Optimized synthesis of vinyl ether sugars and vinyl glycosides through transfer vinylation catalyzed by (4,7-Ph2-phen)Pd(OOCCF3)2

Article abstract of DOI:10.1080/07328300802030852

Sugar vinyl ethers and vinyl glycosides are conveniently synthesized by catalytic transfer vinylation with butyl vinyl ether, which serves as both the solvent and source of vinyl. The air-stable catalyst (4,7-diphenyl-1,10- phenanthroline)Pd(OOCCF3)2 is p

Full text of DOI:10.1080/07328300802030852

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Optimized Synthesis of Vinyl Ether Sugars and
Vinyl Glycosides through Transfer Vinylation
Catalyzed by (4,7‐Ph2‐phen)Pd(OOCCF3)2
Martin Bosch a , Sean Handerson a & Marcel Schlaf a
a The Guelph‐Waterloo Centre for Graduate Work in Chemistry (GWC)2,
Department of Chemistry , University of Guelph , Guelph, Ontario, Canada
Published online: 28 May 2008.
To cite this article: Martin Bosch , Sean Handerson & Marcel Schlaf (2008) Optimized Synthesis of Vinyl Ether
Sugars and Vinyl Glycosides through Transfer Vinylation Catalyzed by (4,7‐Ph2‐phen)Pd(OOCCF3)2 , Journal of
Carbohydrate Chemistry, 27:2, 103-112, DOI: 10.1080/07328300802030852
To link to this article: http://dx.doi.org/10.1080/07328300802030852
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Journal of Carbohydrate Chemistry, 27:103–112, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300802030852
Optimized Synthesis of Vinyl
Ether Sugars and Vinyl
Glycosides through Transfer
Vinylation Catalyzed
by (4,7-Ph2-phen)
Pd(OOCCF3)2
Martin Bosch, Sean Handerson, and Marcel Schlaf
The Guelph-Waterloo Centre for Graduate Work in Chemistry (GWC)2,
Department of Chemistry, University of Guelph, Guelph, Ontario, Canada
Sugar vinyl ethers and vinyl glycosides are conveniently synthesized by catalytic
transfer vinylation with butyl vinyl ether, which serves as both the solvent and source
of vinyl. The air-stable catalyst (4,7-diphenyl-1,10-phenanthroline)Pd(OOCCF3)2 is
prepared in situ from commercially available components.
Keywords Vinyl sugars, Catalytic synthesis
INTRODUCTION
Vinyl glycosides and vinyl ether sugars have been employed as glycosyl donors
and acceptors[1–4] and also constitute a class of potential components of sugar-
based amphiphiles and surfactants or sugar-modified polymers and polymer
surfaces obtained by the copolymerization of a vinyl ether sugar with a bulk
alkene (e.g., styrene or propylene, methyl methacrylate, vinyl acetate, or
acrylonitrile).
Early examples of vinyl sugars are 6-O-vinyl-1,2:3,4-di-O-isopropylidene-
D-galacto-pyranoside,[5] obtained in 58% yield by reaction of diacetone-
galactose with acetylene in sodium hydroxide melt, and 3-O-vinyl-1,2:5:6-di-
Received November 30, 2007; accepted February 2, 2008.
Address correspondence to Marcel Schlaf, Department of Chemistry, University of
Guelph, Guelph, Ontario N1G 2W1, Canada. E-mail: mschlaf@uoguelph.ca
103

M. Bosch et al.
104
O-isopropylidene-D-glucofuranoside,[6] obtained in 22% yield by transetherifi-
cation of diacetone-glucose catalyzed by mercuric acetate. More recently
sugar vinyl ethers have been synthesized by preparation of the corresponding
b-alkoxyvinyl sulfones followed by desulfonylation with Na/Hg amalgam.[7]
Vinyl glycosides have also been prepared by transformation of vinyl acetates
with Tebbe’s reagent (yielding the corresponding isopropenyls),[1] by Hofmann
degradation of N-2-trimethyl-ammonium-ethyl-O-glycosides,[8] through the
use of selenium[9] or mercury reagents,[10] by photochemically induced
rearrangement of 4-oxo-pentyl-glycosides,[11] and by acid-catalyzed alcohol
elimination from mixed acetal glycosides.[12] The latter method is now also
applicable to the synthesis of sugar vinyl ethers.[13] Recently we described a
very atom-efficient and simple method for the transfer vinylation of a series of
sugar substrates catalyzed by the air-stable complex (4,7-diphenyl-1,10-
phenanthroline)Pd(OAc)2 prepared in situ and using butyl vinyl ether as the
sole reagent and solvent.[14–16] Equation (1) illustrates the reaction principle.
The reaction is driven by providing either the sugar alcohol ROH or—as in
the present case—the vinyl ether R0OCH55CH2 in large excess.
(1)
We subsequently optimized this catalyst system by exchanging the coun-
terion to the less coordinating trifluoroacetate, which reduces the reaction
time required to attain equilibrium by a factor of up to eight, and successfully
applied the catalyst to the synthesis of a variety of alkyl and allyl vinyl
ethers.[17] Here we present the application of this optimized catalyst system
to a representative series of protected monosaccharides with one, two, or
three free hydroxyl functions resulting in the isolation of the corresponding
vinyl glycosides and mono-, di-, or trivinyl ethers in moderate to good and in
a few cases excellent yields, which may facilitate their incorporation into
new sugar polymer formulations.
RESULTS AND DISCUSSION
The reaction protocol employed for the transfer vinylation was in all cases
2 mmol of sugar substrate, 0.04 mmol palladium trifluoroacetate (2 mol %),
0.04 mmol 4,7-diphenyl-1,10-phenantholine ligand, and 0.16 mmol triethyl
amine dissolved in 400 mmol (200-fold excess) of butyl vinyl ether (BVE) to
give a clear yellow solution, which was heated to 758C in a sealed flask. After
5 to 12 h qualitative evaluation of TLC samples and quantitative GC of
samples drawn in hourly intervals and monitored for the following 24 to 48 h
showed that the equilibrium (Eq. (1)) had been established as indicated by

Optimized Synthesis of Vinyl Ether Sugars and Vinyl Glycosides
105
the constant relative concentrations of the n-butanol generated by the reac-
tions. The presence of the auxiliary base triethyl amine prevents the
formation of mixed ethyl butyl acetals catalyzed by free trifluoro-acetic acid
formed in the catalytic cycle.[14,17]
Table 1 summarizes the results obtained with this reaction protocol for the
monohydroxyl substrates 2,3,4,6-tetra-O-benzyl-D-glucopyranose (1a), 2,3,4,6-
tetra-O-acetyl-D-glucopyranose (2a), 2,3,5-tri-O-benzyl-D-arabinofuranose
(3a), 1,2:5,6-di-O-isopropylidene-a-D-glucofuranoside (4a), 1,2:3,4-di-O-isopro-
pylidene-a-D-galactopyranoside (5a), methyl 2,3,6-tri-O-benzoyl-a-D-galacto-
pyranoside (6a), methyl 2,3,6-tri-O-benzoyl-a-D-mannopyranoside (7a),
1,2:4,5-di-O-isopropylidene-b-D-fructopyranoside (8a), and 2,3:4,5-di-O-isopro-
pylidene-b-D-fructopyranoside (9a). Table 2 lists the results for the dihydroxyl
substrates 1,2-O-isopropylidene-a-D-xylofuranoside (10a), 1,2:5,6-di-O-isopro-
pylidene-D-mannitol (11a), methyl 4,6-O-isopropylidene-a-D-mannopyranoside
(12a), methyl 4,6-O-isopropylidene-a-D-glucopyranoside (13a), phenyl 4,6-O-
isopropylidene-b-D-glucopyranoside (14a), methyl 4,6-O-benzylidene-a-D-glu-
copyranoside (15a), phenyl 4,6-O-benzylidene-b-D-glucopyranoside (16a), and
the trihydroxyl substrate levoglucosan (17a).
The first five entries in Table 1 also compare the reaction times and yields
to those achieved earlier with the nonoptimized catalyst.[14] Slightly higher
yields were realized with the optimized protocol described above that
employs a 200:1 rather than the 100:1 BVE-to-sugar ratio used earlier.[14]
With the exception of entry 8, 1,2:4,5-di-O-isopropylidene-b-D-fructopyra-
noside (8a), good to excellent yields (68%–95%) of mono vinyl ethers or vinyl
glycosides are achieved with sugar substrates protected by acetals or benzyl
ethers, while ester protection groups (acetate, benzoyl) result in moderate
yields of 45% (2b, entry 2, Table 1) and 42% or 43% (6b and 7b, entries 6
and 7, Table 1). As noted previously,[14] the presence of ester functionalities
(2a, 6a, 7a, entries 2, 6, and 7) leads to a darkening of the reaction mixture
to a more intense yellow, pointing to a coordinative interaction between
either the carbonyl oxygen or possibly an ester enolate and the metal center.
This can, however, not account for the lower yields with these substrates, as
addition of more catalyst at equilibrium did not result in additional product for-
mation excluding irreversible catalyst poisoning as a possible explanation.
As the vinyl exchange Eq. (1) is an isodesmic reaction, the main factors
governing the overall yields obtained with any of the substrates should be
steric interactions within the vinylated products. However, the conformational
variability and subtle structural complexity of the sugar substrates renders
a general and predictive model for these interactions and quantitative ration-
alization of the resulting observed yields elusive. For the monohydroxyl
substrates, the observed yields qualitatively scale with the steric accessi-
bility of the free hydroxyl functions, which also correlates with the confor-
mational flexibility of an attached vinyl group in the corresponding

M. Bosch et al.
106
Table 1: Vinylation of protected sugars with one free hydroxyl function.
Yield with
Pd(OAc)2
(4–7 d)a
Yield with
Pd(O2CCF3)2
Entry
Sugar substrate (#a)
Vinyl sugar (#b)
ꢀ12 ha
1
70%
74%
a/b ¼ 9:1b
a/b ¼ 7:1b
2
3
36%
45%
a/b ¼ 6.5:1a
a/b ¼ 7:1a
60%
68%
a/b ¼ 4.4:1b
a/b ¼ 6:1b
4
5
6
72%
79%
81%
95%
42%
not det.
7
8
not det.
not det.
43%
24%
9
not det.
73%
aIsolated yield.
bAnomeric ratios determined by 1H NMR.

Optimized Synthesis of Vinyl Ether Sugars and Vinyl Glycosides
107
Table 2: Vinylation of protected sugars with two or three free hydroxyl functions.
Yield and
reaction
Entry
Sugar substrate
Vinyl sugar
time (h)a
1
51% (6 h)
25% (6 h)
6% (6 h)
Total yield of vinylated
products: 82%
2
3
24% (6 h)
6% (12 h)
30% (12 h)
Total yield of vinylated
products: 56%
20% (12 h)
5% (12 h)
4
(continued)

M. Bosch et al.
108
Table 2: Continued.
Yield and
reaction
time (h)a
Entry
Sugar substrate
Vinyl sugar
35% (12 h)
Total yield of vinylated
20% (12 h)
products:
50%
5
36% (24 h)
21% (24 h)
33% (24 h)
Total yield of vinylated
products:
90%
6
24% (24 h)
26% (24 h)
16% (24 h)
Total yield of vinylated
products:
66%
(continued)

Optimized Synthesis of Vinyl Ether Sugars and Vinyl Glycosides
109
Table 2: Continued.
Yield and
reaction
Entry
Sugar substrate
Vinyl sugar
time (h)a
7
13% (24 h)
17% (24 h)
14% (24 h)
4% (6 h)
Total yield of vinylated
products: 44%
8
13% (6 h)
26% (6 h)
Total yield of vinylated
products isolable as pure
compounds: 43%
aIsolated yield.
product vinyl ether. For example, the lowest yield of 24% was obtained with
1,2:4,5-di-O-isopropylidene-b-D-fructopyranoside (8a) (entry 8, Table 1). A
simple molecular model of 8b suggests that the b-oriented conformationally
fixed isopropylidene ring at the anomeric center hinders a free rotation of
the vinyl group about the two oxygen-carbon bonds. The effect is also present
in 9b, but less pronounced, while the vinyl groups in the other sugar substrates
listed in Table 1 can freely rotate. Given that the equilibrium constant in equation
(1) is close to unity for all substrates, subtle differences in the entropy of the viny-
lated products originating from more or less restricted rotation of the vinyl group

M. Bosch et al.
110
compared to BVE could in fact account for the substantially different yields
between the acetal protected vinyl sugars 4b, 5b, and 8b.
Based on the results with mono-hydroxyl substrates where the best yields
were achieved with acetal protecting groups (Table 1), the di- and trihydroxyl
substrates investigated were limited to isopropylidene and benzylidene sugar
derivatives. All possible mono- and di-vinylated products derived from com-
pounds 10a to 16a (entries 1–7 in Table 2) could be separated and isolated
by preparative flash column chromatography. The vinylation of 1,2:5,6-di-O-
isopropylidene-D-mannitol (11a), entry 2, gave the monovinylated product in
24% yield. Only one monovinylated product can be formed due to the
symmetry of the starting sugar alcohol and the divinyl sugar product did not
form. As with 8b, a simple molecular model of 11b suggests a severely
hindered rotation of the vinyl group compared to BVE leading to the same
explanation for the low yield discussed above. For the trihydroxyl substrate
1,6-anhydro-b-D-glucopyranoside (17a) (entry 8, Table 2, levoglucosan), the
potential number of vinylated products is seven (three monovinylated, three
divinylated, and one pervinylated) and their separation constitutes a major
challenge. Of the seven products formed, we were able to purify three fractions:
the trivinylated product 17b and two separate monovinylated products 17c
and 17d. A fourth fraction appeared to be a mixture of three divinylated
products that in our hands could not be individually separated by chromato-
graphic means (both flash and HPLC methods).
EXPERIMENTAL
General Procedure for the Transfer Vinylation of Protected
Sugar Substrates Using Diacetone-a-D-glucopyranoside
as an Example
In an oven-dried round bottom Schlenk flask, 4,7-diphenyl-1,10-phenanthro-
line (13.3 mg ¼ 0.04 mmol) was added to butyl vinyl ether (40 g ¼ 52 mL ¼
400 mmol) with stirring. Palladium(II) trifluoroacetate (13.3 mg ¼ 0.04 mmol)
was added, and the mixture left to stir at 758C until all solids were dissolved
and a clear bright yellow solution was obtained. To prevent acetylization, tri-
ethylamine (0.16 mmol) was added before addition of the sugar substrate. The
sugar substrate, diacetone-a-D-glucopyranoside (520.5 mg ¼ 2.0 mmol), was
added to the mixture and allowed to react at 758C until TLC and quantitative
GC analysis for n-butanol revealed that equilibrium had been established
(10 h). The reaction mixture was passed through a 10 ꢁ 2.5 cm plug of
charcoal using ethyl acetate as the eluant (removes most of the catalyst) and
concentrated under reduced pressure, and the residue was subjected to flash
chromatography with various ratios of TLC pretested eluant combinations

Optimized Synthesis of Vinyl Ether Sugars and Vinyl Glycosides
111
(hexane, pentane, ether, ethyl acetate, acetonitrile, dichloromethane) yielding
the pure vinylated sugars. See supporting information for details of the chroma-
tographic separation and NMR data.
SUPPORTING INFORMATION
Sources of sugar starting materials. Detailed experimental procedures for syn-
thesis and purification of vinylated products. Extensive collection of 1D and 2D
1H/13C-NMR data and spectrum images for all new vinyl sugars synthesized
(82 pages).
ACKNOWLEDGMENTS
The authors thank NSERC Canada, the Canadian Foundation for Innovation
(CFI), the Ontario Innovation Trust Fund (OIT), and the University of
Guelph for funding.
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