Protecting group-free glycoligation by the desulfurative rearrangement of allylic disulfides as a means of assembly of oligosaccharide mimetics

Article abstract of DOI:10.1021/jo102411j

2-(2-Pyridyldithio-3-butenyl) glycosides react with carbohydrate-based thiols in a two-step process involving sulfenyl transfer followed by desulfurative 2,3-allylic rearrangement, promoted by either triphenylphosphine or silver nitrate, to give novel saccharide mimetics. In an alternative embodiment of the same chemistry anomeric thiols are coupled with carbohydrates derivatized in the form of 2-(2-pyridyldithio-3-butenyl) ethers. This new method of glycoligation does not require protection of hydroxyl groups and is compatible with the presence of acetamides, azides, trichloroethoxycarbamates, and thioglycosides. Variations on the general theme enable the preparation of mimetics of reducing and nonreducing oligosaccharides as well as of nonglycosidically linked systems.

Full text of DOI:10.1021/jo102411j

ARTICLE
pubs.acs.org/joc
Protecting Group-Free Glycoligation by the Desulfurative
Rearrangement of Allylic Disulfides as a Means of Assembly of
Oligosaccharide Mimetics
Venkataraman Subramanian,† Myriame Moumꢀe-Pymbock,† Tianshun Hu,† and David Crich*,†,‡
†Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States
‡Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France
S Supporting Information
b
ABSTRACT:
2-(2-Pyridyldithio-3-butenyl) glycosides react with carbohydrate-based thiols in a two-step process involving sulfenyl transfer
followed by desulfurative 2,3-allylic rearrangement, promoted by either triphenylphosphine or silver nitrate, to give novel saccharide
mimetics. In an alternative embodiment of the same chemistry anomeric thiols are coupled with carbohydrates derivatized in the
form of 2-(2-pyridyldithio-3-butenyl) ethers. This new method of glycoligation does not require protection of hydroxyl groups and
is compatible with the presence of acetamides, azides, trichloroethoxycarbamates, and thioglycosides. Variations on the general
theme enable the preparation of mimetics of reducing and nonreducing oligosaccharides as well as of nonglycosidically linked
systems.
’ INTRODUCTION
problems but do not lessen the challenges to be faced in such
syntheses. Other oligosaccharides of interest include the
β-(1f6)-glucans, which are critical components of yeast cell
walls,8 and the mycobacterial polysaccharides 3-O-methyl-
R-(1f4)-mannan and 6-O-methyl-R-(1f4)-glucan. These lat-
ter methylated glycans enhance the rate of fatty acid biosynthesis
by the FA synthetase I from Mycobacterium smegmatis through
association with the tetraenonic fatty acid products, for which at
least a dodecasaccharide is required for optimal binding.9 An-
other oligosaccharide of interest is the adhesin poly-β-(1f6)-N-
acetyl-D-glucosamine from Escherichia coli10 and Staphylococcus
aureus11 implicated in the growth of biofilms of these organisms
and for which oligomers up the undecamer have been assembled
by stepwise and block organic syntheses.12 Yet another situation
is presented by the glycan heparin of which a pentasaccharide
motif suffices for association with antithrombin III, while an
octadecasaccharide is the optimal chain length for the formation
of a tertiary complex with both thrombin and antithrobin III.13
Ideally, large glycans can be constructed by the block assembly
approach;14 unfortunately, with certain exceptions,15 such
Peptide chemistry has benefitted enormously from the advent
of chemical ligation techniques and native chemical ligation
techniques enabling the assembly of larger peptides from two or
more smaller segments using minimalist protecting group strategies;1
the synthesis of complex oligosaccharides would similarly be
considerably advanced by methods for the linking together of
smaller preassembled oligosaccharides, preferably in an unpro-
tected form. The need for the synthesis of such oligosaccharides,
however, is increasing as it becomes apparent that for optimal
binding certain carbohydrate-protein interactions require
longer oligosaccharides. A case in point is the β-(1f3)-glucan
interaction with the lectin dectin 1 for which the minimal binding
motif is the decasaccharide.2 While the synthesis of a β-(1f3)-
glucodecaose has been reported,2c the assembly of even relatively
short β-(1f3)-glucans3 is challenging4 and is frequently com-
plicated by the unanticipated formation of R-glycosidic bonds
depending on the substituent pattern in both the donor and the
acceptor despite the reliance on neighboring group participa-
tion.5 The established adoption of nonchair conformations by
some pyranoside residues in the growing chain,3,6 stereochemical
matching and mismatching effects,7 and the conformation of
the polymer go some way toward explaining the origin of these
Received: December 7, 2010
Published: March 23, 2011
r
2011 American Chemical Society
3691
dx.doi.org/10.1021/jo102411j J. Org. Chem. 2011, 76, 3691–3709
|

The Journal of Organic Chemistry
ARTICLE
Scheme 1. Two Strategies for the Construction of Oligosac-
charide Mimetics
Scheme 2. The Allylic Xanthate Rearrangement Pathway to
Mono- and Disaccharyl Anomeric Sulfenyl Donors
or negatively on the binding of the construct to its biological
target. In our laboratory we have been engaged in the develop-
ment of the highly functional group respective dechalcogenative
2,3-sigmatropic rearrangement of allylic disulfides and selenosul-
fides as a means of the functionalizationof thiols under mild protic
conditions.21 This method, which is somewhat related to the
thiol-ene and thiol-yne reactions in that it requires derivatiza-
tion of one of the substrates with a thiol and results in a thioether
linkage, has been successfully applied to the formation of glyco-
peptides mimetics22 and to the functionalization of proteins.23
Here, we describe the extension of this method to the formation
of oligosaccharide mimetics and, out of necessity, describe
syntheses of carbohydrate-based thiols that may also find applica-
tion in the thiol-ene and thiol-yne reactions and in other
conjugation processes relying on thiolate alkylations.24
’ RESULTS AND DISCUSSION
methods have enjoyed only modest success owing to the com-
plexities of the structures involved and especially the need for very
high levels of stereocontrol. As such, chemists have turned to
alternative methodologies that enable the ligation of preformed
oligosaccharides into larger glycan-like structures. Among these
methods the copper-catalyzed variant of the Huisgen 1,3-dipolar
cycloaddition of alkynes and azides, known as Click chemistry,16
because of the mildness of its reaction conditions and very broad
functional group tolerance, has come to dominate the area of
glycoconjugate and oligosaccharide mimetic chemistry.17 The
rigid nature of the triazole unit introduced in this process,
however, leaves room for the development of alternative ligation
techniques. For this reason, and because of their functional group
tolerance, the so-called thiol-ene and thiol-yne click reactions18
in which thiols undergo additions to alkenes or alkynes, respec-
tively, resulting in thioether linkages have gained increased
popularity in recent years albeit with most examples still involving
the conjugation of sugars to peptides.19 The thiol-ene and
thiol-yne reactions differ from the copper-catalyzed Huisgen
1,3-dipolar cycloaddition click process not only in the nature of
the fundamental chemistry and the functional groups required for
ligation, but also in terms of the physical nature of the linkage unit
introduced. Thus, the planar triazole moiety capable of imitating
either a trans- or a cis-amide with its extensive hydrogen bonding
capabilities20 is replaced by the less-polar and more conforma-
tionally labile thioether unit, which may impact either positively
Application of the desulfurative rearrangement of allylic dis-
ulfides to the problem of the formation of oligosaccharide
mimetics can be envisaged as involving the coupling of an allylic
sulfenyl donor 1 affixed to the anomeric position to a carbohy-
drate based thiol 2 (Scheme 1, strategy a) or, conversely, through
the coupling of an anomeric thiol 4 with a sulfenyl donor located
elsewhere in the second partner 5 (Scheme 1, strategy b).
Ultimately, the two strategies give mimetics 3 and 6 that are
close structural analogues differing only in the placement of the
oxygen and sulfur atoms in the linker. Additionally, the rearran-
gement step can be executed with the aid of either triphenylpho-
sphine or silver nitrate (Scheme 1). Both strategies and both
reagents have been investigated as described below.
The anomeric sulfenyl donor strategy was targeted first,
necessitating the synthesis of anomeric allylic sulfenyl donors
and of deoxy sugar thiols. With the direct glycosylation of 2-(2-
pyridyldisulfenyl)-3-buten-1-ol giving only moderate yields as
previously described,22b attention was focused on approaches
involving construction of the allylic sulfenyl donor moiety after
formation of the glycosidic bond. As described previously,21e,22b,25
the readily assembled glycoside 7 can be converted into thio-
carbonate 9 and subjected to [3,3]-sigmatropic rearrangement to
afford the secondary allylic thiol derivative 11, which can be
converted to the sulfenyl donor 13 by saponification and installa-
tion of the disulfide moiety (Scheme 2). While this method
requires several steps it has the advantage of using only simple
3692
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
Scheme 3. Alternative Approach to an Anomeric Sulfenyl
Donor
Scheme 5. Synthesis of a 3-O-Sulfenyl Donor
Scheme 4. A More Direct Preparation of an Anomeric
Sulfenyl Donor
3-position of the glucopyranosyl systems based on the allylic
xanthate rearrangement. Thus, alkylation of diisopropylidene-D-
glucofuranose with the mesylate derived from cis-2-butene-1,4-
diol mono naphthylmethyl ether 23 gave a fully protected
derivative 24 that was taken through a standard protocol to
achieve rearrangement to the pyranose isomer 25 (Scheme 5).
The anomeric acetate formed in this protocol was converted
uneventfully to the corresponding methyl β-glycoside 27 by
Schmidt’s trichloroacetimidate chemistry29 before the naphthyl-
methyl group was removed oxidatively, setting the stage for the
application of the thiocarbonyl ester chemisty and conversion to
an allylic sulfenyl donor (Scheme 5).
With respect to the synthesis of monosaccharyl thiols these
were typically handled as their acetate esters to minimize
problems of oxidation, with cleavage under Zemplen-like condi-
tions immediately prior to use (Table 1, column 3). Depending
on the synthetic route employed the hydroxyl groups of these
thiol precursors were either free or protected in the form of
acetate esters. In the latter case, the esters were cleaved con-
comitantly with the thioesters under Zemplen conditions prior to
the ligation reaction. A 6-deoxyglucose-6-thiol 32 was prepared
according to a literature route in the form of its derived
thioacetate,30 while an analogous N-acetyl glucosamine 6-thioa-
cetate 33 was assembled by selective Mitunsobu reaction31 at the
6-position without the need for protecting groups. A glucose-
based 3-deoxy-3-mercapto sugar precursor 37 was prepared in a
straightforward manner from peracetyl 3-thioglucopyranoside32
via the trichloroacetimidate 36, while the known phenylthio
analogue 38 was obtained directly from the anomeric acetate
(Scheme 6). The 1-deoxy-mercapto-β-D-glucopyranose perester
39 was a commercial compound.
robust chemistry and can generally be conducted in high
overall yield.
Seeking to lower the temperature of the sigmatropic rearran-
gement step and at the same time to dissociate saponification
of the acetate protecting groups from the unmasking of the
allylic thiol, we briefly investigated a variant on this approach
(Scheme 3). This modification features the use of a thionocar-
bamate rather than a thiocarbonate, such that differential
saponification can be affected, that of a palladium-catalyzed
[3,3]-sigmatropic rearrangement of the allylic thiocarbonyl sys-
tem related to ones developed earlier by ourselves25 and by other
laboratories,26 and, recalling the work of Kahne on the release of
esters under neutral conditions,27 cleavage of the rearranged
thiocarbamate by a reductive cyclization process (Scheme 3).
Although certainly longer than the approach employing the
thermal sigmatropic rearrangement, the chemistry described in
Scheme 3 may be advantageous for more complex and thermally
sensitive substrates.
A third more efficient approach is exemplified for the case of
N-acetylglucosamine, which was converted to the oxazoline 19
by standard means28 and coupled with the acceptor 2022b in the
presence of cupric chloride (Scheme 4). The subsequent steps of
saponifcation and sulfenyl transfer took place under the standard
conditions and led to the formation of the anomeric sulfenyl
donor 22.
With a series of monomeric sulfenyl donors and thiols in hand,
attention was turned to the ligation protocol. This was typically
conducted in methanolic solution by admixture of the two
components, with monitoring of the sulfenyl transfer step either
by TLC or electrospray mass spectrometry, followed by promo-
tion of the desulfurative rearrangement by addition of triphenyl-
phosphine or silver nitrate. As we have discussed previously,21b,c
the use of trialkylphosphines in place of triarylphosphines
generally results in the competing nucleophilic cleavage of the
With respect to the alternative strategy based on the use
of anomeric thiols, a protocol for the synthesis of O-[2-(2-
pyridyldisulfenyl)-3-butenyl] ethers was developed for the
3693
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
Table 1. Ligation of Monosaccharyl Sulfenyl Donors and Thiols
disulfide intermediate and related processes. For this reason the
use of highly water-soluble phosphines such as tris(carboxy-
ethyl)phosphine, which are otherwise expected to increase the
rearrangement rate, is precluded. The silver nitrate-based system
is a later variant on the original phosphine-mediated rearrange-
ment that was developed to circumvent the reliance on the
insoluble phosphine.25 Examples of both methods are presented
in the reactions set out in Table 1.
All of the couplings illustrated in Table 1 proceeded in
moderate to good yield, whether promoted by triphenylpho-
sphine or by silver nitrate, and gave excellent trans-selectivity for
the 2-butenyl linker. The examples set out in Table 1 further
demonstrate that this ligation protocol is compatible with
acetamide groups and thioglycosidic units in addition to hydroxyl
groups and O-glycosidic bonds. The reaction sequence can be
used to assemble mimics of either classical “head-to-tail”-linked
3694
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
Scheme 6. Synthesis of 3-Deoxy-3-mercapto Sugar
Precursors
Scheme 8. Synthesis of Two Primary Disaccharyl Thiol
Precursors
Scheme 7. Synthesis of a Disaccharyl Sulfenyl Donor
exemplified in Schemes 7 and 8, and as is described fully in the
Experimental Section (Schemes 9-14), these units were as-
sembled by the combination of standard coupling methods with
variations on the themes set out in Schemes 2-5 for the
introduction of the allylic disulfide and thiol moieties. These
syntheses were generally uneventful and featured, inter alia, the
use of acetonitrile to direct glycosylations to the β-stereochem-
istry in the 2-azido-2-deoxyglucose series,34 the use of the
sulfoxide glycosylation35 method and the activation of glycosyl
sulfoxides in the presence of thioglycosides as described origin-
ally by the van Boom group,35b,36 the application of the Ley-type
bisacetal protecting group for the 3- and 4-positions in the
glucosamine series,37 and the employment of both diisopropy-
lidene glucofuranose and a 4,6-O-benzylidene protected gluco-
pyranosyl-3-ol3,38 as acceptors in the synthesis of laminaribiose
derivatives. As in the monosaccharide series thiols were, with the
exception of the laminaribiosyl thiol 65, generated and handled
as thioacetates which were cleaved immediately prior to use
typically with concomitant removal of any residual acetate esters.
The various disaccharyl sulfenyl donors and thiols synthesized in
this manner were coupled in methanol at room temperature
leading to the results set out in Table 2.
oligosaccharides (Table 1, entries 1-7 and 9) or can be used to
provide mimics of nonglycosidically linked disaccharides
(Table 1, entry 8) which are of current interest.33 For the mimics
of the classical head-to-tail oligomers, the ligation can be con-
ducted according to either of the two design principles set out in
Scheme 1, but at least for the mimics of the β-(1f3)-glucans the
employment of the anomeric thiol (Scheme 1b) results in a
shorter reaction time than the use of an anomeric sulfenyl donor
(Scheme 1a) as is seen from a comparison of entries 6 and 7
(Table 1). We believe that this difference in reactivity is due to
the steric hindrance about the thiol derived from precursor 37
(Table 1, entry 6) which retards both sulfenyl transfer and
especially the critical desulfurative 2,3-sigmatropic rearrange-
ment step. This retarding effect of steric bulk around the thiol
component on the sigmatropic rearrangement is in accord with
predictions from computational studies.21e
The results set out in Table 2 follow the pattern of moderate to
good yield and excellent trans-selectivity established for the
monosaccharides in Table 1. The results presented in Table 2
also bring the azide and trichloroethoxycarbamates into the range
With proof of principle established at the level of monosac-
charyl sulfenyl donors and thiols, attention was turned to the
synthesis of a set of disaccharyl allylic disulfides and thiols. As
3695
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
Table 2. Ligation of Disaccharyl Sulfenyl Donors and Thiols
of functional groups tolerated by this ligation protocol and
extend the type of linkages mimicked to include the head-to-
head linkage of the nonreducing oligosaccharides (Table 2, entry 5)
such as present in sucrose, trehalose, and the antibiotic ever-
ninomycin.39 As was the case with the monosaccharyl examples
(vide supra) application of the protocol to a thiol located at
the 3-position of a glucopyranose ring resulted in longer reaction
times, presumably for steric reasons (Table 2, entry 3) than the
employment of the alternative mode of operation with an anomeric
thiol and a 3-O-allylic sulfenyl donor (Table 2, entry 4).
Overall, the results presented in Tables 1 and 2 demonstrate
sulfenyl transfer to give allyl disulfides followed by desulfura-
tive rearrangement to provide a potentially useful means of
combining short oligosaccharides into larger oligosaccharide
mimetics. The ligation process takes place at room tempera-
ture in protic solvents and does not require the presence of
protecting groups. It may be effectively promoted through
the use of silver nitrate or triphenylphosphine, and tolerates
the presence of various functional groups such as the azide,
thioglycoside, and trichloroethoxycarbamate systems. Mimics
of reducing and nonreducing oligosaccharides as well as of
nonglycosidically linked systems can be produced by this
facile ligation process.
sulfate and concentrated at ambient temperature under water aspirator
vacuum. Column chromatography was conducted over silica gel unless
otherwise stated.
General Procedure 1 for the Preparation of Allylic Thio-
nocarbonates. A solution of phenyl chlorothionocarbonate (2.0 mmol)
in CH2Cl2 (2 mL) was added to a solution of the alcohol (1.0 mmol),
pyridine (15.0 mmol), and DMAP (0.1 mmol) in CH2Cl2 (10.0 mL) and
the resulting dark-yellow solution was stirred at room temperature for 4 h.
The reaction mixture was poured into H2O (20 mL) and extracted with
CH2Cl2 (3 ꢀ 10 mL). The combined organic phases were dried, filtered,
evaporated, and purified by column chromatography.
General Procedure 2 for the [3,3]-Sigmatropic Rearrange-
ment of Allylic Thionocarbonates. A solution of allylic thiono-
carbonate (1 mmol) in toluene (10.0 mL) was heated at reflux for 12 h.
Evaporation of the solvent and chromatographic purification of the
crude products with EtOAc/hexanes as eluent afforded the products.
General Procedure 3 for Saponification of Phenoxycarbo-
nylthioxybutenyl Groups and Installation of the Pyridyl
Disulfide Moiety. To a solution of the glycosyl thiocarbonate (0.5
mmol) in MeOH (2.5 mL) was added, dropwise at 0 °C, a freshly
prepared solution of 1 M KOH (2.3 mmol, 1.5 equiv per group to be
saponified). The resulting mixture was stirred for 0.5 h then neutralized
by careful addition of Amberlyst-15 resin and then filtered. The filtrate
was added dropwise to a solution of 2,20-dipyridyl disulfide (0.7 mmol)
in MeOH at 0 °C. The resulting mixture was allowed to warm to room
temperature and stirred for 4 h. The solvent was removed in vacuo and
the residue was purified by silica gel column chromatography to give the
desired products.
’ EXPERIMENTAL SECTION
General Experimental. Unless otherwise stated 1H and 13C NMR
spectra were carried out at 500 and 125 MHz, respectively, in deuterio-
chloroform solution, with chemical shifts downfield from tetramethylsilane.
Specific rotations were measured in chloroform solution unless other-
wise stated. Unless otherwise stated extracts were dried over sodium
General Procedure 4 for the Preparation of Cyclic Bisace-
tals. Camphorsulfonic acid (0.34 mmol) was added to a stirred solution
of the glycoside (3.4 mmol) in MeOH (32 mL) at room temperature.
Then, trimethyl orthoformate (18.5 mmol) and butane-2,3-dione
3696
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
(4.0 mmol) were added and the mixture was heated at reflux for 14-16
h. The mixture was then basified to pH 8 by addition of triethylamine
and the solvents were removed under reduced pressure. The residue was
purified by silica gel column chromatography to give the desired
bisacetals.
General Procedure 5 for the Preparation and Isolation of
Tosylates. p-Toluenesulfonyl chloride (4.86 mmol) and tetramethy-
lethylenediamine (4.86 mmol) were added sequentially to a stirred
solution of the glycoside (0.24 mmol) in acetonitrile (25 mL) at room
temperature. The mixture was stirred for 2-5 h, then poured into ice
and extracted twice with CH2Cl2. The combined organic layers were
dried, filtered, and concentrated in vacuo. The residue was purified by
silica gel chromatography.
General Procedure 6 for the Introduction of the 6-Acetyl-
thio Group from the Corresponding Tosylates. To a solution
of tosylate (2.12 mmol) in DMF (28 mL) was added potassium
thioacetate (4.24 mmol). The reaction mixture was heated to 80 °C
(50 °C in the case of the disaccharide) for 18-36 h then concen-
trated in vacuo. The residue was taken up in CH2Cl2 and washed
with water. The aqueous phase was extracted twice with CH2Cl2.
The combined organic layers were dried, filtered, and concentrated
and the 6-acetylthio derivatives were isolated by silica gel column
chromatography.
General Procedure 7 for the Oxidation of Thioglycosides
to Glycosyl Sulfoxides. To a stirred solution of thioglycoside
(1.06 mmol) in CH2Cl2 (30 mL) was added dropwise at -80 °C
a freshly prepared solution of m-chloroperoxybenzoic acid (1.04
mmol) in CH2Cl2 (3.8 mL). The resulting mixture was stirred
at -80 °C for 0.5-1.5 h then quenched by addition of saturated
aqueous NaHCO3. The resulting mixture was allowed to warm to
room temperature and the aqueous phase was extracted twice with
CH2Cl2. The combined organic layers were dried, filtered, concen-
trated, and purified by silica gel column chromatography to yield the
desired glycosyl sulfoxides.
General Procedure 8 for Glycosylation under NIS/TfOH
Conditions. The glycosyl donor (0.56 mmol) and glycosyl acceptor
(0.73 mmol) were stirred in CH2Cl2 (4 mL) at room temperature in the
presence of activated 4 Å powdered molecular sieves for 0.5 h before the
reaction mixture was cooled to -35 °C. Then, N-iodosuccinimide (1.12
mmol) and trifluoromethanesulfonic acid (0.34 mmol) were added
sequentially and the resulting mixture was stirred for 2 h. The reaction
was quenched by addition of 20% Na2S2O3 and allowed to warm to
room temperature and the aqueous phase was extracted twice with
CH2Cl2. The combined organic layers were dried, filtered, concentrated,
and purified by silica gel column chromatography to yield the desired
product.
General Procedure 9 for Deprotection of 2-(Pheny-
loxycarbonylthioxy)-3-butenyl Disaccharides with Trifluor-
oacetic Acid. To a stirred solution of the disaccharide (0.14 mmol)
and thioanisole (1.35 mmol) in CH2Cl2 (8 mL) was added an
aqueous solution of trifluoroacetic acid, TFA/H2O (19:1) (4 mL),
at room temperature. The resulting mixture was stirred for 0.5 to 1 h
at room temperature, taken up in toluene, and then evaporated.
The deprotected disaccharide was isolated by silica gel column
chromatography.
General Procedure 10 for Acetonide Removal from Deri-
vatives of 1,2;5,6-Diisopropylideneglucofuranose Deriva-
tives and the Subsequent Installation of Acetate Groups.
The acetonide protected glucofuranoside (1.0 mmol) was dissolved in
80% acetic acid (10.0 mL) and heated with stirring to 95 °C for 8 h. After
cooling the solvents were removed under reduced pressure, and the
reaction mixture was azeotroped with toluene (2 ꢀ 30 mL). The crude
product was dried under vacuum and dissolved in acetic anhydride (10.0
mmol), pyridine (10.0 mmol), and DMAP (0.1 mmol) and stirred at
room temperature for 12 h. The solvents were evaporated under vacuum
and the crude product was partitioned between EtOAc (30.0 mL) and
water. The organic part was washed with brine (50 mL), dried, and
evaporated to dryness.
General Procedure 11 for the Preparation of Glycosyl
Trichloroacetimidates. To a stirred solution of the anomeric acetate
(1.0 mmol) in DMF (10.0 mL) was added NH2NH2 AcOH (1.5
3
mmol), after which the reaction mixture was stirred at room temperature
for 3-4 h before it was diluted with EtOAc (100 mL) and washed with
brine (50 mL). The organic portion was separated and dried to give the
hemiacetal, which was dissolved in CH2Cl2 (100 mL) and treated with
trichloroacetonitrile (10.0 mmol), followed by DBU (0.1 mmol). The
reaction mixture was stirred at room temperature for 12 h before the
solvents were evaporated and the crude product was purified by column
chromatography with EtOAc/hexanes as eluent.
General Procedure 12 for Glycosylation with Trichloroa-
cetaimidates. The trichloroacetimidate (1.2 mmol), alcohol (1.0
mmol), and activated 4 Å molecular sieves were mixed in CH2Cl2
(10 mL) and stirred at room temperature for 0.5 h before TMSOTf
(0.125 mmol) was added. Stirring was continued at room temperature
for 12 h before triethylamine (0.2 mmol) was added and the reaction
mixture was filtered. The solvents were evaporated and the crude
product was purified by column chromatography with EtOAc/hexanes
as eluent.
General Procedure 13 for the Deprotection of Naphthyl-
methyl Groups. The protected pyranoside (1.0 mmol) was dissolved
in a mixture of ∼9:1 CH2Cl2 and water (10 mL) and DDQ (1.3 mmol)
was added. The reaction mixture was stirred at room temperature for 3-
4 h until TLC showed the starting material had been consumed. The
reaction mixture was diluted with EtOAc (100 mL) and washed with
saturated aqueous NaHCO3 (50 mL). The combined organic part was
dried and evaporated to dryness. The crude product was purified by
column chromatography with ethyl acetate/hexanes as eluent.
General Procedure 14 for Triphenylphosphine-Promoted
Rearrangement of Allylic Disulfides. A solution of acetylthio
sugar (0.20 mmol) in MeOH (1.7 mL) was sparged with nitrogen before
a freshly prepared solution of 1 M NaOMe in degassed MeOH (0.2 mL)
was added. The resulting mixture was stirred for 0.5 h, quickly
neutralized by addition of dry Amberlyst IR 120 resin, filtered, and then
directly added to a stirred solution of the allylic sulfenyl donor (0.24
mmol) in MeOH (2 mL) at room temperature. The resulting mixture
was stirred at room temperature until TLC showed complete consump-
tion of the thiol (14 h). Then, triphenylphosphine (0.24 mmol) was
added at room temperature and the resulting mixture was stirred for an
additional 16 h. The mixture was evaporated in vacuo and subjected to
chromatographic purification eluting with dichloromethane/methanol
(15:1).
General Procedure 15 for Silver Nitrate Promoted Rear-
rangement of Allylic Disulfides. A stirred solution of protected
thiol in degassed MeOH (1 mmol, 2.0 mL, 0.5 M) was treated with
metallic sodium (2-3 equiv) and stirred under a N2 atmosphere for 4-
6 h until the saponification was complete (monitored by ESI mass
spectrometry and TLC). The reaction mixture was acidified with
Amberlyst 15 resin and filtered. The resin was washed with MeOH
(3 ꢀ 5 mL). The combined washings and the filtrate were concentrated
to a final volume of 1-2 mL and transferred to a stirred solution of
disulfide (1.0 mmol, 20 mL, 0.05 M) in MeOH. The reaction mixture
was stirred at room temperature under an atmosphere of nitrogen until
complete disulfide exchange was visible on TLC (usually less than an
hour). The reaction mixture was then treated with solid silver nitrate
(2.0 equiv) and stirred in the dark for 16 h. After completion of the
reaction (monitored by ESI mass spectrometry), NaCl (10 equiv) was
added and the reaction mixture was stirred for 3-4 h. The reaction
mixture was diluted with MeOH and centrifuged to remove the black
3697
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
precipitate. The solvent was then concentrated to afford the crude
product, which was purified by column chromatography
4-(Phenyloxythionocarbonyloxy)-2Z-butenyl Tetra-O-acet-
yl-β-D-glucopyranoside (9). The title compound was prepared in
90% yield from 7 by the literature procedure.22b It had spectral data
identical with the literature values.22b
2-(Phenyloxycarbonylthioxy)-3-butenyl Tetra-O-acetyl-β-
D-glucopyranoside (11). The title compound was prepared in 90%
yield from 9 by the literature procedure.22b It had spectral data identical
with the literature values.22b
5.82 (m, 1H), 5.36 (dd, J = 17.0, 5.0 Hz, 1H), 5.22 (dd, J = 11.5, 10.5 Hz,
1H), 5.14-5.10 (m, 1H), 5.07-4.99 (m, 2H), 4.96-4.91 (m, 1H), 4.88
(t, J = 9.0 Hz, 1H), 4.58 (dd, J = 8.0, 6.0 Hz, 1H), 4.43 (t, J = 8.0 Hz, 1H),
4.35 (dd, J = 12.5, 4.5 Hz, 1H), 4.20-4.16 (m, 3H), 4.14-4.09 (m, 1H),
4.07-4.02 (m, 1H), 3.89-3.85 (m, 1H), 3.74 (dd, J = 10.5, 6.5 Hz, 1H),
3.68-3.65 (m, 2H), 2.14 (s, 3H), 2.12 (s, 3H), 2.07 (s, 3H ꢀ 2), 2.06 (s,
3H), 2.05 (s, 3H), 2.02 (s, 3H), 2.01 (s, 3H), 2.00 (s, 3H), 1.99 (s, 3H ꢀ
3), 1.97 (s, 3H), 1.96 (s, 3H); 13C NMR δ 170.9, 170.7, 170.6, 169.6,
169.5, 169.4, 169.2, 169.0, 168.9, 151.3, 133.8, 133.5, 129.7, 126.5, 121.4,
119.1, 119.0, 101.5, 101.2 (2C), 100.7, 79.0, 78.9, 73.2, 72.7, 72.6, 72.2,
71.9, 71.7, 71.3, 70.3, 68.5, 68.4, 68.3, 62.3, 62.2, 61.9, 48.8, 48.0, 21.2,
21.1, 20.9, 20.8, 20.7, 20.7, 20.6, 20.5; ESIHRMS calcd for C37H46O20S-
Naþ [M þ Na]þ 865.2201, found 865.2220.
2-(2-Pyridyldithio)-3-butenyl β-D-Glucopyranoside (13).
The title compound was prepared in 76% yield as an approximately
1.1:1 mixture of isomers from 11 by general procedure 3 in the form of a
white foam. 1H NMR (CD3OD) δ 8.35-8.36 (m, 1H), 7.92-7.94 (m,
1H), 7.19-7.36 (m, 1H), 5.79-5.88 (m, 1H), 5.23 (dd, J = 17.0, 9.0 Hz,
1H), 5.13-5.16 (m, 1H), 4.27 (dd, J = 14.5, 8.0 Hz, 1H), 4.10-4.18 (m,
1H), 3.75-3.86 (m, 3H), 3.62-3.66 (m, 1H), 3.17-3.32 (m, 8H); 13C
NMR δ 160.6, 148.8, 138.0, 134.22, 134.17, 121.1, 120.41, 120.38, 118.4,
118.2, 103.4, 103.3, 76,88, 76.86, 73.9, 70.42, 70.38, 70.10, 70.07, 61.6,
61.5, 54.3, 54.2; ESIHRMS calcd for C15H21NO6S2Na [M þ Na]þ
398.0708, found 398.0717.
4-Hydroxy-2Z-butenyl Hepta-O-acetyl-β-D-laminaribio-
side (8). To a stirred solution of peracetyl laminaribiosyl bromide38
(698 mg, 1.0 mmol) in CH2Cl2 (10.0 mL) was added cis-butene-1,4-diol
(1.76 g, 20.0 mmol), Ag2CO3 (411 mg, 1.5 mmol), CaSO4 (1.0 g), and a
catalytic amount of I2. The reaction mixture was shielded from light and
stirred at room temperature for 12 h, then was diluted with CH2Cl2
(50.0 mL) and filtered through a pad of Celite. The filtrate was washed
with saturated NaHCO3 (50.0 mL), and the combined organic portion
was dried over Na2SO4 and evaporated to dryness. The crude product
was purified by column chromatography over silica gel (EtOAc/
hexanes) to give the title compound as a colorless liquid in 80% yield.
[R]23D -43.5 (c 1.5); 1H NMR δ 5.84-5.79 (m, 1H), 5.60-5.55 (m,
1H), 5.11 (t, J = 9.5 Hz, 1H), 5.04 (t, J = 9.5 Hz, 1H), 4.98 (t, J = 8.0 Hz,
1H), 4.93 (t, J = 10.0 Hz, 1H), 4.87 (t, J = 8.5 Hz, 1H), 4.57 (d, J = 8.0 Hz,
1H), 4.41 (d, J = 8.0 Hz, 1H), 4.35 (dd, J = 12.5, 4.0 Hz, 1H), 4.31 (dd,
J = 12.5, 5.5 Hz, 1H), 4.21 (dd, J = 13.0, 8.0 Hz, 1H), 4.17 (s, 2H), 4.16
(s, 2H), 4.02 (dd, J = 7.5, 2.5 Hz, 1H), 3.86 (t, J = 9.5 Hz, 1H), 3.67-3.64
(m, 2H), 2.12 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 2.01 (s, 3H), 1.98 (s,
3H ꢀ 2), 1.96 (s, 3H); 13C NMR δ 171.1, 170.7, 170.6, 169.6, 169.5,
169.4, 169.2, 133.6, 126.9, 101.2, 99.3, 79.1, 73.2, 72.8, 72.1, 71.9, 71.2,
68.6, 68.3, 64.0, 62.5, 61.9, 58.7, 21.1, 20.9, 20.8, 20.7, 20.7, 20.6, 20.5;
ESIHRMS calcd for C30H42O19Naþ [M þ Na]þ 729.2218, found
729.2210.
2-(2-Pyridyldithio)-3-butenyl β-D-Laminaribioside (14).
Following general procedure 3, and eluting with MeOH/CH2Cl2 the
title compound was obtained as an approximately 1:1 mixture of
1
stereoisomers in 70% yield. H NMR (CD3OD) δ 8.36 (d, J = 7.0
Hz, 1H), 7.95-7.92 (m, 1H), 7.79 (t, J = 9.0 Hz, 1H), 7.20 (dd, J = 9.0,
6.0 Hz, 1H), 5.88-5.78 (m, 1H), 5.27-5.20 (m, 1H), 5.16-5.13 (m,
1H), 4.55 (d, J = 10.0 Hz, 1 H), 4.33 (dd, J = 15.0, 10.0 Hz, 1H), 4.16-
4.09 (m, 1H), 3.89-3.86 (m, 3H), 3.85-3.80 (m, 1H), 3.78-3.77 (m,
1H), 3.69-3.61 (m, 2H), 3.56-3.51 (m, 1H), 3.42-3.36 (m, 4H),
3.33-3.25 (m, 6H); 13C NMR (CD3OD) δ 160.6, 148.8, 137.9, 134.2,
134.1, 121.1, 120.4, 118.5, 118.3, 104.1, 102.9, 102.9, 86.7, 77.0, 76.6,
76.5, 74.3, 73.2, 70.4, 70.1, 68.8, 68.7, 61.4, 54.2, 54.1; ESIHRMS calcd
for C21H31NO11S2Na [M þ Na]þ 560.1236, found 560.1220.
4-(4-Nitrophenyloxythionocarbonyloxy)-2Z-butenyl Tet-
ra-O-acetyl-β-D-glucopyranoside (15). Alcohol 722b (209.2 mg,
0.5 mmol), pyridine (687.5 μL, 8.5 mmol), and DMAP (12.2 mg, 0.01
mmol) were dissolved in dry CH2Cl2 (4.0 mL), and 4-nitrophenyl
chlorothionoformate (119.7 mg, 0.55 mmol) in CH2Cl2 (1.0 mL) was
added dropwise. The reaction mixture was stirred at room temperature
for 5 h and then diluted with CH2Cl2 (10 mL) and washed with 2 N HCl
and brine. The organic layer was dried and concentrated and purified by
column chromatography over silica gel (eluent: EtOAc/hexanes = 1/2)
to give the title compound (209.8 mg, 70%) as a colorless oil. [R]D
-
12.2 (c, 2.0); 1H NMR (400 Hz) δ 8.28-8.32 (m, 2H), 7.26-7.30 (m,
2H), 5.82-5.85 (m, 2H), 5.19 (t, J = 9.6 Hz, 1H), 5.06-5.12 (m, 3H),
4.97-5.02 (m, 1H), 4.56 (d, J = 7.2 Hz, 1H), 4.41-4.45 (m, 1H), 4.30-
4.34 (m, 1H), 4.24 (dd, J = 12.0, 4.8 Hz, 1H), 4.13 (dd, J = 12.0, 2.4 Hz,
1H), 3.67-3.71 (m, 1H), 2.03 (s, 3H), 2.06 (s, 3H), 1.98 (s, 3H), 2.00
(s, 3H); 13C NMR δ 193.7, 170.8, 170.5, 169.6, 169.5, 157.7, 146.2, 11.3,
125.6, 123.5, 99.8, 73.0, 72.1, 71.4, 70.0, 68.5, 64.9, 62.1, 21.0, 20.9, 20.8;
ESIHRMS calcd for C25H29NO14SNa [M þ Na]þ 622.1206, found
622.1212.
4-(Phenyloxythionocarbonyloxy)-2Z-butenyl Hepta-O-
acetyl-β-D-laminaribioside (10). Following general procedure 1,
and eluting with 75% EtOAc/hexanes the title compound was obtained
in 88% yield. [R]23D -11.0 (c 1); 1H NMR δ 7.43 (t, J = 8.0 Hz, 2H),
7.30 (t, J = 7.5 Hz, 1H), 7.11-7.09 (m, 2H), 5.88-5.84 (m, 1H), 5.82-
5.77 (m, 1H), 5.15-5.11 (m, 2H), 5.09-5.06 (m, 2H), 5.04-4.99 (m,
1H), 4.96 (t, J = 10.0 Hz, 1H), 4.89 (t, J = 9.5 Hz, 1H), 4.58 (d, J = 8.5 Hz,
1H), 4.44 (d, J = 8.5 Hz, 1H), 4.38-4.33 (m, 3H), 4.19-4.18 (m, 2H),
4.03 (dd, J = 12.5, 2.0 Hz, 1H), 3.87 (t, J = 9.5 Hz, 1H), 3.68-3.66 (m,
2H), 2.14 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 2.02 (s, 3H), 2.01 (s, 3H),
2.00 (s, 3H), 1.98 (s, 3H); 13C NMR δ 195.1, 170.9, 170.7, 170.6, 169.6,
169.5, 169.4, 169.1, 153.6, 130.9, 129.8, 126.9, 126.2, 122.1, 101.2, 99.6,
79.2, 73.2, 72.7, 72.2, 71.9, 71.3, 69.5, 68.4, 68.3, 64.4, 62.3, 61.9, 21.2,
21.0, 20.8, 20.8, 20.7, 20.7, 20.6; ESIHRMS calcd for C37H46O20SNaþ
[M þ Na]þ 865.2201, found 865.2190.
4-[N-(2-Azidoethyl)-N-(benzyl)thionocarbamoyloxy]-2Z-
butenyl 2,3,4,6-Tetra-O-acetyl-β-D-glucopyranoside (16).
The thionocarbonate 15 (196 g, 0.33 mmol), N-(2-azidoethyl)ben-
zylamine40 (86.3 mg, 0.49 mmol), and DMAP (80.0 mg, 0.65 mmol)
were dissolved in dry CH2Cl2 (2 mL), and the reaction mixture was
stirred at room temperature overnight. The reaction mixture was diluted
with CH2Cl2 (5 mL) and washed with 2 N HCl and brine. The organic
layer was dried and concentrated and purified chromatographically
(eluent: EtOAc/hexanes = 1/2) to give the title compound (152.1
1
mg, 73%) as a colorless oil. [R]D -2.9 (c, 0.6); H NMR (CDCl3) δ
7.30-7.36 (m, 4H), 7.14 (d, J = 7.0 Hz, 1H), 5.65-5.83 (m, 2H), 5.16-
5.20 (m, 3H), 5.04-5.12 (m, 2H), 4.97-5.03 (m, 2H), 4.81 (s, 1H),
4.51-4.59 (m, 1H), 4.32-4.33 (m, 1H), 4.24-4.29 (m, 1H), 4.12-
4.17 (m, 1H), 3.90 (t, J = 6.5 Hz, 1H), 3.65-3.72 (m, 2H), 3.57 (t, J = 6.5
Hz, 1H), 3.37 (t, J = 6.0 Hz, 1H), 2.04 (s, 3H), 2.08 (s, 3H), 2.02 (s, 3H),
2.00 (s, 3H); 13C NMR δ 189.6, 188.7, 170.9, 170.5, 169.62, 169.57,
136.2, 136.1, 129.9, 129.8, 129.1, 129.0, 128.2, 128.1, 128.0, 127.7, 127.6,
127.3, 126.4, 99.8, 99.7, 73.1, 72.10, 72..06, 71.5, 68.5, 67.5, 67.1, 65.0,
64.9, 62.1, 57.1, 53.7, 52.0, 49.4, 48.8, 46.9, 21.0, 20.9, 20.84, 20.83;
2-(Phenyloxycarbonylthioxy)-3-butenyl Tetra-O-acetyl-β-
D-laminaribioside (12). Following general procedure 2, and eluting
with 75% EtOAc/hexanes the title compound was obtained as an
1
approximately 1:1 mixture of stereoisomers in 95% yield. H NMR δ
7.39-7.36 (m, 2H), 7.24-7.23 (m, 1H), 7.16-7.13 (m, 2H), 5.94-
3698
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
ESIHRMS calcd for C28H36N4O11SNa [M þ Na]þ 659.1999, found
659.1979.
(dd, J = 3.2, 16.8 Hz, 2 ꢀ 1H), 5.28 (dd, J = 10.4, 11.6 Hz, 2 ꢀ 1H), 5.21
(dd, J = 4.4, 10.8 Hz, 2 ꢀ 1H), 5.04 (t, J = 9.6 Hz, 2 ꢀ 1H), 4.74 (t, J = 8.0
Hz, 2 ꢀ 1H), 4.02-4.28 (m, 2 ꢀ 4H), 3.86 (q, J = 8.8, 17.8 Hz, 2 ꢀ 1H),
3.82-3.66 (m, 2 ꢀ 2H), 2.04 (s, 2 ꢀ 3H), 2.00 (s, 2 ꢀ 6H), 1.92 (s, 2 ꢀ
3H); 13C NMR (100 MHz) δ 171.1, 171.0, 170.6, 169.6, 151.2, 134.0,
133.8, 129.8, 126.5, 121.5, 119.1, 119.0, 101.4,100.7, 72.4, 72.1, 71.6,
70.4, 68.8, 62.2, 54.8, 54.6, 48.9, 48.2, 23.6, 23.5, 20,9, 20.8; ESIHRMS
calcd for C25H31NO11SNa [M þ Na]þ 576.1516, found 576.1516.
2-(2-Pyridyldithio)-3-butenyl 2-Acetamido-2-deoxy-β-D-
glucopyranoside (22). The title compound was prepared according
to general procedure 3 as a white foam eluting from silica gel with
CH2Cl2/MeOH (25:1) as an approximately 1:1 mixture of diastereo-
mers in 60% yield over two steps. 1H NMR (400 MHz, CD3OD) δ 8.36
(s, 2 ꢀ 1H), 7.94-7.78 (m, 2 ꢀ 2H), 7.21 (t, J = 5.6 Hz, 2 ꢀ 1H), 5.87-
5.67 (m, 2ꢀ 1H), 5.19 (dd, J = 4.8, 16.8 Hz, 2 ꢀ 1H), 5.11 (d, J = 10.4
Hz, 2 ꢀ 1H), 4.47-4.39 (m, 2 ꢀ 1H), 4.16-4.50 (m, 2 ꢀ 1H), 3.86
(dd, J = 5.6, 9.6, Hz, 2 ꢀ 1H), 3.82-3.75 (m, 2 ꢀ 1H), 3.74-3.63 (m, 2
ꢀ 4H), 3.50-3.42 (m, 2 ꢀ 1H), 3.36-3.23 (m, 2 ꢀ 4H), 1.98 (s, 2 ꢀ
3H); 13C NMR (100 MHz, CD3OD) δ 172.5, 160.5, 148.9, 148.8, 138.1,
138.0, 134.2, 133,8, 121.1, 121,0, 120.2, 121.1, 118.4, 118.3, 116.9, 102.1,
101.7, 76.9, 76.7, 74.8, 74.7, 74.6, 71.4, 70.9, 69.9, 69.8, 61.6, 61.5, 56.1,
56.0, 54.4, 54.1, 22.1, 22.0; ESIHRMS calcd for C17H24N2O6S2Na [M þ
Na]þ 439.0974, found 439.0978.
4-(2-Naphthylmethyloxy)-2Z-butene-1-ol (23). A stirred so-
lution of cis-1,4-but-2-ene-diol (2.39 g, 27.1 mmol) in THF (10 mL) was
treated under an atmosphere of N2 with sodium hydride (0.38 g, 9.5
mmol) at 0 °C and stirring was continued at room temperature for 1 h.
2-(Bromomethyl)naphthalene (2.0 g, 9.0 mmol) was added and stirring
was continued at room temperature for 2 h before the reaction mixture
was heated to reflux for 6 h, then cooled to room temperature and
diluted with saturated aqueous NH4Cl (30 mL) and ethyl acetate
(20 mL). The organic portion was separated, dried, and evaporated to
dryness. The crude product was purified over silica gel with EtOAc/
hexanes as eluent to give the title compound 23 as a thick oil (1.76 g,
85%). 1H NMR δ 7.87-7.85 (m, 3H), 7.80 (s, 1H), 7.51-7.48 (m, 3H),
5.83 (dt, J = 11.0, 6.0 Hz, 1H), 5.78 (dt, J = 11.0, 6.0 Hz, 1H), 4.69 (s,
2H), 4.17 (d, J = 6.0 Hz, 2H), 4.13 (d, J = 6.5 Hz, 2H), 2.39 (br s, 1H);
13C NMR δ 135.6, 133.5, 133.3, 132.8, 128.5, 128.3, 128.1, 127.9, 126.9,
126.4, 126.2, 126.1, 72.8, 65.9, 58.8; ESIHRMS calcd for C15H16O2Na
[M þ Na]þ 251.1048, found 251.1055.
2-[N-(2-Azidoethyl)-N-(benzyl)carbamoylthioxy]-3-bute-
nyl 2,3,4,6-Tetra-O-acetyl-β-D-glucopyranoside (17). The
thionocarbamate 16 (91.4 mg, 0.15 mmol) and PdCl2(CH3CN)2 (3.9
mg, 0.015 mmol) were dissolved in CH2Cl2 (1.5 mL), and the reaction
mixture was stirred at 40 °C for 20 h before it was concentrated and
purified by column chromatography over silica gel (eluent: EtOAc/
hexanes = 1/2) to give the title compound (90.4 mg, 99%) as a complex
mixture of diastereomers and rotamers in the form of a colorless oil. 1H
NMR δ 7.22-7.37 (m, 5H), 5.85-5.95 (m, 1H), 5.36 (dd, J = 17.0, 6.0
Hz, 1H), 5.18-5.23 (m, 2H), 5.06-5.12 (m, 1H), 5.01 (t, J = 9.0 Hz,
1H), 4.64 (d, J = 7.5 Hz, 2.5H), 4.57 (d, J = 7.5 Hz, 0.5H), 4.35-4.39 (m,
0.5H), 4.24-4.31 (m, 1.5H), 4.12-4.16 (m, 1.5H), 4.01 (dd, J = 10.0,
8.0 Hz, 0.5 H), 3.84 (dd, J = 11.0, 4.0 Hz, 0.5 H), 3.70-3.76 (m, 1.5H),
3.44 (br s, 4H), 2.09 (s, 3H), 2.08 (s, 3H), 2.02 (s, 3H), 2.00 (s, 3H); 13C
NMR δ 170.9, 170.5, 169.6, 169.4, 134.8, 134.6, 129.1, 128.2, 127.5,
118.4, 118.3, 100.7, 100.5, 73.03, 72.95, 72.8, 72.1, 71.42, 71.37, 71.3,
68.7, 68.6, 62.2, 62.1, 52.8, 49.5, 47.9, 46.8, 46.5, 46.4, 21.0, 20.9, 20.85,
20.83; ESIHRMS calcd for C28H36N4O11SNa [M þ Na]þ 659.1999,
found 659.1969.
2-[N-(2-Azidoethyl)-N-(benzyl)carbamoylthioxy]-3-bute-
nyl β-D-Glucopyranoside (18). Compound 17 (46.0 mg, 0.07
mmol) was dissolved in dry MeOH (1 mL), and NaOMe (1.5 μL,
25%, 0.007 mmol) was added. The reaction mixture was stirred at room
temperature for 30 min, checked by TLC, and once the starting material
had disappeared, was neutralized with Amberlyst-15 resin, filtered,
concentrated, and purified by column chromatography over silica gel
(eluent: CH2Cl2/MeOH = 5/1) to give the title compound (25.5 mg,
75%) as a complex mixture of diastereomers and rotamers in the form of
a colorless oil. 1H NMR (CD3OD) δ 7.09-7.35 (m, 5H), 6.00-6.05
(m, 1H), 5.38 (d, J = 17.0 Hz, 1H), 5.16-5.19 (m, 1H), 4.68 (s, 2H),
4.38-4.43 (m, 1H), 4.34 (t, J = 8.5 Hz, 1H), 4.06-4.10 (m, 1H), 3.80-
3.88 (m, 2H), 3.64-3.69 (m, 1H), 3.50 (t, J = 6.0 Hz, 2H), 3.43 (br s,
4H), 3.34-3.37 (m, 1H), 3.27-3.31 (m, 4H), 3.20 (t, J = 8.5 Hz, 1H);
13C NMR δ 135.4, 135.2, 128.8, 128.7, 128.0, 127.65, 127.61, 117.0,
116.9, 103.8, 103.3, 76.93, 76.86, 76.8, 73.9, 73.8, 71.9, 71.3, 70.5, 70.4,
61.7, 61.6; ESIHRMS calcd for C20H28N4O7SNa [M þ Na]þ 491.1576,
found 491.1587.
2-(2-Pyridyldithio)-3-butenyl β-D-Glucopyranoside (13).
Compound 18 (50.2 mg, 0.11 mmol) was dissolved in dry THF (1 mL),
PPh3 (28.1 mg, 0.11 mmol) was added, and the reaction mixture was heated
to reflux for 30 min. Then H2O (0.5 mL) was added and then the reac-
tion mixture was dried over Na2SO4 and filtered. 2,20-Dipyridyl disulfide
(21.4 mg, 0.11 mmol) in CHCl3 (1 mL) was added dropwise to this
solution and the resulting reaction mixture was stirred at room temperature
for 30 min before it was concentrated. The residue was purified by column
chromatography over silica gel (eluent: CH2Cl2/MeOH = 5/1) to give the
title compound (23.4 mg, 58%) as a white foam with identical characteristics
to the sample described above.
1,2:5,6-Di-O-isopropylidene-3-O-4-(2-naphthylmethyloxy)-
2Z-butenyl-r-D-glucofuranose (24). To a stirred solution of 4-(2-
naphthylmethyloxy)-2Z-butene-1-ol (23) (1.76 g, 7.7 mmol) in CH2Cl2
(20 mL) under an atmosphere of N2 was added Et3N (1.60 mL, 11.6
mmol) followed by DMAP (94 mg, 0.77 mmol) at 0 °C. A solution of
methanesulfonyl chloride (0.75 mL, 9.64 mmol) in CH2Cl2 (2 mL) then
was added dropwise and the reaction mixture was stirred for 2 h and then
diluted with saturated NaCl solution (20 mL). The organic portion was
separated and the aqueous part was again washed with CH2Cl2 (15 mL).
The combined organic part was dried and evaporated to dryness. The
crude mesylate (2.36 g, ∼100%) so obtained in DMF (50 mL) was
added at 0 °C to a solution of diacetone-D-glucose (2.0 g, 7.7 mmol) and
sodium hydride (338 mg, 8.5 mmol) in DMF (10.0 mL) that had been stirred
for 1 h. The reaction mixture was heated to 60 °C and stirred for 12 h before
it was cooled and diluted with water (100 mL) and ethyl acetate (100 mL).
The organic layer was separated and washed with brine (100 mL), dried, and
evaporated to dryness. The crude product was purified by column chroma-
tography with 60% EtOAc/hexanes as eluent to give the title compound as a
thick gum (2.65 g, 75%). [R]23D -2.0 (c 0.85); 1H NMR δ 7.86-7.84 (m,
3H), 7.80 (s, 1H), 7.51-7.47 (m, 3H), 5.87 (d, J = 4.0 Hz, 1H), 5.85-5.83
(m, 1H), 5.79-5.74 (m, 1H), 4.69 (s, 2H), 4.52 (d, J = 4.0 Hz, 1H), 4.32-
4.28 (m, 1H), 4.26-4.22 (dd, J = 13.0, 6.5 Hz, 1H), 4.19 (d, J = 6.0 Hz, 1H),
4.17-4.15(m,2H),4.13-4.11(m,1H),4.09-4.07(m,1H),4.03-3.99(m,
1H), 3.92 (d, J=3.0 Hz, 1H), 1.51 (s, 3H), 1.42 (s, 3H), 1.34 (s, 3H), 1.30 (s,
2-(Phenyloxycarbonylthioxy)-3-butenyl
2-Acetamido-
3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside (21). To a
stirred solution of the oxazolinone28 19 (2.5 g, 7.6 mmol) and 2--
(phenoxycarbonylthioxy)-3-butenol25 20 (425 mg, 1.9 mmol) in CHCl3
(13 mL) was added, at room temperature, copper chloride (1.5 g, 11.4
mmol). The resulting mixture was heated at reflux for 14 h then allowed
to cool to room temperature before saturated aqueous NaHCO3 was
added. The resulting mixture was filtered through Celite and washed
twice with saturated aqueous NaHCO3. The combined organic layers
were dried, filtered, and concentrated. The glycoside was isolated
chromatographically, eluting with hexanes/CH2Cl2/EtOAc (1:1:2) as
a white foam as an approximately 1:1 mixture of diastereomers (473 mg,
45%). 1H NMR (400 MHz) δ 7.35 (t, J = 8.0 Hz, 2 ꢀ 2H), 7.22 (t, J = 7.6
Hz, 2 ꢀ 1H), 7.12 (d, J = 6.4 Hz, 2 ꢀ 2H), 5.74-5.98 (m, 2 ꢀ 2H), 5.36
3699
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
3H); 13CNMRδ135.8, 133.5, 133.3, 130.0, 129.3, 128.5, 128.1, 127.9, 126.7,
126.4, 126.2, 125.9, 112.0, 109.2, 105.5, 83.0, 81.8, 81.4, 72.7, 72.6, 67.6, 66.5,
66.0, 27.1, 27.0, 26.5, 25.6; ESIHRMS calcd for C27H34O7Na [M þ Na]þ
493.2202, found 493.2216.
169.5, 153.7, 131.9, 129.8, 126.9, 125.1, 122.1, 101.9, 80.0, 72.4, 72.2,
69.6, 69.5 (2C), 67.2 (2C), 62.4, 57.0, 21.2, 21.1, 21.0; ESIHRMS calcd
for C24H30O11SNa [M þ Na]þ 549.1407, found 549.1398.
Methyl
2,4,6-Tri-O-acetyl-3-O-[(2-phenyloxycarbonyl-
thioxy)-3-butenyl]-β-D-glucopyranoside (30). Following gener-
al procedure 2, and eluting with 45% EtOAc/hexanes the title com-
pound was obtained in 90% yield as an approximately 1.25:1 mixture of
1,2,4,6-Tetra-O-acetyl-3-O-[4-(2-naphthylmethyloxy)-2Z-
butenyl]-D-r,β-glucopyranose (25). Following general procedure
10, and eluting with 50% EtOAc/hexanes the title compound was
obtained as an approximately 1.4:1 mixture of stereoisomers in 89%
yield. 1H NMR δ 7.84-7.83 (m, 3H), 7.78 (s, 1H), 7.50-7.46 (m, 3H),
6.29 (d, J = 3.5 Hz, 1H), 5.81-5.77 (m, 1H), 5.67-5.58 (m, 2H), 5.09-
5.03 (m, 2H), 4.99-4.97 (m, 1H), 4.67 (s, 2H, major), 4.66 (s, 2H,
minor), 4.25-4.13 (m,3H), 4.12-4.04 (m, 3H), 4.00-3.97 (m, 1H),
3.81 (t, J = 9.5 Hz, 1H), 3.64-3.62 (m, 1H), 3.58-3.54 (m, 1H), 2.12-
1.97 (s, 12H major þ 12H minor); 13C NMR δ 170.9, 169.7, 169.4,
169.2, 168.9, 135.7, 133.5, 133.2, 129.6, 129.4, 129.3, 129.2, 128.5, 128.5,
128.1, 128.0, 127.9, 126.7, 126.7, 126.4, 126.2, 125.9, 125.9, 92.1, 89.6,
79.7, 76.6, 73.2, 72.7, 71.6, 71.5, 70.4, 69.3, 69.1, 68.4, 67.8, 65.9, 65.8,
62.0, 61.9, 21.0, 20.9, 20.8, 20.7; ESIHRMS calcd for C29H34O11Na [M
þ Na]þ 581.1999, found 581.1998.
1
stereoisomers. H NMR δ 7.39-7.36 (m, 2H), 7.26-7.23 (m, 1H),
7.15-7.14 (m, 2H), 5.93-5.85 (m, 1H), 5.33 (d, J = 17.0 Hz, 1H), 5.19
(d, J = 10.5 Hz, 1H), 5.10 (t, J = 10.0 Hz, 1H), 5.03-4.99 (m, 1H), 4.33
(dd, J = 8.0, 3.0 Hz, 1H), 4.25-4.21 (m, 1H), 4.15-4.11 (m, 1H),
4.09-4.05 (m, 1H), 3.86-3.80 (m, 2H), 3.62-3.58 (m, 2H), 3.48 (s,
3H, major þ minor), 2.12 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H), 2.08 (s, 3H
ꢀ 3 minor); 13C NMR δ 171.0, 169.6, 169.5, 169.4 (2 C), 151.3, 134.1,
134.0, 129.7, 126.5, 121.5, 118.7 (2 C), 102.0, 81.0, 73.9, 73.8, 72.2 (2
C), 69.6, 69.5, 62.4, 57.0, 48.9 (2 C), 21.3, 21.2 (2 C), 21.1, 21.0;
ESIHRMS calcd for C24H30O11SNa [M þ Na]þ 549.1407, found
549.1385.
Methyl 3-O-[(2-Pyridyldithio)-3-butenyl]-β-D-glucopyra-
noside (31). Following general procedure 3, and eluting with 5%
MeOH/CH2Cl2 the title compound was obtained in 76% yield as an
2,4,6-Tri-O-acetyl-3-O-[4-(2-naphthylmethyloxy)-2Z-bu-
tenyl]-r-D-glucopyranosyl Trichloroacetimidate (26). Follow-
1
approximately 1.5:1 mixture of stereoisomers. H NMR (CD3OD) δ
ing general procedure 11, and eluting with 40% EtOAc/hexanes the title
1
compound was obtained in 76% yield. [R]23 63.8 (c 1); H NMR δ
8.37-8.36 (m, 1H), 7.93-7.91 (m, 1H), 7.81-7.78 (m, 1H), 7.22-
7.19 (m, 1H), 5.87-5.79 (m, 1H), 5.24-5.21 (m, 1H), 5.12 (d, J = 10.0
Hz, 1H), 4.17 (dd, J = 7.5, 1.5 Hz, 1H), 4.13-4.09 (m, 1H), 4.07-4.06
(m, 1H), 4.04-4.01 (m, 1H), 3.88-3.85 (m, 1H), 3.81-3.77 (m, 1H),
3.69-3.65 (m, 1H), 3.53 (s, 3H þ 3H, two isomers), 3.32 (m, 5H),
3.28-3.19 (m, 3H); 13C NMR (CD3OD) δ 160.7, 148.8, 137.8, 134.6,
134.5, 121.0, 120.3, 118.1, 104.2, 85.9, 76.7, 73.8, 73.7 (2C), 70.1, 70.0,
61.4, 56.2, 54.9; ESIHRMS calcd for C15H21NO6S2Na [M þ Na]þ
398.0708, found 398.0700.
D
8.67 (s, 1H), 7.85-7.82 (m, 3H), 7.78 (s, 1H), 7.50-7.46 (m, 3H), 6.5
(d, J = 3.5 Hz, 1H), 5.83-5.78 (m, 1H), 5.68-5.64 (m, 1H), 5.12 (t, J =
10.0 Hz, 1H), 5.01 (dd, J = 10.0, 4.0 Hz, 1H), 4.68 (d, J = 4.5 Hz, 2H),
4.27-4.18 (m, 3H), 4.13-4.07 (m, 4H), 3.92 (t, J = 10.0 Hz, 1H), 2.07
(s, 3H), 2.02 (s, 3H), 1.94 (s, 3H); 13C NMR δ 170.9, 169.9, 169.5,
160.8, 135.7, 133.5, 133.2, 129.6, 129.3, 128.5, 128.0, 127.9, 126.7, 126.4,
126.2, 125.9, 93.5, 91.1, 76.5, 72.7, 72.1, 70.7, 69.1, 68.5, 65.8, 61.9, 20.9,
20.9, 20.7; ESIHRMS calcd for C29H32Cl3NO10Na [M þ Na]þ
682.0989, found 682.0999.
Methyl 2,4,6-Tri-O-acetyl-3-O-[4-(2-napthylmethyloxy)-
2Z-butenyl]-β-D-glucopyranoside (27). Following general proce-
dure 12, and eluting with 60% EtOAc/hexanes the title compound was
obtained in 75% yield. [R]23D -14.5 (c 1); 1H NMR δ 7.85-7.83 (m,
3H), 7.79 (s, 1H), 7.49-7.46 (m, 3H), 5.81-5.76 (m, 1H), 5.64-5.58
(m, 1H), 5.03 (t, J = 10.0 Hz, 1H), 4.94 (dd, J = 9.5, 8.0 Hz, 1H), 4.68 (s,
3H), 4.27 (d, J = 8.0 Hz, 1H), 4.20 (dd, J = 12.0, 5.0 Hz, 1H), 4.14 (d, J =
6.0 Hz, 1H), 4.11 (d, J = 3.0 Hz, 1H), 4.09-4.08 (m, 2H), 3.55-3.50
(m, 2H), 3.46 (s, 3H), 2.08 (s, 3H), 2.03 (s, 3H), 2.00 (s, 3H); 13C NMR
δ 171.0, 169.5, 169.4, 135.7, 133.5, 133.2, 129.4, 128.4, 128.1, 127.9,
126.7, 126.4, 126.2, 125.9, 101.9, 79.8, 72.7 (2C), 72.5, 72.2, 69.7, 67.3,
65.8, 62.5, 56.9, 21.1, 20.9 (2C); ESIHRMS calcd for C28H34O10Na [M
þ Na]þ 553.2050, found 553.2064.
Methyl 6-Acetylthio-r-D-glucopyranoside (32). The title
compound was prepared by a literature method30 and had data
consistent with the literature.30
Methyl 2-Acetamido-6-acetylthio-2-deoxy-β-D-glucopyr-
anoside (33). Diisopropyl azodicarboxylate (0.25 mL, 1.22 mmol)
was added dropwise at 0 °C to a stirred solution of triphenylphosphine
(326 mg, 1.24 mmol) in DMF (2 mL). The mixture was stirred at 0 °C
for 1 h and gave a light yellow precipitate. A solution of methyl
2-acetamido-2-deoxy-β-D-glucopyranoside41 (240 mg, 1.02 mmol)
and thioacetic acid (0.09 mL, 1.22 mmol) in DMF (1.7 mL) then was
added dropwise at 0 °C and the resulting mixture was stirred for 20 h at
room temperature, resulting in a clear yellow solution. The mixture was
concentrated in vacuo and the residue was purified by silica gel
chromatography (eluting with CH2Cl2/MeOH = 15:1) to give the title
compound as a white solid (176 mg, 59%). Mp 195 °C; [R]RTD þ36.8 (c
1, MeOH); 1H NMR (300 MHz, CD3OD) δ 4.26 (d, J = 8.7 Hz, 1H),
3.66-3.55 (m, 2H), 3.48-3.38 (m, 4H), 3.38-3.26 (m, 4H), 3.20 (t, J =
9 Hz, 1H), 2.80 (dd, J = 8.1, 8.7 Hz, 1H), 2.32 (s, 3H), 1.94 (s, 3H); 13C
NMR (75 MHz, CD3OD) δ 195.8, 172.6, 102.2, 75.0, 74.6, 73.9, 56.0,
55.7, 30.9, 29.2, 21.8; ESIHRMS calcd for C11H19NO6S Na [M þ Na]þ
316.0831, found 316.0849.
2,4,6-Tri-O-acetyl-3-acetylthio-r,β-D-glucopyranose (35).
A stirred solution of 3432 (406 mg, 1.0 mmol) in a mixture of EtOAc
(20 mL) and CH2Cl2 (10.0 mL) was treated with TiBr4 (908 mg, 2.5
mmol) and stirred at room temperature for 96 h before it was diluted
with CH2Cl2 (30.0 mL) and filtered through a pad of Celite. The filtrate
was washed with saturated aqueous NaHCO3 (50.0 mL) and the organic
portion was dried and evaporated to dryness. The so-obtained crude
bromide was dissolved in an acetone/water mixture (20.0 mL, 2:1),
treated with Ag2CO3 (411 mg, 1.5 mmol), and stirred at room
temperature for 12 h. The reaction mixture was diluted with EtOAc
(30.0 mL) and filtered through a short Celite pad and washed with
saturated aqueous NaHCO3 (50.0 mL). The organic portion was dried,
Methyl 2,4,6-Tri-O-acetyl-3-O-[4-hydroxy-2Z-butenyl]-β-
D-glucopyranoside (28). Following general procedure 13, and
eluting with 40% EtOAc/hexanes the title compound was obtained in
88% yield. [R]23D -25.4 (c 1); 1H NMR δ 5.77-5.72 (m, 1H), 5.55-
5.51 (m, 1H), 5.06 (t, J = 9.50 Hz, 1H), 4.98-4.95 (m, 1H), 4.34 (d, J =
8.0 Hz, 1H), 4.23 (dd, J = 12.0, 5.0 Hz, 1H), 4.15-4.11 (m, 5H), 3.62-
3.58 (m, 2H), 3.48 (s, 3H), 2.11 (s, 3H), 2.09 (s, 3H), 2.08 (s, 3H); 13C
NMR δ 171.1, 169.8 (2C), 132.4, 127.9, 101.9, 79.8, 72.2 (2C), 69.3,
66.3, 62.5, 58.6, 57.1, 21.2, 21.1, 21.0; ESIHRMS calcd for C17H26O10Na
[M þ Na]þ 413.1424, found 413.1425.
Methyl 2,4,6-Tri-O-acetyl-3-O-[4-(phenyloxythionocarbo-
nyloxy)-2Z-butenyl]-β-D-glucopyranoside (29). Following gen-
eral procedure 1, and eluting with 45% EtOAc/hexanes the title
1
compound was obtained in 90% yield. [R]23 -11.5 (c 1); H NMR
D
δ 7.45-7.42 (m, 2H), 7.32-7.29 (m, 1H), 7.12-7.10 (m, 2H), 5.84-
5.79 (m, 1H), 5.76-5.72 (m, 1H), 5.10-5.06 (m, 3H), 5.01-4.97 (m,
1H), 4.35 (d, J = 7.50 Hz, 1H), 4.26-4.24 (m, 2H), 4.22 (d, J = 5.0 Hz,
1H), 4.13 (dd, J = 12.5, 2.5 Hz, 1H), 3.65-3.59 (m, 2H), 3.48 (s. 3H),
2.13 (s, 3H), 2.11 (s, 3H), 2.08 (s, 3H); 13C NMR δ 195.1, 171.0, 169.5,
3700
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
concentrated, and purified by column chromatography with 50%
EtOAc/hexanes to give the title product in 86% yield as an approxi-
mately 2:1 mixture of stereoisomers in the form of an oil. 1H NMR δ
5.39 (t, J = 4.0 Hz, 1H, major), 5.09-5.07 (m, 1H, major), 5.06-5.04
(m, 1H, minor), 4.95-4.92 (m, 1H, major), 4.84 (dd, J = 11.5, 8.0 Hz,
1H, minor), 4.73 (dd, J = 8.5, 8.0 Hz, 1H, minor), 4.28-4.25 (m, 1H,
major), 4.23-4.15 (m, 2H, major), 4.12-4.11 (m, 1H, minor), 3.97-
3.95 (m, 1H, minor), 3.85-3.83 (m, 1H, minor), 3.81-3.80 (m, 1H,
major), 3.79-3.76 (m, 1H, minor), 2.32 (s, 3H, minor), 2.32 (s, 3H,
major), 2.07 (s, 3H ꢀ 2), 2.06 (s, 3H ꢀ 2), 2.02 (s, 3H, major), 2.01 (s,
3H, minor); 13C NMR δ 193.7 (2C), 171.2, 171.1 (minor), 170.8
(minor), 170.3, 169.7, 169.6 (minor), 97.1 (minor), 89.9, 75.0, 72.4
(minor), 70.3, 68.7 (minor), 67.6, 62.6 (minor), 47.7 (minor), 44.4,
30.9, 30.9 (minor), 21.1 (2C), 20.9, 20.8 (2C), 20.7 (2C), 20.7;
ESIHRMS calcd for C14H20O9SNa [M þ Na]þ 387.0726, found
387.0724.
2,4,6-Tri-O-acetyl-3-acetylthio-r-D-glucopyranosyl Tri-
chloroacetimidate (36). Following general procedure 11, and elut-
ing with 45% EtOAc/hexanes the title compound was obtained in 80%
yield. [R]23D 52.0 (c 1); 1H NMR δ 8.66 (s, 1H), 6.48 (d, J = 3.0 Hz,
1H), 5.21-5.13 (m, 2H), 4.23-4.16 (m, 3H), 4.09-4.06 (m, 1H), 2.31
(s, 3H), 2.04 (s, 3H), 2.02 (s, 3H), 1.97 (s, 3H); 13C NMR δ 193.2,
170.7, 169.8, 169.5, 161.0, 92.8, 91.0, 71.5, 68.9, 66.6, 61.9, 44.7, 30.9,
20.9, 20.7, 20.6; ESIHRMS calcd for C16H20Cl3NO9SNa [M þ Na]þ
529.9822, found 529.9799.
61.6, 56.2, 54.3, 34.0, 32.2, 21.9; ESIHRMS calcd for C19H33NO11SNa
[M þ Na]þ 506.1672, found 506.1655.
Methyl 6-[4-(2-Acetamido-2-deoxy-β-D-glucopyranosy-
loxy)-2E-butenyl]thio-2-acetamido-2-deoxy-β-D-glucopyra-
noside (42). The title compound was prepared according to general
protocol 14 in 82% yield or in 68% yield according to protocol 15 as a
white foam eluting from silica gel with CH2Cl2/MeOH (20:1). [R]RT
D
þ41.0 (c 0.5, MeOH); 1H NMR (400 MHz, CD3OD) δ 5.80-5.60 (m,
2H), 4.40 (d, J = 8.0 Hz, 1H), 4.32 (d, J = 8.8 Hz, 1H), 4.27 (d, J = 8.8 Hz,
1H), 4.09 (dd, J = 5.2, 12.8 Hz, 1H), 3.88 (d, J = 12.0 Hz, 1H), 3.72-3.61
(m, 4H), 3.48-3.20 (m, 12H), 2.94 (d, J = 13.6 Hz, 1H), 2.62 (dd,
J = 8.0, 14.4 Hz, 1H), 1.98 (s, 3H), 1.97 (s, 3H); 13C NMR (100 MHz,
CD3OD) δ 172.6, 129.6, 128.8, 102.4, 102.3, 100.6, 77.0, 76.8, 74.9, 74.8,
73.6, 70.9, 68.7, 61.6, 56.1, 56.0, 55.9, 34.0, 32.1, 21.9, 21.8; ESIHRMS calcd
for C21H36N2O11SNa [M þ Na]þ 547.1938, found 547.1942.
Methyl 3-Deoxy-3-[4-(β-D-glucopyranosyloxy)but-2E-en-
ylthio]-β-D-glucopyranoside (43). Following general procedure
15, and eluting with 12% MeOH/CH2Cl2 the title compound was
obtained in 65% yield. [R]23 -2.0 (c 0.85, MeOH); 1H NMR
D
(CD3OD) δ 5.85 (dt, J = 15.0, 7.5 Hz, 1H), 5.75 (dt, J = 15.5, 6.5 Hz,
1H), 4.36 (d, J = 8.0 Hz, 1H), 4.32 (dd, J = 12.5, 5.0 Hz, 1H), 4.20 (d, J =
8.0 Hz, 1H), 4.17 (dd, J = 12.5, 6.5 Hz, 1H), 3.89-3.86 (m, 2H), 3.69
(dd, J = 12.0, 5.0 Hz, 1H), 3.66 (dd, J = 12.5, 5.5 Hz, 1H), 3.54 (s, 3H),
3.46-3.40 (m, 1H), 3.28-3.27 (m, 6H), 3.25-3.17 (m, 2H), 2.54 (t, J =
10.0 Hz, 1H); 13C NMR (CD3OD) δ 130.8, 128.7, 105.3, 101.5, 79.2,
76.8, 76.6, 73.9, 73.1, 70.5, 68.7, 68.6, 61.7, 61.6, 56.0, 54.6, 33.2;
ESIHRMS calcd for C17H30O11SNa [M þ Na]þ 465.1401, found
465.1407.
Methyl 2,4,6-Tri-O-acetyl-3-acetylthio-β-D-glucopyrano-
side (37). Following general procedure 12, and eluting with 60%
EtOAc/hexanes the title compound was obtained in 76% yield. [R]23
D
-8.7 (c 1); 1H NMR δ 5.06 (dd, J = 11.0, 9.5 Hz, 1H), 4.95 (dd, J = 11.0,
7.5 Hz, 1H), 4.45 (d, J = 7.5 Hz, 1H), 4.26 (dd, J = 12.0, 4.5 Hz, 1H), 4.12
(dd, J = 12.0, 3.0 Hz, 1H), 3.85 (t, J = 11.0 Hz, 1H), 3.76-3.73 (m, 1H),
3.50 (s, 3H), 2.33 (s, 3H), 2.09 (s, 3H), 2.05 (s, 3H), 2.02 (s, 3H); 13C
NMR δ 193.7, 170.9, 169.5 (2C), 103.2, 74.7, 70.3, 67.8, 62.5, 57.1, 47.9,
30.8, 20.9, 20.9, 20.8; ESIHRMS calcd for C15H22O9SNa [M þ Na]þ
401.0882, found 401.0878.
Methyl 3-O-[4-(1-thio-β-D-glucopyranosyl)-2E-butenyl]-
β-D-glucopyranoside (44). Following general procedure 15, and
eluting with 12% MeOH/CH2Cl2 the title compound was obtained in
70% yield. [R]23D -45.1 (c 1, MeOH); 1H NMR (CD3OD) δ 5.79-
5.77 (m, 2H), 4.38 (d, J = 9.5 Hz, 1H), 4.35-4.34 (m, 2H), 4.19-4.18
(m, 1H), 3.89-3.86 (m, 2H), 3.70-3.63 (m, 2H), 3.53 (s, 3H), 3.50-
3.46 (m, 1H), 3.32-3.31 (m, 3H), 3.29-3.27 (m, 2H), 3.26-3.22 (m,
4H); 13C NMR (CD3OD) δ 130.3, 128.9, 104.2, 84.3, 83.9, 80.5, 78.5,
76.6, 73.9, 73.2, 72.7, 70.5, 70.1, 61.8, 61.5, 56.1, 30.9; ESIHRMS calcd
for C17H30O11SNa [M þ Na]þ 465.1401, found 465.1407.
Phenyl 2,4,6-Tri-O-acetyl-3-acetylthio-1-thio-β-D-gluco-
pyranoside (38). The title compound was obtained by the literature
procedure from 34 in 60% yield and had physical characteristics
consistent with the literature.32
Methyl 3-O-[4-(Methyl r-D-glucopyranosid-6-thio)but-
2E-enyl]-β-D-glucopyranoside (45). Following general procedure
15, and eluting with 10% MeOH/CH2Cl2 the title compound was
Methyl 6-[4-(β-D-Glucopyranosyloxy)-2E-butenyl]thio-r-
D-glucopyranoside (40). General coupling procedure 14 gave the
title compound (17.4 mg, 57%) as a white foam after purification by
column chromatography over silica gel (eluent: CH2Cl2/MeOH = 1/1).
(When using phosphate buffer solution as solvent, the yield is 93%.)
obtained in 70% yield. [R]23 -26.0 (c 0.75, MeOH); 1H NMR
D
(CD3OD) δ 5.78-5.69 (m, 2H), 4.65 (d, J = 3.5 Hz, 1H), 4.36-4.35
(m, 1H), 4.19-4.18 (m, 1H), 3.86 (dd, J = 12.0, 2.5 Hz, 1H), 3.69-3.54
(m, 3H), 3.44 (s, 3H), 3.43 (s, 3H), 3.44-3.37 (m, 1H), 3.32-3.31 (m,
2H), 3.29-3.19 (m, 6H), 2.94 (dd, J = 14.0, 2.0 Hz, 1H), 2.59 (dd, J =
14.6, 8.0 Hz, 1H); 13C NMR (CD3OD) δ 130.2, 129.3, 104.2, 99.8, 84.5,
76.6, 73.9, 73.8, 73.5, 72.8, 72.4, 70.1, 61.5, 56.2, 54.4, 34.1, 32.1;
ESIHRMS calcd for C18H32O11SNa [M þ Na]þ 479.1563, found
479.1550.
1
[R]D þ31.3 (c 1.3, CH3OH); H NMR (CD3OD) δ 5.68-5.79 (m,
2H), 4.63 (d, J = 4.0 Hz, 1H), 4.35 (dd, J = 12.0, 5.0 Hz, 1H), 4.31 (d, J =
8.0 Hz, 1H), 4.13-4.18 (m, 1H), 3.87 (d, J = 12.0 Hz, 1H), 3.60-3.68
(m, 2H), 3.57 (t, J = 9.5 Hz, 1H), 3.42 (s, 3H), 3.39 (dd, J = 10.0, 4.0 Hz,
1H), 3.33-3.36 (m, 2H), 3.30-3.31 (m, 6H), 3.17-3.28 (m, 6H), 2.91
(dd, J = 14.0, 2.0 Hz, 1H), 2.56 (dd, J = 14.0, 9.0 Hz, 1H); 13C NMR δ
130.1, 128.9, 101.9, 99.9, 76.9, 76.8, 73.9, 73.8, 73.5, 72.5, 72.4, 70.5,
68.8, 61.6, 54.3, 33.9, 32.1; ESIHRMS calcd for C17H30O11SNa [M þ
Na]þ 465.1407, found 465.1407.
Phenyl 3-Deoxy-3-[4-(β-D-glucopyranosyloxy)but-2E-en-
ylthio]-1-thio-β-D-glucopyranoside (46). Following general
procedure 15, phenyl 2,4,6-tri-O-acetyl-3-acetylthio-1-thio-β-D-gluco-
pyranoside (38) was coupled with sulfenyl donor 13. Chromatographic
purification eluting with 8% MeOH/CH2Cl2 gave the title compound in
Methyl 6-[4-(2-Acetamido-2-deoxy-β-D-glucopyranosy-
loxy)-2E-butenyl]thio-2-deoxy-β-D-glucopyranoside (41).
The title compound was prepared according to general protocol 14 in
80% yield or in 57% yield according to protocol 15 as a white foam
eluting from silica gel in CH2Cl2/MeOH (20:1). [R]RTD þ74.0 (c 1.0,
MeOH); 1H NMR (400 MHz, CD3OD) δ 5.76-5.58 (m, 2H), 4.63 (d,
J = 4.4 Hz, 1H), 4.44 (d, J = 8.0 Hz, 1H), 4.31 (dd, J = 4, 4.8 Hz, 1H), 4.09
(dd, J = 5.6, 6.0 Hz, 1H), 3.88 (d, J = 12.0 Hz, 1H), 3.74-3.54 (m, 4H),
3.47-3.16 (m, 11H), 2.90 (dd, J = 2.4, 14.0 Hz, 1H), 2.56 (dd, J = 8.8,
13.6 Hz, 1H), 1.98 (s, 3H); 13C NMR (100 MHz, CD3OD) δ 172.6,
129.6, 128.7, 100.5, 99.9, 76.8, 74.9, 73.8, 73.6, 72.5, 72.4, 70.9, 68.5,
70% yield. [R]23 -36.0 (c 0.75, MeOH); 1H NMR (400 MHz,
D
CD3OD) δ 7.57-7.54 (m, 2H), 7.32-7.23 (m, 3H), 5.86-5.79 (m,
1H), 5.74-5.67 (m, 1H), 4.62 (d, J = 12.0 Hz, 1H), 4.34 (d, J = 10.0 Hz,
1H), 4.30 (dd, J = 16.5, 7.0 Hz, 1H), 4.14 (dd, J = 16.0, 9.0 Hz, 1H), 3.87
(dd, J = 15.0, 2.0 Hz, 2H), 3.69-3.62 (m, 2H), 3.46-3.26 (m, 8H), 3.18
(t, J = 11.0 Hz, 1H), 2.58 (t, J = 11.0 Hz, 1H); 13C NMR (100 MHz,
CD3OD) δ 133.9, 131.6, 130.8, 128.7, 127.1, 101.5, 89.6, 82.7, 76.8,
76.6, 73.9, 72.4, 70.5, 68.6, 68.5, 61.8, 61.6, 56.7, 33.6; ESIHRMS calcd
for C22H32O10S2Na [M þ Na]þ 543.1335, found 543.1346.
3701
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
Scheme 9. Preparation of 2-Azido-2-deoxyglucose-Based
Monosaccharyl Units
Phenyl 2-Azido-2-deoxy-6-acetylthio-3,4-O-(2,3-dimethoxy-
butane-2,3-diyl)-1-thio-β-D-glucopyranoside (74): The title
compound was prepared by general procedure 6 and isolated as a light
yellow foam eluted from silica gel with hexanes/EtOAc (6:1) in 78%
yield. [R]RTD þ132.1 (c 1.0); 1H NMR (400 MHz) δ 7.57 (dd, J = 6.4,
7.2 Hz, 2H), 7.35-7.30 (m, 3H), 4.35 (d, J = 9.6 Hz, 1H), 3.67 (t, J = 9.6
Hz, 1H), 3.62-3.55 (m 1H), 3.51-3.45 (m, 2H), 3.44-3.30 (m, 2H),
3.30 (s, 3H), 3.22 (s, 3H), 3.07 (q, J = 7.2, 14.0 Hz, 1H), 2.35 (s, 3H),
1.31 (s, 3H), 1.28 (s, 3H); 13C NMR (100 MHz) δ 194.9, 134.5, 133.2,
130.7, 129.2, 129.1, 128.9, 100.4, 100.13, 86.2, 76.7, 73.0, 68.6, 61.5, 48.4,
48.3, 30.7, 30.1, 17.8, 17.7; ESIHRMS calcd for C20H27N3O6S2Na [M þ
Na]þ 492.1239, found 492.1245.
Phenyl 6-Acetylthio-2-azido-2-deoxy-3,4-O-(2,3-dimethoxy-
butane-2,3-diyl)-1-thio-β-D-glucopyranoside S-Oxide (54).
The title compound was prepared by general procedure 7 and isolated
as a white solid eluting from silica gel in hexanes/EtOAc (4:1) in 70%
yield. Mp 125 °C; [R]RTD -12.3 (c 1.0); 1H NMR (400 MHz) δ 7.62-
7.58 (m, 2H), 7.55-7.51 (m, 3H), 4.01 (dd, J = 9.6, 10.8 Hz, 1H), 3.83
(t, J = 9.6 Hz, 1H), 3.72 (d, J = 9.6 Hz, 1H), 3.54 (d, J = 9.6 Hz), 3.43-
3.31 (m, 5H), 3.20 (s, 3H), 2.83 (dd, J = 8.0, 14.0 Hz, 1H), 2.19 (s, 3H),
1.27 (s, 3H); 13C NMR (100 MHz) δ 194.7, 139.1, 131.5, 129.2, 125.6,
100.5, 100.2, 91.9, 77.8, 73.3, 68.8, 57.6, 48.4, 48.3, 30.6, 29.8, 17.8, 17.7;
ESIHRMS calcd for C20H27N3O7S2Na [M þ Na]þ 508.1188, found
508.1183.
Phenyl 2-Azido-2-deoxy-3,4,6-tri-O-(p-methoxybenzyl)-
1-thio-β-D-glucopyranoside (75). To a stirred solution of 7142
(800 mg, 2.7 mmol) in DMF (6.4 mL) was added portionwise at 0 °C
sodium hydride (542 mg, 16.1 mmol). The resulting mixture was stirred
for 0.5 h at 0 °C before p-methoxybenzyl chloride (2.2 mL, 16.1 mmol)
was added dropwise. The resulting mixture was allowed to warm to
room temperature and stirred for 2 h. The reaction was quenched by
addition of MeOH, concentrated, and purified by column chromatog-
raphy eluting with 0.5% Et3N in hexanes/EtOAc (4:1) to give the title
compound (1.6 g, 92%) as a light yellow solid. Mp 72 °C; [R]RTD -45.8
(c 1.0); 1H NMR (400 MHz) δ 7.60 (dd, J = 7.2, 8.0 Hz, 2H), 7.32-7.24
(m, 7H), 7.12 (d, J = 8.8 Hz, 2H), 6.92-6.82 (m, 6H), 4.78 (s, 2H), 4.72
(d, J = 10.4 Hz, 1H), 4.56 (d, J = 11.2 Hz, 1H), 4.52-4.46 (m, 2H), 4.40
(d, J = 9.6 Hz, 1H), 3.80 (s, 9H), 3.76-3.66 (m, 2H), 3.58-3.42 (m,
3H), 3.32 (t, J = 9.6 Hz, 1H); 13C NMR (100 MHz) δ 159.7, 159.6,
159.4, 133.8, 131.5, 130.5, 130.3, 130.1, 130.0, 129.8, 129.6, 129.2, 128.5,
114.2, 114.1, 114.0, 86.1, 85.0, 79.6, 76.9, 75.7, 74.9, 73.3, 65.6, 65.3,
55.5; ESIHRMS calcd for C36H39N3O7SNa [M þ Na]þ 680.2406,
found 680.2404.
Phenyl 2-Azido-2-deoxy-3,4-O-(2,3-dimethoxybutane-
2,3-diyl)-1-thio-β-D-glucopyranoside (48). The title compound
was prepared as a white solid from 7142 by general procedure 4 and
eluted from silica gel with hexanes/EtOAc (2:1) in 83% yield
(Scheme 9). Mp 110 °C; [R]RTD þ47.3 (c 1.0); 1H NMR (400 MHz)
δ 7.55 (dd, J = 2.4, 5.6 Hz, 2H), 7.37-7.30 (m, 3H), 4.40 (d, J = 9.6 Hz,
1H), 3.92-3.83 (m, 1H), 3.77-3.68 (m, 2H), 3.63 (t, J = 9.6 Hz, 1H),
3.54-3.49 (m, 1H), 3.39 (t, J = 9.6 Hz, 1H), 3.33 (s, 3H), 3.28 (d, J = 5.6
Hz, 1H), 3.23 (s, 3H), 1.94 (dd, J = 5.6, 7.2 Hz, 1H), 1.33 (s, 3H), 1.27
(s, 3H); 13C NMR (100 MHz) δ:134.1, 129.4, 128.9, 100.4, 99.9, 86.3,
78.3, 73.2, 65.8, 61.7, 61.5, 48.3, 48.3, 17.8, 17.7; ESIHRMS calcd for
C18H25N3O6SNa [M þ Na]þ 434.1362, found 434.1354.
Methyl 2-Azido-2-deoxy-3,4-O-(2,3-dimethoxybutane-
2,3-diyl)-β-D-glucopyranoside (55). The title compound was
prepared as a white foam from 7242b,43 by the general procedure 4
and eluted from silica gel with hexanes/EtOAc (2:1) in 81% yield.
[R]RTD þ70.3 (c 1.0); 1H NMR (400 MHz) δ 4.2 (d, J = 8 Hz, 1H),
3.88-3.80 (m, 1H), 3.76-3.66 (m, 2H), 3.60 (dd, J = 9.6, 10.8 Hz, 1H),
3.53 (s, 3H), 3.48-3.42 (m, 1H), 3.39 (dd, J = 7.2, 8.4 Hz, 1H), 3.28 (s,
3H), 3.23 (s, 3H), 2.50 (dd, J = 5.6, 8.0 Hz, 1H), 1.31 (s, 3H), 1.26 (s,
3H); 13C NMR (100 MHz) δ 103.6, 100.3, 99.9, 76.9, 74.2, 71.0, 66.0,
62.9, 61.2, 57.6, 48.3, 17.8, 17.7; ESIHRMS calcd for C13H23N3O7Na
[M þ Na]þ 365.1434, found 365.1432.
Phenyl 2-Azido-2-deoxy-3,4,6-tri-O-(p-methoxybenzyl)-
1-thio-β-D-glucopyranoside S-Oxide (47). The title compound
was prepared as a white solid by general procedure 7 and eluted from
silica gel with 0.5% Et3N in hexanes/EtOAc (4:1) as a mixture of
diastereomers, in 92% yield. 1H NMR (400 MHz) δ 7.71-7.63 (m, 2H),
7.51 (d, J = 4.8 Hz, 2H), 7.45 (dd, J = 2.4, 3.2 Hz, 2H), 7.32 (d, J = 8.4 Hz,
1H), 7.25 (t, J = 8.0 Hz, 3H), 7.18-6.79 (m, 3H), 6.92-6.81 (m, 7H),
4.83 (d, J = 1.6 Hz, 1H), 4.89-4.65 (m, 3H), 4.48 (dd, J = 7.2, 8.0 Hz,
3H), 4.31 (d, J = 11.6 Hz, 1H), 4.17 (dd, J = 9.6, 12.0 Hz, 1H), 3.86-
3.3.77 (m, 13H), 3.74-3.67 (m, 2H), 3.66-3.57 (m, 1H), 3.56-3.45
(m, 4H); 13C NMR (100 MHz) δ 159.7, 159.6, 140.3, 139.4, 131.6,
131.5, 130.1, 130.0, 129.9, 129.7, 129.6, 129.3, 129.2, 125.6, 124.9, 114.2,
114.1, 114.0, 113.9, 94.5, 91.8, 84.8, 84.7, 80.9, 80.4, 75.8, 75.7, 74.9,
73.5, 73.4, 68.4, 68.3, 61.0, 60.2, 55.5; ESIHRMS calcd for
C36H39N3O8SNa [M þ Na]þ 696.2356, found 696.2369.
Phenyl 2-Azido-2-deoxy-3,4-O-(2,3-dimethoxybutane-
2,3-diyl)-1-thio-6-O-p-toluenesulfonyl-β-D-glucopyranoside
(73). The title compound was prepared by general procedure 5 as a
white solid eluted from silica gel with hexanes/EtOAc (3:1) in a
quantitative yield. Mp 141 °C; [R]RT D þ12.3 (c 1.0); 1H NMR (400
MHz) δ 7.80 (d, J = 8.8 Hz, 2H), 7.64 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 7.6
Hz, 2H), 7.34-7.25 (m, 3H), 4.29 (t, J = 10.4 Hz, 2H), 4.21 (dd, J = 4.0,
10.8 Hz, 1H), 3.67-3.53 (m, 3H), 3.31 (d, J = 9.6 Hz, 1H), 3.28 (s, 3H),
3.23 (d, J = 7.6 Hz, 1H), 3.20 (s, 3H), 2.67 (s, 3H), 1.29 (s, 3H), 1.25 (s,
3H); 13C NMR (100 MHz) δ 145.2, 134.4, 133.0, 130.3, 130.1, 129.3,
129.0, 128.2, 100.5, 100.1, 86.1, 77.6, 75.4, 73.0, 67.3, 65.3, 61.1, 48.6,
48.4, 21.9, 17.8, 17.7; ESIHRMS calcd for C25H31N3O8S2Na [M þ
Na]þ 588.1450, found 588.1440.
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-1-thio-2-(2,2,2-trichloro-
ethoxycarbonylamino)-β-D-glucopyranoside (77). To a stirred
solution of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-(2,2,2-trichloroethoxycar-
bonylamino)-R,β-D-glucopyranose44 (76) (10 g, 19.2 mmol) in CH2Cl2
(100 mL) was added, at room temperature, trimethylsilyl trifluo-
romethanesulfonate (4.2 mL, 23 mmol) and thiophenol (2.4 mL, 23 mmol).
3702
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
The resulting mixture was stirred for 4 h, then neutralized by addition of
triethylamine and concentrated. Chromatographic purification (hexanes/
EtOAc = 3:1) afforded the title compound (9.2 g, 84%) as a light yellow solid
(Scheme 10). Mp 87 °C; [R]RT D þ18.5 (c 1.0); 1H NMR (400 MHz)
δ7.49 (dd, J= 3.2, 4.0 Hz, 2H), 7.29 (dd, J = 2.0, 3.2 Hz, 3H), 4.95 (d, J= 9.6
Hz, 1H), 5.27 (t, J = 9.6 Hz, 1H), 5.01 (t, J = 9.6 Hz, 1H), 4.85 (d, J = 10.8
Hz, 1H), 4.74 (q, J = 12.0 Hz, 2H), 4.24-4.412 (m, 2H), 3.76-3.66 (m,
2H), 2.06 (s, 3H), 1.99 (s, 3H), 1.97 (s, 3H); 13C NMR (100 MHz) δ170.9,
169.7, 154.2, 133.1, 132.3, 129.2, 128.5, 119.2, 86.8, 77.6, 75.9, 74.7, 73.4,
68.8, 62.6, 55.2, 21.0, 20.9, 20.8; ESIHRMS calcd for C21H24Cl3NO9SNa
[M þ Na]þ 594.0135, found 594.0112.
Scheme 10. Preparation of 2-Deoxy-2-(trichloroethoxy-
carbonylamino)glucose-Based Monosaccharyl Units
Methyl 3,4,6-Tri-O-acetyl-2-(2,2,2-trichloroethoxycarb-
onylamino)-2-deoxy-β-D-glucopyranoside (79). The title com-
pound was prepared as a white solid by general NIS/TfOH protocol and
eluted from silica gel with hexanes/EtOAc (2:1) in 94% yield. Mp
115 °C (lit.45 mp 119-124 °C); [R]RTD þ12.5 (c 1.0); 1H NMR (400
MHz) δ 5.30 (dd, J = 9.2, 10.4 Hz, 1H), 5.20 (br s, 1H), 5.07 (dd, J = 8.8,
10.0 Hz, 1H), 4.80 (d, J = 11.2 Hz, 1H), 4.65 (d, J = 12 Hz, 1H), 4.54 (d,
J = 7.6 Hz, 1H), 4.28 (dd, J = 4.0, 4.8 Hz, 1H), 4.15 (d, J = 10.0 Hz, 1H),
3.72 (d, J = 7.2 Hz, 1H), 3.64 (dd, J = 8.8, 17,6 Hz, 1H), 3.52 (s, 3H),
2.03 (s, 6H), 2.09 (s, 3H); 13C NMR (100 MHz) δ 170.9, 169.7, 154.3,
119.2, 102.0, 74.7, 72.0, 68.9, 62.2, 57.4, 56.4, 55.1, 21.0, 20.8; ESIHRMS
calcd for C16H22Cl3NO10Na [M þ Na]þ 516.0207, found 516.0211.
Methyl 3,4-O-(2,3-Dimethoxybutane-2,3-diyl)-2-(2,2,2-
trichloroethoxycarbonylamino)-2-deoxy-β-D-glucopyrano-
side (81). Compound 79 (600 mg, 1.66 mmol) was dissolved in MeOH
(8.3 mL) at room temperature and a catalytic amount of 25% NaOMe in
MeOH (0.16 mmol) was added. The resulting mixture was stirred for 1 h
before the pH of the solution was adjusted to 7 by addition of dry
Amberlyst IR 120 resin. The resulting mixture was filtered and con-
centrated to give methyl 2-(2,2,2-trichloroethoxycarbonylamino)-2-
deoxy-β-D-glucopyranoside (82), which was immediately subjected to
general procedure 4 and eluted from silica gel with hexanes/EtOAc
(1:1) in 72% yield. White solid, mp 105 °C; [R]RT RD þ123.0 (c 1.0);
1H NMR (400 MHz) δ 5.20 (s, 1H), 4.72 (m 3H), 4.10 (dd, J = 7.2, 9.2
Hz, 1H), 3.92-3.84 (m, 1H), 3.80-3.74 (m, 1H), 3.69 (t, J = 10.0 Hz,
1H), 3.58-3.53 (m, 1H), 3.50 (s, 3H), 3.40-3.28 (m, 1H), 3.25 (s,
3H), 3.21 (s, 3H), 2.01 (dd, J = 4.8, 8.0 Hz, 1H), 1.28 (s, 6H); 13C NMR
(100 MHz) δ 119.2, 119.1, 102.2, 100.2, 99.8, 74.6, 74.1, 68.3, 67.2, 61.4,
57.2, 56.0, 48.2, 48.1, 17.9, 17.8; ESIHRMS calcd for C16H26Cl3NO9Na
[M þ Na]þ 504.0571, found 504.0572.
(1.5:1) in 72% yield. [R]RTD þ54.5 (c 1.0); 1H NMR (400 MHz) δ 7.48
(dd, J = 2.4, 4.0 Hz, 2H), 7.31 (dd, J = 2.4, 4.4 Hz, 3H), 5.10 (d, J = 8.8 Hz,
2H), 4.75 (s, 2H), 4.10 (dd, J=7.2, 9.6Hz, 1H), 3.93-3.85 (m, 1H), 3.77-
3.70 (m, 1H), 3.66 (t, J = 9.6 Hz, 1H), 3.62-3.56 (m, 1H), 3.41 (br s, 1H),
3.10 (dd, J = 4.4, 5.6 Hz, 1H), 3.24 (s, 3H), 3.21 (s, 3H), 1.91 (dd, J = 5.6,
7.6 Hz, 2H), 1.27 (s, 6H); 13C NMR (100 MHz) δ 153.8, 133.0, 132.0,
129.4, 129.3, 128.4, 100.3, 99.8, 86.1, 78.1, 77.4, 74.7, 70.1, 67.0, 61.7, 54.7,
48.2, 48.1, 17.8, 17.8; ESIHRMS calcd for C21H28Cl3NO8SNa [M þ Na]þ
582.0449, found 582.0494.
Phenyl 2-Deoxy-3,4-O-(2,3-dimethoxybutane-2,3-diyl)-1-
thio-6-O-p-toluenesulfonyl-2-(2,2,2-trichloroethoxycarbonyl-
amino)-β-D-glucopyranoside (57). The title compound was pre-
pared as a white solid by general procedure 5 and eluted from silica gel
Phenyl 3,4,6-O-Acetyl-2-deoxy-1-thio-2-(2,2,2-trichloro-
ethoxycarbonylamino)-β-D-glucopyranoside S-oxide (78).
The title compound was prepared as a white foam by general procedure
7 and eluted from silica gel in hexanes/EtOAc (2:1) in 88% yield. Mp
134 °C; [R]RTD þ31.0° (c 1.0); 1H NMR (400 MHz) δ 7.71 (dd, J = 2.5,
3.2 Hz, 2H), 7.52 (dd, J = 2.4, 3.2 Hz, 3H), 5.68 (d, J = 8.8 Hz, 1H), 5.44
(t, J = 9.6 Hz, 1H), 4.92 (t, J = 9.6 Hz, 1H), 4.80 (d, J = 10.4 Hz, 1H), 4.62
(d, J = 12.4 Hz, 1H), 4.44 (d, J = 12.0 Hz, 1H), 4.16 (m, 2H), 3.86 (dd,
J = 9.6, 10.8 Hz, 1H), 3.78 (m, 1H), 2.00 (s, 9H); 13C NMR (100 MHz)
δ 170.7, 170.6, 169.6, 153.9, 138.8, 131.6, 129.1, 125.9, 95.3, 93.3, 76.4,
74.6, 72.6, 68.1, 61.7, 51.7, 20.9, 20.8; ESIHRMS calcd for C21H24Cl3-
NO10SNa [M þ Na] 610.0084, found 610.0067.
with hexanes/EtOAc (3:1) in a quantitative yield. Mp 144 °C; [R]RT
D
þ84.2° (c 1.0); 1H NMR (400 MHz) δ 7.81 (d, J = 7.2 Hz, 2H), 7.41 (d,
J = 8.0 Hz, 2H), 7.34-7.21 (m, 5H), 5.03 (dd, J = 6.4, 10.0 Hz, 2H), 4.73
(s, 2H), 4.30 (d, J = 10.8 Hz, 1H), 4.23 (dd, J = 4.0 Hz, 10.8 Hz, 1H),
4.07 (dd, J = 10.0, 11.2 Hz, 1H), 3.67 (dd, J = 2.4, 3.2 Hz, 1H), 3.59 (t,
J = 9.6 Hz, 1H), 3.31-3.23 (m, 1H), 3.29 (s, 3H), 3.18 (s, 3H), 2.40 (s,
3H), 1.25 (s, 6H); 13C NMR (100 MHz) δ 145.1, 133.3, 130.1, 129.2,
128.5, 128.2, 100.4, 100.0, 85.6, 77.6, 75.4, 74.6, 69.7, 67.7, 66.5, 54.3,
48.5, 48.2, 21.9, 17.9, 17.7; ESIHRMS calcd for C28H34Cl3NO10Na
[M þ Na]þ 736.0587, found 736.0594.
Phenyl 2-Deoxy-3,4-O-(2,3-dimethoxybutane-2,3-diyl)-1-
thio-2-(2,2,2-trichloroethoxycarbonylamino)-β-D-glucopyr-
anoside (83). To a stirred solution of phenyl 3,4,6-tri-O-acetyl-2-deoxy-
1-thio-2-(20,20,20-trichloroethoxycarbonylamino)-β-D-glucopyranoside46
(77) (1 g, 1.75 mmol) in MeOH (8.8 mL) was added a catalytic amount
of 25% sodium hydroxide in MeOH (0.18 mmol) at room temperature.
The resulting mixture was stirred for 1 h, neutralized by addition of
Amberlyst IR 120 resin, filtered, and concentrated to give phenyl 2-
(2,2,2-trichloroethoxycarbonylamino)-1-thio-β-D-glucopyranoside (82),47
which was subjected to general protocol 4 directly, giving the title
compound as a white foam, eluted from silica gel with hexanes/EtOAc
Phenyl 2-Azido-2-deoxy-3,4-O-(2,3-dimethoxybutane-2,
3-diyl)-1-thio-20-azido-20-deoxy-30,40,60-tri-O-(p-methoxyben-
zyl)]-β-D-gentiobioside (49). Glycosyl sulfoxide 47 (1.2g, 1.78mmol)
was premixed with acceptor 48 (880 mg, 2.14 mmol), 2,4,6-tri-tert-
butylpyrimidine (886 mg, 3.57 mmol), and activated 4 Å powdered
molecular sieves in CH2Cl2/acetonitrile (4:3) (3.6 mL) and the result-
ing mixture was stirred at room temperature for 0.5 h then cooled to -
80 °C before trifluoromethanesulfonic anhydride (0.33 mL, 1.96 mmol)
was added dropwise. The reaction mixture was stirred at -80 °C for
3703
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
1.5 h, quenched by addition of aqueous saturated NaHCO3, and then
allowed to warm to room temperature. The aqueous phase was extracted
twice with CH2Cl2. The organic layers were combined, dried, filtered,
and concentrated in vacuo. Chromatographic purification eluting with
0.5% Et3N in hexanes/EtOAc (4:1 to 2.5:1) gave the title compound
(1.05 g, 62%) as a white foam. [R]RTD þ29.6° (c 1.0); 1H NMR (400
MHz) δ 7.61-7.53 (m, 2H), 7.36-7.27 (m, 5H), 7.27-7.22 (m, 3H),
7.07 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 6.83 (dd, J = 5.6, 8.8 Hz,
3H), 4.83-4.69 (m, 3H), 4.58-4.37 (m, 4H), 4.14 (d, J = 10.8 Hz, 1H),
3.90-3.46 (m, 16H), 3.44-3.19 (m, 11H), 1.32 (s, 3H), 1.27 (s, 3H);
13C NMR (100 MHz) δ 159.6, 159.5, 134.1, 133.8, 130.4, 130.0, 129.8,
129.3, 128.6, 114.1, 114.0, 102.4, 100.4, 100.0, 86.4, 83.1, 78.2, 75.9, 75.8,
75.5, 75.2, 74.9, 74.7, 73.4, 72.2, 71.2, 68.4, 68.1, 66.6, 66.3, 65.6, 61.7,
60.2, 55.5, 55.4, 48.3, 17.8, 17.7; ESIHRMS calcd for C48H58N6O13SNa
[M þ Na]þ 981.3680, found 981.3682.
procedure 9 eluted from silica gel with CH2Cl2/MeOH (20:1) as an
approximately 1:1 mixture of diastereomers in 67% yield. NMR (400
MHz) δ 7.40 (t, J = 7.3 Hz, 2 ꢀ 2H), 7.26 (t, J = 7.2 Hz, 2 ꢀ 1H), 7.15 (d,
J = 9.2 Hz, 2 ꢀ 2H), 6.06-5.95 (m, 2 ꢀ 1H), 5.41 (d, J = 15.2 Hz, 2 ꢀ
1H), 5.23 (d, J = 10.8 Hz, 2 ꢀ 1H), 4.48 (dd, J = 7.3, 8.8 Hz, 2 ꢀ 1H),
4.41 (d, J = 8.0 Hz, 2 ꢀ 1H), 4.28-4.18 (m, 2 ꢀ 3H), 3.93-3.60 (m, 2
ꢀ 7H), 3.47 (dd, J = 6.4, 8.0 Hz, 2 ꢀ 1H), 3.34-3.06 (m, 2 ꢀ 9H); 13C
NMR (100 MHz) δ 164.0, 134.9, 129.5, 126.2, 121.3, 117.7, 117.6,
102.7, 102.3, 102.1, 101.9, 94.7, 76.8, 76.2, 75.1, 75.0, 70.7, 70.6, 70.3,
69.0, 67.1, 61.3, 48.6; ESIHRMS calcd for C23H30N6O11SNa [M þ
Na]þ 621.1591, found 621.1593.
2-(Pyridyldithio)but-3-enyl 2,20-diazido-2,20-dideoxy-β-D-
gentiobioside (53). The title compound was prepared as a white
foam by general procedure 3 and eluting from silica gel in CH2Cl2/
MeOH (20:1) as an approximately 1:1 mixture of diastereomers in 65%
yield over two steps. 1H NMR (400 MHz, CD3OD) δ 8.37 (d, J = 4.0
Hz, 2 ꢀ 1H), 8.75 (dd, J = 4.0, 8.4 Hz, 2 ꢀ 1H), 7.83-7.77 (m, 2 ꢀ 1H),
7.21 (dd, J = 4.8, 7.2 Hz, 2 ꢀ 1H), 5.90-5.78 (m, 2 ꢀ 1H), 5.30-5.21
(m, 2 ꢀ 1H), 5.15 (d, J = 10.8 Hz, 2 ꢀ 1H), 4.96-4.85 (m, 2 ꢀ 1H),
4.47-4.32 (m, 2 ꢀ 2H), 4.24-3.98 (m, 2 ꢀ 3H), 3.91-3.64 (m, 2 ꢀ
7H), 4.48-3.05 (m, 2 ꢀ 9H); 13C NMR (100 MHz, CD3OD) δ 148.9,
137.9, 133.9, 121.1, 120.3, 120.2, 118.4, 102.7, 101.8, 76.8, 76.2, 75.1,
74.9, 70.6, 70.4, 69.8, 69.0, 67.0, 61.4, 53.8; ESIHRMS calcd for
C21H29N7O9S2Na [M þ Na]þ 610.1366, found 610.1379.
Phenyl 2-Azido-2-deoxy-3,4-O-(2,3-dimethoxybutane-2,
3-diyl)-1-thio-[20-azido-20-deoxy-30,40,60-tri-O-(p-methoxyben-
zyl)]-β-D-gentiobioside S-Oxide (50). The title compound was
prepared as a white foam by general procedure 7 and eluted from silica
gel with 0.5% Et3N in hexanes/EtOAc (3:1) in 88% yield, in an
1
approximately 1:1 mixture of diastereomers. H NMR (400 MHz) δ
7.68-7.60 (m, 2 ꢀ 2H), 7.55-7.45 (m, 2 ꢀ 3H), 7.33-7.20 (m, 2 ꢀ
4H), 7.12-7.02 (m, 2 ꢀ 2H), 6.91-6.79 (m, 2 ꢀ 6H), 4.80-4.66 (m,
2 ꢀ 3H), 4.54 (dd, J = 9.6, 10.8 Hz, 1 ꢀ 1H), 4.48-4.38 (m, 2 ꢀ 2H),
4.21 (dd, J = 5.6, 9.6 Hz, 1 ꢀ 1H), 4.02-3.84 (m, 2 ꢀ 3H), 3.83-3.73
(m, 2 ꢀ 10H), 3.73-3.44 (m, 2 ꢀ 6H), 3.43-3.14 (m, 2 ꢀ 9H), 1.34 (s,
2 ꢀ 3H), 1.26 (s, 2 ꢀ 3H); 13C NMR (100 MHz) δ 159.6, 139.1, 131.7,
131.4, 130.3, 130.0, 129.9, 129.8, 129.7, 129.6, 129.4, 129.3, 125.4, 124.7,
114.2, 114.1, 114.0, 102.9, 102.1, 100.5, 100.1, 95.2, 91.7, 91.4, 82.7, 79.8,
78.8, 77.5, 75.4, 75.3, 75.0, 74.9, 74.8, 73.5, 73.4, 73.1, 68.5, 68.2, 67.7,
66.4, 66.1, 65.8, 57.7, 55.5, 55.4, 48.4, 48.3, 17.8, 17.7; ESIHRMS calcd
for C48H58N6O14SNa [M þ Na]þ 997.3629, found 997.3614.
Methyl 2,20-Diazido-2,20-dideoxy-60-acetylthio-β-D-gen-
tiobioside (56). Glycosyl sulfoxide (54) (340 mg, 0.70 mmol) was
mixed with 2,4,6-tri-tert-butylpyrimidine (244 mg, 0.98 mmol) and
activated 4 Å powdered molecular sieves in CH2Cl2/acetonitrile (3:1)
(2.6 mL). The resulting mixture was stirred at room temperature for 0.5
h then cooled to -65 °C before trifluoromethanesulfonic anhydride
(0.14 mL, 0.84 mmol) was added dropwise. The glycoside sulfoxide was
preactivated for 10 min and a solution of 55 (466 mg, 1.4 mmol) in
CH2Cl2 (0.8 mL) was added. The resulting mixture was stirred for 8 h at
-65 °C quenched by addition of aqueous saturated NaHCO3 and then
allowed to warm to room temperature. The aqueous phase was extracted
twice with CH2Cl2. The organic layers were combined, dried, filtered,
and concentrated in vacuo. The crude protected disaccharide was
subjected directly to the standard acid hydrolysis step after which the
title compound was obtained as a white foam eluted from silica gel with
2-(Phenyloxycarbonylthioxybut-3-enyl 2-Azido-2-deoxy-
3,4-O-(2,3-dimethoxybutane-2,3-diyl)-[20-azido-20deoxy-30,
40,60-tri-O-(p-methoxybenzyl)]-β-D-gentiobioside (51). The
glycosyl sulfoxide 50 (560 mg, 0.57 mmol) was mixed with 2022b
(266 mg, 1.20 mmol), 2,4,6-tri-tert-butylpyrimidine (314 mg, 1.26
mmol), and activated 4 Å powdered molecular sieves in CH2Cl2/
acetonitrile (4:3) (2 mL) and the resulting mixture was stirred at room
temperature for 0.5 h then cooled to -60 °C before trifluoromethane-
sulfonic anhydride (0.15 mL, 0.86 mmol) was added dropwise. The reaction
mixture was stirred at -60 °C for 8 h and was then cooled to -80 °C,
quenched by addition of aqueous saturated NaHCO3, and then allowed to
warm to room temperature. The aqueous phase was extracted twice with
CH2Cl2. The organic layers were combined, dried, filtered, and concentrated
in vacuo. Chromatographic purification eluting with 0.5% Et3N in hexanes/
EtOAc (6:1 to 3:1) gave the title compound (390 mg, 63%) as a white foam
as an approximately 1:1 mixture of diastereomers. 1H NMR (400 MHz) δ
7.41-7.11 (m, 2 ꢀ 10H), 7.17-7.10 (m, 2 ꢀ 2H), 7.45 (d, J = 7.2 Hz, 2 ꢀ
2H), 6.90-6.79 (m, 2 ꢀ 7H), 6.03-5.92 (m, 2 ꢀ 1H), 5.43 (d, J = 16.8 Hz,
2ꢀ 1H), 5.25 (d, J=9.6Hz, 2ꢀ 1H), 4.80-4.67 (m, 2 ꢀ 4H), 4.55 (dd, J=
7.2, 11.6 Hz, 2 ꢀ 1H), 4.47-4.35 (m, 2 ꢀ 4H), 4.29-4.17 (m, 2 ꢀ 3H),
3.92-3.81 (m, 2 ꢀ 1H), 3.79 (s, 2 ꢀ 6H), 3.78 (s, 2 ꢀ 3H), 3.73-4.49 (m,
2 ꢀ 7H), 3.49-3.19 (m, 2 ꢀ 10H), 1.33 (s, 2 ꢀ 3H), 1.27 (s, 2 ꢀ 3H); 13C
NMR (100 MHz) δ 169.3, 169.2, 169.0, 159.6, 159.5, 159.4, 156.6, 151.4,
134.2, 134.1, 130.3, 130.2, 130.0, 130.0, 129.9, 129.8, 129.7, 126.4, 126.3,
124.7, 121.7, 121.6, 121.5, 120.3, 118.9, 115.7, 114.2, 114.1, 114.0, 103.0,
102.9, 102.8, 102.7, 100.2, 100.0, 83.2, 83.0, 75.4, 75.2, 74.9, 74.6, 73.4, 73.3,
71.4, 71.2, 70.8, 70.1, 70.0, 68.4, 67.1, 66.5, 63.2, 55.5, 55.4, 48.7, 48.3, 45.9,
18.0, 17.9, 17.8, 17.7; ESIHRMS calcd for C53H64N6O16SNa [M þ Na]þ
1095.3997, found 1095.4004.
CH2Cl2/MeOH (20:1) in 26% overall yield. [R]RT þ18.5 (c 1.0,
D
MeOH); NMR (400 MHz) δ 4.42 (d, J = 7.8 Hz, 1H), 4.24 (d, J = 7.8
Hz, 1H), 4.16 (dd, J = 1.8, 11.4 Hz, 1H), 3.70 (dd, J = 6.9 11.7 Hz, 1H),
3.60-3.51 (m, 5H), 3.46 (dd, J = 7.2, 8.1 Hz, 1H), 3.35 (s, 1H), 3.32-
3.24 (m 8H), 3.23-3.08 (m, 4H), 2.98 (dd, J = 8.1, 14.1 Hz, 1H), 2.33
(s, 3H); 13C NMR (100 MHz) δ 195.7, 102.9, 102.6, 75.9, 75.2, 75.0,
74.7, 73.4, 70.6, 69.1, 67.0, 48.7, 47.0, 30.6, 29.2; ESIHRMS calcd for
C15H24N6O9SNa [M þ Na]þ 487.1223, found 487.1232.
Phenyl 30,40,60-Tri-O-acetyl-2,20-dideoxy-3,4-O-(2,3-dime-
thoxybutan-2,3-diyl)-1-thio-2,20-bis(2,2,2-trichloroethoxy-
carbonylamino)-β-D-gentiobioside (84). Glycosyl sulfoxide 78
(310 mg, 0.53 mmol) was stirred in CH2Cl2 (1.6 mL) with activated 4 Å
powdered molecular sieves at room temperature for 0.5 h. The resulting
mixture was cooled to -65 °C before trifluoromethanesulfonic anhy-
dride (0.10 mL, 0.58 mmol) was added dropwise. After the mixture was
stirred for 10 min a solution of 83 (350 mg, 0.62 mmol) in CH2Cl2
(0.4 mL) was added. The resulting mixture was stirred for 7 h at -65 °C,
quenched by addition of aqueous saturated NaHCO3, and then allowed
to warm to room temperature. The aqueous phase was extracted twice
with CH2Cl2. The organic layers were combined, dried, filtered, and
concentrated in vacuo. Chromatographic purification eluting with
hexanes/EtOAc (5:1 to 2:1) gave the title disaccharide as a white foam
(230 mg, 43%) (Scheme 11): [R]RTD þ44.2 (c 1.0); 1H NMR δ 7.52 (d,
J = 7.2 Hz, 2H), 7.43-7.33 (m, 3H), 5.36-5.06 (m, 2H), 5.00 (d, J = 7.6
Hz, 2H), 4.81-4.69 (m, 3H), 4.64 (dd, J = 8.8, 12.0 Hz, 1H), 4.52 (d,
2-(Phenyloxycarbonylthioxy)but-3-enyl 2,20-diazido-2,20-
dideoxy-β-D-gentiobioside (52). The title compound as a white
foam was obtained by treatment of 51 with TFA according to general
3704
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
Scheme 11. Preparation of the N-Troc Glucosamine-Based
Disaccharyl Sulfenyl Donor 62
Hz, 2 ꢀ 2H), 6.00-6.57 (m, 2 ꢀ 1H), 5.55-5.45 (d, J = 16.8 Hz, 2 ꢀ 1H),
5.40 (d, J = 16.8 Hz, 2 ꢀ 1H), 5.25 (d, J = 10.4 Hz, 2 ꢀ 1H), 5.25-5.20 (m,
2 ꢀ 1H), 5.05 (t, J = 9.6 Hz, 2 ꢀ 1H), 4.80-4.65 (m, 2 ꢀ 4H), 4.55 (br s,
2 ꢀ 1H), 4.30-4.05 (m, 2 ꢀ 5H), 3.90-3.60 (m, 2 ꢀ 6H), 3.60-3.30 (m,
2ꢀ 4H), 2.10 (s, 2 ꢀ 3H), 2.03 (s, 2 ꢀ 6H); 13C NMR (100 MHz) δ171.1,
171.0, 169.7, 155.3, 154.6, 151.3, 134.1, 133.8, 129.8, 126.5, 121.6, 121.5,
119.4, 119.3, 101.5, 95.5, 77.0, 75.1, 75.0, 74.8, 74.7, 74.3, 72.2, 71.5, 69.3,
68.7, 62.1, 58.3, 58.1, 56.4, 48.8, 48.4, 29.9, 21.1, 20.8; ESIHRMS calcd for
C35H42Cl6N2O18SNa [M þ Na]þ 1043.0182, found 1043.0209.
2-(2-Pyridyldithio)but-3-enyl 2,20-Dideoxy-2,20-bis(2,2,2-
trichloroethoxycarbonylamino)-β-D-gentiobioside (62). In-
stallation of the disulfide moiety on 86 by standard procedure 3 gave
the title compound as a white foam eluting from silica gel with CH2Cl2/
MeOH (20:1) as an approximately 1:1 mixture of diastereomers in 62%
yield over two steps. 1H NMR (400 MHz, CD3OD) δ 8.36 (d, J = 4.8
Hz, 2 ꢀ 1H), 7.91 (dd, J = 7.2, 8.4 Hz, 2 ꢀ 1H), 7.87-7.79 (m, 2 ꢀ 1H),
7.20 (dd, J = 4.8, 7.2 Hz, 2 ꢀ 1H), 5.90-5.74 (m, 2 ꢀ 1H), 5.15 (dd, J =
9.6, 16.8 Hz, 2 ꢀ 2H), 4.85-4.64 (m, 2 ꢀ 10H), 4.53-4.33 (m, 2 ꢀ
2H), 4.21-4.00 (m, 2 ꢀ 2H), 3.88 (d, J = 12.0 Hz, 2 ꢀ 1H), 3.82-3.59
(m, 2 ꢀ 4H), 3.50-3.21 (m, 2 ꢀ 9H); 13C NMR (100 MHz, CD3OD)
δ 155.8, 149.1, 148.8, 138.1, 134.1, 133.8, 122.2, 121.0, 120.3, 118.6,
118.3, 102.1, 101.8, 101.7, 76.8, 75.8, 74.6, 74.5, 74.4, 71.1, 70.9, 70.0,
69.8, 69.0, 61.6, 58.0, 57.8, 54.4, 54.3, 29.6; ESIHRMS calcd for C27H35-
Cl6N3O13S2Na [M þ Na]þ 905.9637, found 905.9640.
J = 8.0 Hz, 1H), 4.28-4.21 (m, 2H), 4.15-4.02 (m, 3H), 3.75-3.52 (m,
4H), 3.39 (t, J = 9.6 Hz, 2H), 3.20 (s, 3H), 3.17 (s, 3H), 2.07 (s, 3H),
2.03 (s, 3H), 2.01 (s, 3H), 1.26, (s, 3H), 1.24 (s, 3H); 13C NMR δ 169.7,
169.3, 168.4, 153.1, 152.5, 132.2, 128.5, 127.7, 100.2, 99.0, 98.7, 94.5,
84.9, 78.1, 75.7, 73.5, 71.2, 70.5, 67.7, 67.3, 66.6, 66.3, 60.9, 54.9, 53.4,
47.0, 46.9, 19.7, 19.6, 16.6, 16.5; ESIHRMS calcd for C36H46Cl6N2O17-
SNa [M þ Na]þ 1043.0549, found 1043.0546.
Methyl 2,20-Dideoxy-3,4;30,40-di-O-(2,3-dimethoxybutan-
2,3-diyl)-2,20-bis(2,2,2-trichloroethoxycarbonylamino)-60-O-
p-toluenesulfonyl-β-D-gentiobioside (59). The title compound
was prepared as a white foam by general procedure 8 from 57 and 58 and
eluted from silica gel with hexanes/EtOAc (5:1 to 3:1) in 89% yield.
[R]23D þ72.7 (c 1.0); 1H NMR (400 MHz) δ 7.82 (d, J = 8.0 Hz, 2H),
7.35 (d, J = 8.0 Hz, 2H), 5.10 (br s, 2H), 4.88 (br s, 1H), 4.80-4.62 (m,
5H), 4.31 (d, J = 10.8 Hz, 1H), 4.16 (dd, J = 5.6, 10.8 Hz, 1H), 4.12-
3.97 (m, 3H), 3.68 (dd, J = 6.4, 8.8 Hz, 3H), 3.59-3.45 (m, 5H), 3.40-
3.12 (m, 14H), 2.45 (s, 3H), 1.28 (s, 6H), 1.25 (s, 6H); 13C NMR (100
MHz) δ 154.6, 154.1, 145.2, 132.9, 130.1, 128.4, 128.2, 101.9, 101.6,
100.2, 99.8, 95.8, 95.7, 74.8, 74.5, 73.8, 73.6, 72.3, 71.7, 69.7, 69.2, 68.5,
67.7, 67.0, 57.3, 57.2, 56.5, 55.7, 55.6, 48.5, 48.4, 48.2, 48.1, 29.9, 21.9,
18.9, 17.8; ESIHRMS calcd for C38H54Cl6N2O19SNa [M þ Na]þ
1107.1070, found 1107.1086.
2-(Phenyloxycarbonylthioxy)but-3-enyl 30,40,60-Tri-O-acetyl-
2,20-dideoxy-3,4-O-(2,3-dimethoxybutan-2,3-diyl)-2,20-bis-
(2,2,2-trichloroethoxycarbonylamino)-β-D-gentiobioside (85).
The thioglycoside 84 was converted to the corresponding glycosyl sulfoxide
according to general procedure 7 and 280 mg of this sulfoxide (0.27 mmol)
was mixed with 2022b (120 mg, 0.54 mmol) and activated 4 Å powdered
molecular sieves in CH2Cl2 (1.2 mL) then the mixture was stirred at room
temperature for 0.5 h and cooled to -60 °C before trifluoromethanesul-
fonic anhydride (0.07 mL, 0.40 mmol) was added dropwise. The reaction
mixture was stirred at -60 °C for 12 h, then was cooled to -75 °C,
quenched by addition of aqueous saturated NaHCO3, and allowed to warm
to room temperature. The aqueous phase was extracted twice with CH2Cl2.
The organic layers were combined, dried, filtered, and concentrated in
vacuo. Purification by column chromatography eluting with hexanes/
EtOAc (4:1 to 2:1) gave the title compound as a white foam as an
approximately 1:1 mixture of diastereomers (202 mg, 40% over two steps):
1H NMR (400 MHz) δ 7.36 (t, J = 7.2 Hz, 2 ꢀ 2H), 7.25-7.13 (m, 2 ꢀ
3H), 6.1-5.85 (m, 2 ꢀ 1H), 5.40 (d, J = 16.8 Hz, 2 ꢀ 1H), 5.35-5.20 (m,
2ꢀ 3H), 5.05 (dd, J=8.8, 9.6Hz, 2ꢀ 2H), 4.85-4.65 (m, 2 ꢀ 6H), 4.30-
3.95 (m, 2 ꢀ 6H), 3.90-3.80 (m, 2 ꢀ 1H), 3.75-3.50 (m, 2 ꢀ 5H), 3.45
(dd, J = 8.0, 10.0 Hz, 2 ꢀ 1H), 3.25 (s, 2 ꢀ 3H), 3.15 (s, 2 ꢀ 3H), 2.08 (s,
2 ꢀ 3H), 1.98 (s, 2 ꢀ 6H), 1.28 (s, 2 ꢀ 3H), 1.24 (s, 2 ꢀ 3H); 13C NMR
(100 MHz) δ 170.9, 170.6, 169.7, 154.2, 151.3, 134.1, 133.8, 129.7, 126.4,
121.6, 121.5, 119.2, 119.1, 101.1, 100.1, 99.9, 95.7, 76.9, 74.7, 72.2, 71.9,
71.6, 70.2, 68.8, 68.6, 68.3, 67.7, 62.2, 62.1, 56.5. 55.7, 55.4, 49.0, 48.6, 48.2,
48.1, 29.9, 21.0, 20.8, 17.9, 17.8; ESIHRMS calcd for C41H52Cl6N2O20SNa
[M þ Na]þ 1157.0885, found 1157.0890.
Methyl 60-Acetylthio-2,20-dideoxy-3,4;30,40-di-O-(2,3-di-
methoxybutan-2,3-diyl)-2,20-bis(2,2,2-trichloroethoxycarbonyl-
amino)-β-D-gentiobioside (60). The title compound was prepared
as a light yellow foam by displacement of the tosylate from 59 according
to general procedure 6 and eluted from silica gel with hexanes/EtOAc
(6:1) in 71% yield. [R]RTD þ82.3 (c 1.0); 1H NMR (400 MHz) δ 5.16-
5.0 (m, 1H), 4.92-4.83 (m, 1H), 4.78-4.63 (m, 5H), 4.12-3.99 (m,
3H), 3.74-3.65 (m, 2H), 3.64-3.56 (m, 1H), 3.53-3.42 (m, 6H), 3.33
(dd, 5.2, J = 7.2 Hz, 3H), 3.23 (s, 3H), 3.21 (s, 3H), 3.20 (s, 3H), 3.18 (s,
3H), 3.04 (q, J = 10.0, 18.8 Hz, 1H), 2.33 (s, 3H), 1.29 (s, 3H), 1.27 (s,
3H); 13C NMR (100 MHz) δ 195.1, 154.6 154.0, 129.2, 128.8, 101.8,
101.6, 100.1, 100.0, 99.8, 95.8, 77.6, 75.9, 74.8, 74.6, 74.2, 74.1, 72.7,
72.5, 70.1, 68.4, 67.8, 57.6, 57.3, 55.9, 48.5, 48.3, 48.1, 30.7, 30.2, 19.0,
17.9, 17.8; ESIHRMS calcd for C33H50Cl6N2O17SNa [M þ Na]þ
1011.0859, found 1011.0869.
Methyl 2,20-Dideoxy-2,20-bis(2,2,2-trichloroethoxycarbo-
nylamino)-60-acetylthio-β-D-gentiobioside (61). Removal of
the bisacetal groups from 60 according to general procedure 9 gave
the title compound as a white foam eluted from silica gel with CH2Cl2/
MeOH (20:1) in 68% yield. [R]RTD -6.0 (c 1.0); NMR (400 MHz) δ
4.84-4.69 (m, 6H), 4.60 (s, 1H), 4.45 (d, J = 7.6 Hz, 1H), 4.29 (d, J = 8.8
Hz, 1H), 4.11 (d, J = 10.4 Hz, 1H), 3.72-3.56 (m, 2H), 3.45-3.29 (m,
7H), 3.21 (dd, J = 8.8, 9.4 Hz, 3H), 2.90 (dd, J = 7.2, 13.6 Hz, 1H), 2.34
(s, 3H); 13C NMR (100 MHz) δ 196.0, 155.9, 102.4, 102.1, 91.5, 75.6,
75.0, 74.6, 74.4, 74.2, 74.1, 74.0, 72.1, 71.4, 69.5, 48.5, 47.4, 30.8, 29.3,
2-(Phenyloxycarbonylthioxy)but-3-enyl 30,40,60-Tri-O-acetyl-
2,20-dideoxy-2,20-bis(2,2,2-trichloroethoxycarbonylamino)-
β-D-gentiobioside (86). Cleavage of the bis(acetal) groups from 85
according to general procedure 9 gave the title compound as a white foam
that eluted from silica gel with hexanes/EtOAc (1:1 to 1:3) as an approxi-
mately 1:1 mixture of diastereomers in 68% yield. NMR (400 MHz) δ 7.38
(dd, J = 7.2, 8.4 Hz, 2 ꢀ 2H), 7.28-7.21 (m, 2 ꢀ 1H), 7.16 (dd, J = 4.0, 8.4
3705
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
Scheme 12. Preparation of the Laminaribiosyl 30-Sulfenyl
Donor 63
general procedure 12, and eluting with 75% EtOAc/hexanes the title
compound was obtained in 60% yield. [R]23D -17.0 (c 1); 1H NMR δ
7.85-7.83 (m, 3H), 7.78 (s, 1H), 7.49-7.45 (m, 3H), 5.79-5.74 (m,
1H), 5.59-5.55 (m, 1H), 5.03-4.91 (m, 3H), 4.86 (t, J = 9.0 Hz, 1H),
4.66 (s, 2H), 4.46 (d, J = 8.5 Hz, 1H), 4.30-4.25 (m, 2H), 4.19-4.18
(m, 2H), 4.11 (d, J = 6.5 Hz, 2H), 4.07 (d, J = 6.0 Hz, 2H), 4.00 (dd, J =
12.0, 2.5 Hz, 1H), 3.85 (t, J = 9.0 Hz, 1H), 3.69-3.67 (m, 1H), 3.51-
3.49 (m, 2H), 3.47 (s, 3H), 2.11 (s, 3H), 2.09 (s, 3H), 2.07 (s, 3H), 2.02
(s, 3H), 2.02 (s, 3H), 1.98 (s, 3H); 13C NMR δ 171.1, 170.9, 169.5,
169.4, 169.4, 169.0, 135.7, 133.5, 133.2, 129.5, 129.2, 128.5, 128.1, 127.9,
126.7, 126.4, 126.2, 125.9, 101.7, 101.4, 79.8, 78.8, 72.9, 72.7, 72.1, 72.1,
72.0, 69.3, 68.7, 66.8, 65.9, 62.4, 62.3, 56.8, 21.2, 21.0, 20.9, 20.9, 20.8,
20.7; ESIHRMS calcd for C40H50O18Na [M þ Na]þ 841.2895, found
841.2870.
Methyl 2,20,4,40,6,60-Hexa-O-acetyl-30-O-[4-hydroxybut-
2Z-enyl]-β-D-laminaribioside (91). Following general procedure
13, and eluting with 90% EtOAc/hexanes the title product was obtained
in 85% yield. [R]23D -37.0 (c 1); 1H NMR δ 5.75-5.69 (m, 1H), 5.50-
5.45 (m, 1H), 5.02 (t, J = 9.5 Hz, 1H), 4.97-4.90 (m, 2H), 4.86 (dd, J =
9.5, 8.5 Hz, 1H), 4.49 (d, J = 8.0 Hz, 1H), 4.31-4.28 (m, 2H), 4.20-
4.16 (m, 2H), 4.14-4.09 (m, 4H), 4.02 (dd, J = 12.0, 2.5 Hz, 1H), 3.85
(t, J = 9.5 Hz, 1H), 3.67-3.64 (m, 1H), 3.59-3.52 (m, 2H), 3.45 (s,
3H), 2.13 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 2.06 (s, 3H), 2.06 (s, 3H),
2.01 (s, 3H); 13C NMR δ 171.0, 170.8, 169.7, 169.6, 169.5, 169.1, 132.3,
127.7, 101.7, 101.4, 79.8, 78.9, 72.9, 72.1, 72.0, 71.7, 68.8, 68.6, 65.9,
62.4, 62.3, 58.5, 56.8, 21.2, 21.0, 21.0, 20.9, 20.9, 20.7; ESIHRMS calcd
for C29H42O18Na [M þ Na]þ 701.2269, found 701.2289.
25.6, 19.8; ESIHRMS calcd for C21H30Cl6N2O13SNa [M þ Na]þ
782.9497, found 782.9501.
3-O-{2,4,6-Tri-O-acetyl-3-O-[4-(2-naphthylmethyloxy)but-
2Z-enyl]-β-D-glycopyranosyl}-1,2:5,6-di-O-isopropylidene-r-
D-glucofuranose (87). Following general procedure 12, diacetone-D-
glucose was glycosylated with trichloroacetimidate 26 and after eluting
with 70% EtOAc/hexanes from silica gel the title compound was ob-
tained in 60% yield (Scheme 12). [R]23D -15.7 (c 1); 1H NMR δ 7.86-
7.83 (m, 3H), 7.79 (s, 1H), 7.51-7.46 (m, 3H), 5.84 (d, J = 3.5 Hz, 1H),
5.81-5.76 (m, 1H), 5.62-5.57 (m, 1H), 5.03 (t, J = 10.0 Hz, 1H), 4.92
(dd, J = 9.5, 7.5 Hz, 1H), 4.68 (s, 2H), 4.50 (d, J = 8.0 Hz, 1H), 4.42 (d,
J = 4.0 Hz, 1H), 4.35 (dd, J = 12.0, 6.0 Hz, 1H), 4.27 (dd, J = 5.5, 3.0 Hz,
1H), 4.25-4.24 (m, 1H), 4.18-4.11 (m, 3H), 4.08-4.03 (m, 3H), 3.97
(dd, J = 9.0, 6.0 Hz, 1H), 3.53-3.49 (m, 2H), 2.08 (s, 3H), 2.02 (s, 3H),
2.00 (s, 3H), 1.50 (s, 3H), 1.43 (s, 3H), 1.35 (s, 3H), 1.32 (s, 3H); 13C
NMR δ 170.9, 169.4, 168.9, 135.7, 133.5, 133.2, 129.5, 129.3, 128.5,
128.1, 127.9, 126.7, 126.5, 126.2, 125.9, 112.3, 108.8, 105.3, 99.6, 83.0,
81.2, 80.8, 79.7, 73.3, 72.7, 72.6, 69.5, 67.3, 66.4, 65.8, 62.4, 27.1, 26.8,
26.6, 25.5, 20.9; ESIHRMS calcd for C35H47NO17Na [M þ Na]þ
776.2742, found 776.2740.
Methyl 2,20,4,40,6,60-Hexa-O-acetyl-30-O-[4-(phenyloxy-
thionocarbonyloxy)but-2Z-enyl]-β-D-laminaribioside (92).
Following general procedure 1, and eluting with 70% EtOAc/hexanes
1
the title product was obtained in 88% yield. [R]23 -32.0 (c 1); H
D
NMR δ 7.43-7.40 (m, 2H), 7.29 (t, J = 7.5 Hz, 1H), 7.09-7.07 (m,
2H), 5.80-5.75 (m, 1H), 5.71-5.66 (m, 1H), 5.05-5.02 (m, 3H),
4.97-4.87 (m, 3H), 4.48 (d, J = 8.0 Hz, 1H), 4.31-4.28 (m, 2H), 4.21-
4.17 (m, 4H), 4.02 (dd, J = 12.5, 2.5 Hz, 1H), 3.86 (t, J = 9.5 Hz, 1H),
3.68-3.65 (m,1H), 2.12 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.07 (s, 3H),
2.06 (s, 3H), 2.02 (s, 3H); 13C NMR δ 195.1, 171.0, 170.8, 169.5, 169.4,
169.1, 153.6, 131.8, 129.8 (2C), 126.9, 125.1, 122.1 (2C), 101.7, 101.4,
80.4, 78.8, 77.0, 72.9, 72.1, 72.0, 71.9, 69.5, 69.2, 68.6, 66.8, 62.4, 62.2,
56.8, 21.1, 21.1, 21.0, 20.9 (2C), 20.7; ESIHRMS calcd for C36H46O19S-
Na [M þ Na]þ 837.2252, found 837.2239.
Methyl 2,20,4,40,6,60-Hexa-O-acetyl-30-O-[2-phenyloxycar-
bonylthioxy]but-3-enyl]-β-D-laminaribioside (93). Following
general procedure 2, and eluting with 70% EtOAc/hexanes the title
product was obtained as an approximately 1:1 mixture of stereoisomers
in 90% yield. 1H NMR δ 7.39-7.36 (m, 2H), 7.24 (t, J = 7.5 Hz, 1H),
7.16-7.15 (m, 1H), 7.14-7.13 (m, 1H), 5.19 (dd, J = 10.0, 3.5 Hz, 1H),
4.10-5.05 (m, 1H), 4.99-4.91 (m, 3H), 4.49 (d, J = 8.5 Hz, 1H), 4.33-
4.29 (m, 2H), 4.19-4.18 (m, 2H), 4.05-4.01 (m, 2H), 3.86 (t, J = 9.5
Hz, 1H), 3.82-3.77 (m, 2H), 3.47 (s, 3H), 2.13 (s, 3H), 2.11 (s, 3H),
2.09 (s, 3H ꢀ 3), 2.08 (s, 3H ꢀ 2), 2.08 (s, 3H), 2.07 (s, 3H), 2.06 (s,
3H), 2.03 (s, 3H), 2.02 (s, 3H); 13C NMR δ 171.0, 171.9, 169.5, 169.4
(2C), 169.1, 151.3, 133.9, 133.8, 129.7, 126.5, 121.5, 118.8, 118.7, 101.7,
101.4, 81.0, 80.8, 78.8, 73.5, 73.4, 72.9, 72.1, 72.1, 71.9, 71.7, 69.1, 68.9,
68.6, 62.4, 62.2, 56.8, 48.9, 48.7, 21.2, 21.1, 21.0 (2C), 20.9, 20.9, 20.9
(2C), 20.7 (2C); ESIHRMS calcd for C36H46O19SNa [M þ Na]þ
837.2252, found 837.2224.
2,20,4,40,6,60-Hexa-O-acetyl-30-O-[4-(2-naphthylmethyloxy)-
but-2Z-enyl]-r-D-laminaribiosyl Trichloroacetimidate (89).
Following general procedure 10, the acetonide groups were cleaved
and the acetate groups were reinstalled to give the peracetate 88 in 60%
yield as a mixture of stereoisomers that was applied directly to general
procedure 11, after which elution from silica gel with 70% EtOAc/hexanes
gave the title compound in 68% yield as yellow oil. [R]23D þ28.0 (c 1); 1H
NMR δ 8.70 (s, 1H), 7.85-7.82 (m, 3H), 7.77 (s, 1H), 7.50-7.45 (m,
3H), 6.46 (d, J = 4.0 Hz, 1H), 5.79-5.74 (m, 1H), 5.59-5.54 (m, 1H),
5.12-5.06 (m, 2H), 4.99 (t, J = 9.5 Hz, 1H), 4.89-4.85 (m, 1H), 4.66 (s,
2H), 4.54 (d, J = 8.5 Hz, 1H), 4.23 (dd, J = 12.0, 5.0 Hz, 1H), 4.19 (dd, J =
12.5, 4.5 Hz, 1H), 4.16-4.03 (m, 8H), 3.55-3.49 (m, 2H), 2.08 (s, 3H),
2.08 (s, 3H), 2.07 (s, 3H), 2.05 (s, 3H), 1.98 (s, 3H), 1.97 (s, 3H); 13C
NMR δ 170.9, 170.8, 169.7, 169.4, 169.3, 169.1, 160.8, 135.7, 133.5, 133.2,
129.5, 129.2, 128.5, 128.1, 127.9, 126.7, 126.5, 125.9, 101.4, 93.4, 79.8, 76.3,
72.7, 72.3, 72.1, 72.0, 70.5, 69.4, 67.5, 66.8, 65.9, 62.3, 61.8, 20.9, 20.9, 20.9,
20.9, 20.8, 20.8, 20.7; ESIHRMS calcd for C41H48Cl3NO18Na [M þ Na]þ
970.1835, found 970.1845.
Methyl 30-O-(2-Pyridin-2-yldithio)but-3-enyl-β-D-laminar-
ibioside (63). Following general procedure 3, and eluting with 10%
MeOH/CH2Cl2 the title product was obtained in 68% yield as an
1
approximately 1.1:1 mixture of stereoisomers. H NMR δ 8.37-8.36
(m, 1H), 7.94-7.90 (m, 2H), 7.82-7.78 (m, 1H), 7.22-7.19 (m, 1H),
5.87-5.79 (m, 1H), 5.25-5.21 (m, 1H), 5.14-5.12 (m, 1H), 4.55 (dd,
J = 7.5, 4.5 Hz, 1H), 4.23 (dd, J = 7.5, 1.5 Hz, 1H), 4.12 (dd, J = 10.5,
Methyl 2,20,4,40,6,60-Hexa-O-acetyl-30-O-[4-(2-naphthyl-
methyloxy)but-2Z-enyl]-β-D-laminaribioside (90). Following
3706
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
Scheme 13. Preparation of the 1-Deoxymercaptolaminari-
biose Precursor 65
7.2 Hz, 1H), 4.84 (d, J = 8.4 Hz, 1H), 4.64-4.58 (m, 3H), 4.38 (dd, J =
10.8, 4.8 Hz, 1H), 4.11-4.04 (m, 2H), 3.91-3.79 (m, 3H), 3.59 (t, J =
11.2 Hz, 1H), 3.52-3.46 (m, 2H), 2.21 (s, 3H), 1.94 (s, 3H), 1.92 (s,
3H), 1.68 (s, 3H); 13C NMR (100 MHz) δ 193.7, 169.4, 165.6, 137.4,
136.8, 133.5, 130.2, 130.0, 129.9, 129.3, 128.7, 128.6, 128.4, 128.1, 128.0,
126.3, 119.2, 102.1, 101.5, 99.8, 79.3, 79.1, 77.6, 77.3, 76.9, 74.4, 73.6,
70.6, 69.9, 68.8, 67.8, 66.8, 62.3, 47.9, 30.7, 20.9, 20.7, 20.2; ESIHRMS
calcd for C41H44O15SNa [M þ Na]þ 831.2299, found 831.2259.
Benzyl 2-O-Benzoyl-20,40,60-tri-O-acetyl-30-acetylthio-β-D-
laminaribioside (64). Compound 95 (41 mg, 0.05 mmol) was stirred
in 50% aqueous AcOH (1.0 mL) at 50 °C for 4-6 h. After the solvents
were evaporated the residue was purified by column chromatography
Scheme 14. Preparation of the Laminaribiosyl-30-thiol Pre-
cursor 64
over silica gel eluting with 90% EtOAc/hexanes to afford the title
1
product in 90% yield (Scheme 14). [R]23 -38.7 (c 1); H NMR
D
(400 MHz) δ 7.99-7.97 (m, 2H), 7.64-7.61 (m, 1H), 7.51-7.47 (m,
2H), 7.19-7.14 (m, 1H), 7.12-7.11 (m, 4H), 5.25 (t, J = 11.0 Hz, 1H),
4.99-4.92 (m, 2H), 4.82-4.79 (m, 1H), 4.63-4.59 (m, 1H), 4.53 (d, J
= 10.5 Hz, 2H), 4.17-4.08 (m, 2H), 3.99-3.94 (m, 1H), 3.83-3.75 (m,
4H), 3.73-3.71 (m, 1H), 3.67-3.62 (m, 2H), 3.41-3.36 (m, 1H), 2.23
(s, 3H), 2.07 (s, 3H ꢀ 2), 1.97 (s, 3H); 13C NMR δ 193.4, 170.7, 169.4,
169.3, 165.1, 137.0, 133.6, 130.0, 129.8, 128.7, 128.5, 128.0, 127.9, 102.7,
99.7, 85.7, 75.8, 74.8, 72.5, 70.7, 69.9, 69.5, 67.8, 63.1, 62.3, 47.9, 30.7,
20.8, 20.6, 20.1; ESIHRMS calcd for C34H40O15SNa [M þ Na]þ
743.1986, found 743.1971.
Methyl 6-[4-O-(2,20-Azido-2,20-dideoxy-β-D-gentiobiosy-
loxy)but-2E-enyl]thio-2,20-azido-2,20-dideoxy-r-D-gentiobio-
side (66). Thiol precursor 56 (40 mg, 0.09 mmol) was dissolved
in DMF (0.8 mL) at room temperature and hydrazine acetate (12 mg,
0.13 mmol) was added. The resulting mixture was stirred for 0.75 h and
then directly transferred to a stirred solution of sulfenyl donor 53
(56 mg, 0.1 mmol) in MeOH (1 mL) at room temperature. The
resulting mixture was stirred until TLC showed complete consumption
of the thiol (18 h). Silver nitrate (26 mg, 0.20 mmol) was then added and
the resulting mixture was stirred at room temperature, with exclusion of
light, for an additional 36 h. The resulting mixture was filtered through a
pad of Celite and silica gel and concentrated. Chromatographic purifica-
tion eluting with CH2Cl2/MeOH (15:1) afforded the title compound as
a white foam in 52% yield. [R]RTD þ65.8 (c 1.0, MeOH); 1H NMR (400
MHz, CD3OD) δ 5.84-5.67 (m, 2H), 4.62 (s, 2H), 5.52-4.36 (m, 5H),
4.23 (dd, J = 9.5, 12.0 Hz, 5H), 3.87 (d, J = 12.0 Hz, 2H), 3.83-3.62 (m,
5H), 3.56 (s, 3H), 3.54-3.43 (m, 5H), 3.42-3.05 (m, 15H), 2.95 (d, J =
15.0 Hz, 1H), 2.63 (q, J = 7.0 Hz, 1H); 13C NMR (100 MHz, CD3OD) δ
130.4, 128.6, 102.9, 102.6, 100.6, 77.2, 76.8, 76.1, 75.9, 75.2, 75.1, 74.8,
72.9, 70.6, 70.5, 70.3, 69.1, 69.0, 68.9, 67.0, 66.9, 61.3, 56.2, 33.9, 31.4;
ESIHRMS calcd for C29H46N12O17SNa [M þ Na]þ 889.2722, found
889.2736.
6.0 Hz, 1H, minor), 4.08-4.07 (m, 1H), 4.03 (dd, J = 10.0, 6.0 Hz, 1H,
minor), 3.90-3.86 (m, 2H), 3.80 (dd, J = 15.0, 6.5 Hz, 1H), 3.70 (dd, J =
11.5, 5.5 Hz, 1H), 3.65-3.61 (m, 1H), 3.54 (s, 3H major þ 3H minor),
3.43-3.33 (m, 7H), 3.23 (t, J = 8.5 Hz, 1H); 13C NMR δ 160.7, 148.8,
137.8, 134.6, 134.5, 121.0, 120.3, 118.1, 104.1, 103.7, 86.9, 85.7, 85.6,
76.8, 76.4, 74.4, 74.3, 73.7, 73.2, 69.9, 69.8, 68.8, 61.4, 61.3, 56.2, 54.9,
54.8; ESIHRMS calcd for C22H33NO11S2Na [M þ Na]þ 574.1393,
found 574.1385.
1-Thiohepta-O-acetyl-β-D-laminaribiose (65). A stirred solu-
tion of peracetyl laminaribiosyl bromide38 (698 mg, 1.0 mmol) in
acetone/water (5.0 mL) was treated with thiourea (114 mg, 1.5 mmol)
and heated to reflux for 4-6 h. After cooling to room temperature the
solvents were evaporated and a stirred solution of the residue in
CH2Cl2/water (10.0 mL) was treated with sodium metabisulfite (2.0
mmol) and heated to reflux under an atmosphere of N2 for 2-4 h. The
reaction mixture was diluted with CH2Cl2 (10.0 mL) and washed with
saturated aqueous NaHCO3 (10.0 mL). The combined organic portion
was dried over Na2SO4 and evaporated to dryness. The crude product
was purified by column chromatography over silica gel 70% (EtOAc/
hexanes) to give the title product as colorless oil in 65% yield
1
(Scheme 13). [R]23 -18.2 (c 1); H NMR δ 5.13 (t, J = 9.5 Hz,
D
Methyl 6-[4-O-(2,20-Dideoxy-2,20-(2,2,2-trichloroethoxy-
carbonylamino)-β-D-gentiobiosyloxy)but-2E-enyl]thio-2,20-
dideoxy-(2,2,2-trichloroethoxycarbonylamino)-r-D-gentio-
bioside (67). Thiol precursor 61 (30 mg, 0.04 mmol) was dissolved
in DMF (0.5 mL) at room temperature and hydrazine acetate (12 mg,
0.13 mmol) was added. The resulting mixture was stirred for 1.25 h and
directly transferred to a stirred solution of sulfenyl donor 62 (42 mg,
0.05 mmol) in MeOH (0.8 mL). The resulting mixture was stirred until
TLC showed complete consumption of the thiol compound (20 h).
Triphenylphosphine (13 mg, 0.05 mmol) was then added and the resulting
mixture was stirred at room temperature for an additional 40 h before it was
concentrated. Purification by silica gel chromatography CH2Cl2/MeOH
(15:1) afforded the title compound as a white foam in 54% yield.
[R]RTD þ72.6 (c 1.0, MeOH); 1H NMR (400 MHz, CD3OD) δ 5.85-
5.58 (m, 2H), 4.92 (d, J = 4.1 Hz, 3H), 4.93-4.86 (m, 12H), 4.85 (d, J = 4.0
Hz, 2H), 4.80 (d, J= 12.1 Hz, 2H), 4.73 (dd, J= 9.7, 12.2, 3 Hz), 4.62 (dd, J=
8.9, 11.3, 2 Hz), 4.54-4.37 (m, 2H), 4.36-4.24 (m, 2H), 4.19 (d, J=4.0Hz,
2H), 4.13-4.01 (m, 1H), 3.89 (d, J = 11.3, 1H), 3.77-3.59 (m, 4H),
1H), 5.06 (t, J = 9.5 Hz, 1H), 4.99-4.94 (m, 2H), 4.91-4.88 (m, 1H),
4.60 (d, J = 7.5 Hz, 1H), 4.42-4.36 (m, 2H), 4.19-4.12 (m, 2H), 4.03
(dd, J = 10.5, 2.0 Hz, 1H), 3.85 (t, J = 9.5 Hz, 1H), 3.70-3.66 (m, 2H),
2.29 (d, J = 10.5 Hz, 1H), 2.17 (s, 3H), 2.09 (s, 3H), 2.07 (s, 3H), 2.03 (s,
3H), 2.01 (s, 3H), 2.00 (s, 3H), 1.97 (s, 3H); 13C NMR δ 170.9, 170.7,
170.6, 169.6, 169.5, 169.5, 169.4, 101.1, 80.1, 79.0, 76.6, 75.3, 73.2, 71.9,
71.3, 68.2, 68.1, 62.5, 61.8, 21.3, 21.0, 20.8, 20.7, 20.7, 20.6, 20.5;
ESIHRMS calcd for C26H36O17SNa [M þ Na]þ 675.1571, found
675.1541.
Benzyl 2-O-Benzoyl-4,6-O-benzylidene-20,40,60-tri-O-acet-
yl-30-acetylthio-β-D-laminaribioside (95). Following general pro-
cedure 12, benzyl 2-O-benzoyl-4,6-O-benzylidene-β-D-glucopyranoside
(94) was glycosylated with the trichloroacetimidate 36. Purification was
achieved by eluting from silica gel with 70% EtOAc/hexanes. The title
product was obtained in 25% yield. [R]23D -47.7 (c 1); 1H NMR (400
MHz) δ 7.99-7.97 (m, 2H), 7.64-7.60 (m, 1H), 7.51-7.45 (m, 4H),
7.35-7.33 (m, 3H), 7.21-7.16 (m, 1H), 7.14-7.12 (m, 4H), 5.57 (s,
1H), 5.35 (t, J = 10.0 Hz, 1H), 4.97 (t, J = 9.6 Hz, 1H), 4.90 (dd, J = 11.2,
3707
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
3.53-3.18 (m, 18H), 2.96 (d, J = 13.0 Hz, 1H), 2.63 (dd, J = 5.7, 8.1 Hz,
1H); 13C NMR (100 MHz, CD3OD) δ 153.8, 153.6, 130.4,128.7, 102.8,
102.5, 100.7, 78.2, 77.7, 76.2, 75.9, 75.8, 75.3, 75.2, 74.9, 72.5, 72.3, 70.7, 70.6,
70.4, 69.2, 69.0, 68.6, 67.5, 67.3, 61.5, 56.3, 33.9, 32.2; ESIHRMS calcd for
C41H58Cl12N4O25SNa [M þ Na]þ 1480.9271, found 1480.9316.
Papp-Szabo, E.; Lowman, D. W.; Power, T. D.; Wempe, M. F.; Williams,
D. L. J. Pharmacol. Exp. Ther. 2008, 325, 115–123.
(3) Jamois, F.; Ferriꢁeres, V.; Guꢀegan, J.-P.; Yvin, J.-C.; Plusquellec,
D.; Vetvicka, V. Glycobiology 2005, 15, 393–407.
(4) Descroix, K.; Ferrieres, V.; Jamois, F.; Yvin, J.-C.; Plusquellec, D.
Mini-Rev. Med. Chem. 2006, 6, 1341–1349.
(5) (a) Zeng, Y.; Ning, J.; Kong, F. Tetrahedron Lett. 2002,
43, 3729–3733. (b) Zeng, Y.; Ning, J.; Kong, F. Carbohydr. Res. 2003,
338, 307–311.
(6) Mo, K.-F.; Li, H.; Mague, J. T.; Ensley, H. E. Carbohydr. Res.
2009, 344, 439–447.
(7) Sylla, B.; Descroix, K.; Pain, C.; Gervaise, C.; Jamois, F.; Yvin, J.-C.;
Legentil, L.; Nugier-Chauvin, C.; Daniellou, R.; Ferrieres, V. Carbohydr. Res.
2010, 345, 1366–1370.
(8) (a) Humbel, B. M.; Konomi, M.; Takagi, T.; Kamasawa, N.;
Ishijima, S. A.; Osumi, M. Yeast 2001, 18, 433–444. (b) Kollar, R.; Reinhold,
B.; Petrakova, E.; Yeh, H. J.; Ashwell, G.; Drgonova, J.; Kapteyn, J. C.; Klis,
F. M.; Cabib, E. J. Biol. Chem. 1997, 272, 17762–17775.
(9) (a) Cheon, H.-S.; Lian, Y.; Kishi, Y. Org. Lett. 2007, 9, 3323–3326.
(b) Meppen, M.; Wang, Y.; Cheon, H.-S.; Kishi, Y. J. Org. Chem. 2007,
72, 1941–1950. (c) Hsu, M. C.; Lee, J.; Kishi, Y. J. Org. Chem. 2007,
72, 1931–1940.
Benzyl 3-Deoxy-3-[4-(β-D-laminaribiosyloxy)but-2E-enyl-
thio]-β-D-laminaribioside (68). Following general procedure 15,
the title compound was obtained in 50% yield. [R]23 -16.0 (c 0.75,
D
1
MeOH); H NMR (CD3OD) δ 7.44-7.42 (m, 2H), 7.36-7.32 (m,
2H), 7.29-7.27 (m, 1H), 5.88-5.83 (m, 1H), 5.76-5.71 (m, 1H), 4.94
(d, J = 12.0 Hz, 1H), 4.69 (d, J = 8.5 Hz, 1H), 4.58 (t, J = 8.0 Hz, 1H),
4.47-4.41 (m, 2H), 4.31 (dd, J = 13.0, 5.0 Hz, 1H), 4.20 (dd, J = 13.0,
7.5 Hz, 1H), 3.93-3.87 (m, 14H), 3.74-3.26 (m, 12H), 2.59 (t, J = 10.0
Hz, 1H); 13C NMR (CD3OD) δ 137.7, 131.2, 128.6, 128.2, 128.1, 127.6,
105.3, 104.2, 101.6, 100.7, 86.9, 86.8, 79.4, 76.9, 76.5, 76.4, 76.2, 74.4,
73.8, 73.4, 73.3, 72.6, 70.6, 70.4, 69.0, 68.9, 68.7, 68.4, 63.2, 61.7, 61.5,
61.4, 53.9, 33.3; ESIHRMS calcd for C35H54O21SNa [M þ Na]þ
865.2776, found 865.2768.
Methyl 3-O-[4-(1-thio-β-D-laminaribiosyl)but-2E-enyl]-β-
D-laminaribioside (69). Following general procedure 15, the title
compound was obtained in 55% yield. [R]23D -15.0 (c 0.75, MeOH);
1H NMR (CD3OD) δ 5.79-5.77 (m, 2H), 4.57 (d, J = 7.5, 4.0 Hz, 2H),
4.46 (d, J = 9.5 Hz, 1H), 4.36-4.35 (m, 2H), 4.24 (d, J = 7.5 Hz, 1H),
3.89 (dd, J = 7.0, 2.0 Hz, 4H), 3.72-3.67 (m, 2H), 3.66-3.62 (m, 3H),
3.58-3.53 (m, 2H), 3.54 (s, 3H), 3.52-3.47 (m, 2H), 3.45-3.21 (m,
13H); 13C NMR (CD3OD) δ 130.3, 129.1, 104.1, 104.0, 103.7, 88.3,
86.9, 83.6, 83.3, 80.2, 76.9, 76.8, 76.6, 76.4, 74.6, 74.4, 73.2, 72.5, 72.4,
70.4, 70.0, 69.0, 68.9, 61.7, 61.4, 56.1, 30.8; ESIHRMS calcd for
C29H50O21SNa [M þ Na]þ 789.2463, found 789.2451.
(10) Itoh, Y.; Rice, J. D.; Goller, C.; Pannuri, A.; Taylor, J.; Meisner,
J.; Beveridge, T. J.; Preston, J. F.; Romeo, T. J. Bacteriol. 2008,
190, 3670–3680.
(11) Cerca, N.;Maira-Litran, T.;Jefferson, K. K.; Grout, M.; Goldmann,
D. A.; Pier, G. B. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 7528–7533.
(12) (a) Gening, M. L.; Tsvetkov, Y. E.; Pierb, G. B.; Nifantiev, N. E.
Carbohydr. Res. 2007, 342, 567–575. (b) Melean, L. G.; Love, K. R.;
Seeberger, P. H. Carbohydr. Res. 2002, 337, 1893–1916. (c) Fridman,
M.; Solomon, D.; Yogev, S.; Baasov, T. Org. Lett. 2002, 4, 281–283. (d)
Yang, F.; Du, Y. Carbohydr. Res. 2003, 338, 495–502. (e) Yang, F.; He,
H.; Du, Y. Tetrahedron Lett. 2002, 43, 7561–7563.
4-(1-Thio-β-D-laminaribiosyl)but-2E-enyl β-D-laminaribio-
side (70). Following general procedure 15, the title compound was
obtained in 55% yield. [R]23 -11.0 (c 0.75, MeOH); 1H NMR
D
(13) Petitou, M.; van Boeckel, C. A. A. Angew. Chem., Int. Ed. 2004,
43, 3118–3133.
(14) Boons, G.-J. Tetrahedron 1996, 52, 1095–1121.
(CD3OD) δ 5.86-5.80 (m, 1H), 5.77-5.71 (m, 1H), 4.59 (d, J =
11.0, 7.5 Hz, 2H), 4.44-4.41 (m, 2H), 4.33 (dd, J = 12.5, 4.5 Hz, 1H),
4.20 (dd, J = 12.0, 7.5 Hz, 1H), 3.91-3.89 (m, 4H), 3.75-3.62 (m, 5H),
3.59-3.55 (m, 2H), 3.53-3.18 (m, 15H); 13C NMR (CD3OD) δ
130.2, 128.8, 104.1 (2C), 103.9, 100.9, 88.6, 87.3, 83.1, 80.2, 76.9, 76.8,
76.5, 76.4, 74.4, 74.4, 73.2, 72.4, 70.4, 69.0, 68.9, 66.5, 61.7, 61.5, 30.6;
ESIHRMS calcd for C28H48O21SNa [M þ Na]þ 775.2306, found
775.2328.
(15) (a) Fraser-Reid, B.; Lu, J.; Jayaprakash, K. N.; Lopez, J. C.
Tetrahedron: Asymmetry 2006, 17, 2449–2463. (b) Joe, M.; Bai, Y.;
Nacario, R. C.; Lowary, T. L. J. Am. Chem. Soc. 2007, 129, 9885–9901.
(16) (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int.
Ed. 2001, 40, 2004–2021. (b) Tornøe, C. W.; Christensen, C.; Meldal, M.
J. Org. Chem. 2002, 67, 3057–3064. (c) Rostovtsev, V. V.; Green, L. G.;
Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596–2599.
(d) Meldal, M.; Tornøe, C. W. Chem. Rev. 2008, 108, 2952–3015.
(17) (a) Dedola, S.; Nepogodiev, S. A.; Field, R. A. Org. Biomol.
Chem. 2007, 1006–1017. (b) Dondoni, A. Chem. Asian J. 2007, 2, 700–
708. (c) Nicotra, F.; Cipolla, L.; Peri, F.; La Ferta, B.; Redaelli, C. Adv.
Carbohydr. Chem. Biochem. 2007, 61, 353–398. (d) Gyorgydeak, Z.;
Thiem, J. Adv. Carbohydr. Chem. Biochem. 2006, 60, 103–182. (e) Pieters,
R. J.; Rijkers, D. T. S.; Liskamp, R. M. J. QSAR Comb. Sci. 2007,
26, 1181–1190. (f) Santoyo-Gonzalez, F.; Hernandez-Mateo, F. Top.
Heterocycl. Chem. 2007, 7, 133–177. (g) Hanson, S. R.; Greenberg, W. A.;
Wong, C.-H. QSAR Comb. Sci. 2007, 26, 1243–1252.(h) Wilkinson, B. L.;
Bornaghi, L. F.; Houston, T. A.; Poulsen, S.-A. In Drug Design Research
Perspectives; Kaplan, S. P., Ed.; Nova Science Publishers: Hauppauge, NY,
2007; pp 57-102.
’ ASSOCIATED CONTENT
S
Supporting Information. Full experimental details and
b
copies of the 1H and 13C NMR spectra of all compounds. This
material is available free of charge via the Internet at http://pubs.
acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: dcrich@icsn.cnrs-gif.fr.
(18) (a) Dondoni, A. Angew. Chem., Int. Ed. 2008, 47, 8995–8997.
(b) van Dijk, M.; Rijkers, D. T. S.; Liskamp, R. M. J.; van Nostrum, C. F.;
Hennink, W. E. Bioconjugate Chem 2009, 20, 2001–2016. (c) Hoyle,
C. E.; Bowman, C. N. Angew. Chem., Int. Ed. 2010, 49, 1540–1573.
(19) (a) Shiu, H.-Y.; Chan, T.-C.; Ho, C.-M.; Liu, Y.; Wong, M.-K.;
Che, C.-M. Chem.—Eur. J. 2009, 15, 3839–3850. (b) Floyd, N.;
Vijayakrishnan, B.; Koeppe, J. R.; Davis, B. G. Angew. Chem., Int. Ed.
2009, 48. (c) Lo Conte, M.; Pacifico, S.; Chambery, A.; Marra, A.;
Dondoni, A. J. Org. Chem. 2010, 75, 4644–4647.
’ ACKNOWLEDGMENT
We thank the NIH (GM62160) for support of this work.
’ REFERENCES
(1) Kent, S. B. H. Chem. Soc. Rev. 2009, 38, 338–351.
(2) (a) Brown, G. D.; Gordon, S. Nature 2001, 413, 36–37. (b) Palma,
A. S.; Feizi, T.; Zhang, Y.; Stoll, M. S.; Lawson, A. M.; Díaz-Rodríguez, E.;
Campanero-Rhodes, M. A.; Costa, J.; Gordon, S.; Brown, G. D.; Chai, W.
J. Biol. Chem. 2006, 281, 5771–5779. (c) Adams, E. L.; Rice, P. J.; Graves,
B.; Ensley, H. E.; Yu, H.; Brown, G. D.; Gordon, S.; Monteiro, M. A.;
(20) (a) Kolb, H. C.; Sharpless, K. B. Drug Discovery Today 2003,
8, 1128–1137. (b) Appendino, G.; Bacchiega, S.; Minassi, A.; Cascio,
M. G.; De Petrocellis, L.; Di Marzo, V. Angew. Chem., Int. Ed. 2007,
3708
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709

The Journal of Organic Chemistry
ARTICLE
46, 9312–9315. (c) Bock, V. D.; Hiemstra, H.; van Maarseveen, J. H. Eur.
J. Org. Chem. 2006, 51–68.
(21) (a) Crich, D.; Krishnamurthy, V.; Hutton, T. K. J. Am. Chem. Soc.
2006, 128, 2544–2545. (b) Crich, D.; Brebion, F.; Krishnamurthy, V. Org.
Lett. 2006, 8, 3593–3596. (c) Crich, D.; Krishnamurthy, V.; Brebion, F.;
Karatholuvhu, M.; Subramanian, V.; Hutton, T. K. J. Am. Chem. Soc. 2007,
129, 10282–10294. (d) Zhang, D.; Devarie-Baez, N. O.; Pan, J.; Wang, H.;
Xian, M. Org. Lett. 2010, 12, 5674–5676. (e) Li, Z.; Wang, C.; Fu, Y.; Guo,
Q.-X.; Liu, L. J. Org. Chem. 2008, 73, 6127–6136.
(22) (a) Crich, D.; Zou, Y.; Brebion, F. J. Org. Chem. 2006, 71,
9172–9177. (b) Crich, D.; Yang, F. J. Org. Chem. 2008, 73, 7017–7027.
(23) Chalker, J. M.; Lin, Y. A.; Boutureira, O.; Davis, B. G. Chem.
Commun. 2009, 3714–3716.
(24) (a) Hermanson, G. T. Bioconjugate Techniques; Academic
Press: San Diego, CA, 1996. (b) Lundblad, R. L. Chemical Reagents for
Protein Modification; 3rd ed.; CRC Press: Boca Raton, FL, 2005.
(25) Crich, D.; Subramanaian, V.; Karatholuvhu, M. J. Org. Chem.
2009, 74, 9422–9427.
(26) (a) Overman, L. E.; Roberts, S. W.; Sneddon, H. F. Org. Lett.
2008, 10, 1485–1488. (b) Gais, H.-J.; B€ohme, A. J. Org. Chem. 2002,
67, 1153–1161.
(27) Thompson, C.; Ge, M.; Kahne, D. J. Am. Chem. Soc. 1999,
121, 1237–1244.
(28) Nakabayashi, S.; Warren, C. D.; Jeanloz, R. N. Carbohydr. Res.
1986, 150, C7–C10.
(29) (a) Schmidt, R. R. In Preparative Carbohydrate Chemistry;
Hanessian, S., Ed.; Dekker: New York, 1997; pp 283-312. (b) Schmidt,
R. R.; Jung, K.-H. In Carbohydrates in Chemistry and Biology; Ernst, B.,
::
Hart, G. W., Sinay, P., Eds.; Wiley-VCH: Weinheim, Germany, 2000;
Vol. 1, pp 5-59.
(30) Trimnell, D.; Stout, E. I.; Doane, W. M.; Russell, C. R.;
Beringer, V.; Saul, M.; Van Gessel, G. J. Org. Chem. 1975, 40, 1337–1339.
(31) Volante, R. P. Tetrahedron Lett. 1981, 22, 3119–3122.
(32) Stick, R. V.; Stubbs, K. A. Tetrahedron: Asymmetry 2005,
16, 321–335.
(33) Cumpstey, I.; Ramstadius, C.; Akhtar, T.; Goldstein, I. J.;
Winter, H. C. Eur. J. Org. Chem. 2010, 1951–1970.
(34) (a) Schmidt, R. R.; Behrendt, M.; Toepfer, A. Synlett
1990, 694–696. (b) Tsuda, T.; Nakamura, S.; Hashimoto, S. Tetrahedron
2004, 60, 10711–10737.
(35) (a) Kahne, D.; Walker, S.; Cheng, Y.; Engen, D. V. J. Am. Chem.
Soc. 1989, 111, 6881–6882. (b) Crich, D.; Lim, L. B. L. Org. React. 2004,
64, 115–251. (c) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P. Tetra-
hedron 2008, 64, 7659–7683.
(36) Sliedregt, L. A. J. M.; van der Marel, G. A.; van Boom, J. H.
Tetrahedron Lett. 1994, 35, 4015–4018.
(37) (a) Hense, A.; Ley, S. V.; Osborn, H.; Owen, D. R.; Poisson,
J.-F.; Warriner, S. L.; Wesson, K. E. J. Chem. Soc., Perkin Trans. 1
1997, 2023–2031. (b) Montchamp, J.-L.; Tian, F.; Hart, M. E.; Frost,
J. W. J. Org. Chem. 1996, 61, 3897–3900.
(38) Takeo, K. Carbohydr. Res. 1979, 77, 245–251.
(39) Nicolaou, K. C.; Mitchell, H. J.; Rodriguez, R. M.; Fylaktakidou,
K. C.; Suzuki, H.; Conley, S. R. Chem.—Eur. J. 2000, 6, 3149–3165.
(40) Demko, Z. P.; Sharpless, K. B. Org. Lett. 2001, 3, 4091–4094.
(41) Whitworth, G. E.; Macauley, M. S.; Stubbs, K. A.; Dennis, R. J.;
Taylor, E. J.; Davies, G. J.; Greig, I. R.; Vocadlo, D. J. J. Am. Chem. Soc.
2007, 129, 635–644.
(42) (a) Buskasa, T.; Garegg, P. J.; Konradsson, P.; Maloisel, J.-L.
Tetrahedron: Asymmetry 1994, 5, 2187–2194. (b) Goddard-Borger,
E. D.; Stick, R. V. Org. Lett. 2007, 9, 3797–3800.
(43) Boulineau, F. P.; Wei, A. Carbohydr. Res. 2001, 334, 271–279.
(44) Dullenkopf, W.; Castro-Palomino, J. C.; Manzoni, L.; Schmidt,
R. R. Carbohydr. Res. 1996, 296, 135–147.
(45) Higashi, K.; Nakayama, K.; Uoto, K.; Shioya, E.; Kusama, T.
Chem. Pharm. Bull. 1991, 39, 590–592.
(46) Zhang, Z.; Magnusson, G. Carbohydr. Res. 1996, 295, 41–55.
(47) Yan, F.; Mehta, S.; Eichler, E.; Wakarchuk, W. W.; Gilbert, M.;
Schur, M. J.; Whitfield, D. M. J. Org. Chem. 2003, 68, 2426–2431.
3709
dx.doi.org/10.1021/jo102411j |J. Org. Chem. 2011, 76, 3691–3709