mixed acetal
glycosides 2a by this procedure gave poor yields (20%) of vinyl glycoside, with
decomposition being observed. Benzoate esters were not attempted, but these may
be more suitable if competing enolization in the acetates is responsible for the low
yields. In an example of the use of this method for the vinylation of other sites on
the pyranose ring, the 3-O-vinyl ether 8 was obtained in 40% yield from mixed ac-
etal 7, which was readily prepared from methyl 4,6-O-benzylidene-2-deoxy-ꢀ-D-
ribo-hexopyranoside.21
In summary, a mercury-free synthesis of vinyl and isopropenyl glycosides
was developed based on the Gassman method. Vinylation of hydroxyl groups at
other positions also appears to be feasible. Further studies to test the scope of the
reaction, the optimization of experimental conditions, and applications of the viny-
lated sugars are in progress.
EXPERIMENTAL
Preparation of Mixed Acetal Glycosides 2a, 2b, 5, and 7. A solution of the
alcohol (1 mmol), vinyl ether (ethyl vinyl ether or 2-methoxypropene for 5, 5
mmol), and PPTS (10 mg) in dry dichloromethane (20 mL) was stirred at room
temperature until TLC (1:3 ethyl acetate-hexanes) showed that starting material
was consumed (1-3 h). Solid sodium carbonate was added and after stirring for
several minutes, the mixture was filtered and the filtrate concentrated under re-
duced pressure to give syrupy mixed acetal glycosides 2a7 and 2b8 in 85-90%
yields, which were used without further purification. Compound 5 had [ꢀ]D ꢁ60°

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EDATHIL ET AL.
(c 1.1, chloroform); HRMS (ESꢁ) Calcd. for C38H44O7Na [MꢁNa]: 635.3009.
Found: 635.2985. Compound 7: Anal. Calcd for C18H26O6: C, 63.89; H, 7.74.
Found: C, 63.55; H, 7.53.
Preparation of Vinyl Glycosides 3, 6 and Vinyl Ether 8. To a solution of
mixed acetal glycoside (1 mmol) in dichloromethane (3 mL) cooled to 0 °C was
added triethylamine (1.6 equiv) followed by TMS- triflate (1.3 equiv). The reac-
tion mixture was allowed to warm to room temperature and then stirred overnight.
Additional triethylamine (0.4 equiv) and TMS-triflate (0.3 equiv) was added and
stirring was continued until TLC (1:3 ethyl acetate-hexanes) showed the con-
sumption of the starting material, usually another 18-24 h. Vinyl glycosides had
slightly higher Rf values than mixed acetal glycosides, for example 0.38 and 0.54
for 5 and 6, respectively (1:3 ethyl acetate-hexanes). Dilute sodium hydroxide
solution (2 mL) was added slowly to the reaction, after which it was diluted with
dichloromethane (20 mL). The organic phase was washed with saturated sodium
chloride solution, dried (Na2SO4) and concentrated. Vinyl glycosides 312 and 65
were purified by flash chromatography using 10% ethyl acetate-hexanes. The
same procedure was used for the preparation of 3-O-vinyl sugar 8: Rf 0.20 (1:4
ethyl acetate/hexanes); ꢀ]D ꢁ104° (c 1.0, chloroform); Anal. Calcd for C16H20O5:
C, 65.74; H, 6.90. Found: C, 65.43; H, 6.89.
ACKNOWLEDGEMENTS
The authors thank the Howard Hughes Medical Institute and the Chemistry
Department of Villanova University for financial support of this research. Support
for Jocelyn Edathil from the Villanova University Honors Program is also grate-
fully acknowledged.
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Received September 19, 2000
Accepted December 22, 2000

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