1-O-vinyl glycosides via Tebbe olefination, their use as chiral auxiliaries and monomers

Article abstract of DOI:10.1021/jo0600510

A series of anomerically pure 1-O-formyl glycosides 1 was prepared and converted into the corresponding 1-O-vinyl glycosides 2 by Tebbe olefination. The unsubstituted vinyl glycosides were obtained as anomerically pure compounds in good yields, and the me

Full text of DOI:10.1021/jo0600510

1-O-Vinyl Glycosides via Tebbe Olefination, Their Use as Chiral
Auxiliaries and Monomers
Jialong Yuan, Kristof Lindner, and Holger Frauenrath*
Eidgeno¨ssische Technische Hochschule Zu¨rich, Department of Materials, ETH Ho¨nggerberg,
HCI H515, CH-8093 Zu¨rich, Switzerland
frauenrath@mat.ethz.ch
ReceiVed January 9, 2006
A series of anomerically pure 1-O-formyl glycosides 1 was prepared and converted into the corresponding
1-O-vinyl glycosides 2 by Tebbe olefination. The unsubstituted vinyl glycosides were obtained as
anomerically pure compounds in good yields, and the method of preparation was compatible with the
presence of a variety of functional groups. Remarkably, the anomeric formate group was regioselectively
converted into the corresponding olefin in the presence of acetate and benzoate protecting groups. With
the perspective to use the 1-O-vinyl glycosides as monomers for the preparation of glycosylated poly-
(vinyl alcohol) derivatives with controlled tacticity, their scope as chiral auxiliaries for a stereodiffer-
entiation in addition reactions to the olefin function was investigated by using the [2+2] cycloaddition
to dichloroketene as a model reaction. In particular, vinyl 2,3,4,6-tetra-O-benzoyl-R-D-mannopyranoside
(2i) exhibited excellent diastereoselectivity. Finally, the 1-O-vinyl glycosides were successfully subjected
to radical homopolymerization in bulk or used as electron-rich comonomers in radical copolymerizations
with maleic anhydride, yielding alternating, glycosylated poly(vinyl alcohol-alt-maleic anhydride).
Introduction
acryl amide and allyl glycosides.3 Isopropylidene protected
sugars attached to methacrylate or styrene groups as well as
glycosylated HEMA were polymerized by different protocols,4
including, more recently, the preparation of block and brush
copolymers as well as hyperbranched polymers by living radical
polymerization methods.5 Glycosylated polymers and their block
copolymers were also obtained by living cationic polymerization
of (2-vinyloxy ethyl) derivatives of D-glucofuranose as well as
D-glucosamine.6 Recently, 6-O-vinyladipoyl-D-glucopyranose
was polymerized with the RAFT protocol without the use of
protecting groups.7 Roy et al. prepared copolymers of acryl
amide with 4-acrylamidophenyl â-lactoside and the analogous
GM3 trisaccharide acryl amide monomers aimed at lectin
Synthetic glycopolymers,1 i.e., hybrid materials of carbohy-
drates and synthetic polymers, are attracting increasing interest
as potentially biomimetic materials, because carbohydrates play
an important role in biomaterials and cell signaling. Neverthe-
less, while improving biocompatibility by derivatization, modi-
fication, or coating of synthetic polymers with specific peptide
sequences has been thoroughly explored in recent years,
comparably few investigations deal with similar approaches
utilizing carbohydrates.2
Early examples of polymers with sugar residues attached to
the backbone via their anomeric functions are copolymers of
(1) (a) Ladmiral, V.; Melia, E.; Haddleton, D. M. Eur. Polym. J. 2004,
40, 431-449. (b) Wulff, G.; Schmid, J.; Venhoff, T. Macromol. Chem.
Phys. 1996, 197, 259-274.
(2) (a) Leeuwenburgh, M. A.; van der Marel, G. A.; Overkleeft, H. S.
Curr. Opin. Chem. Biol. 2003, 7, 757-765. (b) Kodokawa, J.; Tagaya, H.;
Chiba, K. Synlett 1999, 1845-1856. (c) Roy, R. Curr. Opin. Struct. Biol.
1996, 6, 692-702.
(3) Horejsi, V.; Smolek, P.; Kocourek, J. Biochim. Biophys. Acta 1978,
538, 293-298.
(4) (a) Ambrosi, M.; Batsanov, A. S.; Cameron, N. R.; Davis, B. G.;
Howard, J. A. K.; Hunter, R. J. Chem. Soc., Perkin Trans. 1 2002, 45-52.
(b) Loykulnant, S.; Yamashiro, M.; Hirao, A. Macromol. Chem. Phys. 2001,
202, 1791-1798. (c) Wulff, G.; Zhu, L.; Schmidt, H. Macromolecules 1997,
30, 0, 4533-4539.
10.1021/jo0600510 CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/17/2006
J. Org. Chem. 2006, 71, 5457-5467
5457

Yuan et al.
binding,8 as well as copolymers containing 3′-sulfo-LewisX-
Glc residues.9 Yoshida et al. reported the synthesis of poly-
(methacrylate)s bearing sulfated maltoheptaose side chains
which exhibited anti-HIV activity.10
SCHEME 1. Synthesis of 1-O-Vinyl Glycosides 2 via Tebbe
Olefination (A), Their Use as Chiral Auxiliaries in a [2+2]
Cycloaddition (B), and Their Polymerization to Poly(vinyl
glycoside) Homo- and Copolymers 4 and 5 (C,D)
We were interested in preparing poly(vinyl glycoside)s and
their copolymers, i.e., glycosylated poly(vinyl alcohol) deriva-
tives, with the glycosyl residues directly attached to the
backbone via their anomeric function without a spacer. Such
homo- and copolymers represent the most simple glycosylated
polymers with an all-carbon backbone; they may allow for
tacticity control during polymerization and exhibit secondary
structure formation; and finally, they may be interesting
materials in terms of both biocompatibility and biodegradability.
For this purpose, we needed a fast, efficient, and versatile route
toward 1-O-vinyl glycoside derivatives that is compatible with
various carbohydrate substrates and common protecting group
schemes. Vinyl glycosides have been prepared via (i) transvi-
nylation reactions catalyzed by mercury salts11 or palladium
complexes,12 (ii) elimination reactions such as Hofmann deg-
radation,13 selenoxide pyrolysis,14 or decomposition of mixed
acetals,15 and (iii) photolysis of oxopentyl glycosides.16 The
available routes are typically plagued by poor yields, poor
anomeric selectivity, toxic reactants, or tedious substrate
preparation. Methyl-substituted 1-O-vinyl glycosides (1-O-
isopropenyl glycosides) were also synthesized from 1-O-acetyl
glycosides via Tebbe or Petasis olefination17,18 while a Wittig
olefination of 1-O-formyl glycosides had reportedly failed.19
TABLE 1. Preparation of 1-O-Formyl Glycosides (and
Carbohydrate Formyl Esters) 1a-m and Their Conversion into the
Corresponding 1-O-Vinyl Glycosides (and Vinyl Ethers) 2a-m
formyl
sugar
yield,c
%
vinyl
sugar
yield,c
%
methoda
R: âb
R: âb
1a
1b
1c
1d
1e
1f
1g
1h
1i
A
B
A
B
A
A
B
A
A
A
C
C
1:5
51
69
60
2a
2b
2c
2d
2e
2f
2g
2h
2i
0:100g
100:0 g
0:100g
100:0g
100:0g
n.d.e
63
60
64
83
67
73f
68
46f
53f
43f
89
87
20:1
1:70
99:1
9:1
1:90
1:90
1:22
5:1
86
64
100d
59
0:100
100d
100d
90d
76
n.d.e
n.d.e
1k
1l
1m
1:11
n.a.h
n.a.h
2k
2l
2m
n.d.e
n.a.h
69
n.a.h
a Method A: glycosyl bromide, HCOOH, AgNO3. Method B: ethyl
1-thioglycoside, HCOOH, TfOH, NIS. Method C: ROH, HCOOH, EDCI,
DPTS. b Anomeric ratio in the crude product mixture, determined by 1H
NMR spectroscopy. c Isolated yield of anomerically pure product. d Yield
of crude product. e NMR spectrum of the crude mixture did not allow for
an unambiguous assignment. f Isolated yield of anomerically pure 1-O-vinyl
glycoside over two steps starting from the glycosyl bromide. g Crude 1-O-
vinyl glycoside was anomerically pure (within the error of determination
by 1H NMR spectroscopy). h Not applicable because the product was not a
1-O-formyl or a 1-O-vinyl glycoside.
(5) (a) Bernard, J.; Hao, X.; Davis, T. P.; Barner-Kowollik, C.; Stenzel,
M. H. Biomacromolecules 2006, 7, 232-238. (b) Albertin, L.; Stenzel, M.
H.; Barner-Kowollik, C.; Foster, L. J. R.; Davis, T. P. Macromolecules
2005, 38, 9075-9084. (c) Albertin, L.; Stenzel, M.; Barner-Kowollik, C.;
Foster, L. J. R.; Davis, T. P. Macromolecules 2004, 37, 7530-7537. (d)
Muthukrishnan, S.; Jutz, G.; Andre, X.; Mori, H.; Mu¨ller, A. H. E.
Macromolecules 2005, 38, 9-18. (e) Muthukrishnan, S.; Mori, H.; Mu¨ller,
A. H. E. Macromolecules 2005, 38, 3108-3119. (f) Muthukrishnan, S.;
Zhang, M.; Burkhardt, M.; Drechsler, M.; Mori, H.; Mu¨ller, A. H. E.
Macromolecules 2005, 38, 7926-7934.
(6) (a) Yamada, K.; Minoda, M.; Fukuda, T.; Miyamoto, T. J. Polym.
Sci., Part A: Polym. Chem. 2001, 39, 459-467. (b) Yamada, K.; Minoda,
M.; Miyamoto, T. Macromolecules 1999, 32, 3553-3558. (c) Yamada, K.;
Yamaoka, K.; Minoda, M.; Miyamoto, T. J. Polym. Sci., Part A: Polym.
Chem. 1997, 35, 255-261. (d) Yamada, K.; Minoda, M.; Miyamoto, T. J.
Polym. Sci., Part A: Polym. Chem. 1997, 35, 751-757.
We report here the successful synthesis and olefination of
1-O-formyl glycosides 1 via the Tebbe reaction (Scheme 1),
which furnished the desired 1-O-vinyl glycosides 2 as anomeri-
cally pure compounds in good yields, including derivatives with
ester protecting groups. Furthermore, we studied the propensity
of different 1-O-vinyl glycosides toward stereodifferentiation
in a [2+2] cycloaddition to the olefin function. Finally, we
investigated the polymerizability of the 1-O-vinyl glycosides
in order to prepare poly(vinyl glycoside) homo- and copolymers
4 and 5.
(7) Albertin, L.; Kohlert, C.; Stenzel, M.; Foster, L. J. R.; Davis, T. P.
Biomacromolecules 2004, 5, 255-260.
(8) Cao, S.; Roy, R. Tetrahedron Lett. 1996, 37, 3421-3424.
(9) Roy, R.; Park, W. K. C.; Srivastava, O. P.; Foxall, C. Bioorg. Med.
Chem. Lett. 1996, 6, 1399-1402.
(10) Yoshida, T.; Akasaka, T.; Choi, Y.; Hattori, K.; Yu, B.; Mimura,
T.; Kaneko, Y.; Nakashima, H.; Aragaki, E.; Premanathan, M.; Yamamoto,
N.; Uryu, T. J. Polym. Sci., Part A: Polym. Chem. 1999, 37, 789-800.
(11) (a) Dettinger, H. M.; Lehmann, J.; Wallenfels, K. Carbohydr. Res.
1980, 87, 63-70. (b) De Raadt, A.; Ferrier, R. J. Carbohydr. Res. 1991,
216, 93-107.
Results and Discussion
Synthesis of Formyl and Vinyl Glycosides. To investigate
the scope of the Tebbe reaction in the synthesis of unsubstituted
vinyl glycosides, various 1-O-formyl glycosides 1 were syn-
thesized by using either Koenigs-Knorr conditions (method A)
or NIS promoted reactions of thioglycosides (method B) (Table
1). The 1-O-formyl glycosides, including mono- and disaccha-
rides, substrates with different anomeric configurations, as well
as different protecting group patterns, were obtained in good
yields and with high anomeric diastereoselectivity. While they
appeared to be air and moisture stable compounds, they turned
out to be easily anomerized or hydrolyzed during column
chromatography with both silica gel and aluminum oxide as
the column materials. Therefore, they were typically obtained
in anomerically pure form by recrystallization.
(12) Handerson, S.; Schlaf, M. Org. Lett. 2002, 4, 407-409.
(13) Perrine, T. D.; Glaudemans, C. P. J.; Ness, R. K.; Kyle, J.; Fletcher,
H. G., Jr. J. Org. Chem. 1967, 32, 664-669.
(14) Rollin, P.; Bencomo, V. V.; Sinay, P. Synthesis 1984, 134-135.
(15) (a) Edathil, J.; Nguyen, J.; Hughes, K.; Boyko, W. J.; Giuliano, R.
M. J. Carbohydr. Chem. 2001, 20, 81-85. (b) Hughes, K. D.; Nguyen,
T.-L. N.; Dyckman, D.; Dulay, D.; Boyko, W. J.; Giuliano, R. M.
Tetrahedron: Asymmetry 2005, 16, 273-282.
(16) Cottier, L.; Remy, G.; Descotes, G. Synthesis 1979, 711-712.
(17) Marra, A.; Esnault, J.; Veyrieres, A.; Sinay, P. J. Am. Chem. Soc.
1992, 114, 6354-6360.
(18) Chenault, H. K.; Castro, A.; Chafin, L. F.; Yang, J. J. Org. Chem.
1996, 61, 5024-5031.
(19) Larsen, D. S.; Stoodley, R. J. J. Chem. Soc., Perkin Trans. 1 1989,
1841-1852.
5458 J. Org. Chem., Vol. 71, No. 15, 2006

1-O-Vinyl Glycosides Via Tebbe Olefination
definite advantage over the transvinylation methods11,12 which
produce anomeric mixtures and do not allow for the selective
synthesis of one desired diastereomer, and likewise, the elimina-
tion protocols13-15 which give rise to anomerization as a
consequence of the reaction conditions applied.
SCHEME 2. Preparation of 1-O-Vinyl Glycosides (and
Vinyl Ethers) 2a-m by Tebbe Olefination of 1-O-Formyl
Glycosides (and Carbohydrate Formyl Esters) 1a-m
Furthermore, the Tebbe olefination was successfully per-
formed in the presence of other functional groups including
ether, acetal, as well as, most notably, ester groups. Thus, in
the cases of 1a-c and 1e-k, the anomeric formate group was
regioselectively converted into the corresponding olefin without
affecting the sterically more demanding acetate or benzoate
groups, in agreement with previous investigations concerning
the regioselectivity of Tebbe or Petasis reagents.18,20
The isolated yield was slightly better in the case of the benzyl
ether protected glycoside 1d, but the anomeric formyl group of
acetylated or benzoylated substrates such as 1a-c, 1e, and 1g
was found to be selectively converted with an acceptable yield.
Overall, the formyl esters 1l and 1m appeared to react slightly
better than the formyl glycosides 1a-k, which may, however,
also just be a consequence of the absence of other ester
functions. The somewhat poorer yields in the cases of 1f and
1h-k can be attributed to the fact that in these cases, all
recrystallization attempts had failed. Therefore, the compounds
were subjected to the Tebbe olefination as anomeric mixtures,
and the yields were determined as the isolated yields of
anomerically pure 1-O-vinyl glycosides over two steps.
Vinyl Glycosides as Chiral Auxiliaries. As the vinyl
glycosides were to serve as chiral monomers in the preparation
of glycosylated poly(vinyl alcohol) derivatives with the aim to
control polymer tacticity, we attempted to investigate their
propensity to stereodifferentiation in a typical addition reaction
to the olefin function. While cycloadditions of tetracyanoeth-
ylene, methyl 2-pyrone-3-carboxylate, and ethyl diazoacetate
had worked well for vinyl ether derivatives used as test
substrates, they failed in our hands when applied to vinyl
glycosides. Therefore, we finally resorted to the [2+2] addition
of dichloroketene.21 This reaction had been reported to show
efficient diastereofacial differentiation in the synthesis of various
natural products, using optically pure 2-phenylcyclohexanol as
the chiral auxiliary,22 and had also been studied in the enantio-
selective synthesis of chiral cyclobutanol derivatives, using
carbohydrates as chiral auxiliaries.23
The acetylated â- and R-D-glucopyranosides 2a and 2b, the
benzoylated â-D-glucopyranoside 2c, the â-D-ribopyranoside 2f,
as well as the R-D-mannopyranoside 2i were chosen as the
substrates in order to study the influence of different carbohy-
drate residues, anomeric configurations, and protecting group
schemes. The vinyl glycosides were reacted with dichloroketene
generated in situ by dehalogenation of trichloroacetyl chloride
with Zn-Cu (Scheme 3).21 As the obtained dichlorocyclobu-
tanone derivatives turned out to decompose during workup, they
were reduced to the corresponding dichlorocyclobutanol deriva-
tives in situ with NaBH4 in 2-propanol.23 Consistent with results
reported in the literature, the two cis diastereomers were obtained
exclusively in all cases (within the error of determination from
The formyl ester derivatives 1l and 1m were prepared from
the corresponding alcohol derivatives and included in the present
study as comparative compounds.
The methylenation of the formyl functions of compounds 1a-
m, leading to the 1-O-vinyl glycosides 2a-k and the vinyl ethers
2l and 2m, respectively, was achieved via Tebbe olefination
(Scheme 2). In a typical procedure, the 1-O-formyl glycoside
was dissolved in THF and pyridine at -78 °C. The solution
was treated with 2 equiv of Tebbe reagent, which was added
dropwise, maintaining the temperature in the reaction mixture
at -78 °C. The mixture was then allowed to warm to 0 °C, and
finally quenched by the addition of a 15% solution of NaOH.
A crucial parameter for a successful reaction turned out to be
the very careful and slow addition of the NaOH solution over
a time period of at least 30 min, waiting after each drop for the
gas evolution to cease. Furthermore, while the Tebbe reagent
can reportedly be stored for weeks at room temperature, we
found it advantageous to use it within the first 5 days after
preparation.
The 1-O-vinyl glycosides 2a-k as well as the vinyl ether 2l
and 2m were obtained in acceptable or good yields in all cases
(Table 1). The substrates 1a-m were straightforwardly acces-
sible in pure form on a large scale, and the Tebbe reactions
could easily be performed on a reaction scale of up to 5 g of
the carbohydrate substrate. No anomerization occurred under
the reaction conditions applied, as confirmed by 1H NMR
spectra of the crude products. Hence, anomerically pure vinyl
glycosides were obtained whenever anomerically pure formyl
glycosides had been used as the starting material. This is a
(20) Hartley, R. C.; McKiernan, G. J. J. Chem. Soc., Perkin Trans. 1
2002, 2763-2793.
(21) (a) Brady, W. T.; Watts, R. D. J. Org. Chem. 1980, 45, 3525-
3527. (b) Brady, W. T. Tetrahedron 1981, 37, 2949-2966.
(22) (a) Greene, A. E.; Charbonnier, F.; Luche, M. J.; Moyano, A. J.
Am. Chem. Soc. 1987, 109, 4752-4753. (b) De Azevedo, M. B. M.; Murta,
M. M.; Greene, A. E. J. Org. Chem. 1992, 57, 4567-4569.
(23) Ganz, I.; Kunz, H. Synthesis 1994, 1353-1358.
J. Org. Chem, Vol. 71, No. 15, 2006 5459

Yuan et al.
SCHEME 3. Dichloroketene Addition to the 1-O-Vinyl
Glycoside 2 Followed by Reduction
FIGURE 1. Single-crystal structures of the 1-O-vinyl glycoside 2a
(left) and the corresponding product of dichloroketene addition 3a
(right).
In summary, in all cases with the exception of 3f, the major
diastereomer resulted from an addition of the dichloroketene
from the Si side of the olefin in the 1-O-vinyl glycoside 2. The
observed diastereoselectivities (Table 2) were only moderate
for the glucopyranoside 2a-c. However, good diastereoselec-
tivities were found for the â-D-ribopyranoside 2f, and, in
particular, for the R-D-mannopyranoside 2i. In the latter case,
only one diastereomer was observed both in the 1H NMR spectra
and by LC-MS.
Attempting to rationalize the observed diastereoselectivities,
we found the glucopyranoside derivatives 2a-c and the R-D-
mannopyranoside 2i to exist preferably in the 4C1(D) conforma-
tion, while the â-D-ribopyranoside 2f was more stable in the
1
1C4(D) conformation. This was confirmed by H NMR spectra
TABLE 2. Results of the Dichloroketene Addition to 1-O-Vinyl
which revealed coupling constants of 3J12 ) 7.8 Hz for 2a and
Glycosides 2 and Subsequent Reduction
3
3
2c, J12 ) 2.5 Hz for 2f, and J12 ) 1.8 Hz for 2i, all in
agreement with previous studies.24 Furthermore, we expected
the EGT conformers25 of 2a and 2c as well as the AGT
conformers of 2f and 2i to be most favorable (Figure 2).26
Assuming that rotation around the O1-C7 bond is hindered to
a certain extent, two conformers remain, one of which is
supposedly preferred due to steric interactions (Figure 2). The
above analysis coincides with the conformation of the vinyl
group observed in single crystalline 2a (Figure 1), which may,
of course, just be the result of packing considerations in the
solid state. For substrates 2a and 2c, the experimentally observed
preferred Si addition may then be explained in terms of a
competitive shielding of the olefin function by both the
protecting groups on O(6) and O(2), leading to a favored
addition from the Si side and a better diastereoselectivity in the
case of the smaller acetyl group on O(2) in the case of 2a. In
the cases of 2f and 2i, shielding of the addition trajectory by
the sugar backbone should lead to a strong preference of addition
from the Re and the Si side, respectively. Of course, the above
model has many variables and is, thus, just to be regarded as
an attempted rationalization post facto rather than a model with
predictive power.
1-O-cyclobutyl glycoside
diastereomers
diastereomeric ratio
major
minor
1H NMR
LC-MS
yield,a %
3a (1′S,3′R)
3b (1′S,3′R)* c
3c (1′S,3′R)
3f (1′R,3′S)
3i (1′S,3′R)
3a′ (1′R,3′S)
100:0b
3.0:1c
3.3:1
2.4:1
1.8:1
2.1:1
4.9:1
100:0b
53
56a
48
67
60
3c′ (1′R,3′S)
3f′ (1′S,3′R)
3i′ (1′R,3′S)
10.1:1
100: 0b
a Isolated yield of diastereomerically pure major product (except 3b,
which was isolated as a mixture of diastereomers). b Just one diastereomer
was visible in the 1H NMR spectra, or in LC-MS, respectively. c The
absolute configuration could not be assigned.
1H NMR spectra), indicating that the reduction proceeded
diastereospecifically. The ratio of the obtained two diastereomers
resulting from the cycloaddition was determined both from the
1H NMR spectra and via an LC-MS analysis of the crude
product mixtures (Table 2).
The crude products 3 were then purified by silica gel
chromatography. Thus, the pure major diastereomers of 3a, 3f,
and 3i were obtained, and both major and minor diastereomers
3c and 3c′ could be isolated in pure form. Recrystallization of
the major diastereomer of the â-D-glucopyranoside derivative
3a afforded crystals suitable for X-ray structure analysis (Figure
1), which allowed us to assign the absolute stereoconfiguration
as (1′S,3′R)-2′,2′-dichloro-3′-hydroxycyclobutyl 2,3,4,6-tetra-
O-acetyl-â-D-glucopyranoside. The absolute stereoconfigurations
of the other major diasteromers were then unambiguously
deduced from the known stereoconfiguration of 3a as (1′S,3′R)
for 3c, (1′R,3′S) for 3f, and (1′S,3′R) for 3i by chemical
derivatization (Scheme 4). Unfortunately, neither recrystalliza-
tion nor separation by column chromatography was successful
in the case of 3b so that the absolute stereoconfiguration of the
two obtained diastereomers could not be assigned.
Polymerization of the Vinyl Glycosides. In our initial
attempts to polymerize the obtained vinyl glycoside derivatives,
2,3,4,6-tetra-O-acetyl-â-D-glucopyranoside (2a) and 1-O-vinyl
2,3,4,6-tetra-O-benzoyl-R-D-mannopyranoside (2i) were chosen
as the monomers because they are both easily available from
(24) (a) James, V. J.; Stevens, J. D. Carbohydr. Res. 1972, 21, 334-
335. (b) Horton, D.; Durette, P. L. Carbohydr. Res. 1971, 18, 57-80.
(25) The three-letter code refers to the orientation of the anomeric group
(equatorial or axial) and the conformation (gauche or trans) of the anomeric
group in relation to O-5 and C-2, respectively.
(26) (a) Tvaroska, I.; Kozar, T. J. Am. Chem. Soc. 1980, 102, 6929-
6936. (b) Tvaroska, I.; Kozar, T. Carbohydr. Res. 1981, 90, 173-185.
5460 J. Org. Chem., Vol. 71, No. 15, 2006

1-O-Vinyl Glycosides Via Tebbe Olefination
SCHEME 4. Deduction of the Absolute Configuration of 3c, 3c′, 3f, and 3i from the Known Stereoconfiguration of 3aa
a Reactants: ethyl 2,3,4,6-tetra-O-benzoyl-1-thio-â-D-glucoside 6, phenyl 2,3,4-tri-O-benzoyl-1-thio-â-D-riboside 7, ethyl 2,3,4,6-tetra-O-benzoyl-1-thio-
â-D-mannoside 8. Reaction conditions: (a) Ac2O, pyridine, rt; (b) NaOMe, MeOH, rt; (c) TfOH, NIS, DCM, 0 °C.
FIGURE 2. Attempted rationalization of the observed diastereose-
lectivities.
commercial substrates in a few steps in good yield on a
multigram scale. In addition, 2i had exhibited a very good
diastereoselectivity in the [2+2] cycloaddition of dichloroketene
that we used as a test reaction for the stereodifferentiation (vide
supra). All attempts to polymerize vinyl glycosides 2a or 2i
with different cationic initiators failed in our hands, which may
not be too surprising given the fact that 1-O-isopropenyl
FIGURE 3. 1H NMR spectra of copolymer 5a, recorded in C2D2Cl4
glycosides have successfully been used as glycosyl donors.17,18
at different temperatures.
Preliminary free radical polymerization experiments produced
relatively low molecular weight poly(vinyl glycoside)s 4i in poor
yields. These results are consistent with investigations by
Ringsdorf et al., who reported that cationic polymerizations of
simple vinyl acetals were unsuccessful, and radical homopoly-
merizations failed or proceeded only sluggishly.27 On the other
hand, some examples of radical polymerizations of vinyl acetals
have been reported in the literature.28 One important factor to
consider in this context is the substantial steric demand of the
1-O-vinyl glycoside monomers which may even be comparable
to highly sterically hindered dendronized monomers.29 Work
on improved homopolymerization protocols is in progress.
Assuming that the 1-O-vinyl glycosides are electron-rich vinyl
monomers, we investigated their radical copolymerization with
the electron-poor maleic anhydride (MA). Thus, radical copo-
lymerizations of 2a and 2i in solution initiated by AIBN at 60
°C were performed successfully, leading to the copolymers 5a
(27) Beyer, U.; Mu¨ller, F. H.; Ringsdorf, H. Makromol. Chem. 1967,
101, 74-90.
(28) (a) Tsukino, M.; Kunitake, T. Polym. J. 1979, 11, 437-447. (b)
Tsukino, M.; Kunitake, T. Polym. J. 1985, 17, 943-951.
(29) (a) Schlu¨ter, A. D.; Rabe, J. P. Angew. Chem., Int. Ed. 2000, 39,
864-883. (b) Frauenrath, H. Prog. Polym. Sci. 2005, 30, 325-384.
J. Org. Chem, Vol. 71, No. 15, 2006 5461

Yuan et al.
1
SCHEME 5. Copolymerization of the 1-O-Vinyl Glycosides
of H NMR spectra (Figure 3). Despite its excellent solubility
in CDCl3 and other chlorinated solvents such as C2D2Cl4, the
1H NMR spectra of the copolymer 5a exhibited extremely broad
peaks at room temperature. While the resolution improved to
some extent when the NMR spectra were measured at elevated
temperatures, the lines were still too broad to allow for a simple
structure determination. In our eyes, this feature of the 1H NMR
spectra does not have its origin in the polydispersity of the
polymer alone but may point to a reduced segmental mobility
of the macromolecules, indicating a rigidification of the
backbone similar to that of dendronized polymers.29 Neither the
solution nor the solid phase 13C NMR spectra could be used to
assess the polymer tacticity for the same reason.
2 with Maleic Anhydride
Conclusions
TABLE 3. Results of the Radical Copolymerization of 2a and 2i
In conclusion, the Tebbe olefination proved to be a versatile
method for the preparation of various unsubstituted 1-O-vinyl
glycosides 2. The 1-O-formyl glycosides 1 used as the substrates
were easily prepared in pure form on the multigram scale. The
products were obtained as anomerically pure compounds in good
yields, and the reaction was found to be compatible with
different functional groups, most notably, ester protecting
groups. Thus, the anomeric formate group was regioselectively
converted into the corresponding olefin in the presence of acetate
or benzoate groups. The application of the 1-O-vinyl glycosides
as chiral auxiliaries for a stereodifferentiation in addition
reactions to the olefin function was investigated by using the
[2+2] cycloaddition of dichloroketene and subsequent reduction
as a test reaction. All vinyl glycosides showed diastereofacial
differentiation, and, in particular, 1-O-vinyl 2,3,4,6-tetra-O-
benzoyl-R-D-mannopyranoside 2i was found to exhibit excellent
diastereoselectivity. Finally, the â-D-glucopyranoside 2a and the
R-D-mannopyranoside 2i were successfully used as the mono-
mers in free radical homopolymerizations as well as alternating
copolymerizations with maleic anhydride. For example, the
alternating poly(vinyl R-D-mannopyranoside-alt-maleic anhy-
dride) 5i with a molecular weight of Mn ) 93 700 (PDI ) 2.25)
was obtained in 80% yield. Such copolymers may combine the
features of alternating maleic anhydride copolymers and syn-
thetic glycopolymers and, therefore, be a promising platform
for new biomaterials or biocompatible surface modifications.
with Maleic Anhydride with AIBN as the Initiator at 60 °C
vinyl
copolymers 5a, 5i
Mn PDIa yield,b %
a
glycoside MA,
AIBN,
time,
h
entry (mmol) mmol 10-3 mmol solvent (mL)
1
2
3
4
5
6
7
2a (0.40) 0.41
2a (0.40) 0.82
2a (0.37) 0.61
2a (0.37) 0.37
2i (0.36) 0.18
2i (0.11) 0.22
2i (0.14) 0.14
48
24
6
6
6
toluene (0.15) 12 25 900 2.23
toluene (0.15) 12 25 100 2.86
CHCl3 (0.15) 12 14 400 1.94
CHCl3 (0.08) 12 7 700 2.35
toluene (0.10) 36 22 000 2.84
toluene (0.08) 36 93 700 2.25
toluene (0.08) 36 49 900 2.09
63
68
94
95
98
80
73
6
6
a Determined by GPC vs PS standards with triple detection. b Isolated
yield of the polymer after repricipitation, with respect to the monomer
present in minor concentration (i.e., the vinyl glycoside, except entry 5).
and 5i (Scheme 5, Table 3). Polymer yields seemed to improve
with lower AIBN concentration, and molecular weights obtained
in toluene as the solvent were higher than those in CHCl3, which
may be expected from the respective typical chain transfer rates
of the solvents. Overall, the R-mannoside 2i appeared to give
better results as compared to the â-glucoside 2a in terms of
both yield and molecular weight. This result is particularly
interesting because 2i had also exhibited the better diastereo-
selectivity in the cycloaddition test reactions. Furthermore, an
excess of MA furnished the best results, so that, in one case,
copolymer 5i with a molecular weight of Mn ) 93 700 (PDI )
2.25) was obtained. This result may be rationalized by assuming
that the more reactive vinyl glycoside centered radical chain
ends are more prone to chain transfer or termination reactions
which are, hence, suppressed to some extent by an excess of
the MA comonomer.
As a homopolymerization of MA is not possible and its
copolymerization with electron-rich vinyl monomers typically
leads to strictly alternating copolymers,30 we expected to obtain
an alternating glycosylated poly(vinyl alcohol-alt-maleic anhy-
dride). Accordingly, the polymer yield was near quantitative
with respect to MA, when the vinyl glycoside was used in excess
(Table 3, entry 5) and vice versa (Table 3, entries 3 and 6).
The residual comonomer was quantitatively recovered in both
cases. In all polymerization attempts, irrespective of the ratio
of vinyl glycoside and maleic anhydride in the feed, elemental
analyses of the copolymers were found to be consistent with a
1:1 ratio of vinyl glycoside and maleic anhydride repeating units.
Unfortunately, a direct determination of the structure of
copolymers 5a and 5i turned out to be infeasible on the basis
Experimental Section
General Procedure for the Preparation of the Tebbe Reagent.
A solution of the Tebbe reagent in toluene was prepared according
to a modified literature procedure.31 Thus, titanocene dichloride
(3.74 g, 15 mmol, 1 equiv) and AlMe3 (2.0 M solution in toluene;
15 mL, 30 mmol, 2 equiv) were dissolved in dry toluene (30 mL).
The solution was stirred at room temperature for 72 h prior to use.
The Tebbe reagent can reportedly be stored for weeks at room
temperature, but we found it to be advantageous to use it within
the first 5 days after preparation.
General Procedure for the Preparation of Formyl Glycosides
from Glycosyl Bromides (Procedure A). The glycosyl bromide
(typically 10 mmol) is dissolved in a large excess of formic acid
(25 mL/g of glycosyl bromide). AgNO3 (typically 2 equiv) is added,
the mixture is stirred for 1 h at room temperature, diluted with
DCM (10 mL/g of glycosyl bromide), and filtered over Celite. The
filtrate is washed three times with saturated aqueous NaHCO3
solution and once with brine. The pure products are obtained by
flash column chromatography or recrystallization.
(30) (a) Baldwin, M. G. J. Polym. Sci. 1965, 3, 703-710. (b) Hallensle-
ben, M. L. Makromol. Chem. 1971, 144, 267-281. (c) Hao, X.-J.; Fujimori,
K.; Henry, P. C. Macromol. Rapid Commun. 2001, 22, 111-113.
(31) Tebbe, F. N.; Parshall, G. W.; Reddy, G. S. J. Am. Chem. Soc.
1978, 100, 3611-3613.
5462 J. Org. Chem., Vol. 71, No. 15, 2006

1-O-Vinyl Glycosides Via Tebbe Olefination
General Procedure for the Preparation of R Formyl Glyco-
sides from Ethylthio Glycosides (Procedure B). The ethylthio
glycoside (typically 10 mmol), 4 Å molecular sieves, and DCM
(20 mL/g of ethylthio glycoside) are placed in a dried Schlenk flask
under a nitrogen atmosphere. The mixture is cooled to 0 °C, and
formic acid (typically 2.2 equiv), N-iodosuccinimide (1.2 equiv),
and TfOH (0.9 equiv) are added. After 3-120 min of stirring,
depending on the substrate, the reaction is quenched with triethyl-
amine (large excess). The solution is diluted with DCM (ap-
proximately 100 mL/g of ethylthio glycoside) and filtered through
Celite. It is washed two times each with 1 M HCl and saturated
aqueous NaHCO3 solution and once with brine, dried over MgSO4,
filtered, and evaporated to dryness. The pure products are obtained
by flash column chromatography, followed by recrystallization in
some cases.
General Procedure for the Preparation of Formyl Esters of
Sugar Alcohols (Procedure C). The alcohol (typically 20 mmol),
DPTS (41 mmol), and EDCI (41 mmol) are dissolved in DCM
(typically 50 mL) and HCOOH (40 mmol). The reaction is stirred
at room temperature for 3 h. Then the solution is washed with
saturated aqueous NaHCO3 solution as well as brine and dried over
MgSO4. The pure products are obtained by flash column chroma-
tography followed by recrystallization in some cases.
General Procedure for the Preparation of Vinyl Glycosides
via Tebbe Olefination of Formyl Glycosides (Procedure D). The
formyl glycoside (typically 0.5 mmol) is dissolved in THF (20 mL/g
of formyl glycoside) and pyridine (4 mL/g of formyl glycoside),
and the reaction mixture is cooled to -78 °C. After 20 min, a
solution of the Tebbe reagent (0.333 M in toluene, 2 equiv) is added
very slowly, maintaining the temperature in the reaction mixture
at -78 °C. The mixture is stirred for 15 min, then allowed to warm
to 0 °C, and stirred for an additional 15 min. A 15% solution of
NaOH (1 equiv) is added dropwise very carefully and slowly over
a time period of at least 30 min, waiting after each drop for the
gas evolution to cease. The mixture is then diluted with DCM (200
mL/g of formyl glycoside), and the blue-green precipitate formed
during the addition of NaOH is filtered off over Celite. The filtrate
is washed with aqueous 1 M HCl, saturated aqueous NaHCO3
solution, and brine, dried over MgSO4, filtered, and evaporated to
dryness. The pure products are obtained by flash column chroma-
tography, followed by recrystallization in some cases.
General Procedure for the Cycloadditon of Dichloroketene
to the Vinyl Glycosides 2 (Procedure E). Zn/Cu was freshly
prepared by stirring zinc powder (1.0 g) in a solution of CuSO4‚
5H2O (100 mg/30 mL of water) for 1 h, washing with water,
acetone, and diethyl ether, and drying in high vacuum. It was then
added to a solution of the vinyl glycoside (typically 0.5 mmol) in
diethyl ether (50 mL/g of vinyl glycoside). A solution of trichlo-
roacetyl chloride (0.2 mL, 1.8 mmol typically 3-4 equiv) in 5 mL
of diethyl ether was added at room temperature over a time period
of 3 h. After additional stirring for 12 h, the mixture was diluted
with 100 mL of diethyl ether then washed three times with saturated
aqueous NaHCO3 solution and once with brine. The organic phase
was dried over MgSO4, filtered, and evaporated to dryness in high
vacuum. NaBH4 (2.6 mmol, typically 5 equiv) was added to an
ice-cold solution of the crude product (0.5 mmol) in 2-propanol
(20 mL). The mixture was stirred for 3 h, diluted with 100 mL of
diethyl ether, and washed with brine. The organic layer was
separated, dried, and concentrated in a vacuum. The pure products
were obtained by flash column chromatography, followed by
recrystallization in some cases.
The solution is diluted with diethyl ether (500 mL/g of substrate),
washed with 1 M HCl, saturated aqueous NaHCO3 solution, and
brine, dried over MgSO4, filtered, and evaporated to dryness. The
pure products are obtained by flash column chromatography,
followed by recrystallization in some cases.
Copolymerization of Vinyl Glycosides and Maleic Anhydride.
Maleic anhydride, the vinyl glycoside, AIBN, and dry toluene or
chloroform were placed in a Schlenk flask and carefully degassed
with 3 freeze-pump-thaw cycles. The mixture was then heated
to 60 °C and kept at that temperature for 12-36 h. The crude
product mixture was dissolved in DCM, and the pure copolymer
was obtained by precipitation in MeOH, filtered off, and dried in
high vacuum.
Formyl 2,3,4,6-Tetra-O-acetyl-â-D-glucopyranoside (1a). The
product was prepared according to procedure A, using 2,3,4,6-tetra-
O-acetyl-D-glucopyranosyl bromide (3.4 g, 8.3 mmol), formic acid
(85 mL, 2.3 mol), and AgNO3 (1.6 g, 9.4 mmol, 1.1 equiv). After
recrystallization from ethyl acetate/hexane, 1a (1.6 g, 51%) was
obtained as a white crystalline solid. 1H NMR (CDCl3, 500 MHz)
δ 8.00 (s, 1H), 5.78 (d, 1H, J ) 8.2 Hz), 5.22 (dd, 1H, J ) 9.4, 8.4
Hz), 5.11 (dd, 1H, J ) 8.4, 8.2 Hz), 5.05 (dd, 1H, J ) 9.7, 9.4
Hz), 4.23 (dd, 1H, J ) 12.5, 4.6 Hz), 4.06 (dd, 1H, J ) 12.5, 2.3
Hz), 3.84 (ddd, 1H, J ) 9.7, 4.6, 2.3 Hz), 2.01 (s, 3H), 1.97 (s,
6H), 1.94 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 170.4, 169.9,
169.3, 169.1 (4C), 158.6, 91.1, 72.8, 72.5, 70.0, 67.6, 61.3, 20.6-
20.4 (4C). Anal. Calcd for C15H20O11: C, 47.88; H, 5.36. Found:
C, 47.85; H, 5.55. MS (ESI) m/z 399.1 ([M + Na]+). Rf 0.53 (ethyl
acetate/hexane 1:1).
Formyl 2,3,4,6-Tetra-O-acetyl-R-D-glucopyranoside (1b). The
product was prepared according to procedure B, using ethyl 2,3,4,6-
tetra-O-acetyl-1-thio-â-D-glucopyranoside (5 g, 12.7 mmol), 50 mL
of DCM, formic acid (0.79 mL, 21 mmol, 1.7 equiv), N-
iodosuccinimide (3.44 g, 15.3 mmol, 1.2 equiv), and TfOH (0.91
mL, 10.2 mmol, 0.8 equiv). The reaction mixture was stirred for 2
h at 0 °C before it was quenched with triethylamine (5 mL, 36
mmol, 2.8 equiv). After purification by flash column chromato-
graphy (silica gel, ethyl acetate/hexane 1:5, 0.5% of formic acid)
and recrystallization from ethyl acetate/hexane, 1b (3.3 g, 69%)
1
was obtained as a white crystalline solid. H NMR (CDCl3, 500
MHz) δ 8.10 (s, 1H), 6.38 (d, 1H, J ) 3.7 Hz), 5.42 (t, 1H, J )
10.0 Hz), 5.09 (t, 1H, J ) 10.0 Hz), 5.05 (dd, 1H, J ) 10.0, 3.7
Hz), 4,21 (dd, 1H, J ) 12.5, 4.4 Hz), 4.12-4.08 (m, 1H), 4.04
(dd, 1H, J ) 12.5, 2.2 Hz), 2.03 (s, 3H), 1.98 (s, 3H), 1.97 (s, 3H),
1.96 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 170.3-169.2 (4C),
158.4, 88.8, 70.0, 69.4, 69.0, 67.5, 61.2, 20.4-20.2 (4C). Anal.
Calcd for C15H20O11: C, 47.88; H, 5.36. Found: C, 48.05; H, 5.45.
MS (ESI) m/z 399.0 ([M + Na]+). Rf 0.53 (ethyl acetate/hexane
1:1).
Formyl 2,3,4,6-Tetra-O-benzoyl-â-D-glucopyranoside (1c).
The product was prepared according to procedure A, using 2,3,4,6-
tetra-O-benzoyl-D-glucopyranosyl bromide (3.0 g, 4.6 mmol),
formic acid (85 mL, 1.8 mol), and AgNO3 (1.5 g, 8.8 mmol, 1.9
equiv). After purification by flash column chromatography (silica
gel, ethyl acetate/hexane 1:6, 0.5% of formic acid) and recrystal-
lization from ethyl acetate/hexane, 1c (1.7 g, 60%) was obtained
as a white crystalline solid. 1H NMR (CDCl3, 500 MHz) δ 8.10-
7.26 (m, 21H), 6.26 (d, 1H, J ) 8.1 Hz), 6.04 (t, 1H, J ) 9.6 Hz),
5.86-5.75 (m, 2H), 4.70 (dd, 1H, J ) 12.4, 2.9 Hz), 4.54 (dd, 1H,
J ) 12.4, 4.9 Hz), 4.43-4.36 (m, 1H); 13C NMR (CDCl3, 125 MHz)
δ 166.0-164.9 (4C), 158.5, 133.5-128.2 (24C), 91.5, 73.3, 72.7,
70.6, 68.5, 62.5. Anal. Calcd for C35H28O11: C, 67.30; H, 4.52.
Found: C, 67.17; H, 4.56. MS (ESI) m/z 646.7 ([M + Na]+), 618.7
([M + Na - CHO]+). Rf 0.53 (ethyl acetate/hexane 1:1).
Formyl 2,3,4,6-Tetra-O-benzyl-R-D-glucopyranoside (1d). The
product was prepared according to procedure B, using ethyl 2,3,4,6-
tetra-O-benzyl-1-thio-â-D-glucopyranoside (0.23 g, 0.39 mmol), 20
mL of DCM, formic acid (0.10 mL, 2.6 mmol, 6.7 equiv),
N-iodosuccinimide (100 mg, 0.44 mmol, 1.1 equiv), and TfOH (0.03
mL, 0.34 mmol, 0.9 equiv). The reaction mixture was stirred for
General Procedure for the Glycosylation of the 1-O-(2′,2′-
Dichloro-3′-hydroxycyclobutyl) Glycosides 3 (Procedure F). The
alcohol 3 (typically 0.1 mmol) and the ethylthio or phenylthio
glycoside (typically 5 equiv), 4 Å molecular sieves, and DCM (50
mL/g of ethylthio glycoside) are placed in a dried Schlenk flask
under a nitrogen atmosphere. The mixture is cooled to 0 °C, and
N-iodosuccinimide (5 equiv) and TfOH (5 equiv) are added. After
3 min, the reaction is quenched with triethylamine (large excess).
J. Org. Chem, Vol. 71, No. 15, 2006 5463

Yuan et al.
30 min at 0 °C before it was quenched with triethylamine (5 mL,
36 mmol). After purification by flash column chromatography (silica
gel, ethyl acetate/hexane 1:6, 0.5% of formic acid), 1d (0.19 g,
159.5, 112.2, 109.3, 104.9, 83.1, 79.5, 75.6, 72.1, 67.2, 26.8, 26.6,
26.1, 25.0. Anal. Calcd for C13H20O7: C, 54.16; H, 6.99. Found:
C, 53.99; H, 7.09. MS (ESI) m/z 311.2 ([M + Na]+). Rf 0.56 (ethyl
acetate/hexane 1:1).
1
86%) was obtained as a white crystalline solid. H NMR (CDCl3,
500 MHz) δ 8.19 (s, 1H), 7.40-7.20 (m, 20H), 6.47 (d, 1H, J )
3.4 Hz), 5.01-3.68 (m, 14H); 13C NMR (CDCl3, 125 MHz) δ
159.3, 138.5-127.5 (24C), 90.1, 81.6, 78.6, 76.7, 75.6, 75.0, 73.4,
73.3, 73.0, 70.0. Anal. Calcd for C35H36O7: C, 73.92; H, 6.38.
Found: C, 73.68; H, 6.44. MS (EI) m/z 591.2 ([M + Na]+). Rf
0.65 (ethyl acetate/hexane 1:1).
Vinyl 2,3,4,6-Tetra-O-acetyl-â-D-glucopyranoside (2a). The
product was prepared according to procedure D, using 1a (0.30 g,
0.8 mmol), Tebbe reagent (4.8 mL, 1.6 mmol, 2.0 equiv), and
aqueous NaOH solution (0.21 mL, 0.8 mmol, 1.0 equiv). After flash
column chromatography (silica gel, ethyl acetate/hexane 1:6) and
recrystallization from ethyl acetate/hexane, 2a (0.19 g, 63%) was
obtained as a white crystalline solid. 1H NMR (CDCl3, 500 MHz)
δ 6.38 (dd, 1H, J ) 14.1, 6.4 Hz), 5.17 (t, 1H, J ) 9.4 Hz), 5.05
(dd, 1H, J ) 9.4, 7.5 Hz), 5.03 (dd, 1H, J ) 9.4, 7.8 Hz), 4.75 (d,
1H, J ) 7.8 Hz), 4,50 (dd, 1H, J ) 14.1, 2.1 Hz), 4.21 (dd, 1H, J
) 6.4, 2.1 Hz), 4.19 (dd, 1H, J ) 12.4, 2.5 Hz), 4.07 (dd, 1H, J )
12.4, 5.1 Hz), 3.72 (m, 1H), 1.99 (s, 3H), 1.96 (s, 3H), 1.94 (s,
3H), 1.92 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 170.4, 170.0,
169.2, 169.0, 148.6, 98.8, 92.9, 72.5, 72.0, 70.7, 68.0, 61.7, 20.5-
20.4 (4C). Anal. Calcd for C16H22O10: C, 51.34; H, 5.92. Found:
C, 51.32; H, 5.86. MS (ESI) m/z 397.1 ([M + Na]+). Rf 0.59 (ethyl
acetate/hexane 1:1). HRMS (MALDI) m/z calcd for C16H22O10 ([M
+ Na]+) 397.1105, found 397.1105.
Vinyl 2,3,4,6-Tetra-O-acetyl-R-D-glucopyranoside (2b). The
product was prepared according to procedure D, using 1b (0.30 g,
0.8 mmol), Tebbe reagent (4.8 mL, 1.6 mmol, 2.0 equiv), and
aqueous NaOH solution (0.21 mL, 0.8 mmol, 1.0 equiv). After flash
column chromatography (silica gel, ethyl acetate/hexane 1:6) and
recrystallization from ethyl acetate/hexane, 2b (0.18 g, 60%) was
obtained as a white crystalline solid. 1H NMR (CDCl3, 500 MHz)
δ 6.31 (dd, 1H, J ) 14.0, 6.4 Hz), 5.48 (t, 1H, J ) 9.7 Hz), 5.33
(d, 1H, J ) 3.7 Hz), 5.05 (dd, 1H, J ) 10.2, 9.7 Hz), 4.89 (dd, 1H,
J ) 10.2, 3.7 Hz), 4.61 (dd, 1H, J ) 14.0, 1.9 Hz), 4.24 (dd, 1H,
J ) 6.6, 1.9 Hz), 4.20 (dd, 1H, J ) 12.5, 4.4 Hz), 4.03 (dd, 1H, J
) 12.5, 2.2 Hz), 3.97-3.93 (m, 1H), 2.03 (s, 3H), 2.02 (s, 3H),
1.98 (s, 3H), 1.97 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 170.5-
169.5 (4C), 147.9, 94.5, 93.5, 70.2, 70.0, 68.2, 67.9, 61.5, 20.6,
20.6, 20.6, 20.5. Anal. Calcd for C16H22O10: C, 51.34; H, 5.92.
Found: C, 51.33; H, 5.84. MS (ESI) m/z 397.1 ([M + Na]+). Rf
0.63 (ethyl acetate/hexane 1:1).
Vinyl 2,3,4,6-Tetra-O-benzoyl-â-D-glucopyranoside (2c). The
product was prepared according to procedure D, using 1c (0.3 g,
0.48 mmol), Tebbe reagent (2.9 mL, 0.96 mmol, 2.0 equiv), and
aqueous NaOH solution (0.13 mL, 0.48 mmol, 1.0 equiv). After
purification by column chromatography (silica gel, ethyl acetate/
hexane 1:6) and recrystallization from ethyl acetate/hexane, 2c (0.19
g, 64%) was obtained as a white crystalline solid. 1H NMR (CDCl3,
300 MHz) δ 8.10-7.25 (m, 20H), 6.50 (dd, 1H, J ) 14.0, 6.5 Hz),
6.04 (t, 1H, J ) 9.6 Hz), 5.82-5.71 (m, 2H), 5.27 (d, 1H, J ) 7.8
Hz), 4.72 (dd, 1H, J ) 12.3, 3.0 Hz), 4.64 (dd, 1H, J ) 14.0, 2.1
Hz), 4.59 (dd, 1H, J ) 12.3, 5.6 Hz), 4.35 (m, 1H), 4.29 (dd, 1H,
J ) 6.5, 2.1 Hz); 13C NMR (CDCl3, 75 MHz) δ 166.1-165.1 (4C),
148.7, 133.6-128.4 (24C), 99.3, 93.3, 72.8, 72.7, 71.5, 69.5, 63.2.
Anal. Calcd for C36H30O10: C, 69.45; H, 4.86. Found: C, 69.23;
H, 4.95. MS (ESI) m/z 644.8 ([M + Na]+). Rf 0.59 (ethyl acetate/
hexane 1:1).
Formyl 2,3,4-Tri-O-benzoyl-R-D-arabinopyranoside (1e). The
product was prepared according to procedure A, using 2,3,4-tri-
O-benzoyl-D-arabinopyranosyl bromide (3.0 g, 5.7 mmol), formic
acid (50 mL, 1.3 mol), and AgNO3 (2.0 g, 11.8 mmol, 2.1 equiv).
After purification by flash column chromatography (silica gel, ethyl
acetate/hexane 1:6, 0.5% of formic acid) and recrystallization from
ethyl acetate/hexane, 1e (1.8 g, 64%) was obtained as a crystalline
1
white solid. H NMR (CDCl3, 300 MHz) δ 8.17 (s, 1H), 8.13-
7.95 (m, 6H), 7.63-7.33 (m, 9H), 6.22 (d, 1H, J ) 6.1 Hz), 5.91
(dd, 1H, J ) 7.9, 6.1 Hz), 5.85-5.77 (m, 2H), 4.41 (dd, 1H, J )
12.7, 4.5 Hz), 4.14 (dd, 1H, J ) 12.7, 2.3 Hz); 13C NMR (CDCl3,
75 MHz) δ 165.5, 165.4, 165.0, 158.9, 133.7-128.5 (18 C) 91.6,
70.1, 68.8, 67.7, 63.4. Anal. Calcd for C27H22O9: C, 66.12; H, 4.52.
Found: C, 66.05; H, 4.51. MS (ESI) m/z 513.0 ([M + Na]+), 484.9
([M + Na - CHO]+). Rf 0.49 (ethyl acetate/hexane 1:1).
Formyl 2,3-Di-O-benzoyl-4,6-O-benzylidene-â-D-glucopyra-
noside (1g). The product was prepared according to procedure B,
using ethyl 2,3-di-O-benzoyl-4,6-O-benzylidene-1-thio-â-D-glu-
copyranoside (1.3 g, 2.5 mmol), DCM (50 mL), formic acid (0.15
mL, 3.9 mmol, 1.6 equiv), N-iodosuccinimide (0.67 g, 3.0 mmol,
1.2 equiv), and TfOH (0.22 mL, 2.5 mmol, 1.0 equiv). The reaction
was quenched with triethylamine (5 mL, 36 mmol) after 3 min.
After purification by flash column chromatography (silica gel, ethyl
acetate/hexane 1:6, 0.5% of formic acid) and recrystallization from
ethyl acetate and hexane, 1g (0.74 g, 59%) was obtained as a
crystalline white solid. 1H NMR (CDCl3, 300 MHz) δ 8.09 (s, 1H),
8.05-7.32 (m, 15H), 6.18 (d, 1H, J ) 8.1 Hz), 5.90 (t, 1H, J )
9.3 Hz), 5.70 (dd, 1H, J ) 9.3, 8.1 Hz), 5.60 (s, 1H), 4.49 (dd, 1H,
J ) 15.6, 9.9 Hz), 4.05 (t, 1H, J ) 9.3 Hz), 3.97-3.85 (m, 2H);
13C NMR (CDCl3, 75 MHz) δ 165.5, 165.2, 158.7, 136.6-126.2
(18C), 101.7, 92.0, 78.4, 72.0, 71.3, 68.4, 67.6. Anal. Calcd for
C28H24O9: C, 66.66; H, 4.80. Found: C, 66.69; H, 4.86. MS (ESI)
m/z 526.8 ([M + Na]+), 542.7 ([M + K]+). Rf 0.68 (ethyl acetate/
hexane 1:1).
6-O-Formyl-1,2:3,4-di-O-isopropylidene-R-D-galactopyran-
ose (1l). The product was prepared according to procedure C, using
1,2:3,4-di-O-isopropylidene-R-D-galactopyranose (5 g, 19 mmol),
DPTS (12.0 g, 41 mmol, 2.2 equiv), EDCI (7.9 g, 41 mmol, 2.2
equiv), and HCOOH (1.5 mL, 40 mmol, 2.0 equiv). After flash
column chromatography (silica gel, ethyl acetate/hexane 1:8), 1l
1
(4.2 g, 76%) was obtained as a crystalline white solid. H NMR
(CDCl3, 300 MHz) δ 7.94 (s, 1H), 5.37 (d, 1H, J ) 5.1 Hz), 4.48
(dd, 1H, J ) 7.9, 2.6 Hz), 4.21-3.85 (m, 5H), 1.35 (s, 3H), 1.29
(s, 3H), 1.18 (s, 3H), 1.17 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ
160.6, 109.3, 108.4, 96.0, 70.7, 70.4, 70.1, 65.6, 62.6, 25.7-24.2
(4C). Anal. Calcd for C13H20O7: C, 54.16; H, 6.99. Found: C,
53.96; H, 6.94. MS (ESI) m/z 311.1 ([M + Na]+). Rf 0.71 (ethyl
acetate/hexane 1:1).
3-O-Formyl-1,2:5,6-di-O-isopropylidene-R-D-glucofuranose
(1m). The product was prepared according to procedure C, using
1,2:5,6-di-O-isopropylidene-R-D-glucofuranose (2.1 g, 8.1 mmol),
DPTS (4.6 g, 16 mmol, 2.0 equiv), EDCI (3.1 g, 16 mmol, 2.0
equiv), and HCOOH (0.6 mL, 16 mmol, 2.0 equiv). After flash
column chromatography (silica gel, ethyl acetate/hexane 1:8), 1m
(1.6 g, 69%) was obtained as a colorless syrup. 1H NMR (CDCl3,
300 MHz) δ 8.01 (s, 1H), 5.80 (d, 1H, J ) 3.8 Hz), 5.24 (d, 1H,
J ) 2.3 Hz), 4.44 (d, 1H, J ) 3.8 Hz), 4.17-4.06 (m, 2H), 4.00
(dd, 1H, J ) 8.8, 5.5 Hz), 3.91 (dd, 1H, J ) 8.8, 4.0 Hz), 1.42 (s,
3H), 1.31 (s, 3H), 1.22 (s, 6H); 13C NMR (CDCl3, 75 MHz) δ
Vinyl 2,3,4,6-Tetra-O-benzyl-R-D-glucopyranoside 2d. The
product was prepared according to procedure D, using 1d (1.1 g,
1.93 mmol), Tebbe reagent (11.6 mL, 3.87 mmol, 2.0 equiv), and
aqueous NaOH solution (0.51 mL, 1.9 mmol, 1.0 equiv). After
purification by column chromatography (silica gel, ethyl acetate/
hexane 1:10) and recrystallization from ethyl acetate/hexane, 2d
1
(0.91 g, 83%) was obtained as a white crystalline solid. H NMR
(CDCl3, 500 MHz) δ 7.46-7.02 (m, 20), 6.43 (dd, 1H, J ) 14.0,
6.5 Hz), 5.15 (d, 1H, J ) 3.4 Hz), 5.07 (d, 1H, J ) 11.0 Hz), 4.92
(d, 1H, J ) 11.0 Hz), 4.91 (d, 1H, J ) 11.0 Hz), 4.86 (d, 1H, J )
12.0 Hz), 4.73 (d, 1H, J ) 12.0 Hz), 4.70 (dd, 1H, J ) 14.0, 2.1
Hz), 4.67 (d, 1H, J ) 12.0 Hz), 4.55 (d, 1H, J ) 11.0 Hz), 4.50 (d,
1H, J ) 12.0 Hz), 4.28 (dd, 1H, J ) 6.5, 2.1 Hz), 4.13 (t, 1H, J )
9.0 Hz), 3.87-3.65 (m, 5H); 13C NMR (CDCl3, 125 MHz) δ 148.4,
5464 J. Org. Chem., Vol. 71, No. 15, 2006

1-O-Vinyl Glycosides Via Tebbe Olefination
138.7-127.6 (24 C), 96.2, 92.5, 81.9, 79.2, 77.2, 75.7, 75.0, 73.3,
73.2, 70.7, 68.0. Anal. Calcd for C36H38O6: C, 76.30; H, 6.76.
Found: C, 76.02; H, 6.77. MS (ESI) m/z 588.7 ([M + Na]+). Rf
0.69 (ethyl acetate/hexane 1:1). HRMS (MALDI) m/z calcd for
C36H38O6 ([M + Na]+) 589.2561, found 589.2550.
NMR (CDCl3, 75 MHz) δ 166.1-165.2 (4C), 148.9, 133.7-128.4
(24C), 99.7, 93.3, 71.8, 71.7, 69.3, 68.0, 62.1. Anal. Calcd for
C36H30O10: C, 69.45; H, 4.86. Found: C, 69.31; H, 5.01. MS (ESI)
m/z 644.8 ([M + Na]+). Rf 0.53 (ethyl acetate/hexane 1:1).
Vinyl 2,3,4,6-Tetra-O-benzoyl-R-D-mannopyranoside (2i). The
product was prepared according to procedure D, using the crude
formyl 2,3,4,6-tetra-O-benzoyl-R-D-mannopyranoside (1i; 2.8 g)
[prepared from 2,3,4,6-tetra-O-benzoyl-R-D-mannopyranosyl bro-
mide (3 g, 4.5 mmol), AgNO3 (2 g, 11.7 mmol), and HCOOH (50
mL, 1.3 mmol) following procedure A], Tebbe reagent (27 mL,
9.0 mmol), and aqueous NaOH solution (1.2 mL, 4.5 mmol). After
purification by column chromatography (silica gel, ethyl acetate/
hexane 1:6), 2i (1.51 g, 53% over two steps) was obtained as a
Vinyl 2,3,4-Tri-O-benzoyl-R-D-arabinopyranoside (2e). The
product was prepared according to procedure D, using 1e (0.24 g,
0.49 mmol), Tebbe reagent (3.3 mL, 1 mmol, 2.0 equiv), and
aqueous NaOH solution (0.12 mL, 0.45 mmol, 0.9 equiv). After
purification by column chromatography (silica gel, ethyl acetate/
hexane 1:6) and recrystallization from ethyl acetate/hexane, 2e (0.16
g, 67%) was obtained as a white crystalline solid. 1H NMR (CDCl3,
300 MHz) δ 8.10-7.99 (m, 6H), 7.63-7.33 (m, 9H), 6.51 (dd,
1H, J ) 13.8, 6.6 Hz), 5.84-5.70 (m, 3H), 5.17 (d, 1H, J ) 5.1
Hz), 4.67 (dd, 1H, J ) 13.8, 1.9 Hz), 4.39 (dd, 1H, J ) 12.3, 5.1
Hz), 4.31 (dd, 1H, J ) 6.6, 1.9 Hz), 4.01 (dd, 1H, J ) 12.3, 2.5
Hz); 13C NMR (CDCl3, 75 MHz) δ 165.7-165.2 (3C), 148.7,
133.6-128.5 (18C), 98.6, 93.1, 69.9, 69.4, 67.7, 61.8. Anal. Calcd
for C28H24O8: C, 68.85; H, 4.95. Found: C, 68.56; H, 4.78. MS
(ESI) m/z 511.0 ([M + Na]+). Rf 0.54 (ethyl acetate/hexane 1:1).
Vinyl 2,3,4-Tri-O-benzoyl-â-D-ribopyranoside (2f). The prod-
uct was prepared according to procedure D, using the crude formyl
2,3,4-tri-O-benzoyl-â-D-ribopyranoside (1f; 0.30 g) [prepared from
2,3,4-tri-O-benzoyl-â-D-ribopyranosyl bromide (0.31 g, 0.59 mmol),
AgNO3 (0.32 g, 1.9 mmol), and HCOOH (20 mL, 0.53 mol)
following procedure A], Tebbe reagent (5.0 mL, 1.7 mmol), and
aqueous NaOH solution (0.16 mL, 0.6 mmol). After purification
by column chromatography (silica gel, ethyl acetate/hexane 1:7),
2f (0.21 g, 73% over two steps) was obtained as a white solid. 1H
NMR (CDCl3, 300 MHz) δ 8.12-7.29 (m, 15H), 6.51 (dd, 1H, J
) 14.1, 6.5 Hz), 5.92 (t, 1H, J ) 3.9 Hz), 5.72-5.67 (m, 1H),
5.66-5.62 (m, 1H), 5.50 (d, 1H, J ) 2.5 Hz), 4.75 (dd, 1H, J )
14.1, 2.1 Hz), 4.37 (dd, 1H, J ) 6.5, 2.1 Hz), 4.32 (dd, 1H, J )
13.2, 2.1 Hz), 4.16 (dd, 1H, J ) 13.2, 2.4 Hz); 13C NMR (CDCl3,
75 MHz) δ 166.3-165.2 (3C), 147.9, 133.4-128.5 (18C), 97.4,
93.5, 68.1, 67.5, 65.9, 61.8. Anal. Calcd for C28H24O8: C, 68.85;
H, 4.95. Found: C, 68.70; H, 5.07. MS (ESI) m/z 511.0 ([M +
Na]+). Rf 0.56 (ethyl acetate/hexane 1:1).
Vinyl 2,3-Di-O-benzoyl-4,6-O-benzylidene-â-D-glucopyrano-
side (2g). The product was prepared according to procedure D,
using 1g (190 mg, 0.38 mmol), Tebbe reagent (2.3 mL, 0.77 mmol,
2.0 equiv), and aqueous NaOH solution (0.1 mL, 0.38 mmol, 1.0
equiv). After flash column chromatography (silica gel, ethyl acetate/
hexane 1:7) and recrystallization from ethyl acetate/hexane, 2g (130
mg, 68%) was obtained as a white crystalline solid. 1H NMR
(CDCl3, 300 MHz) δ 8.06-7.31 (m, 15H), 6.45 (dd, 1H, J ) 13.8,
6.3 Hz), 5.85 (t, 1H, J ) 9.3 Hz), 5.62 (dd, 1H, J ) 9.3, 7.8 Hz),
5.59 (s, 1H), 5.15 (d, 1H, J ) 7.8 Hz), 4.63 (dd, 1H, J ) 13.8, 2.1
Hz), 4.49 (dd, 1H, J ) 10.2, 4.8 Hz), 4.29 (dd, 1H, J ) 6.3, 2.1
Hz), 4.03 (t, 1H, J ) 9.3 Hz), 3.95 (t, 1H, J ) 10.2 Hz), 3.81 (dt,
1H, J ) 9.4, 4.8 Hz); 13C NMR (CDCl3, 75 MHz) δ 165.7, 165.2,
148.9, 136.8-126.2 (18C) 101.6, 100.0, 93.5, 78.6, 72.1, 72.1, 68.6,
67.0. Anal. Calcd for C29H26O8: C, 69.31; H, 5.21. Found: C,
69.42; H, 5.23. MS (ESI) m/z 525.0 ([M + Na]+). Rf 0.74 (ethyl
acetate/hexane 1:1). HRMS (MALDI) m/z calcd for C29H26O8 ([M
+ Na]+) 525.1520, found 525.1529.
1
white solid. H NMR (CDCl3, 300 MHz) δ 8.17-7.28 (m, 20H),
6.54 (dd, 1H, J ) 14.1, 6.7 Hz), 6.22 (t, 1H, J ) 10.1 Hz), 6.03
(dd, 1H, J ) 10.1, 3.2 Hz), 5.83 (dd, 1H, J ) 3.2, 1.8 Hz), 5.50 (d,
1H, J ) 1.8 Hz), 4.83 (dd, 1H, J ) 14.1, 2.1 Hz), 4.78-4.70 (m,
1H), 4.56-4.45 (m, 2H), 4.40 (dd, 1H, J ) 6.7, 2.1 Hz); 13C NMR
(CDCl3, 75 MHz) δ 166.2-165.4 (4C), 147.6, 133.7-128.4 (24C),
96.4, 93.9, 69.9, 69.9, 69.5, 66.6, 62.6. Anal. Calcd for C36H30O10:
C, 69.45; H, 4.86. Found: C, 69.47; H, 4.97. MS (ESI) m/z 644.8
([M + Na]+). Rf 0.58 (ethyl acetate/hexane 1:1).
Vinyl 2,3,6,8,9,10,12-Hepta-O-benzoyl-â-D-cellobioside (2k).
The product was prepared according to procedure D, using the crude
formyl 2,3,6,8,9,10,12-hepta-O-benzoyl-â-D-cellobioside (1k; 0.60
g) [prepared from 2,3,6,8,9,10,12-hepta-O-benzoyl-â-D-cellobiosyl
bromide (0.69 g, 0.61 mmol), AgNO3 (0.50 g, 2.9 mmol), and
HCOOH (20 mL, 0.53 mol) following procedure A], Tebbe reagent
(4.0 mL, 1.33 mmol), and aqueous NaOH solution (0.15 mL, 0.56
mmol). After flash column chromatography (silica gel, ethyl acetate/
hexane 1:4), 2k (0.29 g, 43% over two steps) was obtained as a
1
white solid. H NMR (CDCl3, 300 MHz) δ 8.15-7.18 (m, 35H),
6.35 (dd, 1H, J ) 14.1, 6.7 Hz), 5.86 (t, 1H, J ) 9.2 Hz), 5.77 (t,
1H, J ) 9.6 Hz), 5.56 (dd, 1H, J ) 9.4, 7.8 Hz), 5.55 (dd, 1H, J
) 9.9, 7.8 Hz), 5.41 (t, 1H, J ) 9.6 Hz), 5.03, 4.98 (d, d, 2H, J )
7.8 Hz), 4.64 (dd, 1H, J ) 12.4, 2.1 Hz), 4.52 (dd, 1H, J ) 14.1,
2.1 Hz), 4.50 (dd, 1H, J ) 12.3, 5.1 Hz), 4.31 (t, 1H, J ) 9.6 Hz),
4.19 (dd, 1H, J ) 6.7, 2.1 Hz), 4.10 (dd, 1H, J ) 11.5, 2.5 Hz),
4.00-3.75 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ 165.8-164.9
(7C), 148.8, 133.5-128.4 (42C), 101.0, 99.1, 93.1, 76.3, 73.5, 72.9,
72.7, 72.6, 72.0, 71.5, 69.5, 62.7, 62.5. Anal. Calcd for C63H52O18:
C, 68.97; H, 4.78. Found: C, 68.70; H, 4.92. MS (ESI) m/z 1119.2
([M + Na]+). Rf 0.49 (ethyl acetate/hexane 1:1).
1,2:3,4-Di-O-isopropylidene-6-O-vinyl-R-D-galactopyranose (2l).
The product was prepared according to procedure D, using 1l (1 g,
3.5 mmol), Tebbe reagent (21 mL, 7 mmol, 2.0 equiv), and 15%
solution of NaOH (0.85 mL, 3.2 mmol, 0.9 equiv). After flash
column chromatography (silica gel, ethyl acetate/hexane 1:10), 2l
(0.89 g, 89%) was obtained as a colorless syrup. 1H NMR (CDCl3,
300 MHz) δ 6.45 (dd, 1H, J ) 14.4, 6.8 Hz), 5.50 (d, 1H, J ) 4.8
Hz), 4.58 (dd, 1H, J ) 8.0, 2.4 Hz), 4.28 (dd, 1H, J ) 4.8, 2.4
Hz), 4.23 (dd, 1H, J ) 7.8, 1.8 Hz), 4.18 (dd, 1H, J ) 14.4, 2.4
Hz), 4.04 (m, 1H), 3.98 (dd, 1H, J ) 6.8, 2.4 Hz), 3.88-3.75 (m,
2H), 1.49 (s, 3H), 1.41 (s, 3H), 1.30 (s, 3H), 1.29 (s, 3H); 13C
NMR (CDCl3, 75 MHz) δ 151.6, 109.3, 108.6, 96.3, 86.7, 71.0,
70.6, 70.5, 66.5, 66.1, 26.0-24.4 (4C). Anal. Calcd for C14H22O6:
C, 58.73; H, 7.74. Found: C, 59.00; H, 7.71. MS (ESI) m/z 309.2
([M + Na]+), Rf 0.76 (ethyl acetate/hexane 1:1).
1,2:5,6-Di-O-isoproplidene-3-O-vinyl-R-D-glucofuranose (2m).
The product was prepared according to procedure D, using 1m (0.40
g, 1.4 mmol), Tebbe reagent (8.4 mL, 2.8 mmol, 2.0 equiv), and
15% solution of NaOH (0.36 mL, 1.4 mmol, 1.0 equiv). After flash
column chromatography (silica gel, ethyl acetate/hexane 1:8), 2m
(0.35 g, 87%) was obtained as a colorless syrup. 1H NMR (CDCl3,
300 MHz) δ 6.35 (dd, 1H, J ) 14.1, 6.6 Hz), 5.83 (d, 1H, J ) 3.8
Hz), 4.54 (d, 1H, J ) 3.8 Hz), 4.35 (dd, 1H, J ) 14.1, 2.3 Hz),
4.30 (d, 1H, J ) 3.0 Hz), 4.29-4.22 (m, 1H), 4.14 (dd, 1H, J )
7.7, 3.0 Hz), 4.11 (dd, 1H, J ) 6.6, 2.3 Hz), 4.04 (dd, 1H, J ) 8.9,
6.2 Hz), 3.97 (dd, 1H, J ) 8.5, 5.3 Hz), 1.47 (s, 3H), 1.38 (s, 3H),
Vinyl 2,3,4,6-Tetra-O-benzoyl-â-D-galactopyranoside (2h).
The product was prepared according to procedure D, using the crude
formyl 2,3,4,6 tetra-O-benzoyl-â-D-galactopyranoside (1h; 0.80 g)
[prepared from 2,3,4,6-tetra-O-benzoyl-â-D-galactopyranosyl bro-
mide (0.85 g,1.3 mmol), AgNO3 (0.45 g, 2.6 mmol) ,and HCOOH
(50 mL, 1.3 mmol) following procedure A], Tebbe reagent (8.0
mL, 2.7 mmol), and aqueous NaOH solution (0.35 mL, 1.3 mmol).
After flash column chromatography (silica gel, ethyl acetate/hexane
1:6), 2h (0.37 g, 46% over two steps) was obtained as a white
1
solid. H NMR (CDCl3, 300 MHz) δ 8.19-7.23 (m, 20H), 6.55
(dd, 1H, J ) 14.1, 6.5 Hz), 6.11 (d, 1H, J ) 3.3 Hz), 6.00 (dd, 1H,
J ) 10.2, 7.8 Hz), 5.74 (dd, 1H, J ) 10.2, 3.3 Hz), 5.24 (d, 1H, J
) 7.8 Hz), 4.79-4.46 (m, 4H), 4.32 (dd, 1H, J ) 6.5, 2.2 Hz); 13
C
J. Org. Chem, Vol. 71, No. 15, 2006 5465

Yuan et al.
1.29 (s, 3H), 1.27 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 150.1,
111.9, 109.1, 105.2, 89.4, 82.1, 80.4, 80.4, 72.2, 67.1, 26.9-25.3
(4C). Anal. Calcd for C14H22O6: C, 58.73; H, 7.74. Found: C,
58.82; H, 7.62. MS (ESI) m/z 309.2 ([M + Na]+). Rf 0.62 (ethyl
acetate/hexane 1:1).
9.64. Found: C, 61.79; H, 4.41; Cl, 9.67. MS (ESI) m/z 756.9 ([M
+ Na]+). Rf 0.47 (ethyl acetate/hexane 1:1).
Analytical data for 3c′ (minor diastereomer): 1H NMR (CDCl3,
500 MHz) δ 8.12-7.29 (m, 20H), 5.91 (t, 1H, J ) 9.6 Hz), 5.73
(t, 1H, J ) 9.6 Hz), 5.63 (dd, 1H, J ) 9.6, 7.8 Hz), 4.94 (d, 1H,
J ) 7.8 Hz), 4.66 (dd, 1H, J ) 12.0, 3.6 Hz), 4.57 (dd, 1H, J )
12.0, 4.8 Hz), 4.23 (ddd, 1H, J ) 9.6, 4.8, 3.6 Hz), 4.16 (t, 1H, J
) 8.4 Hz), 4.10 (t, 1H, J ) 8.4 Hz), 2.62 (dt, 1H, J ) 12.0, 7.5
Hz), 1.86 (dt, 1H, J ) 12.0, 9.0 Hz), 1.7 (s, 1H); 13C NMR (CDCl3,
75 MHz) δ 166.3-165.1 (4C), 133.6-128.4 (24C), 100.9, 91.2,
78.2, 72.9, 72.7, 72.0, 71.8, 69.7, 63.2, 36.1. Anal. Calcd for C38H32-
Cl2O11: C, 62.05; H, 4.38; Cl, 9.64. Found: C, 61.87; H, 4.34; Cl,
9.81. MS (ESI) m/z 756.8 ([M + Na]+). Rf 0.38 (ethyl acetate/
hexane 1:1).
(1′S,3′R)-2′,2′-Dichloro-3′-hydroxycyclobutyl 2,3,4,6-Tetra-O-
acetyl-â-D-glucopyranoside (3a). The product was prepared ac-
cording to procedure E, using 2a (130 mg, 0.35 mmol) and
trichloroacetyl chloride (0.1 mL, 0.89 mmol, 2.5 equiv), as well as
NaBH4 (80 mg, 2 mmol, 5.7 equiv). 1H NMR spectra of the crude
product were consistent with the presence of only one diastereomer.
After flash column chromatography (silica gel, ethyl acetate/hexane
1:5) and recrystallization from ethyl acetate/hexane, 3a (91 mg,
1
53%) was obtained as a white crystalline solid. H NMR (CDCl3,
(1′R,3′S)-2′,2′-Dichloro-3′-hydroxycyclobutyl 2,3,4-Tri-O-ben-
zoyl-â-D-ribopyranoside (3f). The product was prepared according
to procedure E, using 2f (207 mg, 0.42 mmol) and trichloroacetyl
chloride (0.15 mL, 1.3 mmol, 3.1 equiv), as well as NaBH4 (50
300 MHz) δ 5.26 (t, 1H, J ) 9.4 Hz), 5.09 (t, 1H, J ) 9.4 Hz),
5.04 (dd, 1H, J ) 9.4, 7.8 Hz), 4.84 (d, 1H, J ) 7.8 Hz), 4.41 (t,
1H, J ) 8.5 Hz), 4.29-4.12 (m, 3H), 3.74 (ddd, 1H, J ) 9.8, 4.5,
2.6 Hz), 3.13 (d, 1H, J ) 9.6 Hz), 2.70 (dt, 1H, J ) 11.7, 7.8 Hz),
2.09 (s, 3H), 2.07 (s, 3H), 2.03 (s, 3H), 2.01 (s, 3H), 1.93 (dt, 1H,
J ) 11.7, 9.2 Hz); 13C NMR (CDCl3, 75 MHz) δ 170.8-169.6
(4C), 98.8, 90.6, 74.4, 72.6, 72.3, 71.7, 71.0, 68.3, 61.78, 35.6,
20.8-20.6 (4C). Anal. Calcd for C18H24Cl2O11: C, 44.37; H, 4.96;
Cl, 14.55. Found: C, 44.54; H, 5.09; Cl, 14.53. MS (ESI) m/z 508.8
([M + Na]+). Rf 0.26 (ethyl acetate/hexane 1:1).
1
mg, 1.3 mmol, 3.1 equiv). H NMR spectra of the crude product
showed the presence of two diastereomers in a ratio of 10.1:1. After
purification by column chromatography (silica gel, ethyl acetate/
hexane 1:5), the major diastereomer 3f (172 mg, 67%) was obtained
1
as a white solid. H NMR (CDCl3, 300 MHz) δ 8.10-7.29 (m,
15H), 5.87 (t, 1H, J ) 3.9 Hz), 5.73-5.69 (m, 1H), 5.62-5.59
(m, 1H), 5.24 (d, 1H, J ) 1.8 Hz), 4.63 (dd, 1H, J ) 13.3, 1.9
Hz), 4.28-4.15 (m, 3H), 2.83 (dt, 1H, J ) 11.7, 7.5 Hz, major),
2.70 (dt, 1H, J ) 11.4, 7.5 Hz, minor), 2.63 (d, 1H, J ) 10.7 Hz),
2.07 (dt, 1H, J ) 11.7, 9.3 Hz, major), 1.88 (dt, 1H, J ) 11.4, 9.3
Hz, minor); 13C NMR (CDCl3, 75 MHz) δ 166.4-165.3 (3 C),
133.4-128.4 (18 C), 99.1, 91.4, 77.1, 71.6, 68.3, 67.5, 65.9, 62.3,
36.26. Anal. Calcd for C30H26Cl2O9: C, 59.91; H, 4.36. Found:
C, 60.31; H, 4.59. MS (ESI) m/z 622.9 ([M + Na]+). Rf 0.44 (ethyl
acetate/hexane 1:1). HRMS (MALDI) m/z calcd for C30H26Cl2O9
([M + Na]+) 623.0846, found 623.0835.
(1′S*,3′R*)-2′,2′-Dichloro-3′-hydroxycyclobutyl 2,3,4,6-Tetra-
O-acetyl-R-D-glucopyranoside (3b). The product was prepared
according to procedure E, using 2b (98 mg, 0.26 mmol) and
trichloroacetyl chloride (0.1 mL, 0.89 mmol, 3.4 equiv), as well as
NaBH4 (40 mg, 1 mmol, 3.8 equiv). 1H NMR spectra of the crude
product showed the presence of two diastereomers in a ratio of
3.0:1. After flash column chromatography (silica gel, ethyl acetate/
hexane 1:4), an inseparable diastereomeric mixture of 3b (71 mg,
1
56%) was obtained as a colorless syrup. H NMR (CDCl3, 300
MHz) δ 5.53 (t, 1H, J ) 9.9 Hz), 5.41 (d, 1H, J ) 3.9 Hz, minor),
5.22 (d, 1H, J ) 3.9 Hz, major), 5.14 (t, 1H, J ) 9.9 Hz), 4.91
(dd, 1H, J ) 9.9, 3.9 Hz, minor), 4.88 (dd, 1H, J ) 9.9, 3.9 Hz,
major), 4.45-4.02 (m, 5H), 2.95 (d, 1H, J ) 9.8 Hz, major), 2.93
(d, 1H, J ) 9.8 Hz, minor), 2.72 (dt, 1H, J ) 11.7, 7.8 Hz), 2.11
(s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H), 1.99 (dt, 1H, J )
11.7, 9.0 Hz); 13C NMR (CDCl3, 75 MHz) δ 170.80-169.65 (4C,
major and minor), 96.9 (major), 94.5 (minor), 91.3 (major), 90.5
(minor), 78.0 (major), 73.6 (minor), 71.7 (minor), 71.4 (major),
70.8 (major), 69.9 (major), 68.4 (major), 68.0 (major), 70.2 (minor),
69.6 (minor), 68.4 (minor), 67.9 (minor), 61.7 (minor), 61.5 (major),
36.0 (major), 35.5 (minor), 20.8-20.6 (4C, major and minor). Rf
0.23 (ethyl acetate/hexane 1:1). HRMS (MALDI) m/z calcd for
C18H24Cl2O11 ([M + Na]+) 509.0588, found 509.0579.
(1′S,3′R)-2′,2′-Dichloro-3′-hydroxycyclobutyl 2,3,4,6-Tetra-O-
benzoyl-â-D-glucopyranoside (3c) and (1′R,3′S)-2′,2′-Dichloro-
3′-hydroxycyclobutyl 2,3,4,6-Tetra-O-benzoyl-â-D-glucopyra-
noside (3c′). The product was prepared according to procedure E,
using 2c (0.55 g, 0.88 mmol) and trichloroacetyl chloride (0.3 mL,
2.7 mmol, 3.1 equiv), as well as NaBH4 (100 mg, 2.6 mmol, 3.0
equiv). 1H NMR spectra of the crude product showed the presence
of two diastereomers in a ratio of 3.3:1. After flash column
chromatography (silica gel, ethyl acetate/hexane 1:5) and recrys-
tallization from ethyl acetate/hexane, the major and the minor
diastereomer 3c (0.31 g, 48%) and 3c′ (0.11 g, 17%), respectively,
were isolated as a white crystalline solids.
(1′S,3′R)-2′,2′-Dichloro-3′-hydroxycyclobutyl 2,3,4,6-Tetra-O-
benzoyl-R-D-mannopyranoside (3i). The product was prepared
according to procedure E, using 2i (128 mg, 0.2 mmol) and
trichloroacetyl chloride (0.1 mL, 0.89 mmol, 4.5 equiv), as well as
NaBH4 (40 mg, 1 mmol, 5.0 equiv). 1H NMR spectra of the crude
product were consistent with the presence of only one diastereomer.
After purification by column chromatography (silica gel, ethyl
acetate/hexane 1:5), 3i (91 mg, 60%) was obtained as a white solid.
1H NMR (CDCl3, 300 MHz) δ 8.25-7.25 (m, 20H), 6.28 (t, 1H,
J ) 10.0 Hz), 5.97 (dd, 1H, J ) 10.0, 3.1 Hz), 5.80 (dd, 1H, J )
3.1, 0.5 Hz), 5.24 (d, 1H, J ) 0.5 Hz), 4.87-4.80 (m, 2H), 4.53
(dd, 1H, J ) 9.6, 3.9 Hz), 4.30-4.19 (m, 2H), 2.85 (dt, 1H, J )
11.7, 7.8 Hz), 2.67 (d, 1H, J ) 9.9 Hz), 2.14 (dt, 1H, J ) 11.7, 9.2
Hz); 13C NMR (CDCl3, 75 MHz) δ 166.4-165.6 (4C), 133.8-
128.5 (24C), 98.7, 91.6, 71.7, 70.3-70.1 (4C), 66.3, 62.6, 36.6. Rf
0.38 (ethyl acetate/hexane 1:1). HRMS (MALDI) m/z calcd for
C38H32Cl2O11 ([M + Na]+) 757.1214, found 757.1201.
Phenyl 2,3,4-Tri-O-benzoyl-1-thio-â-D-ribopyranoside (7).
PhSH (0.5 mL) was added at room temperature to a stirred solution
of 2,3,4-tri-O-benzoyl-D-ribopyranosyl bromide (630 mg, 1.2 mmol)
and 2 mL of NEt3 in dry CH3CN. The reaction mixture was stirred
overnight, diluted with Et2O and washed with 1 M HCl, saturated
aqueous NaHCO3 solution, and brine, dried over MgSO4, filtered,
and evaporated to dryness. After purification by flash column
chromatography (silica gel, ethyl acetate/hexane 1:10), 7 (72 mg,
1
11%) was obtained as a colorless syrup. H NMR (CDCl3, 300
Analytical data for 3c (major diastereomer): 1H NMR (CDCl3,
500 MHz) δ 8.12-7.29 (m, 20H), 5.98 (t, 1H, J ) 9.6 Hz), 5.71
(t, 1H, J ) 9.6 Hz), 5.60 (dd, 1H, J ) 9.6, 7.8 Hz), 5.23 (d, 1H,
J ) 7.8 Hz), 4.67 (dd, 1H, J ) 12.2, 2.9 Hz), 4.56-4.50 (m, 2H),
4.23 (ddd, 1H, J ) 10.1, 5.2, 2.9 Hz), 4.10 (t, 1H, J ) 8.4 Hz),
2.65 (dt, 1H, J ) 11.7, 7.8 Hz), 2.52 (s, 1H), 1.86 (dt, 1H, J )
11.7, 9.2 Hz); 13C NMR (CDCl3, 75 MHz) δ 166.3-165.2 (4C),
133.6-128.4 (24C), 98.8, 90.5, 73.9, 72.9, 72.8, 71.7, 71.6, 69.6,
63.0, 35.6. Anal. Calcd for C38H32Cl2O11: C, 62.05; H, 4.38; Cl,
MHz) δ 8.05-7.29 (m, 20H), 5.95 (t, 1H, J ) 3.6 Hz), 5.65 (d,
1H, J ) 4.8 Hz), 5.63-5.56 (m, 2H), 4.62 (dd, 1H, J ) 12.3, 3.3
Hz,), 4.17 (dd, 1H, J ) 12.3, 5.4 Hz); 13C NMR (CDCl3, 75 MHz)
δ 165.8-165.2 (3C), 133.4-128.2 (24 C), 85.2, 69.4, 67.5 (2C),
63.3. Anal. Calcd for C32H26O7S: C, 69.30; H, 4.72. Found: C,
69.03; H, 4.76. Rf 0.66 (ethyl acetate/hexane 1:1). HRMS (MALDI)
m/z calcd for C32H26O7S ([M + Na]+) 577.1291, found 577.1281.
(1′S,3′R)-3′-Acetoxy-2′,2′-dichlorocyclobutyl 2,3,4,6-Tetra-O-
acetyl-â-D-glucopyranoside (9a). (i) Preparation Starting from
5466 J. Org. Chem., Vol. 71, No. 15, 2006

1-O-Vinyl Glycosides Via Tebbe Olefination
3a. Ac2O (3 mL, large excess) was added to a solution of 3a (100
mg, 0.2 mmol) in 5 mL of pyridine via a syringe over a time period
of 3 h. The reaction mixture was stirred at room temperature for
another 3 h and then diluted with Et2O. The organic phase was
washed with 1 M HCl, saturated aqueous NaHCO3 solution as well
as brine, and dried over MgSO4. After flash column chromato-
graphy, 9a (97 mg, 92%) was obtained as a colorless syrup.
(ii) Preparation Starting from 3c. 3c (150 mg, 0.2 mmol) was
dissolved in 10 mL of methanol, and NaOMe (50 mg, 0.9 mmol)
was added. The reaction mixture was stirred at room temperature
for about 20 min and followed by TLC until the conversion was
complete. Then, Amberlite IR-120 (H+) (500 mg, 2.2 mmol) was
added into the reaction mixture. After 3 min, when the pH value
of the reaction mixture reached 7-8, the Amberlite was filtered
off. The solution was concentrated and dried in high vacuum for
12 h. Pyridine (5 mL) was added, and then Ac2O (3 mL, large
excess) was added slowly via a syringe over a time period of 3 h.
The reaction mixture was stirred at room temperature for another
3 h and then diluted with Et2O. The organic phase was washed
with 1 M HCl, saturated aqueous NaHCO3 solution as well as brine,
and dried over MgSO4. After purification by column chromato-
graphy, 9a (103 mg, 97%) was obtained as a colorless syrup.
The analytical data for the products obtained via both pathways
tetra-O-benzoyl-R-D-mannopyranosyl)oxycyclobutyl 2,3,4,6-
Tetra-O-benzoyl-â-D-glucopyranoside (9c′). (i) Preparation
Starting from 3c. The product was prepared according to procedure
F, using ethyl 2,3,4,6-tetra-O-benzoyl-1-thio-R-D-mannopyranoside
(8; 150 mg, 0.23 mmol), 4 Å molecular sieves, 3c (71 mg, 0.097
mmol), N-iodosuccinimide (60 mg, 0.27 mmol), and TfOH (0.022
mL, 0.25 mmol). After 3 min, the reaction was quenched with
triethylamine (1 mL, 7.2 mmol). After flash column chromatography
(silica gel, ethyl acetate/hexane 1:4), 9c (93 mg, 73%) was obtained
as a white solid.
(ii) Preparation Starting from 3c′. The product was prepared
according to procedure F, using ethyl 2,3,4,6-tetra-O-benzoyl-1-
thio-R-D-mannopyranoside (8; 300 mg, 0.47 mmol), 3c′ (90 mg,
0.12 mmol), N-iodosuccinimide (110 mg, 0.49 mmol), and TfOH
(0.04 mL, 0.45 mmol). After 3 min, the reaction was quenched
with triethylamine (1 mL, 7.2 mmol). After flash column chroma-
tography (silica gel, ethyl acetate/hexane 1:4), 9c′ (130 mg, 82%)
was obtained as a white solid.
(iii) Preparation Starting from 3i. The product was prepared
according to procedure F, using ethyl 2,3,4,6-tetra-O-benzoyl-1-
thio-â-D-glucopyranoside (6; 200 mg, 0.31 mmol), 3i (70 mg 0.095
mmol), N-iodosuccinimide (70 mg, 0.31 mmol), and TfOH (0.027
mL, 0.31 mmol). After 3 min, the reaction was quenched with
triethylamine (1 mL, 7.2 mmol). After flash column chromatography
(silica gel, ethyl acetate/hexane 1:4), 9c′ (73 mg, 58%) was obtained
were identical within experimental error. [R]25 -14.6 (c 0.9,
D
1
CHCl3). H NMR (CDCl3, 300 MHz) δ 5.25 (t, 1H, J ) 9.6 Hz),
5.12-4.99 (m, 3H), 4.83 (d, 1H, J ) 7.8 Hz), 4.51 (m, 1H), 4.26
(dd, 1H, J ) 12.6, 4.8 Hz), 4.17 (dd, 1H, J ) 12.6, 2.4 Hz), 3.74
(ddd, 1H, J ) 10.0, 4.8, 2.4 Hz), 2.73 (dt, 1H, J ) 12.0, 7.8 Hz),
2.19-2.12 (m, 4H), 2.08 (s, 3H), 2.06 (s, 3H), 2.02 (s, 3H), 2.00
(s, 3H); 13C NMR (CDCl3, 300 MHz) δ 170.5-169.3 (5C), 98.6,
87.5, 75.0, 72.5, 72.3, 70.9 (2C), 68.2, 61.7, 32.0, 20.7-20.3 (5C).
Anal. Calcd for C20H26Cl2O12: C, 45.38; H, 4.95; Cl, 13.40.
Found: C, 45.51; H, 5.08; Cl, 13.62. MS (ESI) m/z 550.8 ([M +
Na]+). Rf 0.35 (ethyl acetate/hexane 1:1). HRMS (MALDI) m/z
calcd for C20H26Cl2O12 ([M + Na]+) 551.0694, found 551.0684.
(1′S,3′R)-2′,2′-Dichloro-3′-(2′′,3′′,4′′-tri-O-benzoyl-â-D-ribopy-
ranosyl)oxycyclobutyl 2,3,4,6-Tetra-O-benzoyl-â-D-glucopyra-
noside (9b). (i) Preparation Starting from 3f. The product was
prepared according to procedure F, using ethyl 2,3,4,6-tetra-O-
benzoyl-1-thio-â-D-glucopyranoside (6; 500 mg, 0.78 mmol), 3f
(111 mg, 0.18 mmol), N-iodosuccinimide (175 mg, 0.78 mmol),
and TfOH (0.07 mL, 0.78 mmol). After 3 min, the reaction was
quenched with triethylamine (1 mL, 7.2 mmol). After flash column
chromatography (silica gel, ethyl acetate/hexane 1:4), 9b (195 mg,
92%) was obtained as a white solid.
as a white solid.
1
Analytical data for 9c: [R]25 -20.7 (c 1.7, CHCl3). H NMR
D
(CDCl3, 300 MHz) δ 8.20-7.20 (m, 40H), 6.14 (t, 1H, J ) 10.0
Hz), 6.02 (t, 1H, J ) 9.6 Hz), 5.88 (dd, 1H, J ) 10.0, 3.3 Hz),
5.80 (dd, 1H, J ) 3.3, 1.8 Hz), 5.75 (t, 1H, J ) 9.6 Hz), 5.66 (dd,
1H, J ) 9.6, 8.1 Hz), 5.36 (d, 1H, 1.8 Hz), 5.28 (d, 1H, J ) 8.1
Hz), 4.71 (dd, 2H, J ) 12.6, 2.7 Hz), 4.62-4.49 (m, 3H), 4.42-
4.36 (m, 2H), 4.30-4.23 (m, 1H), 2.73 (dt, 1H, J ) 11.7, 7.8 Hz),
2.27 (dt, 1H, J ) 11.7, 9.3 Hz); 13C NMR (CDCl3, 75 MHz) δ
166.2-165.3 (8C), 133.7-128.4 (48C), 98.6, 96.5, 87.5, 77.4, 74.0,
73.8, 73.0, 72.9, 71.5, 69,9, 69.7, 69.6, 66.9, 63.0, 62.8, 32.6. Rf
0.51 (ethyl acetate/hexane 1:1). HRMS (MALDI) m/z calcd for
C72H58Cl2O20 ([M + Na]+) 1335.2791, found 1335.2765.
1
Analytical data for 9c′: [R]25 -14.0 (c 0.8, CHCl3). H NMR
D
(CDCl3, 300 MHz) δ 8.20-7.28 (m, 40H), 6.29 (t, 1H, J ) 10.0
Hz), 5.98 (t, 1H, J ) 9.6 Hz), 5.93 (dd, 1H, J ) 10.0, 3.3 Hz),
5.83-5.75 (m, 2H), 5.72 (dd, 1H, J ) 9.6, 7.8 Hz), 5.21 (d, 1H,
1.8 Hz), 5.04 (d, 1H, J ) 7.8 Hz), 4.85-4.61 (m, 4H), 4.48 (dd,
1H, J ) 12.6, 3.0 Hz), 4.34-4.15 (m, 3H), 2.70 (dt, 1H, J ) 11.7,
7.8 Hz), 2.29 (dt, 1H, J ) 11.7, 9.6 Hz); 13C NMR (CDCl3, 75
MHz) δ 166.2-165.1 (8C), 133.7-128.4 (48C), 100.8, 98.9, 89.4,
78.0 (2C), 73.0, 72.7, 71.9, 70.3, 70.2, 70.1, 69.8, 66.2, 63.2, 62.4,
33.5. Anal. Calcd for C72H58Cl2O20: C, 65.81; H, 4.45; Cl, 5.40.
Found: C, 65.52; H, 4.71; Cl, 5.37. MS (ESI) m/z 1335.5 ([M +
Na]+). Rf 0.46 (ethyl acetate/hexane 1:1). HRMS (MALDI) m/z
calcd for C72H58Cl2O20 ([M + Na]+) 1335.2791, found 1335.2766.
(ii) Preparation Starting from 3c. The product was prepared
according to procedure F, using phenyl 2,3,4-tetra-O-benzoyl-1-
thio-â-D-ribopyranoside (7; 60 mg, 0.11 mmol), 3c (25 mg, 0.034
mmol), N-iodosuccinimide (34 mg, 0.15 mmol), and TfOH (0.01
mL, 0.11 mmol). After 3 min, the reaction was quenched with
triethylamine (1 mL, 7.2 mmol). After flash column chromatography
(silica gel, ethyl acetate/hexane 1:4), 9b (28 mg, 70%) was obtained
as a white solid.
Acknowledgment. The authors would like to thank the
Deutsche Forschungsgemeinschaft (DFG) for financial support
(Emmy Noether program, FR 1567/2-1), Karolin Geyer from
the Seeberger group at ETH Zurich for performing the LCMS,
Thresen Mathew from the Vasella group at ETH Zurich for
helping us with determining the optical rotations, Dr. Volker
Gramlich for the X-ray crystal structure analysis, Martin Colussi
for measuring GPC, and Prof. A. Dieter Schlu¨ter for valuable
suggestions and discussions.
The analytical data for the products obtained via both pathways
were identical within experimental error. [R]25 -30.7 (c 0.25,
D
CHCl3). 1H NMR (CDCl3, 300 MHz) δ 8.15-7.25 (m, 35H), 6.03
(t, 1H, J ) 9.6 Hz), 5.80-5.53 (m, 5H), 5.30 (d, 1H, J ) 7.8 Hz),
5.20 (d, 1H, J ) 1.8 Hz), 4.71 (dd, 1H, J ) 12.0, 3.0 Hz), 4.63-
4.52 (m, 3H), 4.31-4.23 (m, 1H), 4.19-4.10 (m, 2H), 2.72 (dt,
1H, J ) 11.7, 7.8 Hz), 2.20 (dt, 1H, J ) 11.7, 9.6 Hz); 13C NMR
(CDCl3, 75 MHz) δ 166.3-165.2 (7C), 133.6-128.4 (42C), 99.4,
98.7, 88.6, 77.3, 73.7, 73.0, 72.9, 71.5, 69.6, 68.3, 67.5, 66.0, 63.0,
62.4, 33.1. Anal. Calcd for C64H52Cl2O18: C, 65.14; H, 4.44.
Found: C, 65.19; H, 4.52. Rf 0.51 (ethyl acetate/hexane 1:1). HRMS
(MALDI) m/z calcd for C64H52Cl2O18 ([M + Na]+) 1201.2423,
found 1201.2438.
Supporting Information Available: General experimental
1
methods, H and 13C NMR spectra of 1a, 1b, 1c, 1d, 1e, 1g, 1l,
1m, 2a-2k, 3a, 3b, 3c, 3c′, 3f, 3i, 7, 9a, 9b, 9c, and 9c′; ORTEP
representations and complete crystallographic data (CIF) of 2a and
3a; representative GPC result of a copolymer 5i. This material is
available free of charge via the Internet at http://pubs.acs.org.
(1′S,3′R)-2′,2′-Dichloro-3′-(2′′,3′′,4′′,6′′-tetra-O-benzoyl-R-D-
mannopyranosyl)oxycyclobutyl 2,3,4,6-Tetra-O-benzoyl-â-D-glu-
copyranoside (9c) and (1′R,3′S)-2′,2′-Dichloro-3′-(2′′,3′′,4′′,6′′-
JO0600510
J. Org. Chem, Vol. 71, No. 15, 2006 5467