Vinyl glycosides in oligosaccharide synthesis. 2. The use of allyl and vinyl glycosides in oligosaccharide synthesis

Article abstract of DOI:10.1021/jo960131b

A novel latent-active glycosylation strategy has been described that relies on the isomerization of substituted allyl glycosides to give the corresponding vinyl glycosides, which can subsequently be used in Lewis acid-mediated glycosylations. The isomerization reaction was performed by a rhodium catalyst obtained by treating tris(triphenylphosphine)rhodium(I) chloride with n-butyllithium. This catalyst has many advantageous properties over the use of conventional Wilkinson's catalyst. The glycosylation reactions gave high yields for both primary and secondary sugar alcohols, and the anomeric selectivity could be controlled by the constitution of the glycosyl donor and reaction conditions. The new isomerization and glycosylation approach enables complex oligosaccharides of biological importance to be prepared in a highly convergent manner.

Full text of DOI:10.1021/jo960131b

4262
J . Org. Chem. 1996, 61, 4262-4271
Vin yl Glycosid es in Oligosa cch a r id e Syn th esis. 2. Th e Use of Allyl
a n d Vin yl Glycosid es in Oligosa cch a r id e Syn th esis
Geert-J an Boons* and Stephen Isles
School of Chemistry, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, U.K.
Received J anuary 22, 1996X
A novel latent-active glycosylation strategy has been described that relies on the isomerization of
substituted allyl glycosides to give the corresponding vinyl glycosides, which can subsequently be
used in Lewis acid-mediated glycosylations. The isomerization reaction was performed by a rhodium
catalyst obtained by treating tris(triphenylphosphine)rhodium(I) chloride with n-butyllithium. This
catalyst has many advantageous properties over the use of conventional Wilkinson’s catalyst. The
glycosylation reactions gave high yields for both primary and secondary sugar alcohols, and the
anomeric selectivity could be controlled by the constitution of the glycosyl donor and reaction
conditions. The new isomerization and glycosylation approach enables complex oligosaccharides
of biological importance to be prepared in a highly convergent manner.
In tr od u ction
activator iodonium dicollidine perchlorate (IDCP), to give
a dimer. Next, the disarmed dimer can be further
glycosylated using the more powerful activating system
N-iodosuccinimide/catalytic triflic acid (NIS/TfOH) to
yield a trisaccharide. Thus, the difference in reactivity
between the two anomeric centers of the glycosyl donor
and acceptor is achieved through differential protection
of the 2-OH (ether/ester, armed/disarmed). Therefore,
the preparation of oligosaccharide donors by this ap-
proach is limited as only very few types of protecting
groups are available.5 A glycosylation strategy in which
the reactivity of the carbohydrate units is controlled only
by the anomeric group6 would not require differential
protection and, hence, would allow the synthesis of
oligosaccharide building blocks of any size.
It is now well established that, in the living cell,
carbohydrates play key roles in many different pro-
cesses.1 Examples include fertilization, embryogenesis,
neuronal development, hormone activities, and cell pro-
liferation and their organization into specific tissues. To
establish the biological roles of oligosaccharides, sufficient
amounts of pure and well-defined saccharides of different
sizes are often required. Organic synthesis provides an
important means of obtaining these fragments. The
preparation of complex oligosaccharide fragments re-
quires a highly convergent synthetic strategy.2 In such
a glycosylation strategy, most of the synthetic effort is
directed toward the preparation of the monomeric gly-
cosyl donors and acceptors. The assembly of these units
to an oligomer should involve a minimum number of
synthetic steps, and each reaction should proceed with
high stereoselectivity and yield. Furthermore, an ef-
ficient synthetic strategy should make optimal use of
common intermediates and saccharide building blocks.
The anomeric substituent of a saccharide building block
should be sufficiently stable to withstand protecting
group manipulations (i.e., acts as a protecting group) but
also have an adequate reactivity to permit its use as a
glycosyl donor (i.e., acts as a leaving group). Thioglyco-
sides3 and n-pentenyl glycosides4 have been shown to
possess these features. These substrates have also been
used in chemoselective glycosylations (the “armed-
disarmed” approach). In this approach, a C-2 ether-
protected donor (armed) is coupled with a C-2 ester
protected acceptor (disarmed), in the presence of the mild
Isopropenyl glycosides, which can be prepared by
reacting anomeric acetates with Tebbe reagent, undergo
glycosylation reactions with primary and secondary
carbohydrate alcohols in the presence of trimethylsilyl
triflate or boron trifluoride etherate.7 Since many func-
tional and protecting groups are sensitive toward Tebbe
reagent, this glycosylation method is not widely ap-
plicable.
We report here in full8 a novel latent-active glycosyl-
ation strategy based on the isomerization of 3-buten-2-
yl glycosides to give 2-buten-2-yl glycosides that, in turn,
can undergo Lewis acid-catalyzed glycosylations. In this
glycosylation strategy, the anomeric 3-buten-2-yl group
acts as an effective anomeric protecting group (latent)
but can be converted efficiently into a leaving group by
isomerization to a 2-buten-2-yl glycoside (active). The
latter glycosyl donor can be coupled to a suitably pro-
tected 3-buten-2-yl glycosyl acceptor (latent), and the
resulting dimer can be converted into a glycosyl donor
by isomerization of the 3-buten-2-yl moiety or into a
glycosyl acceptor by selective removal of a protecting
group. Thus, the reactivity of the carbohydrate units is
X Abstract published in Advance ACS Abstracts, J une 1, 1996.
(1) Varki, A. Glycobiology 1993, 397.
(2) For recent examples of elegant strategies for oligosaccharide
synthesis see: (a) Friesen, R. W.; Danishefsky, S. J . J . Am. Chem. Soc.
1989, 111, 6656. (b) Mehta, S.; Pinto, B. M. Tetrahedron Lett. 1991,
32, 4435. (c) Nicolaou, K. C.; Caulfield, T. J .; Croneberg, R. D. Pure
Appl. Chem. 1991, 63, 555. (d) Raghavan, S.; Kahne, D. J . Am. Chem.
Soc. 1993, 115, 1580. (e) Mehta, S.; Pinto, B. M. J . Org. Chem. 1993,
58, 3269. (f) Sliedrecht, L. A. J . M.; Zegelaar-J aarveld, K.; van der
Marel, G. A.; van Boom, J . H. Synlett 1993, 335. (g) Yamada, H.;
Harada, T.; Miyazaki, H.; Takahishi, T. Tetrahedron Lett. 1994, 35,
3979. (h) Kanie, O.; Ito, Y.; Ogawa, T. J . Am. Chem. Soc. 1994, 116,
12073. (i) Schmidt, R. R. Tetrahedron Lett. 1994, 35, 7927.
(3) (a) Veeneman, G. H.; van Boom, J . H. Tetrahedron Lett. 1990,
31, 275. (b) Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J . H.
Tetrahedron Lett. 1990, 31, 1331.
(5) Recently, thioglycosides with novel reactivities have been re-
ported: (a) Boons, G. J .; Grice, P.; Ley, S. V.; Yeung, L. L. Tetrahedron
Lett. 1993, 34, 8523. (b) Boons, G. J .; Geurtsen, R.; Holmes, D.
Tetrahedron Lett. 1995, 36, 6325.
(6) Roy, R.; Anderson, F. O.; Telellier, M. Tetrahedron Lett. 1992,
33, 6053.
(7) Marra, A.; Esnault, J .; Veyrieres, A.; Sinay¨, P. J . Am. Chem.
Soc. 1992, 114, 6354.
(8) Boons, G. J .; Isles, S. Tetrahedron Lett. 1994, 35, 3593.
(4) Fraser Reid, B.; Udodong, U. E.; Wu, Z.; Ottoson, H.; Merritt, J .
R.; Rao, S.; Roberts, C.; Madsen, R. Synlett 1992, 12, 927.
S0022-3263(96)00131-4 CCC: $12.00 © 1996 American Chemical Society

Vinyl Glycosides in Oligosaccharide Synthesis
J . Org. Chem., Vol. 61, No. 13, 1996 4263
Sch em e 1
controlled only by the anomeric group and does not
require differential protection. The isomerization reac-
tions have been performed by a new isomerization
procedure9 involving the treatment of tris(triphenylphos-
phine)rhodium(I) chloride with n-butyllithium. This
rhodium catalyst is able to isomerize a wide range of
substituted and unsubstituted allylic ethers and glyco-
sides and has many advantageous properties over the use
of conventional Wilkinson’s catalyst.10 The new isomer-
ization procedure also allows the isomerization and
glycosylation to be performed as a one-pot procedure.
vinyl moiety. Many metal catalysts have been applied
successfully for the conversion of unsubstituted allyl
ethers into propenyl ethers. However, isomerization of
the substituted allyl moiety of 8 proved to be more
difficult, and the application of commonly used catalysts
such as dihydrotetrakis(triphenylphosphine)ruthenium-
(II),12 10% palladium on active charcoal,13 and trans-
dichlorodiaminepalladium(II)14 failed to perform the
required isomerization. However, treatment of 8 with
Wilkinson’s catalyst10 in the presence of diazabicyclo-
[2.2.2]octane (DABCO) in a refluxing mixture of methanol/
water gave the substituted vinyl glycoside 9 as a mixture
of cis and trans isomers in a 71% yield. Minor amounts
of hydrolyzed and reduced products were observed.
Having vinyl glycosyl donor 9 in hand, we turned our
attention to Lewis acid-promoted glycosylations (Scheme
1). Thus, coupling of acceptor 7 with active donor 9 in
the presence of a catalytic amount of TMSOTf (0.25
equiv) at -25 °C in acetonitrile gave, after a reaction time
of 1.5 h, mainly the â-linked dimer 10 in an excellent
yield (78%, R/â 1/20). When the same glycosylation was
performed in dichloromethane, a mixture of anomers
(72%, R/â 4/3) was obtained. The R-selectivity could be
improved (74%, R/â 4/1) by using NIS/TfOH as the
activator in a mixture of ether/dichloroethane at 0 °C,
and under these conditions the glycosylation was almost
instantaneous. Dimer 10 could be converted into glycosyl
donor 11 by isomerization of its allyl group to a vinyl
moiety (latent f active).
Resu lts a n d Discu ssion
The substituted allyl glycoside 3 was readily prepared
by coupling acetoxy bromide 1 with 3-buten-2-ol (2) under
modified Koenigs-Knorr conditions.11 Compound 3 can
undergo many different functional and protecting group
manipulations. For example, glycosyl acceptor 7 was
readily available from compound 3 via a four-step
procedure. Thus, deacetylation of compound 3 with
sodium methoxide in methanol gave compound 4, and
regioselective silylation of this product with TBDMSCl
in pyridine yielded compound 5 which was benzylated
with benzyl bromide and sodium hydride in DMF to
afford the fully protected compound 6. The TBDMS
protecting group of compound 6 was removed by treat-
ment with a mixture of acetic acid/water to yield glycosyl
acceptor 7. Benzylation of compound 4 with benzyl
bromide and sodium hydride in DMF gave the fully
benzylated glycoside 8.
Previously Sinay¨ et al. reported the use of isopropenyl
glycosides as glycosyl donors, and it is of interest to note
that the activation of these compounds requires stoichio-
metric amounts of Lewis acid.7 The higher reactivity of
the substituted vinyl glycoside 9 can be explained as
In order to prepare glycosyl donor 9, the allyl group of
the latent compound 8 has to be isomerized to an active
(9) Boons, G. J .; Burton, A.; Isles, S. J . Chem. Soc., Chem Commun.
1996, 141.
(10) Corey, E. J .; Suggs, W. J . J . Org. Chem. 1973, 38, 3224.
(11) For reviews on oligosaccharide synthesis including the Koenigs-
Knorr approach see: (a) Paulsen, H. Angew. Chem., Int. Ed. Engl.
1982, 21, 155. (b) Schmidt, R. R. Angew. Chem., Int. Ed. Engl. 1986,
25, 212. (c) Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503. (d)
Boons, G. J . Tetrahedron 1996, 52, 1095.
(12) Nicolaou, K. C.; Caulfield, T. J .; Kataoka, H.; Styliandes, N. A.
J . Am. Chem. Soc. 1990, 112, 3693.
(13) Boss, R.; Scheffold, R. Angew. Chem., Int. Ed. Engl. 1976, 15,
558.
(14) Beig, T.; Szeja, W.; Windmu¨ller, R.; Schmidt, R. R. Tetrahedron
Lett. 1985, 4, 441.

4264 J . Org. Chem., Vol. 61, No. 13, 1996
Boons and Isles
Sch em e 2
follows: protonation of the double bond is the rate-
determining step in the activation of a vinyl glycoside,15
and the additional methyl substituent of the vinyl moiety
of 9 makes the double bond more electron rich and hence
more susceptible to protonation and glycosylation. Fur-
thermore, these results indicate that vinyl glycosyl donor
9 is less prone to form trehaloses than the corresponding
isopropenyl glycoside.7
Racemic 3-buten-2-ol was used for the preparation of
3, resulting in the formation of a mixture of diastereo-
isomers. While the diastereoisomeric nature of the
glycoside does not affect the chemistry, it complicates the
interpretation of the NMR spectra. Multigram quantities
of optically pure 3-buten-2-ol can, however, easily be
obtained by resolving the corresponding acid phthalate
as the (S)- or (R)-R-phenylethylamine salt.16
The isomerization reaction that the novel latent-active
strategy relies upon initially could only be achieved by
the use of Wilkinson’s catalyst. A drawback of this
catalyst is that it partly reduces an allyl ether into a
propyl ether.17 Furthermore, the mild base, DABCO, has
to be included to avoid hydrolysis of the enol ether since
the ketone produced will poison the catalyst. Prior to
glycosylation, the DABCO has to be removed by basic
alumina column chromatography. These factors account
for the relatively low yield of the isomerization. The
drawbacks associated with the use of this catalyst led
us to search for an alternative isomerization procedure.
Motherwell et al. have shown18 that in the presence of
Wilkinson’s catalyst a wide range of allylic alkoxides in
THF can be isomerized to enolates which may undergo
in situ aldol condensations with ketones. Wilkinson’s
catalyst in THF, however, is unable to isomerize allylic
alcohols.19 Therefore, we expected that under the applied
reaction conditions the rhodium catalyst was being
converted into another more reactive catalytic species.
Indeed, treatment of Wilkinson’s catalyst (5-10 mol %)
in freshly distilled THF with n-BuLi, for 10 min, gave a
deep red solution which isomerizes compound 8 smoothly
to give, after flash silica gel column chromatography,
pure 9 as a mixture of cis-trans isomers in an excellent
yield of 92%. The unpurified enol ether could also be
cleaved by treatment with HgCl2/HgO in acetone to give
the corresponding lactol in high yield (93%). It is
important to note that n-BuLi alone failed to promote a
reaction, proving that the isomerization is not catalyzed
by the base. In order to find out whether reduction of
the allyl ether to a propyl ether could occur, the allyl
glycoside 8 was subjected to the reaction conditions
((Ph3P)3RhCl/BuLi in refluxing THF) for a prolonged
period of time (16 h). 1H NMR spectroscopy and FAB-
mass spectroscopy of the product thus obtained did not
reveal the presence of any reduced material, and the
isomerized compound was isolated in high yield.
hydrido tris[triphenylphosphine]rhodium(I).20 This rhod-
ium species has been described,21 and we have prepared
(Ph3P)3RhH by a published procedure. The catalyst thus
obtained was also able to isomerize allyl ethers and
glycosides at similar reaction rates as for the procedure
described above, and the products were isolated in similar
yields.
Recently, one-pot multistep reactions have received
considerable attention.22 This type of synthetic procedure
minimizes tedious workup and purification steps and
often gives better overall yields. We envisaged that the
new isomerization conditions could allow the isomeriza-
tion and glycosylation to be performed as a one-pot
procedure. Thus, after isomerization of the allyl moiety
of compound 8, glycosyl acceptor 7 in acetonitrile was
added to the mixture, the reaction mixture was cooled
to -25 °C, and a promotor was added. Unfortunately,
TMSOTf or BF3‚OEt2 was unable to promote the glyco-
sylation. It appeared that the rhodium catalyst had, in
some way, reacted with the Lewis acid, resulting in the
slow hydrolysis of the donor. However, when, prior to
glycosylation, the Rh-catalyst was exposed to O2, BF3‚OEt2-
promoted glycosylation gave clean formation of disac-
charide 10 in high overall yield (71%, R/â 1/20).
Encouraged by the promising results obtained, we
explored glycosylations with the less reactive glycosyl
acceptor 14 (Scheme 2). Compound 14 could easily be
obtained from compound 4 via a three-step procedure.
Thus, treatment of 4 with benzaldehyde dimethyl acetal
and a catalytic amount of camphorsulfonic acid gave
regioselectively the partially protected saccharide 12.
Benzylation of compound 12 under standard conditions
afforded the fully protected species 13 and reductive
cleavage of the benzylidene acetal with sodium cy-
anoborohydride, and hydrogen chloride yielded the re-
quired glycosyl acceptor 14. Also, a minor amount of the
other regioisomer (6-OH) was isolated. Acceptor 14 was
also the starting material for compound 16, Thus, the
latent substrate 15 was obtained by acetylation with
acetic anhydride and pyridine, and glycosyl donor 16
We believe that under the applied reaction conditions
the chloride of the Wilkinson’s catalyst is substituted by
a butyl group which undergoes a â-hydride shift to give
(15) Chenault, H. K.; Chafin, F. C. J . Org. Chem. 1994, 59, 6167.
(16) Grattan, T. J .; Whitehurst, J . S. J . Chem. Soc., Perkin Trans.
1 1990, 11.
(17) (a) Warren, C. D.; J eanloz, R. W. Carbohydr. Res. 1977, 53, 67.
(b) Nashigushi, T.; Tachi, T.; Fukuzumi, K. J . Org. Chem. 1975, 40,
237. (c) van Boeckel, C. A. A.; van Boom, J . H. Tetrahedron Lett. 1979,
3561.
(18) Motherwell, W. B.; Powell, M. J . Chem. Soc., Chem. Commun.
1991, 1399.
(19) Unpublished results from this laboratory.
(20) Dewhirst, D. K. C.; Keim, W.; Reilly, C. A. Inorg. Chem. 1968,
7, 546.
(21) Strauss, S. H.; Diamond, S. E.; Mares, F.; Shriver, D. F. Inorg.
Chem. 1978, 17, 3064.
(22) (a) Raghavan, S.; Kahne, D. J . Am. Chem. Soc. 1993, 115 1580.
(b) Ley, S. V.; Priepke, H. W. M. Angew. Chem., Int. Ed. Engl. 1994,
33, 2292. (c) Yamada, H.; Harada, T.; Miyazaki, H.; Takahashi, T.
Tetrahedron Lett. 1994, 35, 3979. (d) Yamada, H.; Harada, T.;
Takahashi, T. J . Am. Chem. Soc. 1994, 116, 7919.

Vinyl Glycosides in Oligosaccharide Synthesis
J . Org. Chem., Vol. 61, No. 13, 1996 4265
Sch em e 3
Sch em e 4
could be prepared by isomerization of the allyl moiety
with (Ph3P)3RhCl/n-BuLi. This example illustrates that
base labile functionalities are compatible with the new
isomerization conditions. TMSOTf-promoted condensa-
tion of 16 with 14 in acetonitrile for 1.5 h gave disac-
charide 17 in a 78% yield as mainly the â-anomer (R/â )
1/8). When the same glycosylation reaction was per-
formed in dichloromethane, dimer 17 was isolated in
excellent yield (75%), but the R/â ratio was rather
disappointing (R/â ) 1.5/1). The use of ether as solvent
or BF3‚Et2O as activator had no observable effect on the
product ratio. However, an improved R-selectivity was
obtained (73%, R/â ) 3/1) when the coupling was per-
formed in ether/dichloroethane at 0 °C with NIS/TfOH
as activator.
favorable â-selectivities when the glycosylation is per-
formed in acetonitrile. This behavior has been reported
by others23 and may be due to a steric or electronic
influence of the axial oriented benzyl group at C-4 of the
galactoside. Furthermore, coupling with primary sugar
alcohols gives under these reaction conditions better
â-selectivities.
In order to study galactosylation reactions, the vinyl
galactoside 22 was prepared (Scheme 3). Thus, conden-
sation of acetoxy bromide 18 with alcohol 2 under
Koenigs-Knorr conditions gave glycoside 19. Treatment
of glycoside 19 with KOtBu in methanol gave compound
20, and benzylation of this compound afforded the fully
protected latent substrate 21. Isomerization of the allyl
moiety of compound 21 with Wilkinson’s catalyst treated
with n-BuLi gave the glycosyl donor 22 in a good overall
yield. Treatment of a mixture of acceptor 7 and donor
22 with a catalytic amount of TMSOTf in acetonitrile at
-25 °C afforded the dimer 23 in high yield with modest
â-selectivity (79%, R/â ) 1/3). A reasonable R-selectivity
(75%, R/â ) 4/1) was obtained when the same coupling
was performed in dichloromethane. In this case, the use
of NIS/TfOH as activator did not improve the R/â ratio.
TfOH-mediated coupling of the less reactive alcohol 14
with galactoside 22 in acetonitrile or dichloromethane
gave in both cases dimer 24 in high yield but with modest
â (68%, R/â ) 1/1.5) and reasonable R-selectivity (66%,
R/â ) 4/1), respectively.
The diastereochemical outcome of the previously dis-
cussed glycosylations has been controlled by the choice
of solvent and, to some extent, the choice of activator.
Another approach to control the R/â ratio of a glycosyla-
tion reaction which leads to the formation of 1,2-trans
glycosides is based on neighboring group participation
by a 2-hydroxyl protecting group. It is to be expected
that a vinyl glycoside having a neighboring participating
protecting group at the 2-hydroxyl position can easily be
obtained by isomerization of the corresponding substi-
tuted allyl glycoside. We have prepared the vinyl glu-
coside 29 which could be coupled to the glycosyl acceptors
7 and 28 (Scheme 4). Thus, treatment of the acetoxy
bromide 1 with alcohol 2 in the presence of collidine and
tert-butyl ammonium bromide gave orthoester 25 in an
excellent yield. Orthoester 25 was converted into the
benzylated compound 26 by deacetylation followed by
benzylation. Rearrangement of compound 26 with a
catalytic amount of TMSOTf in dichloromethane at -20
°C resulted in the almost quantitative formation of
Examination of glycosylations of vinyl gluco- and
galactosyl donors reveals that the glucosides give more
(23) Weggmann, B.; Schmidt, R. R. J . Carbohydr. Chem. 1987, 6,
357.

4266 J . Org. Chem., Vol. 61, No. 13, 1996
Boons and Isles
0.09). The reaction mixture was neutralized with Dowex 50
WX4 (H+) (60 mL), filtered, and concentrated in vacuo. After
coevaporation from toluene (3 × 5 mL), compound 4 was
obtained as hygroscopic white crystals (4.36 g, 90%): δ1H (300
MHz; D2O) 5.95-5.60 (1H, m, CH)CH2), 5.30-5.12 (2H, m,
compound 27. Base-mediated removal of the acetate
protecting group of compound 27 gave glycosyl acceptor
28. The latent glycoside 27 could be converted cleanly
into active glycosyl donor 29 by isomerization with the
new catalytic system. Treatment of a mixture of donor
29 and acceptor 7 with a catalytic amount of TMSOTf in
acetonitrile at 0 °C gave, as expected, pure â-linked dimer
30 in a good yield (71%). Compound 28 is a suitable
glycosyl acceptor and was also condensed under standard
coupling conditions with donor 29 to give dimer 31 in a
yield of 72%. The dimers 30 and 31 can be converted
into glycosyl donors by isomerization of the allyl moiety.
In conclusion, we have described a new latent-active
glycosylation strategy that allows glycosyl donors and
acceptors to be prepared from common building blocks.
The anomeric allyl moiety of such a building block can
act as an effective anomeric protecting group but can
easily be converted into a leaving group. These features
allow oligosaccharides to be prepared by an convergent
strategy. Furthermore, we have shown that treatment
of Wilkinson’s catalyst with n-BuLi results in a more
efficient isomerization catalyst.
3
CH)CH2), 4.50 (1H, 2 × d, J 1,2 ) 8 Hz, H-1), 4.30 (1H, m,
CH3CH), 3.82 (1H, m, H-3), 3.63 (1H, m, H-4), 3.45-3.25 (3H,
3
m, H-2, H-6(a,b)), 3.21 (1H, m, H-5), 1.23 (3H, d, J ) 2.9 Hz,
CH3); δ13C (75 MHz; D2O) 142.3, 141.2 (CH)CH2), 120.7, 118.9
(CH)CH2), 103.2, 102.0 (C-1), 80.2, 78.7, 76.1, 76.0, 72.6 (C-
2, C-3, C-4, C-5, CHCH3), 63.7 (C-6), 23.5, 22.1 (CHCH3); m/ z
234 (17, [M]+), 257 (13, [M + Na]+), C10H18O6Na requires
257.1001, found 257.1006.
(R/S)-3-Bu t en -2-yl 6-O-(ter t-Bu t yld im et h ylsilyl)-â-D-
glu cop yr a n osid e (5). tert-Butyldimethylsilyl chloride (2.63
g, 17 mmol) was added to a solution of 4 (3.37 g, 14 mmol) in
pyridine (75 mL), and the mixture was stirred at room
temperature for 18 h. TLC analysis (methanol/CH2Cl2, 1/4,
v/v) showed conversion of 4 (Rf 0.09) into a product (Rf 0.43).
Water (50 mL) was added, and the mixture was stirred for 1
h. Then, the solution was diluted with CH2Cl2 (125 mL), and
the organic phase was extracted with an aqueous NaHCO3
solution (3 × 60 mL) and brine (3 × 60 mL). The combined
organic phases were dried (MgSO4) and filtered, and the
filtrate was concentrated under reduced pressure to afford 5
(3.34 g, 66%) as an oil: δ1H (300 MHz; CDCl3) 5.95-5.60 (1H,
m, CH)CH2), 5.30-5.01 (2H, m, CH)CH2), 4.29 (2H, m, H-1,
CH-CH3), 3.88-3.71 (2H, m, H-6(a,b)), 3.42 (1H, m, H-3), 3.31
(2H, m, H-2, H-4), 3.23 (1H, m, H-5), 1.22 (3H, 2 × d, 3J ) 2.9
Hz, CHCH3), 0.91 (9H, s, C(CH3)3), 0.08 (6H, m, (Si(CH3)2);
δ13C (75 MHz; CDCl3) 140.1, 139.0 (CH)CH2), 117.1, 114.9
(CH)CH2), 100.6, 99.2 (C-1), 76.6, 76.5 (CHCH3), 75.3, 75.2
(C-2), 74.8, 73.3, 71.8 (C-3, C-4, C-5), 62.4 (C-6), 25.8 (C(CH3)3),
21.6, 20.0 (CHCH3), 18.3 (C(CH3)3), -5.2, -5.3 (Si(CH3)2).
(R/S)-3-Bu ten -2-yl 2,3,4-Tr i-O-ben zyl-6-O-(ter t-bu tyld i-
m eth ylsilyl)-â-D-glu cop yr a n osid e (6). Tetra-n-butylam-
monium iodide (0.83 g, 2.2 mmol) and sodium hydride (80%
dispersion in oil, 2.5 g, 83 mmol) were added to a cooled (0 °C)
and vented solution of 5 (2.51 g, 72 mmol) in N,N-dimethyl-
formamide (60 mL). Benzyl bromide (7.17 g, 5 mL, 41 mmol)
was added dropwise (30 min) to the suspension. The reaction
mixture was stirred for 3 h, and then TLC analysis (acetone/
CH2Cl2, 2/96, v/v) showed complete conversion of 5 (Rf 0.2) into
a product (Rf 0.9). After the reaction was quenched with
methanol (30 mL), the mixture was poured into brine (100 mL)
and extracted with ether (4 × 75 mL). The combined organic
extracts were washed with water (3 × 40 mL), and the aqueous
layers were washed with ether (2 × 10 mL). The combined
ether extracts were dried (MgSO4) and filtered, and the filtrate
was concentrated under reduced pressure to give a yellow oil
that was purified on a column of silica gel (150 g, eluant:
acetone/CH2Cl2, 3/97, v/v). Concentration of the appropriate
fractions afforded 6 (3.49 g, 78%): δ1H (300 MHz; CDCl3) 7.46-
7.22 (15H, m, Ar CH), 6.00-5.68 (1H, m, (CH)CH2), 5.29-
5.04 (2H, m, CH)CH2), 5.01-4.62 (6H, m, 3 × Ar CH2), 4.46
Exp er im en ta l Section
Gen er a l Meth od s a n d Ma ter ia ls. All solvents were
distilled prior to use from an appropriate drying agent.
Toluene, CH2Cl2, and CHCl3 were distilled from P2O5. DMF
and CH3CN were distilled from CaH2. THF and diethyl ether
were distilled from LiAlH4. Column chromatography was
carried out on silica gel (Merck 7734). Flash silica ES70X was
obtained from Crosfield Catalysts, Warrington. TLC analysis
was conducted on silica gel plates (Merck 1.05554 Kieselgel
60 F254). Compounds were visualized by UV light (254 nm)
or by dipping with concentrated H2SO4/methanol 1/10, v/v) and
subsequent charring. (()-3-Buten-2-ol was purchased from
Fluka. (Trimethylsilyl)trifluoromethanesulfonate (TMSOTf)
was purchased from Lancaster, and all other reagents were
purchased from Aldrich and used without further purification.
Aqueous NaCl (saturated) and NaHCO3 (10% w/v) were
prepared in advance. Sephadex LH-20 (Pharmacia) was used
for gel filtration chromatography.
(R/S)-3-Bu ten -2-yl 2,3,4,6-Tetr a -O-a cetyl-â-D-glu cop y-
r a n osid e (3). A solution of bromide 1 (30.5 g, 74 mmol) and
(()-3-buten-2-ol (2) (30 mL, 340 mmol) in acetonitrile (35 mL)
was added to a stirred suspension of mercury(II) cyanide (23.1
g, 91 mmol), mercury(II) bromide (34.1 g, 94 mmol), and
powdered 4 Å molecular sieves (30 g) in acetonitrile (60 mL).
After the reaction mixture was stirred for 12 h, TLC analysis
(acetone/CH2Cl2, 2/98, v/v) showed complete conversion of
starting material (Rf 0.53) into a product (Rf 0.64). The
reaction mixture was filtered, and the filtrate was concentrated
under reduced pressure to yield an oil which was dissolved in
CH2Cl2 (100 mL) and washed with NaHCO3 (3 × 60 mL) and
aqueous NaCl (3 × 60 mL). The organic phase was dried
(MgSO4) and concentrated under reduced pressure to give an
orange crystalline residue. This crude product was applied
to a column of silica gel (300 g, eluant: acetone/CH2Cl2, 3/97,
v/v), and concentration of the appropriate fractions afforded 3
(20.8 g, 70%). δ1H (300 MHz; CDCl3) 5.85-5.60 (1H, m,
CH)CH2), 5.20-4.93 (5H, m, CH)CH2, H-2, H-3, H-4), 4.54
(1H, d, 3J 1,2 ) 8 Hz, H-1), 4.30-4.04 (3H, m, CH3CH, H-6(a,b)),
3.64 (1H, m, H-5), 2.10-1.93 (12H, m, Ac CH3), 1.23 (3H, q,
3J ) 7 Hz, CHCH3); δ13C (75 MHz; CDCl3) 170.6-169.2 (Ac
CdO), 139.6, 138.6 (CH)CH2), 117.0, 115.3 (CH2)CH), 99.3,
97.9 (C-1), 77.6, 75.7, 72.9, 68.5 (C-2, C-3, C-4, C-5), 71.9, 71.5
(CHCH3), 62.1 (C-6), 20.7 (CHCH3), 20.5 (Ac CH3); m/ z 425
(100, [M + Na]+), 331 (43, [M - O-3-buten-2-yl]+).
3
(1H, d, J 1,2 ) 8 Hz, H-1), 4.33 (1H, m, CH3CH), 3.82 (2H, m,
H-6(a,b)), 3.61 (2H, m, H-3, H-4), 3.43 (1H, t, 3J 1,2 ) 8 Hz, 3J 2,3
3
) 8 Hz, H-2), 3.24 (1H, m, H-5), 1.32 (3H, 2 × d, J ) 4 Hz,
CHCH3), 0.91 (9H, 2 × s, C(CH3)3), 0.08 (6H, m, (Si(CH3)2);
δ13C (75 MHz; CDCl3) 140.5, 139.3 (CH)CH2), 138.6-138.1
(Ar C quaternary), 128.6-127.6 (Ar CH), 116.7, 114.5 (CH)
CH2), 101.8, 100.3 (C-1), 84.9, 82.6, 75.0 (C-3, C-4, C-5), 77.8,
77.7 (C-2), 76.3, 75.8 (CHCH3), 75.7, 74.9, 72.2 (Ar CH2), 62.4
(C-6), 25.9 (C(CH3)3), 21.6, 20.0 (CHCH3), 18.3 (SiC(CH3)2),
-5.2, -5.3 (Si(CH3)2); m/ z 641 (40, [M + Na]+), 617 (8, [M -
H]+), 439 (100, [M - OBn - 3-buten-2-yl]+), C37H50O6NaSi
requires 641.3274, found 641.3284.
(R/S)-3-Bu ten -2-yl 2,3,4-Tr i-O-ben zyl-â-D-glu cop yr a n o-
sid e (7). Compound 6 (1.42 g, 2.3 mmol) was dissolved in a
mixture of acetic acid/water (4/1, v/v, 50 mL), and the solution
was stirred at 50 °C for 8 h. TLC analysis (acetone/CH2Cl2,
1/24, v/v) showed complete conversion of the starting material
(Rf 0.70) into a product (Rf 0.36). The reaction mixture was
concentrated under reduced pressure, and the resulting oil was
coevaporated from toluene (5 × 10 mL). The crude product
was purified on a short column of silica gel (30 g, eluant:
(R/S)-3-Bu ten -2-yl â-D-Glu cop yr a n osid e (4). Potassium
tert-butoxide (3.0 g) was added to a stirred solution of 3 (8.34
g, 20 mmol) in methanol (100 mL). After a reaction time of 5
h, TLC analysis (acetone/CH2Cl2, 1/49, v/v) showed complete
conversion of the starting material (Rf 0.64) into a product (Rf

Vinyl Glycosides in Oligosaccharide Synthesis
J . Org. Chem., Vol. 61, No. 13, 1996 4267
acetone/CH2Cl2, 1/24, v/v) to afford 7 (1.04 g, 91%): δ1H (300
MHz; CDCl3) 7.38-7.22 (15H, m, Ar CH), 5.95-5.60 (1H, m,
CH)CH2), 5.29-5.07 (2H, m, CH)CH2), 4.83-4.52 (6H, m, 3
quaternary), 128.2-127.1 (Ar CH), 105.1, 100.5 (CHCH3),
100.5, 100.2 (C-1), 84.9, 82.0, 80.9, 77.9 (C-2, C-3, C-4, C-5),
75.0, 74.9, 73.5 (Ar CH2), 69.6 (C-6), 18.7, 15.7 (CH3), 12.0,
10.5 (CHCH3); m/ z 617 (100, [M + Na]+), 593 (7, [M - H]+),
523 (12, [M - O-2-buten-2-yl]+), 415 (19, [M - H - O-Bn -
O-2-buten-2-yl]+), 271 (70, [M - H - 3-O-Bn]+), 253 (17, [M -
H - 2-O-Bn - O-2-buten-2-yl]+), C38H42O6Na requires 617.2879,
found 617.2895.
(R/S)-3-Bu ten -2-yl 2,3,4-Tr i-O-ben zyl-6-O-(2,3,4,6-tetr a -
O-ben zyl-r/â-D-glu copyr an osyl)-â-D-glu copyr an oside (10).
Meth od A. A suspension of 9 (285 mg, 0.48 mmol), 7 (200
mg, 0.40 mmol), and powdered 4 Å molecular sieves (450 mg)
in acetonitrile (5 mL) was stirred for 30 min. The mixture
was cooled (-25 °C), and TMSOTf (20 µL, 0.10 mmol) was
added. After 90 min, TLC analysis (acetone/CH2Cl2, 3/97, v/v)
showed conversion of the starting materials into a product (Rf
0.41). The reaction mixture was neutralized with triethyl-
amine (50 µL) diluted with CH2Cl2 (25 mL), and filtered
through Celite. The filtrate was concentrated under reduced
pressure to afford a solid residue. This residue was purified
on a column of Sephadex LH-20 (100 g, eluant: methanol/
CH2Cl2, 1/1 v/v) affording 10 (320 mg, 78%) as a 1:20 ratio of
10R and 10â.
3
× Ar CH2), 4.53 (1H, 2 × d, J 1,2 ) 8 Hz, H-1), 4.32 (1H, m,
CH3CH), 3.81 (1H, m, H-4), 3.65-3.40 (3H, m, H-3, H-6(a,b)),
3.22 (1H, m, H-5), 1.96 (1H, bs, OH), 1.34 (3H, 2 × d, 3J ) 3.5
Hz, CHCH3); δ13C (75 MHz; CDCl3) 140.8, 139.6 (CH)CH2),
138.6-138.1 (Ar C quaternary), 128.6-127.6 (Ar CH), 117.1,
114.9 (CH)CH2), 104.2, 102.3 (C-1), 82.4, 82.3 (C-2), 84.7, 82.3,
77.7 (C-3, C-4, C-5), 75.5, 75.1 (CHCH3), 75.7, 75.0, 74.9 (3 ×
Ar CH2), 62.3 (C-6), 21.9, 20.8 (CHCH3); m/ z 527 (32, [M +
Na]+), 433 (5, [M - O-3-buten-2-yl]+), 181 (100, [M - 3-OBn]+),
C31H36O6Na requires 527.2409, found 527.2393.
(R/S)-3-Bu ten -2-yl 2,3,4,6-Tetr a -O-ben zyl-â-D-glu cop y-
r a n osid e (8). Sodium hydride (80% dispersion in oil, 2.5 g,
83 mmol) was added to a cooled (0 °C) and vented solution of
4 (3.12 g, 13 mmol) in N,N-dimethylformamide (60 mL).
Benzyl bromide (10 mL, 84 mmol) was added dropwise (30
min) to the suspension. The reaction mixture was stirred for
12 h, and then TLC analysis (acetone/CH2Cl2, 1/99, v/v) showed
complete conversion of 4 (Rf 0.05) into a product (Rf 0.47). The
reaction was quenched by the addition of methanol (30 mL),
and the resulting mixture was concentrated under reduced
pressure to yield a solid. The solid was dissolved in ether (100
mL) and washed with water (3 × 40 mL), and the combined
water layers were washed with ether (2 × 10 mL). The
combined ether extracts were dried (MgSO4) and filtered, and
the filtrate was concentrated under reduced pressure to give
a crude product that was purified on a column of silica gel
(150 g, eluant: acetone/CH2Cl2, 1/99, v/v) to afford 8 (6.51 g,
82 %): δ1H (400 MHz; CDCl3), 7.40-7.22 (20H, m, Ar CH),
5.99-5.72 (1H, m, CH)CH2), 5.25-5.07 (2H, m, CH)CH2),
4.98-4.51 (6H, m, Ar CH2), 4.49 (1H, 2 × d, 3J 1,2 ) 8 Hz, H-1),
4.30 (1H, m, CHCH3), 3.70-3.41 (6H, m, H-6(a,b), H-2, H-3,
H-4, H-5), 1.30 (3H, 2 × d, 3J ) 4 Hz, CHCH3); δ13C (75 MHz;
CDCl3) 140.5, 139.2 (CH)CH2), 138.6-138.2 (Ar C quater-
nary), 128.3-127.5 (Ar CH), 117.0, 114.8 (CH)CH2), 101.9,
100.5 (C-1), 85.0, 78.0, 74.8 (C-3, C-4, C-5), 82.5, 82.4 (C-2),
76.9, 75.3 (CHCH3), 75.7, 74.9, 73.4 (Ar CH2), 69.1 (C-6), 21.9,
20.4 (CHCH3); m/ z 593 (11, [M - H]+), 523 (4, [M - O-3-buten-
2-yl]+), 415 (17, [M - H-OBn-O-3-buten-2-yl]+), 271 (70, [M -
H - 3-OBn]+), 253 (100, [M - H - 2-OBn - O-3-buten-2-yl]+),
C38H42O6Na requires 617.2879, found 617.2881.
Meth od B. When the reaction was performed in CH2Cl2 a
4:3 ratio of 10R and 10â (72%) was recovered.
Meth od C. A suspension of 9 (285 mg, 0.48 mmol), 7 (200
mg, 0.40 mmol), and powdered 4 Å molecular sieves (450 mg)
in dichloroethane/ether (1/1 v/v, 4 mL) was stirred for 30 min
under N2. The mixture was cooled (0 °C), and a solution of
NIS (40 mg, 0.18 mmol) and TfOH (3.3 µL, 11 µmol) in DCM/
diethyl ether (1/1, v/v, 1.8 mL) was added. After 1 min, TLC
analysis (acetone/CH2Cl2, 3/97, v/v) showed conversion of the
starting materials into a product (Rf 0.41). The reaction
mixture was neutralized with triethylamine (15 µL), diluted
with CH2Cl2 (25 mL), and filtered through Celite. The filtrate
was concentrated under reduced pressure to afford a solid
residue. This residue was purified on a column of Sephadex
LH-20 (100 g, eluant: methanol/CH2Cl2, 1/1 v/v), affording 10
(300 mg, 74%) as a 4:1 ratio of 10R and 10â.
Met h od D. n-Butyllithium (1.6 M in hexane, 28 µL, 45
µmol) was added to a stirred, degassed solution of Wilkinson’s
catalyst (30 mg, 33 µmol) in THF (1.5 mL). The resulting red
solution was stirred at 20 °C for 5 min and then transferred
via cannula into a refluxing solution of 8 (200 mg, 0.33 mmol)
in THF (1 mL). After the reaction mixture was heated under
reflux for 5 min, the mixture was cooled to room temperature
and placed under an atmosphere of O2, and stirring was
continued for 30 min. The resulting mixture was added by
cannula to a suspension of 7 (150 mg, 0.30 mmol) and
powdered 4 Å molecular sieves (350 mg) in acetonitrile (5 mL)
After being stirred for 30 min, the mixture was cooled (-25
°C), and BF3‚OEt2 (0.15 mmol) was added dropwise. After 90
min, TLC analysis (acetone/CH2Cl2, 3/97, v/v) showed conver-
sion of the starting materials into a product (Rf 0.41). The
reaction mixture was neutralized with triethylamine (50 µL),
diluted with CH2Cl2 (25 mL), and filtered through Celite. The
filtrate was concentrated under reduced pressure to afford a
solid residue. This residue was purified on a column of
Sephadex LH-20 (100 g, eluant: methanol/CH2Cl2, 1/1 v/v),
affording 10 (218 mg, 71%) as a 1:20 ratio of 10R and 10â.
10r: δ1H (400 MHz; CDCl3) 7.36-7.20 (35H, m, Ar CH),
5.99-5.72 (1H, m, CH)CH2), 5.21-5.00 (2H, m, CH)CH2),
2-Bu ten -2-yl 2,3,4,6-Tetr a -O-ben zyl-â-D-glu cop yr a n o-
sid e (9). Meth od A. Compound 8 (1.01 g, 1.7 mmol), 1,4-
diazabicyclo[2.2.2]octane (0.4 g, 3.5 mmol), and Wilkinson’s
catalyst ([(C6H5)3P]3RhCl) (50 mg, 0.05 mmol) in a methanol/
water (9/1, v/v, 7 mL) mixture was refluxed for 2 h. TLC
analysis (acetone/CH2Cl2, 1/49, v/v) showed mainly the forma-
tion of 9 (Rf 0.74). The mixture was diluted with CH2Cl2 (15
mL), and the aqueous phase was extracted with CH2Cl2 (2 ×
1 mL). The combined organic extracts were dried (MgSO4),
filtered, and concentrated under reduced pressure to yield an
orange crystalline residue. This residue was purified on a
basic alumina column (50 g, eluant: CH2Cl2), and concentra-
tion of the appropriate fractions afforded 9 (720 mg, 71%).
Meth od B. n-Butyllithium (1.6 M in hexane, 28 µL, 45
µmol) was added to a stirred, orange solution of Wilkinson’s
catalyst (30 mg, 33 µmol) in THF (1.5 mL) that was thoroughly
degassed and placed under an argon admosphere. The result-
ing red solution was stirred at 20 °C for 5 min and then
transferred via cannula into a refluxing solution of 8 (200 mg,
0.33 mmol) in THF (1 mL) under an argon atmosphere. TLC
analysis (acetone/CH2Cl2, 1/49, v/v) after 5 min showed
complete conversion of starting material (Rf 0.65) into product
(Rf 0.74). The reaction mixture was diluted with CH2Cl2 (10
mL) and concentrated to an orange/red residue. The residue
was purified by flash silica column chromatography (40 g,
eluant: CH2Cl2) to afford the required product 9 (182 mg,
91%): δ1H (400 MHz; CDCl3) 7.40-7.23 (20H, Ar CH), 4.90
3
4.98-4.53 (14H, m, Ar CH2), 4.49 (1H, d, J 1,2 ) 8 Hz, H-1),
3
4.30 (1H, m, CHCH3), 4.26 (1H, t, J 1′,2′ ) 4 Hz, H-1′), 3.73-
3.32 (12H, m, H-2, H-2′, H-3, H-3′, H-4, H-4′, H-5, H-5′,
H-6(a,b), H-6′(a,b)), 1.30 (3H, t, 3J ) 4 Hz, CHCH3); δ13C (100
MHz; CDCl3) 140.1, 139.0 (CH)CH2), 138.5-139.0 (Ar C
quaternary), 128.3-127.5 (Ar CH), 116.9, 114.7 (CH)CH2),
103.8 (C-1′), 101.4, 100.3 (C-1), 84.8, 84.7, 82.2, 82.1, 78.2, 77.8,
75.9, 75.3 (C-2, C-2′, C-3, C-3′, C-4, C-4′, C-5, C-5′), 75.6, 75.1,
75.0, 74.9, 74.8, 74.7, 73.5 (Ar CH2), 68.9 (C-6′), 68.4 (C-6),
21.9, 19.9 (CHCH3).
3
(1H, m, CdCH), 4.86 (8H, m, Ar CH2), 4.75 (1H, d, J 1,2 ) 8
Hz, H-1), 3.76-3.58 (5H, m, H-2, H-3, H-4, H-6(a,b)), 3.43 (1H,
m, H-5), 1.92 (1.5H, m, CH3 (trans)), 1.86 (1.5H, m, CH3 (cis)),
1.62 (1.5H, 2 × q, 3J ) 6.9 Hz, 5J ) 1.45 Hz, CH3 (trans)),
1.59 (1.5H, 2 × q, 3J ) 6.9 Hz, 5J ) 1.1 Hz, CH3 (cis)); δ13C
(75 MHz; CDCl3) 149.4 (OC(CH3))C), 138.7-138.2 (Ar C
10â: δ1H (400 MHz; CDCl3) 7.36-7.20 (35H, m, Ar CH),
5.99-5.72 (1H, m, CH)CH2), 5.21-5.00 (2H, m, CH)CH2),
3
4.98-4.54 (14H, m, Ar CH2), 4.49 (1H, d, J 1,2 ) 8 Hz, H-1),
3
4.30 (1H, m, CHCH3), 4.26 (1H, t, J 1′,2′ ) 8 Hz, H-1′), 3.73-

4268 J . Org. Chem., Vol. 61, No. 13, 1996
Boons and Isles
3.32 (12H, m, H-2, H-2′, H-3, H-3′, H-4, H-4′, H-5, H-5′,
H-6(a,b), H-6′(a,b)), 1.30 (3H, t, 3J ) 4 Hz, CHCH3); δ13C (100
MHz; CDCl3) 140.1, 139.0 (CH)CH2), 138.5-139.0 (Ar C
quaternary), 128.3-127.5 (Ar CH), 116.9, 114.7 (CH)CH2),
103.8 (C-1′), 101.4, 100.3 (C-1), 84.8, 84.7, 82.2, 82.1, 78.2, 77.8,
75.9, 75.3 (C-2, C-2′, C-3, C-3′, C-4, C-4′, C-5, C-5′), 75.6, 75.1,
75.0, 74.9, 74.8, 74.7, 73.5 (Ar CH2), 68.9 (C-6′), 68.4 (C-6),
21.9, 19.9 (CHCH3); m/ z 1065 (28, [M + K]+), 1049 (100, [M
+ Na]+), 1025 (38, [M - H]+), 523 (6, [M - O-(3-buten-2-yl)-
tri-O-benzyl-â-D-glucopyranosyl]+), 415 (30, [M - O-(3-buten-
2-yl)tetra-O-benzyl-â-D-glucopyranosyl]+), C65H70O11Na re-
quires 1049.4815, found 1049.4794.
137.5 (Ar C quaternary), 128.9-126.6 (Ar CH), 117.3, 115.3
(CH)CH2), 102.2 (PhCH), 101.2, 100.9 (C-1), 82.3, 81.6, 81.1
(C-2, C-3, C-5), 77.3, 75.7 (CHCH3), 75.5, 75.1 (Ar CH2), 68.9
(C-6), 66.1 (C-4), 21.9, 20.4 (CHCH3); m/ z 525 (100, [M +
Na]+), 501 (22, [M - H]+), 431 (9, [M - O-3-buten-2-yl]+).
(R/S)-3-Bu ten -2-yl 2,3,6-Tr i-O-ben zyl-â-D-glu cop yr a n o-
sid e (14). A solution of HCl in ether (1 M, 30 mL) was added
dropwise over a period of 30 min to a mixture of 13 (2.05 g,
4.1 mmol), sodium cyanoborohydride (3.12 g, 49 mmol), and
powdered 3 Å molecular sieves (2.4 g) in THF (35 mL). TLC
analysis (acetone/CH2Cl2, 1/99, v/v) was performed 5 min after
the evolution of gas had ceased and showed complete conver-
sion of 13 (Rf 0.73) into a product (Rf 0.48). The mixture was
diluted with CH2Cl2 (100 mL) and filtered through Celite. The
filtrate was washed with water (3 × 40 mL) and aqueous
NaHCO3 (3 × 40 mL). The organic phase was dried (MgSO4)
and filtered, and the filtrate was concentrated under reduced
pressure. The crude product was purified on a column of silica
gel (60 g, eluant: petroleum ether 40-60 °C/ethyl acetate, 2/1,
v/v), affording 14 (1.76 g, 86 %) as a waxy white solid: δ
(300 MHz; CDCl3) 7.40-7.25 (15H, Ar CH), 6.05-5.70 (1H,
m, CH)CH2), 5.30-5.08 (2H, m, CH)CH2), 4.96-4.61 (6H,
2-Bu ten -2-yl-2,3,4-Tr i-O-ben zyl-6-O-(2,3,4,6-tetr a-O-ben -
zyl-â-D-glu cop yr a n osyl)-â-D-glu cop yr a n osid e (11). Treat-
ment of compound 10â (100 mg, 0.97 mmol) with [(C6H5)3P]3-
RhCl/BuLi as described for the preparation of 9 (method B)
gave, after workup and silica gel comumn chromatography,
compound 11 (92 mg, 92%). 11â: δ1H (400 MHz; CDCl3) 7.36-
7.20 (35H, m, Ar CH), 4.93 (1H, m, CdCH), 4.98-4.53 (14H,
1H
3
m, Ar CH2), 4.71 (1H, d, J 1,2 ) 8 Hz, H-1), 4.26 (1H, 2 × d,
3J 1′,2′ ) 8 Hz, H-1′), 3.73-3.32 (12H, m, H-2, H-2′, H-3, H-3′,
H-4, H-4′, H-5, H-5′, H-6(a,b), H-6′(a,b)), 1.91 (1.5H, m, CH3
3
3
(trans)), 1.80 (1.5H, m, CH3 (cis)), 1.60 (1.5H, 2 × q, J ) 6.8
m, Ar CH2), 4.52 (1H, dd, J 1,2 ) 8 Hz, H-1), 4.36 (1H, m,
5
3
Hz, J ) 1.4 Hz, CH3 (trans)), 1.57 (1.5H, 2 × q, J ) 6.8 Hz,
5J ) 1.2 Hz, CH3 (cis)); δ 13C (75 MHz; CDCl3) 148.3
(OC(CH3))C), 138.5-139.0 (Ar C quaternary), 128.3-127.5
(Ar CH), 104.2, 103.6 (CHCH3), 101.6 (C-1′), 100.3, 99.7 (C-1),
84.9, 84.6, 82.2, 82.0, 78.3, 76.5, 75.7, 75.2 (C-2, C-2′, C-3, C-3′,
C-4, C-4′, C-5, C-5′), 75.5, 75.3, 75.2, 74.8, 74.5, 74.1, 72.9 (Ar
CH2), 68.6 (C-6′), 68.3 (C-6), 18.5, 15.9 (CH3), 11.6, 10.9
(CHCH3); m/ z 1049 (100, [M + Na]+), 523 (20, [M - O-(2-
buten-2-yl)-tri-O-benzyl-â-D-glucopyranosyl]+).
CHCH3), 3.74 (2H, m, H-6(a,b)), 3.59 (1H, m, H-4), 3.45 (3H,
m, H-2, H-3, H-5), 2.58 (1H, dd, 3J ) 2 Hz, OH), 1.36 (3H, 2 ×
d, 3J ) 3 Hz, CHCH3); δ13C (75 MHz; CDCl3) 140.2, 139.1
(CH)CH2
), 138.6, 138.4, 137.9 (Ar C quaternary), 128.4-127.6
(Ar CH), 117.0, 114.8 (CH)CH2
), 101.8, 100.4 (C-1), 84.2, 81.7
(C-3, C-5), 76.9, 75.3 (CHCH3), 75.2, 74.8, 73.5 (Ar CH2), 73.9,
71.7 (C-2, C-4), 70.4 (C-6), 21.8, 20.3 (CHCH3); m/ z 527 (28,
[M + Na]
+), 503 (5, [M - H]+), 433 (10, [M - O-3-buten-2-
yl]
+), 325 (7, [M - H - OBn-O-3-buten-2-yl]+), 181 (100, [M -
3-O-Bn]+), C31H36O6Na requires 527.2409, found 527.2402.
(R/S)-3-Bu t en -2-yl 2,3,6-Tr i-O-b en zyl-4-O-a cet yl-â-D-
glu cop yr a n osid e (15). Acetic anhydride (5 mL) was added
to a stirred solution of 14 (520 mg, 1.03 mmol) in pyridine (7
mL). The resulting mixture was stirred at room temperature
for 5 h, after which time TLC analysis (acetone/CH2Cl2, 2/98,
v/v) showed complete conversion of starting material (Rf 0.23)
to product (Rf 0.47). The mixture was concentrated in vacuo,
and the resulting oil was coevaporated from toluene (3 × 2
mL) to afford 15 (500 mg, 0.91 mmol, 88%) as a colorless oil:
δ1H (300 MHz; CDCl3) 7.38-7.25 (15H, Ar CH), 6.05-5.70 (1H,
m, CH)CH2), 5.30-5.08 (2H, m, CH)CH2), 4.96-4.56 (6H,
m, Ar CH2), 4.50 (2H, m, H-1, H-4), 4.35 (1H, m, CHCH3), 3.52
(5H, m, H-2, H-3, H-5, H-6(a,b)), 1.84, 1.83 (3H, 2 × s, Ac CH3),
1.36 (3H, 2 × d, 3J ) 4 Hz, CHCH3); δ13C (75 MHz; CDCl3)
170.2 (Ac CdO), 140.2, 139.0 (CH)CH2), 138.5-137.7 (Ar C
quaternary), 128.4-127.6 (Ar CH), 117.0, 115.0 (CH)CH2),
101.7, 100.3 (C-1), 82.1, 82.0 (C-3, C-5), 75.4 (CHCH3), 75.1,
75.0, 74.9 (Ar CH2), 73.3, 73.2 (C-2, C-4), 69.9 (C-6), 21.9 (Ac
CH3), 20.8, 20.4 (CHCH3); m/ z 569 (100, [M + Na]+), 546 (8,
[M - H]+), 475 (12, [M - O-3-buten-2-yl]+), 439 (17, [M -
OBn]+).
2-Bu ten -2-yl 3,4,6-Tr i-O-ben zyl-4-O-a cetyl-â-D-glu cop y-
r a n osid e (16). Treatment of 15 (200 mg, 0.36 mmol) with
[(C6H5)3P]3RhCl/BuLi as for described for the preparation of
9 gave, after flash silica gel column chromatography (eluent:
CH2Cl2), 16 (176 mg, 88%): δ1H (300 MHz; CDCl3) 7.38-7.25
(15H, Ar CH), 4.96-4.56 (6H, m, Ar CH2), 4.50 (2H, m, H-1,
H4), 3.58 (5H, m, H-2, H-3, H-5, H-6(a,b)), 1.93 (1.5H, m, CH3
(trans)), 1.86 (1.5H, m, CH3 (cis)), 1.85, 1.84 (3H, 2 × s, Ac
CH3), 1.61 (1.5H, 2 × q, 3J ) 6.9 Hz, 5J ) 1.6 Hz, CH3 (trans)),
1.60 (1.5H, m, CH3 (cis)); δ13C (75 MHz; CDCl3) 169.8 (Ac
CdO), 151.5, 149.0 (OC(CH3))C), 138.4-138.0 (Ar C quater-
nary), 128.4-127.5 (Ar CH), 105.3, 100.0 (CH(CH3)), 100.3,
98.3 (C-1), 81.9, 73.5, 71.0, 70.9 (C-2, C-3, C-4, C-5), 75.1-
74.9 (Ar CH2), 69.6 (C-6), 20.8 (Ac CH3), 18.6, 15.6, (CH3), 11.9,
10.4 (CHCH3); m/ z 617 (100, [M + Na]+), 593 (11, [M - H]+),
523 (18, [M - O-2-buten-2-yl]+), 415 (23, [M - H - O-Bn -
O-2-buten-2-yl]+), 271 (65, [M - H - 3-O-Bn]+).
(R/S)-3-Bu ten -2-yl 4,6-O-Ben zylid en e-â-D-glu cop yr a n o-
sid e (12). Camphorsulfonic acid (1 g) was added to a solution
of 4 (4.0 g, 17 mmol) and benzylidenedimethyl acetal (3.58 mL,
24 mmol) in CHCl3 (10 mL). After the reaction mixture was
heated for 12 h under reflux, TLC analysis (methanol/CH2-
Cl2, 1/9, v/v) showed conversion of starting material 4 (Rf 0.1)
into a product (Rf 0.55). The solution was neutralized with
K2CO3 and filtered, and the filtrate was concentrated under
reduced pressure. The crude product was purified on a column
of silica gel (80 g, eluant: methanol/CH2Cl2, 2/98, v/v) to afford
pure 12 (3.52 g, 64%): δ1H (300 MHz; CDCl3) 7.53-7.37 (5H,
Ar CH), 5.95-5.60 (1H, m, CH)CH2), 5.56 (1H, s, PhCH),
3
5.30-5.12 (2H, m, CH)CH2), 4.50 (1H, d, J 1,2 ) 8 Hz, H-1),
4.34 (2H, m, CHCH3, H-4), 3.76 (2H, m, H-6(a,b)), 3.61-3.40
(3H, m, H-2, H-3, H-5,), 3.31 (1H, bs, OH), 3.07 (1H, bs, OH),
3
1.31 (3H, 2 × d, J ) 2.8 Hz, CHCH3); δ13C (75 MHz; CDCl3)
139.7, 138.7 (CH)CH2), 137.0 (Ar C quaternary), 129.2, 128.3,
126.3 (Ar CH), 117.6, 115.4 (CH)CH2), 101.9 (PhCH), 101.4,
100.0 (C-1), 80.6 (C-2), 76.9, 75.5 (CH-CH3), 74.5, 73.2 (C-3,
C-5), 68.7 (C-6), 66.4 (C-4), 21.6, 20.6 (CHCH3); m/ z 323 (100,
[M + H]+), 305 (11, [M - OH]+), 288 (5, [M - 2(OH)]+), 267
(23, [M - 3-buten-2-yl]+), 251 (90, [M - O-3-buten-2-yl]+),
C17H22O6Na requires 345.1314, found 345.1334.
(R/S)-3-Bu ten -2-yl 2,3-Di-O-ben zyl-4,6-O-ben zylid en e-
â-D-glu cop yr a n osid e (13). Benzyl bromide (2.25 mL, 18.9
mmol) was added dropwise to a cooled (0 °C) suspension of 12
(2.91 g, 9 mmol) and sodium hydride (80% dispersion in oil,
3.5 g, 112 mmol) in DMF (40 mL). After the reaction mixture
was stirred for 12 h, TLC analysis (acetone/CH2Cl2, 1/99, v/v)
showed conversion of 12 (Rf 0.05) into a product (Rf 0.73).
Excess NaH was quenched with methanol (25 mL), and the
reaction mixture was poured into water (70 mL) and extracted
with ether (4 × 30 mL). The combined ether extracts were
washed with brine (2 × 30 mL), dried (MgSO4), and concen-
trated under reduced pressure to an orange crystalline solid.
This crude product was purified on a column of silica gel (150
g, eluant: light petroleum ether/CH2Cl2, 1/3, v/v) to afford 13
(3.27 g, 72%) as a white solid: δ1H (300 MHz; CDCl3) 7.43-
7.24 (15H, Ar CH), 5.97-5.68 (1H, m, CH)CH2), 5.55 (1H, s,
PhCH), 5.30-5.11 (2H, m, CH)CH2), 4.83-4.71 (4H, m, Ar
CH2), 4.57 (1H, 2 × d, 3J 1,2 ) 8 Hz, H-1), 4.32 (2H, m, CHCH3,
(R/S)-3-Bu ten -2-yl 2,3,6-Tr i-O-ben zyl-4-O-(2,3,6-tr i-O-
ben zyl-4-O-a cet yl-r/â-D-glu cop yr a n osyl)-â-D-glu cop yr a -
n osid e (17). Glycosylation of 16 (170 mg, 0.31 mmol) with
14 (131 mg, 0.26 mmol) was performed as described for the
synthesis of 10 (method A, TMSOTf, CH3CN, -25 °C, 90 min)
3
H-4), 3.73 (3H, m, H-3, H-6(a,b)), 3.47 (1H, m, J 1,2 ) 8 Hz,
3
3J 2,3 ) 3 Hz, H-2), 3.38 (1H, m, H-5), 1.34 (3H, dd, J ) 3 Hz,
CHCH3); δ13C (75 MHz; CDCl3) 140.1, 139.1 (CH)CH2), 138.6,

Vinyl Glycosides in Oligosaccharide Synthesis
J . Org. Chem., Vol. 61, No. 13, 1996 4269
to afford 17 as a mixture of anomers (189 mg, 78%, R/â 1/8).
The anomers were separated on a column of silica gel (100 g,
eluant acetone/CH2Cl2, 1/99, v/v), affording the pure anomers
17R (23 mg) and 17â (91 mg) and unseparated anomers (71
mg).
(CHCH3); m/ z 234 (12, [M]+), 257 (48, [M + Na]+), C10H18O6-
Na requires 257.1001, found 257.1010.
(R/S)-3-Bu ten -2-yl 2,3,4,6-Tetr a -O-ben zyl-â-D-ga la cto-
p yr a n osid e (21). Sodium hydride (80% dispersion in oil, 3
g, 100 mmol) was added to a cooled (0 °C) and vented solution
of 20 (3.21 g, 14 mmol) in N,N-dimethylformamide (50 mL).
Benzyl bromide (10 mL, 84 mmol) was added dropwise (30
min) to the suspension. The resulting mixture was stirred for
12 h at room temperature, and after this time TLC analysis
(acetone/CH2Cl2, 1/99, v/v) showed complete conversion of 20
(Rf 0.06) into a product (Rf 0.57). The reaction was quenched
by the addition of methanol (30 mL), and the resulting mixture
was concentrated to a solid under reduced pressure. The solid
was dissolved in ether (100 mL) and washed with water (3 ×
40 mL), and the combined water layers were washed with
ether (2 × 10 mL). The combined ether extracts were dried
(MgSO4) and filtered, and the filtrate was concentrated under
reduced pressure to give a crude product that was purified on
a column of silica gel (100 g, eluant: acetone/CH2Cl2, 1/99, v/v)
to afford 21 (6.23 g, 76%) as a colorless oil: δ1H (400 MHz;
CDCl3), 7.40-7.23 (20H, m, Ar CH), 6.00-5.68 (1H, m,
CH)CH2), 5.23-5.07 (2H, m, CH)CH2), 4.98-4.41 (8H, m,
Ar CH2), 4.41-4.28 (2H, m, H-1, CHCH3), 3.70 (2H, m, H-3,
The same reaction was performed according to method B
to give, after purification, 17 (75%, R/â 1.5/1). The same
reaction was performed according to method C to give, after
purification, 17 (73%, R/â 3/1). 17R: δ1H (300 MHz; CDCl3)
7.36-7.19 (30H, m, Ar CH), 6.04-5.64 (1H, m, CH)CH2),
5.21-5.00 (2H, m, CH)CH2), 4.98-4.20 (16H, m, Ar CH2,
CHCH3, H-1, H-1′, H-4′), 4.00 (1H, m, H-4), 3.59-3.28 (10H,
m, H-2, H-2′, H-3, H-3′, H-5, H-5′, H-6(a,b), H-6′(a,b)), 1.83,
1.82 (3H, 2 × s, Ac CH3), 1.31 (3H, 2 × d, 3J ) 5.5 Hz, CHCH3);
δ13C (100 MHz; CDCl3) 169.8 (Ac CdO), 140.5, 139.2 (CH)CH2),
139.1-138.2 (Ar C quaternary), 128.3-126.5 (Ar CH), 116.8,
114.6 (CH)CH2), 102.2 (C-1′), 101.9, 100.4 (C-1), 82.8, 82.4,
82.0, 81.6, 77.4, 77.9, 76.5, 75.6, 75.2, 71.5 (CH-CH3, C-2, C-2′,
C-3, C-3′, C-4, C-4′, C-5, C-5′) 75.3-73.2 (Ar CH2), 70.0 (C-6′),
68.0 (C-6), 20.9 (Ac CH3), 21.9, 20.5 (CHCH3).
17â: δ1H (300 MHz; CDCl3) 7.36-7.19 (30H, m, Ar CH),
6.04-5.64 (1H, m, CH)CH2), 5.21-5.00 (2H, m, CH)CH2),
4.98-4.20 (16H, m, Ar CH2, CHCH3, H-1, H-1′, H-4′), 4.00 (1H,
m, H-4), 3.59-3.28 (10H, m, H-2, H-2′, H-3, H-3′, H-5, H-5′,
H-6(a,b), H-6′(a,b)), 1.83, 1.82 (3H, 2 × s, Ac CH3), 1.31 (3H,
2 × d, 3J ) 5.5 Hz, CHCH3); δ13C (100 MHz; CDCl3) 169.8 (Ac
CdO), 140.5, 139.2 (CH)CH2), 139.1-138.2 (Ar C quaternary),
128.3-126.5 (Ar CH), 116.8, 114.6 (CH)CH2), 102.2 (C-1′),
101.9, 100.4 (C-1), 82.8, 82.4, 82.0, 81.6, 77.4, 77.9, 76.5, 75.6,
75.2, 71.5 (CH-CH3, C-2, C-2′, C-3, C-3′, C-4, C-4′, C-5, C-5′)
75.3-73.2 (Ar CH2), 70.0 (C-6′), 68.0 (C-6), 20.9 (Ac CH3), 21.9,
20.5 (CHCH3); m/ z 1001 (100, [M + Na]+), C58H64O11Na
requires 1001.4451, found 1001.4446.
3
H-4), 3.58-3.42 (4H, m, H-2, H-5, H-6(a,b)), 1.30 (3H, dd, J
) 3 Hz, CHCH3); δ13C (75 MHz; CDCl3) 140.5, 139.2 (CH)CH2),
138.6-138.2 (Ar C quaternary), 129.3-127.7 (Ar CH), 117.3,
114.5 (CH)CH2), 102.2, 100.7 (C-1), 82.5, 79.7, 77.2, 76.5 (C-
2, C-3, C-4, C-5), 75.3 (CHCH3), 75.4-73.2 (Ar CH2), 69.0 (C-
6), 21.9, 20.5 (CHCH3); m/ z 593 (8, [M - H]+), 523 (10, [M -
O-3-buten-2-yl]+), 415 (23, [M - H - O-Bn - O-3-buten-2-
yl]+), 271 (65, [M - H - 3 O-Bn]+), 253 (100, [M - H - 2 O-Bn
- O-3-buten-2-yl]+), C38H42O6Na requires 617.2879, found
617.2883.
2-Bu ten -2-yl 2,3,4,6-Tetr a -O-ben zyl-â-D-ga la ctop yr a n o-
sid e (22). Treatment of 21 (100 mg, 0.16 mmol) with
[(C6H5)3P]3RhCl/BuLi as described for the preparation of 9
gave, after flash silica gel column chromatography (eluent:
CH2Cl2), 22 (90 mg, 90%): δ1H (300 MHz; CDCl3) 7.40-7.23
(20H, Ar CH), 4.9-4.83 (5H, m, Ar CH2, CHCH3), 4.79 (1H, d,
3J 1,2 ) 8 Hz, H-1), 4.71-4.43 (4H, Ar CH2), 3.77-3.46 (5H, m,
H-3, H-4, H-5, H-6(a,b)), 1.91 (1.5H, m, CH3 (trans)), 1.84
(R/S)-3-Bu t en -2-yl 2,3,4,6-Tet r a -O-a cet yl-â-D-ga la ct o-
p yr a n osid e (19). A solution of bromide 18 (14.45 g, 35 mmol)
and (()-3-buten-2-ol (2) (10 mL, 115 mmol) in acetonitrile (35
mL) was added to a stirred suspension of mercury(II) cyanide
(7.67 g, 30 mmol), mercury(II) bromide (10.03 g, 30 mmol),
and powdered 4 Å molecular sieves (11 g) in acetonitrile (50
mL). After the reaction mixture was stirred for 12 h, TLC
analysis (acetone/CH2Cl2, 2/98, v/v) showed complete conver-
sion of starting material (Rf 0.53) into a product (Rf 0.60). The
reaction mixture was filtered, and the filtrate was concentrated
under reduced pressure to yield an oil. The oil was dissolved
in CH2Cl2 (100 mL) and washed with NaHCO3 (3 × 40 mL)
and aqueous NaCl (3 × 40 mL). The organic phase was dried
(MgSO4) and concentrated under reduced pressure to give an
orange crystalline residue. This crude product was applied
to a column of silica gel (100 g, eluant: acetone/CH2Cl2, 3/97,
v/v), and concentration of the appropriate fractions afforded
19 (8.54 g, 60%): δ1H (300 MHz; CDCl3) 5.89-5.50 (1H, m,
CH)CH2), 5.30-4.91 (5H, m, CH)CH2, H-2, H-3, H-4), 4.48
3
5
(1.5H, m, CH3 (cis)), 1.60 (1.5H, 2 × q, J ) 6.8 Hz, J ) 1.4
3
5
Hz, CH3 (trans)), 1.57 (1.5H, 2 × q, J ) 6.8 Hz, J ) 1.2 Hz,
CH3 (cis)); δ13C (75 MHz; CDCl3) 151.1, 149.5 (OC(CH3))C),
138.7-138.0 (Ar C quaternary), 128.4-127.6 (Ar CH), 104.4,
100.7 (CHCH3), 102.2, 100.6 (C-1), 82.5, 82.1, 81.1, 79.4 (C-2,
C-3, C-4, C-5), 75.0-73.5 (Ar CH2), 68.9 (C-6), 18.8,15.7 (CH3),
12.0, 10.5 (CHCH3); m/ z 617 (100, [M + Na]+), 593 (7, [M -
H]+), 523 (12, [M - O-2-buten-2-yl]+), 415 (15, [M - H - O-Bn
- O-2-buten-2-yl]+), 271 (79, [M - H - 3 O-Bn]+), C38H42O6-
Na requires 617.2879, found 617.2885.
(R/S)-3-Bu ten -2-yl 2,3,4-Tr i-O-ben zyl-6-O-(2,3,4,6-tetr a -
O-b en zyl-r/â-D-ga la ct op yr a n osyl)-â-D-glu cop yr a n osid e
(23). Glycosylation of 22 (106 mg, 0.18 mmol) with 7 (61 mg,
0.12 mmol) was performed as described for the synthesis of
10 (method A, TMSOTf, CH3CN, -25 °C, 90 min), affording
23 (97 mg, 78%) as a mixture of anomers (R/â ) 1/3). The
same glycosylation was also performed according to method
B (TMSOTf, CH2Cl2, -25 °C, 90 min) to give 23 (75%) as a
separable mixture of anomers (R/â ) 4/1). 23â: δ1H (300 MHz;
CDCl3) 7.41-7.19 (35H, m, Ar CH), 5.89-5.58 (1H, m,
CH)CH2), 5.23-5.03 (2H, m, CH)CH2), 5.00-4.73 (14H, m,
Ar CH2), 4.45 (1H, d, 3J 1,2 ) 8 Hz, H-1′), 4.43 (1H, 2 × d, 3J 1′,2′
) 8 Hz, H-1), 4.35 (1H, m, CHCH3), 3.79 (1H, m, H2′), 3.69-
3.25 (11H, m, H-2, H-3, H-3′, H-4, H-4′, H-5, H-5′, H-6(a,b),
H-6′(a,b)), 1.28 (3H, 2 × d, 3J ) 4.5 Hz, CHCH3); δ13C (75 MHz;
CDCl3) 140.1, 139.9 (CH)CH2), 139.2-138.1 (Ar C quater-
nary), 128.4-126.2 (Ar CH), 117.0, 115.6 (CH)CH2,), 102.8
(J H1-C1 ) 160 Hz, C-1′(â)), 101.5, 100.3 (C-1), 84.9, 82.3, 82.2,
79.6, 79.5, 78.5, 78.0, 75.4 (C-2, C-2′, C-3, C-3′, C-4, C-4′, C-5,
C-5′), 75.7-71.9 (Ar CH2), 69.1 (C-6′), 68.6 (C-6), 21.9, 20.5
(CHCH3); m/ z 1049 (100, [M + Na]+), 1025 (21, [M - H]+),
523 (17, [M - O-(3-buten-2-yl)tri-O-benzyl-â-D-glucopyrano-
syl]+), 415 (28, [M - O-(3-buten-2-yl)tetra-O-benzyl-â-D-glu-
copyranosyl]+). Note: 97.9 (J H1-C1 ) 169 Hz, C-1′(R)).
3
(1H, d, J 1,2 ) 8 Hz, H-1), 4.30 (1H, m, CHCH3), 4.09 (2H, m,
H-6(a,b)), 3.82 (1H, m, H-5), 2.10-1.92 (12H, m, Ac CH3), 1.20
(3H, 2 × d, 3J ) 6 Hz, CHCH3); δ13C (75 MHz; CDCl3), 170.3-
169.1 (Ac CdO), 139.6, 138.3 (CH)CH2), 116.8, 115.1 (CH2)
CH), 99.8, 98.5 (C-1), 77.7, 75.8 (CHCH3), 71.0, 69.1, 67.1, 67.0
(C-2, C-3, C-4, C-5), 61.3 (C-6), 21.5-19.7 (Ac CH3, CHCH3);
m/ z 425 (100, [M + Na]+), 331 (52, [M - O-3-buten-2-yl]+).
(R/S)-3-Bu ten -2-yl â-D-ga la ctop yr a n osid e (20). Potas-
sium tert-butoxide (3.0 g) was added to a stirred solution of
19 (8.04 g, 20 mmol) in methanol (100 mL). After a reaction
time of 5 h, TLC analysis (acetone/CH2Cl2, 2/98, v/v) showed
complete conversion of the starting material (Rf 0.60) into a
product (Rf 0.06). The reaction mixture was neutralized with
Dowex 50 WX4 (H+) (60 mL), filtered, and concentrated in
vacuo. After coevaporation from toluene (3 × 5 mL), compound
20 was obtained as a white oil (3.53 g, 75%): δ1H (300 MHz;
D2O) 5.95-5.60 (1H, m, CH)CH2), 5.30-5.12 (2H, m, CH)
3
CH2), 4.50 (1H, 2 × d, J 1,2 ) 8 Hz, H-1), 4.30 (1H, m,
CH)CH3), 3.82-3.64 (2H, m, H-3, H-4), 3.45-3.25 (4H, m,
3
H-2, H-5, H-6(a,b)), 3.21 (1H, m, CH3CH), 1.23 (3H, 2 × d, J
) 2.9 Hz, CHCH3); δ13C (75 MHz; D2O) 142.3, 141.2 (CH)CH2),
120.6, 117.8 (CH)CH2), 103.7, 102.5 (C-1), 80.1, 78.8, 77.8,
76.2, 72.3 (CHCH3, C-2, C-3, C-4, C-5), 63.6 (C-6), 23.2, 22.0

4270 J . Org. Chem., Vol. 61, No. 13, 1996
Boons and Isles
(R/S)-3-Bu ten -2-yl 2,3,6-Tr i-O-ben zyl-4-O-(2,3,4,6-tetr a -
O-b en zyl-r/â-D-ga la ct op yr a n osyl)-â-D-glu cop yr a n osid e
(24). Glycosylation of 22 (95 mg, 0.16 mmol) with 14 (61 mg,
0.12 mmol) carried out as described for the synthesis of 10
(method A, TMSOTf, CH3CN, -25 °C, 90 min) afforded 24 (90
mg, 73%, R/â ) 1/1.5) as a mixture of anomers. 24â: δ1H (300
MHz; CDCl3) 7.39-7.18 (35H, m, Ar CH), 6.01-5.63 (1H, m,
CH)CH2), 5.21-5.00 (2H, m, CH)CH2), 4.97-4.32 (16H, m,
Ar CH2, H-1, H-1′), 4.30 (1H, m, CHCH3), 4.00-3.71 (6H, m,
H-4, H-4′, H-6(a,b), H-6′(a,b)), 3.59-3.31 (6H, m, H-2, H-2′,
H-3, H-3′, H-5, H-5′), 1.37 (3H, m, CHCH3); δ13C (75 MHz;
CDCl3) 140.6, 139.4 (CH)CH2), 139.2-138.1 (Ar C quater-
nary), 128.3-126.6 (Ar CH), 117.1, 114.7 (CH)CH2), 102.8
(J H1-C1 ) 161 Hz, C-1′(â)), 101.9, 100.2 (C-1),) 85.0, 83.2, 82.6,
82.3, 80.0, 79.2, 76.9, 74.3, 73.7, 73.0 (CH-CH3, C-2, C-2′, C-3,
C-3′, C-4, C-4′, C-5, C-5′), 75.4-72.6 (Ar CH2), 68.8 (C-6′), 68.1
(C-6), 21.9, 20.5 (CHCH3); m/ z 1049 (100, [M + Na]+), 1025
(18, [M - H]+), 523 (10, [M - O-(3-buten-2-yl)tri-O-benzyl-â-
D-glucopyranosyl]+), 415 (37, [M - O-(3-buten-2-yl)tetra-O-
benzyl-â-D-glucopyranosyl]+). Note: 97.2 (J H1-C1 ) 173 Hz,
C-1′(R)).
70.1, 69.2, 68.2, 66.9 (CHCH3, C-2, C-3, C-4, C-5), 69.2 (C-6),
30.9 (CH3C), 22.6, 22.4 (CH3CH3); m/ z 569 (75, [M + Na]+),
475 (100, [M - O-3-buten-2-yl]+), C33H38O7Na requires 569.2515,
found 569.2505.
(R/S)-3-Bu t en -2-yl 2-O-Acet yl-3,4,6-t r i-O-b en zyl-â-D-
glu cop yr a n osid e (27). TMSOTf (300 µL, 1.5 mmol) was
added to a cooled (-20 °C) stirred solution of 26 (4.5 g, 8.25
mmol) in CH2Cl2 (60 mL) containing powdered 4 Å molecular
sieves (4 g). TLC analysis (acetone/CH2Cl2, 2/98, v/v) after 4
h showed conversion of 26 (Rf 0.50) into a product (Rf 0.46).
The reaction was neutralized with Et3N (50 µL), diluted with
CH2Cl2, and filtered through Celite. The filtrate was washed
with NaHCO3 (2 × 30 mL). The organic phase was dried
(MgSO4) and concentrated to a yellow oil. Purification on a
silica gel column (110 g, eluant: acetone/CH2Cl2, 1/99, v/v)
afforded pure 27 (4.05 g, 90%): δ1H (300 MHz; CDCl3) 7.38-
7.19 (15H, Ar CH), 6.00-5.55 (1H, m, CH)CH2), 5.30-5.08
(3H, m, CH)CH2, H-2), 4.95-4.59 (6H, m, Ar CH2), 4.50 (2H,
2 × d, 3J 1,2 ) 8 Hz, H-1), 4.24 (1H, m, CHCH3), 3.71-3.62 (4H,
m, H-3, H-4, H-6(a,b), 3.48 (1H, m, H-5), 1.96 (3H, 2 × s, Ac
CH3), 1.36 (3H, 2 × d, 3J ) 4 Hz, CHCH3); δ13C (75 MHz;
CDCl3) 169.4 (Ac CdO), 140.2, 139.0 (CH)CH2), 138.5-137.7
(Ar C quaternary), 128.4-127.6 (Ar CH), 117.0, 115.0 (CH)
CH2), 101.7, 100.3 (C-1), 83.1, 83.0 (C-2), 82.0, 78.5, 75.4, 74.3,
71.2 (CHCH3, C-3, C-4, C-5), 75.1-74.9 (Ar CH2), 70.0 (C-6),
21.9 (Ac CH3), 20.8, 20.4 (CHCH3); m/ z 569 (100, [M + Na]+),
546 (8, [M - H]+), 475 (51, [M - O-3-buten-2-yl]+).
(R/S)-3-Bu ten -2-yl 3,4,6-Tr i-O-ben zyl-â-D-glu cop yr a n o-
sid e (28). Potassium tert-butoxide (100 mg) was added to a
stirred suspension of 27 (460 mg, 0.84 mmol) in methanol (15
mL). After 8 h, TLC analysis (acetone/CH2Cl2, 3/97, v/v)
showed complete conversion of 27 (Rf 0.68) into a product (Rf
0.37). The mixture was neutralized with Dowex 50 WX4 (H+)
(10 mL), filtered, and concentrated to a white oil. Further
purification on a silica gel column (50 g, eluant: acetone/
CH2Cl2, 1/49, v/v) furnished pure 28 (360 mg, 85%) as a
colorless oil: δ1H (300 MHz; CDCl3) 7.41-7.18 (15H, Ar CH),
6.08-5.68 (1H, m, CH)CH2), 5.30-5.08 (2H, m, CH)CH2),
4.86-4.53 (6H, m, Ar CH2), 4.53 (2H, m, H-1, CHCH3), 3.74
(2H, m, H-6(a,b)), 3.59 (3H, m, H-2, H-3, H-4), 3.48 (1H, m,
H-5), 2.35 (1H, bs, OH), 1.37 (3H, dd, 3J ) 4 Hz, CHCH3); δ13C
(75 MHz; CDCl3) 140.1, 138.9 (CH)CH2), 138.7, 138.2, 137.8
(Ar C quaternary), 128.6-127.7 (Ar CH), 117.3, 115.0 (CH)
CH2), 101.0, 99.6 (C-1), 84.7, 84.6 (C-2), 77.6, 76.4, 75.2, 74.7
(CHCH3, C-3, C-4, C-5), 75.1, 74.9, 73.4 (Ar CH2), 69.0 (C-6),
21.7, 20.1 (CHCH3); m/ z 527 (90, [M + Na]+), 433 (15, [M -
O-3-buten-2-yl]+), C31H36O6Na requires 527.2409, found
527.2421.
r-D-Glu cop yr a n osyl 3,4,6-Tr i-O-a cetyl-1,2-(3-bu ten -2-
yl)or th om eth a n oa te (25). 2,4,6-Collidine (5.45 g, 45 mmol),
3-buten-2-ol (5.2 mL, 60 mmol), and tetra-n-ethylammonium
bromide (9.03g, 43 mmol) were added to a stirred solution of
1 (12.3 g, 30 mmol) in CH2Cl2 (100 mL) containing powdered
4 Å molecular sieves (8 g). The resulting mixture was stirred
at room temperature for 18 h. TLC analysis (acetone/CH2Cl2,
4/96, v/v) at this time showed conversion of 1 (Rf 0.58) into a
product (Rf 0.52). The mixture was filtered through Celite and
concentrated to a white solid. The solid was redissolved in
CH2Cl2 (75 mL) and extracted with water (3 × 25 mL),
NaHCO3 (3 × 25 mL), brine (3 × 25 mL), and water (3 × 25
mL). Each extract was itself reextracted with CH2Cl2 (2 × 5
mL). The combined CH2Cl2 extracts were dried (MgSO4),
filtered, and concentrated to a white solid. This compound
was further purified on a silica gel column (200 g, eluant:
acetone/CH2Cl2, 1/99, v/v) to give pure 25 (7.21 g, 60%) as a
white solid: δ1H (300 MHz; CDCl3) 5.78 (1H, m, CH)CH2),
3
5.63 (1H, d, J 1,2 ) 3.5 Hz, H-1), 5.18-4.82 (4H, m, CH)CH2,
H-2, H-3), 4.29 (1H, m, CHCH3), 4.21 (1H, m, H-4), 4.15 (2H,
m, H-6(a,b)), 3.92 (1H, m, H-5), 2.04 (9H, m, Ac CH3), 1.68
(3H, s, CH3C), 1.19 (3H, 2 × s, CHCH3); δ13C (75 MHz; CDCl3)
170.6, 169.6, 169.0 (Ac CdO), 140.7, 140.5 (CH)CH2), 121.4
(C quaternary), 114.3, 114.1 (CH)CH2), 96.9, 96.8 (C-1), 73.2,
72.9 (CHCH3), 70.9, 70.15, 68.2, (C-3, C-4, C-5), 66.9 (C-2), 63.1
(C-6), 22.3, 22.1, 21.9 (Ac CH3), 21.7 (CH3C), 20.7 (CH3CH).
r-D-Glu cop yr a n osyl 3,4,6-Tr i-O-ben zyl-1,2-(3-bu ten -2-
yl)or th om eth a n oa te (26). Potassium tert-butoxide (2.6 g)
was added to a stirred solution of 25 (8.34 g, 20 mmol) in
methanol (100 mL). After a reaction time of 5 h, TLC analysis
(acetone/CH2Cl2, 2/98, v/v) showed complete conversion of the
starting material (Rf 0.64) into a product (Rf 0.09). The
reaction mixture was concentrated in vacuo. After coevapo-
ration from toluene (3 × 15 mL) the crude product was
dissolved in DMF (100 mL). NaH (80% suspension in oil, 2.5
g) was added, and the resulting mixture was cooled (0 °C).
BnBr (7.1 mL, 58.2 mmol) was added dropwise, and the
reaction was allowed to warm to 20 °C and stirred at this
temperature for 5 h, after which time TLC analysis (acetone/
CH2Cl2, 2/98, v/v) showed conversion into 26 (Rf 0.62). Excess
NaH was neutralized by the addition of methanol (25 mL),
and the mixture was concentrated to a brown residue. The
residue was taken up in ether (60 mL) and extracted with
water (3 × 25 mL). The organic phase was dried (MgSO4) and
concentrated to an orange oil. Purification on a silica gel
column (200 g, eluant: acetone/CH2Cl2, 1/99, v/v) gave 26 (9.2
g, 73%) as an off white oil: δ1H (300 MHz; CDCl3) 7.39-7.19
(15H, m, Ar CH), 5.84 (1 H, m, CH)CH2), 5.63 (1H, 2 × d,
3J 1,2 ) 3.5 Hz, H-1), 5.18-5.00 (2H, m, CH)CH2), 4.70-4.40
(6H, m, Ar CH2), 4.38 (1H, m, H-2), 4.23 (1H, m, CH-CH3),
3.88 (1H, m, H-3), 3.78 (4H, m, H-4, H-5, H-6(a,b)), 1.68 (3H,
2 × s, CH3C), 1.19 (3H, 2 × d, CHCH3); δ13C (75 MHz; CDCl3)
141.1 (CH)CH2), 138.2, 138.0, 137.8 (Ar C quaternary), 128.5-
127.6 (Ar CH), 121.2, 121.1 (C quaternary), 113.9, 113.8
(CH)CH2), 97.9, 97.8 (C-1), 73.4, 72.7, 71.8 (Ar CH2), 73.2,
2-Bu ten -2-yl 2-O-Acetyl-3,4,6-tr i-O-ben zyl-â-D-glu cop y-
r a n osid e (29). Treatment of 27 (100 mg, 0.18 mmol) with
[(C6H5)3P]3RhCl) as described for the preparation of 9 gave,
after flash silica gel column chromatography (eluent: CH2Cl2),
29 (85 mg, 85%): δ1H (300 MHz; CDCl3) 7.39-7.20 (15H, Ar
CH), 5.14 (1H, m, CHCH3), 4.81-4.53 (7H, m, Ar CH2, H-1,),
3.78-3.61 (5H, m, H-2, H-3, H-4, H-6(a,b), 3.51 (1H, m, H-5),
1.98 (3H, 2 × s, Ac CH3), 1.86 (1.5H, m, CH3 (trans)), 1.72
(1.5H, m, CH3 (cis)), 1.60 (1.5H, m, CH3 (trans)), 1.59 (1.5H,
m, CH3 (cis)); δ13C (75 MHz; CDCl3) 169.5 (Ac CdO), 151.8,
149.5 (OC(CH3))C), 138.2-137.9 (Ar C quaternary), 128.5-
127.6 (Ar CH), 106.3 (CHCH3), 98.6, 98.5 (C-1), 83.0, 78.0, 75.1,
(C-3, C-4, C-5), 73.2, 73.0 (C-2), 75.1, 75.0, 73.5 (Ar CH2), 68.8
(C-6), 21.0 (Ac CH3), 19.1, 15.5 (CH3), 11.9, 10.2 (CHCH3); m/ z
617 (100, [M + Na]+), 593 (9, [M - H]+), 523 (24, [M - O-2-
buten-2-yl]+), 415 (18, [M - H - O-Bn - O-2-buten-2-yl]+),
271 (43, [M - H - 3-O-Bn]+).
(R/S)-3-Bu t en -2-yl 2,3,4-Tr i-O-b en zyl-6-O-(2-O-a cet yl-
3,4,6-tr i-O-ben zyl-â-D-glu cop yr a n osyl)-â-D-glu cop yr a n o-
sid e (30). Glycosylation of 29 (190 mg, 0.32 mol) with 7 (122
mg, 0.24 mol) as described for the synthesis of 10 (method A,
TMSOTf, CH3CN, 0 °C, 90 min) afforded 30 (156 mg, 69%):
δ1H (300 MHz; CDCl3) 7.43-7.21 (30H, m, Ar CH), 6.01-5.76
(1H, m, CH)CH2), 5.21-5.00 (2H, m, CH)CH2), 4.99-4.38
(14H, m, Ar CH2, H1, H1′), 4.32 (1H, m, CHCH3), 3.87-3.61
(10H, m, H-2, H-2′, H-3, H-3′, H-4, H-4′, H6(a,b), H-6′(a,b)),
3.44 (2H, m, H-5, H-5′), 1.72, 1.71 (3H, 2 × s, Ac CH3), 1.38
3
(3H, 2 × d, J ) 2 Hz, CHCH3); δ13C (75 MHz; CDCl3) 169.4

Vinyl Glycosides in Oligosaccharide Synthesis
J . Org. Chem., Vol. 61, No. 13, 1996 4271
(Ac CdO), 140.5, 139.3 (CH)CH2), 138.5-137.9 (Ar C qua-
ternary), 128.4-127.5 (Ar CH), 116.2, 114.6 (CH)CH2), 100.4
(C-1′), 99.4, 99.1 (C-1), 84.6, 84.2, 83.2, 82.6, 81.8, 80.8, 75.7,
72.3 (CHCH3, C-2, C-2′, C-3, C-3′, C-4, C-4′, C-5, C-5′), 75.9-
72.6 (Ar CH2), 69.1 (C-6′), 68.9 (C-6), 21.6 (Ac CH3) 20.9, 20.2
(CHCH3).
3J ) 1.5 Hz, CHCH3); δ13C (75 MHz; CDCl3) 169.5 (C)O),
140.5, 139.3 (CH)CH2), 138.5-137.9 (Ar C quaternary),
128.4-127.5 (Ar CH), 116.6, 114.8 (CH)CH2), 100.3 (C-1′),
99.2, 99.0 (C-1), 84.8, 84.7, 82.2, 82.1, 81.5, 80.3, 75.5, 75.3
(CHCH3, C-2, C-2′, C-3, C-3′, C-4, C-4′, C-5, C-5′), 75.7-73.2
(Ar CH2), 68.9 (C-6′), 68.7 (C-6), 21.8 (Ac CH3) 21.0, 20.5
(CHCH3); m/ z 1001 (100, [M + Na]+), 475 (23, [M - 2-O-acetyl-
3,4,6-tri-O-benzyl-â-D-glucopyranosyl]+), C60H66O12Na requires
1001.4451, found 1001.4441.
(R/S)-3-Bu ten -2-yl 2-O-(2-O-Acetyl-3,4,6-tr i-O-ben zyl-â-
D-glu cop yr a n osyl)-3,4,6-t r i-O-b en zyl-â-D-glu cop yr a n o-
sid e (31). Glycosylation of 29 (208 mg, 0.38 mol) with 28 (160
mg, 0.317 mol) was performed as described for the synthesis
of 10 (method A, TMSOTf, CH3CN, 0 °C, 90 min) afforded 31
as an oil (214 mg, 72%): δ1H (400 MHz; CDCl3) 7.40-7.18
(30H, m, Ar CH), 5.99-5.75 (1H, m, CH)CH2), 5.21-5.00 (3H,
m, H1′, CH)CH2), 4.99-4.4.51 (12H, m, Ar CH2), 4.48 (1H, 2
Su p p or tin g In for m a tion Ava ila ble: Copies of NMR
spectra (52 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
3
× d, J 1,2 ) 8 Hz, H1), 4.32 (1H, m, CHCH3), 3.83-3.60 (10H,
m, H-2, H-2′, H-3, H-3′, H-4, H-4′, H-6(a,b), H-6′(a,b)), 3.43
(2H, m, H-5, H-5′), 1.81, 1.80 (3H, 2 × s, Ac CH3), (3H, 2 × d,
J O960131B