Synthesis and Glycosylation Properties of C6-Silylated Ido- and Gluco-Pyranosyl Donors

Article abstract of DOI:10.1002/ejoc.202000708

Silyl groups are widely used as alcohol protecting groups and their study has provided insight on some very remarkable structure and reactivity features within carbohydrate chemistry. However, not much work has been put into the effect on the reactivity of silyl groups directly attached to the sugar carbon chain. In this work, we have developed a synthetic methodology to obtain both d-glucosyl and l-idosyl donors containing a dimethylphenylsilyl group directly attached to C6. Glycosylation and competition experiments with different glycosyl acceptors have shown that this group is completely stable under glycosylation conditions and enhances reactivity beyond what a benzyl group attached to the sugar oxygen would do. Finally, we found adequate conditions for the protodesilylation of Si-containing glycosides to yield the 6-deoxy sugar analog.

Full text of DOI:10.1002/ejoc.202000708

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Synthesis and Glycosylation Properties of C6-silylated Ido- and
Gluco-pyranosyl donors
Authors: Ignacio Álvarez-Martínez and Christian Marcus Pedersen
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of the final Version of Record (VoR). This work is currently citable by
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published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
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content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000708
Link to VoR: https://doi.org/10.1002/ejoc.202000708
01/2020

10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
Synthesis and Glycosylation Properties of C6-silylated Ido- and
Gluco-pyranosyl donors
Ignacio Álvarez-Martínez[a,b] and Christian Marcus Pedersen*[a]
[a]
I. Álvarez-Martínez, Prof. C.M. Pedersen
Department of Chemistry
University of Copenhagen
Universitetsparken 5, DK-2100 Copenhagen O, Denmark
E-mail: cmp@chem.ku.dk
[b]
Current address:
Department of Chemistry
University of Natural Resources and Life Sciences, Vienna
Muthgasse 18, 1190 Vienna, Austria
Supporting information for this article is given via a link at the end of the document
Abstract: Both stereoelectronic and steric interactions define the
structure and reactivity of small molecules. Given its complexity, in
carbohydrate chemistry, these interactions give rise to a variety of
chemical behaviours that are often difficult to predict. Silyl groups are
widely used as alcohol protecting groups and their study has provided
insight on some very remarkable structure and reactivity features
within carbohydrate chemistry. However, not much work has been put
into the effect on reactivity of silyl groups directly attached to the sugar
carbon chain. In this work, we have developed a synthetic methodol-
ogy to obtain both D-glucosyl and L-idosyl donors containing a dime-
thylphenylsilyl group directly attached to C6. Glycosylation and com-
petition experiments with different glycosyl acceptors have shown that
this group is completely stable under glycosylation conditions and en-
hance reactivity beyond what a benzyl group attached to the sugar
oxygen would do. Finally, we found adequate conditions for the pro-
todesilylation of Si-containing glycosides to yield the 6-deoxy sugar
analogue.
where they are usually used to protect the sugar hydroxyl group
by forming a silyloxy group. Silyl groups have also been used as
a means in chain elongation in pentoses and hexoses to form
heptoses or other derivatives (e.g., van Boom and co-workers[9–
12]
in the 1990s) due to their potential conversion into hydroxyl
groups – what is known as the Tamao–Fleming oxidation.[13–16]
Another useful reaction replaces the silyl group by a hydrogen
atom; this is known as a protodesilylation (or protiodesilylation).
This reaction is particularly interesting in carbohydrate chemistry
where the less common deoxy-sugars often are desired products.
The reaction was developed by the Hurdlik group[17,18] and later
modifications by the Roush group[19,20] broadened the scope and
allowed much milder conditions when using a dimethylphenylsilyl
group.
In carbohydrate chemistry, the influence of substituents on the re-
activity of glycosyl donors has been known since the work of
Paulsen and colleagues in the late 1970s.[21,22] However, the con-
ceptualization of the phenomenon into the armed-disarmed con-
cept[23] and its potential application was first described by Fraser-
Reid and co-workers in 1990.[24,25] The direct correlation between
the decreasing electron withdrawing abilities of the substituents
and the increasing reactivity of the donors can be rationalized
considering that, under the same circumstances, a more stable
oxocarbenium ion (e.g., from an armed donor) will be more likely
to be formed.
Glycosyl donors O-protected with silyl groups have shown in-
creased reactivity in glycosylation reactions compared to the ben-
zylated counterparts.[8] This increased reactivity is not only due to
silyl groups being somewhat less electron withdrawing than ben-
zyl, but also due to their bulkiness. When several silyl groups are
attached to secondary alcohols on the pyranoside ring, a confor-
mational change into an axially rich conformation can occur. Such
conformational change influence the anomeric selectivity and dra-
matically increases the reactivity in glycosylation reactions com-
pared to benzylated glycosyl donors, which are considered reac-
tive (armed).[26]
Introduction
Silicon (as other elements of group 14, e.g., germanium and tin)
is relatively big in size and less electronegative than any non-
metal (e.g., H, C, O, S). Consequently, a silyl group in organic
chemistry can create electronic stabilizing interactions that can in-
fluence, or even determine, the reactivity and selectivity of the
molecules of which they are part.[1] It has been known since the
1940s that silicon interactions decreases the leaving group depar-
ture rate at α-position, when comparing to a C atom, whereas
placed in β- or γ-positions, it increases the rate, with the greatest
enhancement being when placed in β-position, i.e., the β-silicon
effect.[2,3] These β-silicon stabilizing interactions are maximized in
an anti-periplanar arrangement;[4] γ-silicon interactions in a W-ar-
rangement;[5] and δ-silicon interactions require an extended zig-
zag pattern to maximize the through-bond interaction between the
silyl group and the leaving group.[6]
Carbohydrates with the silyl groups directly attached to the carbon
ring (C-Si bonded) have been much less explored. To the best of
our knowledge, the reactivity of this kind of glycosides has not
been studied, and there are only a handful of examples where
these compounds have been prepared.
The widespread use of silyl groups in organic chemistry has been
possible due to the nature of σ bonds that they form with carbon
or oxygen atoms, which are of similar bond strength as those be-
tween carbon and the same kind of atoms.[7] During the last dec-
ades, silyl groups have experienced an increasing use as protec-
tive groups for orthogonal strategies in carbohydrate chemistry,[8]
1
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10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
SiMe2Ph
OBn
Si
Ph
OMe
Me2PhSi
Et2Si
O
OBn
O
OBn
HO
HO
Ph
O
HO
O
O
O
DMPSLi, THF
O
O
O
BnO
O
O
O
O
Diacetone glucose
BnO
O
–78°C
O
O
Ph3Si
OMe
O
O
OMe
-mannoside
D
-glycero-
1
2
O
O
-
-
-
-
α
L
α
α
-mannoside
D
-altroside
L
-altroside
L
β
1. AcOH 80%
85°C
Si Ph
O
Si Ph
O
PhSH, BF3·OEt2
THF
AcO
BnO
OAc
AcO
BnO
Figure 1. Among the few examples of carbohydrates with silyl groups directly
SPh
2. Py/Ac
2O, 1:1
OAc
attached to the carbon ring (C-Si bonded) found in the literature.
OAc
3
Scheme 1. Synthesis of donor 3.
A few of these examples are shown in Figure 1. The preparation
of D-altroside was described as a part of a work done in method-
ology development for preparation of sugars containing different
elements of group 14; it was done by opening a C2–C3 epox-
ide.[27] Similar case for the L-altroside, which was prepared by a
Rh-catalysed hydrosilation of a double bond.[28] The L-mannoside
was formed by an Ir-catalysed C6–H activation.[29] In heptopyra-
noside, nucleophilic attack on a carbonyl group was used to form
a new C–C bond, providing the sugar with a Si–C bond.[9]
In this work, we have developed a synthetic methodology to ob-
tain glycosyl donors containing a dimethylphenylsilyl group di-
rectly attached to C6, in both D-gluco and L-ido configurations.
Glycosylation and competition experiments with these glycosyl
donors against different acceptors have shown that the silyl group
installed enhance reactivity beyond what a benzyl group attached
to the sugar oxygen would do. Finally, we found adequate condi-
tions for the protodesilylation of Si-containing glycosides to yield
the 6-deoxy sugar analogue.
With epoxide 1 in hand, the silyl group was regioselectively at-
tached to the sugar by epoxide opening (Scheme 1). To that pur-
pose, dimethylphenylsilyl lithium (DMPSLi) was freshly prepared
by treating chloro(dimethyl)phenylsilane with lithium under argon
atmosphere. The resulting solution was added to the sugar (1) at
−78°C.[31] The reaction was left at the low temperature and fol-
lowed by TLC until completion – normally 3 to 4 h. As expected,
the attack occurred on the least hindered carbon atom of the
epoxide, i.e. C6, yielding exclusively the D-gluco product in very
good yields (81%) on a half-gram scale. Uncompleted reactions,
at larger scales, caused challenges in the separation of the prod-
uct from the starting material and smaller scales were therefore
preferred. The most convenient approach was therefore to use
freshly prepared silyl lithium solutions and additions over a period
of 30 to 60 min at −78°C (for 500 mg to 1 g of epoxide 1) under
an argon atm.
The 1,2-O-isopropylidene moiety was then removed by treating 2
with 80% acetic acid in water at 85°C, allowing the sugar to adapt
the pyranose form. Acetylation and subsequent installation of the
phenylsulfide moiety yielded glycosyl donor 3 as a mixture of
anomers (α/β, 1:3) in a 72% yield over three steps.
With glycosyl donor 3 in hand, the 2,3,4-tri-O-benzyl counterpart
5 was synthesized (Scheme 2A). Thus, donor 3 was deacetylated
under Zemplén conditions followed by benzylation via a William-
son ether synthesis for 60 to 90 min yielding glycosyl donor 5 in
89% yield over two steps. It is worth noting that performing the
benzylation reaction for a longer time resulted in lower yields due
to competing elimination reactions giving the terminal alkene 6
(Scheme 2B).
In order to access the L-ido configuration, 3-O-benzyl-1,2-O-iso-
propylidene-α-D-glucofuranose was prepared as previously de-
scribed and then transformed into the aldehyde 3-O-benzyl-1,2-
O-isopropylidene-α-D-xylo-pentodialdo-1,4-furanose by a Mal-
aprade oxidation using NaIO4 in DCM/H2O (1:1) at 0°C, catalyzed
by TBAB.[32]
Results and Discussion
As the preferred silyl group for this study, the dimethylphenylsilyl
group was chosen. This group is known to be reasonable stable
in most of the common reaction conditions in carbohydrate chem-
istry and it can potentially be removed under relatively mild con-
ditions, orthogonally to other functional groups in the carbohy-
drate.
For the synthesis of the glycosyl donors, two approaches for silyl
group insertion were investigated. The first one being a regiose-
lective ring-opening of an epoxide moiety by direct attack of a silyl
lithium reagent; which leads to the D-gluco configuration. The sec-
ond approach is a stereoselective nucleophilic attack on an alde-
hyde moiety by a Si-containing alkyl magnesium chloride, yielding
the carbohydrate with the L-ido configuration.
For the first approach, D-glucose diacetonide was 3-O-benzylated
in an excellent yield, followed by a regioselective deprotection of
the 5,6-isopropylidene moiety under acidic conditions. The 5,6-
anhydro sugar 1 was obtained via an intramolecular Mitsunobu
reaction using standard conditions (DIAD and PPh3) in a very
good yield over two steps with retention of the D-gluco-configura-
tion.[30]
A.
Si Ph
O
Si Ph
O
Si Ph
O
MeONa
MeOH
BnBr, NaH
DMF
AcO
BnO
HO
BnO
BnO
BnO
SPh
SPh
SPh
OAc
OH
OBn
3
4
5
B.
OBn
OBn
O
OBn
6
Scheme 2. (A) Synthesis of donor 5. (B) Side product after prolonged benzyla-
tion conditions.
2
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10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
H
O
HO
Si
SPh
SPh
Ph
+
O
SPh
OBn
Me2PhSiCH
THF
Si
Si
Ph
OBn
O
OBn
O
2MgCl
OBn
O
Ph
Si
BnBr, NaH
DMF
Side
products
OBn
O
+
Diacetone glucose
BnO
O
OH OH
OH OBn
Ph
O
O
OBn
O
7
11
12
13
Ph
Ph
OAc
SPh
1. AcOH 80%
85°C
Si
Si
OBn
O
OBn
O
PhSH, BF3·OEt2
THF
Scheme 4. Product profile of the benzylation of diol 11.
2. Py/Ac
2O, 1:1
OAc OAc
OAc OAc
8
10
+
OBn
O
With L-idosyl donor 10 in hand, attempts to obtain the tri-O-ben-
zylated L-idolsyl donor 13 were done. Zemplén conditions applied
to the L-idosyl donor 10 yielded diol 11 quantitatively. However,
several attempts for the benzylation of the diol gave mixtures of
products (Scheme 4), which seems to stem from the existence of
competing elimination reactions of similar nature to the one ob-
served in the benzylation of the D-glucosyl counterpart 4 on pro-
longed reaction times.
Applying standard benzylation conditions to α-L-idosyl diol 11
(BnBr, NaH, DMF, 0°C) gave, after 30 min reaction time, desired
product 13 as well as 2-O-benzylated α-L-idosyl intermediate 12.
Together with them, three different terminal alkenes were also de-
tected, which form at comparable rates as the desired product 13.
Other conditions for the benzylation were investigated; e.g. BnBr
neat, TBAI with NaH; BnBr/DMF (1:1), TBAI with NaH; BnBr/tolu-
ene (1:1), TBAI with NaH; last, BnBr and Ag2O in Cy/DCM (4:1).
Disappointingly, all of them either yielded terminal alkenes at
comparable rates to the rate of formation of the desired product
13 or gave uncompleted benzylation. Promoting the benzylation
by silver(I) oxide in Cy/DCM (4:1) is supposed to minimize the
formation of side products (e.g., undesired ethers), but the reac-
tion stalls after alkylation of the least hindered alcohol, the
2-OH.[43]
Ph
OAc
O
9
Si
Scheme 3. Synthesis of donor 10.
With the aldehyde in hand, stereoselective nucleophilic addition
of a Si-containing alkyl magnesium chloride was successfully ac-
complished yielding the desired L-ido-configuration in a L-ido/D-
gluco ratio 97:3 (compounds 7 and 2) in a 71% yield (Scheme
3).[33]
The stereochemistry of the addition on the aldehyde follows the
Felkin–Ahn model, in which the stereochemistry of the attack is
determined by the relative orientation of the groups attached to
the α-carbonyl carbon atom (C4–C5 bond) (Figure 2).[34–37] More-
over, this stereochemical outcome is also compatible with the
metal-ion of the nucleophile acting as a chelating agent between
the carbonyl oxygen and the endocyclic oxygen atom.[38–40]
With silylated furanose 7 in hand, the same chemical transfor-
mations and conditions as in the D-gluco configuration were ap-
plied in order to obtain the desired L-idosyl donor 10. Isopropy-
lidene cleavage and subsequent acetylation furnished the product
in 71% yield. Installation of the S-phenyl moiety was done in 68%
yield, furnishing the desired L-idosyl donor 10 as an anomeric mix-
ture (α/β, 2:1). Interestingly, after the isopropylidene cleavage and
acetylation, side product 9 was obtained in 4% yield, presumably
after dehydration of the α-anomer under acidic conditions, which
is a sign of the higher reactivity as a consequence of introducing
a C6-Si group.
While the L-idosyl donor 10 could be assigned to adopt a 1C4 con-
formation, α-L-idosyl donor 13 (which was only obtained in small
amounts) appeared to adopt a different conformation. First, 3JH-H
3
≈ 5-6 Hz, including JH1-H2 = 4.8 Hz; indicate that the hydrogen
atoms are closer to co-planarity (i.e. in an axial or pseudoaxial
orientation), and therefore the functional groups, closer to an
equatorial orientation. Second, W-couplings 4JH2-H4 and 4JH1-H3 are
not observed, supporting an axial or pseudoaxial orientation of the
hydrogen atoms.
Both anomers of the L-idosyl donor 10 were found to exhibit a 1C4
conformation in agreement with the following data. First, a 3JH-H
≲
3 Hz suggested that vicinal protons atoms attached to the sugar
ring are not coplanar to one another, and therefore, not axially
oriented. Second, W-coupling constants (4JH2-H4 and, in the case
of the α-anomer, also 4JH1-H3) were measurable and in agreement
with 1JC1-H1 that indicates the orientation of H-1. This finding is es-
pecially relevant since axially oriented groups do not generally ex-
perience through-bond interactions with the developing positive
charge that commonly forms during a glycosylation reaction as
equatorially oriented groups do. This is usually translated into an
increased reactivity for glycosyl donors with an axially rich confor-
mation.[41,42]
A.
Si Ph
O
1.1 equiv. NIS
0.1 equiv. TfOH
Si Ph
O
+
R'OH
RO
BnO
RO
BnO
SPh
OR'
DCM (0.05
–78ºC to –20ºC
60 to 90 min
M
)
(1.5 equiv.)
OR
OR
: R=Ac
: R=Bn
: R=Ac (
-
: R=Ac
: R=Bn
3
5
10
14 17
18-21
26-29
30-32
: R=Ac (
L
-idosyl)
L
-idosyl)
R'OH:
HO
OBn
O
OBn
O
O
HO
HO
BnO
HO
BnO
BnO
AcHN
OMe
OMe
14
15
16
17
B.
O
O
M
S
Si Ph
O
Si Ph
O
O
H
MgCl
Ph
O
O
=
O
L
AcO
BnO
AcO
BnO
Ph
O
BnO
H
O
Si
OBn
OH
RO
AcHN
25
H
Nu
CH2
OAc
OMe
: R=H
23
22
: R=Ac
24
Figure 2. Stereochemistry of the addition over carbonyl (Felkin–Ahn model).
Scheme 5. (A) Glycosylation reactions and acceptors. (B) Some of the side
products identified during the glycosylation studies.
3
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10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
makes the glycosylation α-D-glucosyl product kinetically inacces-
sible.
Table 1. Results of glycosylation studies.
Entry
Donor
Acceptor
Glycosylation
products
Yield, % / α:β[b]
With challenging acceptor 17 (Entry 4, Table 1), donor 3 was used
in excess (0.67 equiv. of acceptor) in order to achieve a reasona-
ble yield, albeit still low. Thus, β-glycoside 21 was isolated in 38 %
yield as the only anomer of the desired product. From the ano-
meric region of the crude 13C-NMR (85-105 ppm), remaining ac-
ceptor 17 as well as acetyl α-D-glucosides 23 and 24 were identi-
fied. Together with them, benzylidene acetal 25 was also found.
This side product might form from a radical oxidation of the ben-
zylic position followed by benzylidene formation due to the pres-
ence of NIS or I2 (see Supporting Information).[46]
In order to determine whether the reaction is happening under ki-
netic control, an anomerization experiment was performed.
Hereby, β-glycosyl product 18b was treated under the NIS/TfOH
conditions used for the glycosylations studies (including 1.5 equiv.
of acceptor 14). The unmodified starting material was fully recov-
ered (Entry 12, Table 1) indicating that the glycosyl products in
these experiments are formed irreversibly, i.e., the product profile
is determined by the rate at which the products form (kinetic con-
trol), not by their stability (thermodynamic control).
1
3
14
15
16
17
14
15
16
17
14
16
17
14
18a, 18b
19a, 19b
20
82 / 16:84
80 / 14:86
71 / Only β
38[a] / Only β
88 / 52:48
83 / 57:43
67 / 65:35
60[a] / 35:65
81 / 91:9
2
3
3
3
4
3
21
5
5
26a, 26b
27a, 27b
28a, 28b
29a, 29b
30a, 30b
31
6
5
7
5
8
5
9
10
10
10
18b
10
11
12
58 / Only α
59[a] / Only α
SM recovered
32
Glycosyl donor 5 with acceptor 14 (Entry 5, Table 2) gave a clean
reaction, but no selectivity. The yield of 26a and 26b combined
was 88%. With secondary alcohol 15 (Entry 6, Table 2), it also
resulted in a clean glycosylation, in this case with a low α-selec-
tivity (α/β, 57:43 - 27a/27b). The anomers could not be separated,
and the yield was 83%.
–
[a] Glycosylations with acceptor (0.67 equiv.) as a limiting reagent. [b] Ratio of
anomers calculated from crude 1H-NMR; normalized to 100.
Glycosylation Studies: The three new glycosyl donors (3, 5, 10)
were subjected to glycosylation conditions in the presence of four
different glycosyl acceptors (14-17) to determine scope and limi-
tation in terms of selectivity, reactivity and yield (Scheme 5A).
As for the acceptors, 14 was chosen as a primary alcohol; 15, as
an unhindered secondary alcohol; 16, as an example of a pro-
tected sugar; and 17, to challenge the glycosyl donor, since this
acceptor is known for its low reactivity. This low reactivity is due
to the formation of an intermolecular hydrogen-bonding network
by means of the amide. This network increases the steric hin-
drance, which renders the hydroxyl groups poor nucleophiles.[44]
Glycosyl donor 3 with acceptors 14 and 15 shows a clear β selec-
tivity (α/β, 16:84 and 14:86, respectively) (Entries 2 and 3, Table
1). Despite this good selectivity, the amount of α-product obtained
is still higher than expected from the acetyl neighbouring group
participation in the reaction. A hypothesis that accounts for this
observation is that the extra stabilization of the oxocarbenium ion
provided by the silyl group reduces the energy gap between the
acetoxonium and the oxocarbenium ion. This reduction would in-
crease the amount of glycosyl product that forms by direct attack
on the latter, which would give both α and β products. Yields for
the reaction were very good (81% and 80%, resp.), even if acetyl
α-glycoside 24 forms and partial deacetylation at 2-OH in all spe-
cies occurs during the glycosylation (acetyl transfer is a well-
known side reaction during glycosylations)[45]. Upon acetylation of
the 2-OHs, the ratio between glycosyl product (18 and 19) and
side product 24 was 94:6 and 91:9, respectively. D-Glucoside 24
was isolated in a 5% yield from glycosylation with acceptor 14.
As it can be observed, using an unhindered secondary alcohol
(15) as an acceptor instead of a primary alcohol (14) does not
seem to affect the course of the reaction significantly.
With D-glucoside 16 as an acceptor (Entry 7, Table 1), α-selectiv-
ity increased until 65:35 (28a/28b) and products were isolated in
a 67% yield. It seems that as the bulkiness of the acceptor in-
creases, the α product is formed more favourably.
With challenging acceptor 17 (Entry 8, Table 1), the reaction re-
sulted in a complex mixture of products as observed previously.
Desired products 29 were isolated in a 60 % yield (acceptor as a
limiting reagent) in a α/β ratio, 35:65. Benzylidene acetal 25 was
again identified.
Glycosyl donor 10 with acceptor 14 (Entry 9, Table 1) resulted in
a clean reaction, with an α/β ratio of 9:91 (30a/30b) in 81% yield.
Glycosylation of acceptor 16 (Entry 10, Table 1) gave exclusively
the α-glycosyl product 30 in 58% yield, and 46% of acceptor was
recovered. Despite the obtained yield, no other major peaks were
found on the crude NMR spectra.
Glycosylation of challenging acceptor 17 (Entry 11, Table 1) gave
the desired α-glycosyl product 32 as well as the benzylidene ac-
etal 25, isolated in 59% and 10%, respectively (see Supporting
Information).
Competition Experiments: In order to shed light on the effect
caused by a silyl group attached to C6 on the reactivity of glycosyl
donors, a pair of competition experiments were performed
(Scheme 6).
Two glycosyl donors (1 equiv. per donor) were set to compete
under glycosylation conditions, using 5 equiv. of acceptor.
In the first experiment, silylated β-D-glucosyl donor 5b was com-
peting against Si-free analogue 33[47], which was synthesised
from D-glucose pentaacetate (Scheme 6A).
The experiment showed that for each molecule of Si-free glycosyl
donor 33 that reacted, 1.6 molecules of the silylated donor 5b re-
acted, which can solely be attributed to the substitution of the O-
Bn group by the silyl group. The α/β ratio of silylated glycosylation
products was 56:44 (26a/26b), which is in agreement with the ra-
tio observed during the glycosylation experiments (52:48). The
With D-glucoside 16 as an acceptor (Entry 3, Table 1), only β
anomer 20 was obtained in a 71% yield. In addition, acetyl
α-D-glucoside 24 was found on 1H-NMR (20/24, 96:4). The stere-
oselectivity of the reaction suggests that the size of acceptor 16
4
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10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
α/β ratio of Si-free glycosylation products was interestingly 35:65
(34a/34b). No anomerization of the glycosyl donors (5b or 33)
was observed (see Supporting Information).
Si Ph
O
H3C
TBAF, DMF
80ºC
O
BnO
BnO
BnO
BnO
O
O
BnO
O
BnO
O
35
26a
In the second experiment, silylated β-D-glucosyl donor 5b was set
to compete against silylated α-L-idosyl donor 10a (Scheme 6B).
Scheme 7. Desilylation reaction.
A.
(HOR')
Y
O
Y
O
14
Si Ph
O
Si Ph
O
NIS/TfOH, DCM
BnO
BnO
BnO
BnO
HBF4·Et2O
DCM
SPh
X
BnO
BnO
BnO
BnO
BnO
vs.
BnO
O
O
O
OBn
BnO
O
26a
: Y=SiPhMe
5b
33
Y=OBn
5b
33
2; X=SPh
: Y=OBn; X=SPh
26b
Y=SiPhMe2
: Y=SiPhMe
: Y=OBn; X=OR'
26a, 26b
34a, 34b
2; X=OR'
B.
Scheme 8. Anomerization reaction.
Si Ph
O
BnO
BnO
(HOR')
X
Si Ph
O
SPh
14
Si
OBn
O
Ph
+
BnO
BnO
BnO
NIS/TfOH, DCM
5b
X
Interestingly, complete and clean anomerization of glycoside 26b
was observed upon less than 5 min of treatment with HBF4·OEt2
(2 equiv.) in DCM at 0°C (Scheme 8). Upon this observation, and
given that HBF4·OEt2 is both a Brønsted–Lowry acid and a Lewis
acid, two samples of 26b were prepared and one of them was
treated with TfOH and the other with BF3·OEt2 in DCM at 0°C.
While it did not occur as neatly as with HBF4·OEt2, the Brønsted–
Lowry acid seems to induce the anomerization to some extent,
whereas the Lewis acid did not convert the starting material.
BnO
SPh
OAc OAc
Si
OBn
O
Ph
: X=SPh
: X=SPh
10a
30a, 30b:
5b
26a, 26b:
X=OR'
X=OR'
OAc OAc
10a
Scheme 6. Competition experiments. (A) Silylated vs. free-Si donor. (B)
D-Gluco vs. L-ido donor.
The experiment showed that for each molecule of L-idosyl donor
10a that reacted, 1.2 molecules of the D-glucosyl donor 5b re-
acted. The D-glucosyl donor 5b has three equatorially oriented
benzyl groups and is the β anomer, while the L-idosyl donor 10a
has two acetyl and one benzyl group, all axially oriented, and is
the α anomer. The axial rich conformation of L-idosyl donor 10a
increases the reactivity of the otherwise more disarmed donor,
making it of comparable reactivity to the armed benzylated D-glu-
cosyl donor 33 – which is in agreement with the almost 2-fold re-
activity enhancement of L-idosides comparing to D-glucosides
found previously by the Wong group.[48] The α/β ratio of D-glucosyl
products was 57:43 (26a/26b), which is also in agreement with
the α/β ratio 52:48 and 56:44 observed during the glycosylation
experiments and the previous competition experiment, respec-
tively. The α/β ratio of L-idosyl glycosylation products was 88:12
(30a/30b), in agreement with the 91:9 observed during the glyco-
sylation experiments. No anomerization of the glycosyl donors
was observed (see Supporting Information).
Conclusion
In this work, we have described two stereoselective methodolo-
gies to attach a silyl group to C-6 in hexoses, in order to obtain Si-
containing D-glucosyl and L-idosyl donors. It has been shown that
these glycosyl donors are completely stable under glycosylation
conditions and react to give glycosyl products in good to excellent
yields; they are also stable under several established transfor-
mations in carbohydrate chemistry. These glycosyl donors exhibit
a selectivity in glycosylation that is comparable to that observed
for the Si-free analogues. Competition experiments have shown
that a silyl group in C-6 increases the reactivity of the molecule of
which they form part, but only slightly. Finally, a methodology for
a clean substitution of the silyl group by a H atom has also been
described.
Desilylation Studies: With the access to silylated glycosides, the
focus was turned to developing methodologies to convert the silyl
group into other functionalities.
Experimental Section
With that purpose, silylated α-D-glucoside 26a was treated over-
night with TBAF in DMF at 80°C. After workup, desired glycoside
35 was obtained as a pure colourless solid in a 79% yield
(Scheme 7).[20] When using acetylated glycosides as starting ma-
terial, partial deacetylation was observed as a competing reaction.
Tamao-Fleming oxidation was also investigated. Despite a num-
ber of publications reporting a Hg-free, two-pot methodology for
the oxidation of a Me2PhSi–C bond in heterocyclic molecules, at-
tempts in different substrates did not bear the desired product
(see Supporting Information).[16] Vincent and colleagues accom-
plished this transformation on carbohydrates by the use of mer-
curic salts.[33]
General procedure A (for glycosylations with acceptors 14, 15 and
16). To an oven-dried 10-mL flask, glycosyl donor (100 mg) and glycosyl
acceptor (1.5 equiv.) were added and dried under vacuum overnight. Un-
der argon atmosphere, 4Å molecular sieves and dichloromethane (for a
0.05 M in donor) were added. When reagents were dissolved, NIS (1.1
equiv) was added and, within 5 seconds, the flask was submerged into an
acetone–dry-ice bath at −78°C. TfOH (0.1 equiv) was added by syringe.
The dry ice was removed from the bath and the temperature was let rise
from −78°C to −35/−25°C over 60 to 90 min. When the reaction mixture
acquired a full red–violet colour (from iodine in dichloromethane)—approx.
at −40°C—, a TLC was taken. If the reaction was completed, the temper-
ature was allowed to rise additional 10°C and quenched by 0.2 to 0.4 mL
of Et3N. The molecular sieves were removed by filtration through diatomite
and the filtrate was diluted in EtOAc (20 mL). The solution was washed
with water (20 mL), 1 M HCl(aq) (20 mL), 10% Na2S2O3(aq) (20 mL), water
(20 mL) and brine (20 mL) and then dried over MgSO4(s). After concentra-
tion over reduced pressure, the crude was purified by flash silica column
chromatography.
5
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
General procedure B (for glycosylations with 17). To an oven-dried 10-
mL flask, glycosyl donor (40 mg) and glycosyl acceptor (0.67 equiv.) were
added and dried under vacuum overnight. Under an argon atmosphere,
4Å molecular sieves and dichloromethane (for a 0.05 M in donor) were
added. When reagents were dissolved, NIS (1.1 equiv) was added and,
within 5 seconds, the flask was submerged into an acetone–dry-ice bath
at −78°C. TfOH (0.1 equiv) was added by syringe. The dry ice was re-
moved from the bath and the temperature was let rise from −78°C to 0°C
over 60 to 90 min and then kept at 0°C for 4 to 5 h. The reaction was
quenched by 0.2 to 0.4 mL of Et3N. The molecular sieves were removed
by filtration through diatomite and the filtrate was diluted in EtOAc (20 mL).
The solution was washed with water (20 mL), 1 M HCl(aq) (20 mL), 10%
Na2S2O3(aq) (20 mL), water (20 mL) and brine (20 mL) and then dried over
MgSO4(s). After concentration over reduced pressure, the crude was puri-
fied by flash silica column chromatography.
5.1, 3.8 Hz, 1H; H-6a), 2.77 (dd, J = 5.1, 2.6 Hz, 1H; H-6b), 1.45 (s, 3H;
CH3C), 1.31 (s, 3H; CH3C). 13C NMR (126 MHz, CDCl3) δ 137.4 (CAr,q),
128.5 (2×CArH), 128.0 (CArH), 127.6 (2×CArH), 111.9 (C(CH3)2), 105.4 (C-
1), 82.7 (C-2), 82.1 (C-3), 81.7 (C-4), 72.4 (CH2, Bn-3), 48.3 (C-5), 47.0
(C-6), 26.9 (CH3C), 26.3 (CH3C). The analytical data matches the one re-
ported in the literature.[30]
3-O-Benzyl-6-deoxy-1,2-O-isopropylidene-6-dimethylphenylsilyl-α-D-
glucofuranose (2).
Synthesis of dimethyl(phenyl)silyl lithium. To a 25-mL two-necked
flask, Li(s) (0.15 g, 21.4 mmol, 12.5 equiv) was added. Under argon, the
solid was rinsed with three volumes of petroleum ether to remove mineral
oil. Then, THF (6 mL) was added and the mixture was cooled in a water–
ice bath. Chloro(dimethyl)phenylsilane (1.46 mL, 8.55 mmol, 5 equiv) was
added dropwise over 30 s. After 6 h, the temperature was allowed to rise
and the maroon mixture was stirred overnight under argon.
General procedure for competition experiments. To an oven-dried, 10-
mL flask, glycosyl donor A (0.10 mmol) and glycosyl donor B (0.10 mmol;
1 equiv) were added and dried under vacuum overnight. Under an argon
atmosphere, 4Å molecular sieves and dichloromethane (for a 0.05 M in
donor) were added. Acceptor (5 equiv) was then added. When the donors
and acceptors were dissolved, NIS (1 equiv) was added and, within 5 sec-
onds, the flask was submerged into an acetone dry-ice bath at −78°C.
TfOH (0.1 equiv) was added by syringe. The dry ice was removed from the
acetone bath and the temperature was allowed to rise from −78°C to
−25/−15°C over 90 to 120 min. When the reaction mixture acquired a full
red–violet colour (from iodine in dichloromethane)—approx. at −40°C—, a
TLC was taken. Then, the temperature was allowed to rise additional 10°C,
where it was quenched by adding 0.2 to 0.4 mL of Et3N. The molecular
sieves were removed by filtration through diatomite and the filtrate was
diluted in EtOAc (20 mL). The solution was washed with water (20 mL), 1
M HCl(aq) (20 mL), 10% Na2S2O3(aq) (20 mL), water (20 mL) and brine
(20 mL) and then dried over MgSO4(s). After concentration over reduced
pressure, the products ratio was determined by 1H NMR.
To a 50-mL flask, 5,6-anhydro-3-O-benzyl-1,2-O-isopropylidene-α-D-glu-
cofuranose (1) (0.5 g, 1.71 mmol) and THF (7 mL) were added. The mix-
ture was cooled down to −78°C in an acetone–dry-ice bath. Then, the
freshly prepared dimethyl(phenyl)silyl lithium in THF was transfer under
argon and added dropwise to the mixture by syringe pump over 30 min (15
mL/h). The mixture was stirred under argon at −78°C over 3 h. To quench
the reaction, NH4Cl(aq) (4 mL) was added and then brine (50 mL). The
product was extracted with EtOAc (3 × 50 mL) and dried over MgSO4(s).
After concentration over reduced pressure, the residue was purified by col-
umn chromatography (PE/EtOAc, 4:1) yielding the product (2) as a pale
yellow syrup (0.59 g, 1.38 mmol, 81 % yield). Rf 0.53 (PE/EtOAc, 3:1); 1H
NMR (500 MHz, CDCl3) δ 7.55 – 7.29 (m, 10H; HCAr), 5.97 (d, J = 3.9 Hz,
1H; H-1), 4.72 (d, J = 11.8 Hz, 1H; CHH, Bn-3), 4.62 (d, J = 3.9 Hz, 1H, H-
2), 4.46 (d, J = 11.8 Hz, 1H; CHH, Bn-3), 4.10 (dddd, J = 10.3, 7.3, 6.4, 4.2
Hz, 2H; H-5), 4.04 (d, J = 3.4 Hz, 1H; H-3), 3.92 (dd, J = 6.4, 3.4 Hz, 1H;
H-4), 2.27 (d, J = 7.3 Hz, 1H; OH), 1.46 (s, 3H; CH3C), 1.33 (s, 3H; CH3C),
1.18 (dd, J = 14.8, 4.2 Hz, 1H; H-6a), 1.03 (dd, J = 14.8, 10.3 Hz, 1H; H-
6b), 0.35 (s, 3H; CH3Si), 0.33 (s, 3H; CH3Si).13C NMR (126 MHz, CDCl3)
δ 139.3 (CAr,q), 136.9 (CAr,q), 133.7 (2×CArH), 129.0 (CArH), 128.9 (2×CArH),
128.5 (CArH), 128.3 (2×CArH), 127.9 (2×CArH), 111.7 (C(CH3)2), 105.2 (C-
1), 84.1 (C-4), 82.2 (C-3), 82.1 (C-2), 71.9 (CH2, Bn-3), 67.8 (C-5), 26.9
(CH3C), 26.4 (CH3C), 22.5 (C-6), −1.8 (CH3Si), −2.3 (CH3Si). HR-MS:
[M+Na]+ calcd for C24H32KNaO5Si: 451.1917; found: 451.1921.
5,6-Anhydro-3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose (1).
To a 250-mL flask, diacetone D-glucose (10 g, 38.4 mmol), benzyl chloride
(4.6 mL, 40.3 mmol) and dry DMF (100 mL) were added. The mixture was
stirred at 0°C for 15 min and 60 % NaH(s) (1.61 g, 40.3 mmol) was added
in several portions under vigorous stirring. After 60 min, the temperature
was allowed to rise and the mixture was stirred for 3 h until no starting
material was longer present. To quench the reaction, water (5 mL) was
added dropwise preventing vigorous bubbling. An additional amount of wa-
ter (95 mL) was added and the mixture was extracted with EtOAc (3 × 150
mL). The organic layers were combined and washed with water (2 × 150
mL) and brine (2 × 150 mL) and then dried over MgSO4(s). After concen-
tration over reduced pressure, the residue was purified by column chroma-
tography (P.E./EtOAc, 3:1) yielding a colourless syrup (12.4 g, 35.4 mmol,
92 % yield).
Phenyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-
thio-D-glucopyranosides (3a, 3b). To a 250-mL flask, 3-O-benzyl-6-de-
oxy-1,2-O-isopropylidene-6-dimethylphenylsilyl-α-D-glucofuranose
(2)
(4.03 g, 9.40 mmol) and acetic acid/water (4:1, 100 mL) was added. The
mixture was stirred in an oil bath at 80°C overnight. After concentration
under reduced pressure and co-evaporation twice with toluene, the resi-
due was used in the next reaction. To the crude, acetic anhydride/pyridine
(1:1, 100 mL) was added, and the mixture was stirred overnight at RT.
After concentration over reduced pressure and co-evaporation twice with
toluene, the residue was used in the next reaction.
To a 250-mL flask, 3-O-benzyl-1,2:5,6-di-O-isopropylidene-α-D-gluco-
furanose (12.4 g, 35.4 mmol) and acetic acid/water (85:15, 100 mL) were
added. The mixture was stirred overnight until starting material has disap-
peared on TLC. Then, it was concentrated under reduced pressure and
co-evaporated twice with toluene yielding crude 3-O-benzyl-1,2-O-iso-
propylidene-α-D-glucofuranose as an orange-brown syrup.
To a 250-mL flask, the crude acetyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-
dimethylphenylsilyl-D-glucopyranoside and dichloromethane (100 mL)
were added. The mixture was cooled down to 0°C in a water-ice bath. Thi-
ophenol (1.2 mL, 11.28 mmol, 1.2 equiv) and boron trifluoride etherate (1.2
mL, 9.40 mmol, 1 equiv) were added. The mixture was stirred for 5 h while
the temperature was allowed to rise. To quench the reaction, NaHCO3(aq)
(10 mL) was added. After separation and drying over MgSO4(s), the reac-
tion mixture was directly concentrated under reduced pressure and co-
evaporation twice with toluene. The residue was purified by column chro-
matography (30:1, toluene/acetone) yielding a yellow syrup (3.81 g; α/β,
24:76; 72 % over three steps).
To a 500-mL flask, the crude 3-O-benzyl-1,2-O-isopropylidene-α-D-gluco-
furanose, diisopropyl azodicarboxylate (DIAD) (9.7 mL, 46.8 mmol), PPh3
(12.9 g, 46.8 mmol) and toluene (200 mL) were added. The reaction was
refluxed in an oil bath for 3 h. After concentration at reduced pressure, the
residue was purified by column chromatography (P.E./EtOAc, 4:1) yielding
5,6-anhydro-3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose
(1)
(8.00 g; 77% over two steps) as a pale yellow syrup. 1H NMR (500 MHz,
CDCl3) δ 7.36 – 7.27 (m, 5H; HCAr), 5.95 (d, J = 3.7 Hz, 1H; H-1), 4.72 (d,
J = 11.9 Hz, 1H; CHH, Bn-3), 4.65 (d, J = 11.9 Hz, 1H; CHH, Bn-3), 4.63
(d, J = 3.7 Hz, 1H; H-2), 4.08 (d, J = 3.2 Hz, 1H; H-3), 3.76 (dd, J = 7.2,
3.2 Hz, 1H; H-4), 3.30 (ddd, J = 7.2, 3.8, 2.6 Hz, 1H; H-5), 2.91 (dd, J =
Phenyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-
thio-α-D-glucopyranoside (3a). Rf 0.36 (PE/EtOAc, 6:1); [α]D25 +94.4° (c
0.9, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.43 – 7.18 (m, 15H; HCAr), 5.93
6
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
(d, J = 5.6, 1H; H-1), 5.03 (dd, J = 10.1, 5.6, 1H; H-2), 4.88 (dd, J = 9.7,
9.2, 1H; H-4), 4.75 (d, J = 11.8, 1H; CHH, Bn-3), 4.62 (d, J = 11.8, 1H;
CHH, Bn-3), 4.26 (ddd, J = 9.7, 8.7, 4.7, 1H; H-5), 3.79 (dd, J = 10.1, 9.2,
1H; H-3), 2.05 (s, 3H; CH3CO), 1.96 (s, 3H; CH3CO), 1.7 – 1.4 (m, 2H; H-
6a; H-6b), 0.17 (s, 3H; CH3Si), 0.14 (s, 3H; CH3Si). 13C NMR (126 MHz,
CDCl3) δ 170.1 (C=O), 169.9 (C=O), 139.3 (CAr,q), 138.3 (CAr,q), 134.4
(CAr,q-S), 133.7 (2×CArH), 130.1 (2×CArH), 129.2 (2×CArH), 129.0 (CArH),
128.6 (2×CArH), 127.9 (CArH), 127.8 (2×CArH), 127.8 (2×CArH), 127.0
(CArH), 85.4 (C-1), 77.9 (C-3), 75.9 (C-4), 74.9 (CH2, Bn-3), 73.6 (C-2),
69.7 (C-5), 21.1 (CH3CO), 21.1 (CH3CO), 18.9 (C-6), −1.7 (CH3Si), −2.7
(CH3Si). HR-MS: [M+K]+ calcd for C13H36KO6SSi: 603.1639; found:
603.1621.
Phenyl 2,3,4-tri-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-D-glu-
copyranoside (5a, 5b). To a 100-mL flask, phenyl 3-O-benzyl-6-deoxy-6-
dimethylphenylsilyl-1-thio-D-glucopyranoside (4) (528 mg, 1.10 mmol),
benzyl bromide (0.40 mL, 3.30 mmol, 3 equiv) and dry dimethylformamide
(24 mL) were added. The mixture was cooled to 0°C in a water-ice bath.
To the mixture, 60% NaH (132 mg, 3.30 mmol) was added in one portion.
The reaction mixture was stirred at 0°C and monitored by TLC, since elim-
ination-products may form at prolonged reaction times. After 60 min the
reaction was completed. To quench the reaction, water (2 mL) was added
dropwise, avoiding intense bubbling. Then, an additional amount of water
(23 mL) was added and the mixture was extracted with EtOAc (3 × 75 mL).
The organic layers were combined and washed with water (2 × 40 mL) and
brine (2 × 40 mL). After drying over MgSO4(s), the mixture was concen-
trated to dryness over reduced pressure. The residue was purified by col-
umn chromatography (40:1 to 20:1, PE/EtOAc) yielding a colourless syrup
(647 mg; 89% over two steps)
Phenyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-
thio-β-D-glucopyranoside (3b). Rf 0.40 (PE/EtOAc, 6:1); [α]D25 +26.3° (c
1.0, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.46 – 7.18 (m, 15H; HCAr), 5.00
(dd, J = 10.3, 9.0 Hz, 1H; H-2), 4.86 (dd, J = 9.6 Hz, 9.4 Hz,1H; H-4), 4.57
– 4.51 (m, 3H; 2×CHH, Bn-3; H-1), 3.59 (dd, J = 9.6, 9.0 Hz, 1H; H-3), 3.32
(ddd, J = 11.0, 9.4, 3.0 Hz, 1H; H-5), 2.02 (s, 3H; CH3CO), 1.95 (s, 3H;
CH3CO), 1.05 (dd, J = 14.9, 11.0 Hz, 1H; H-6a), 0.95 (dd, J = 14.9, 3.0 Hz,
1H; H-6b), 0.25 (s, 3H; CH3Si), 0.24 (s, 3H; CH3Si). 13C NMR (126 MHz,
CDCl3) δ 169.7 (C=O), 169.3 (C=O), 138.7 (CAr,q), 138.0 (CAr,q), 133.8
(2×CArH), 133.6 (2×CArH), 132.2 (CAr,q-S), 129.1 (2×CArH), 129.1 (CArH),
128.5 (2×CArH), 128.4 (CArH), 128.0 (2×CArH), 127.9 (CArH), 127.9
(2×CArH), 87.0 (C-1), 81.6 (C-3), 77.0 (C-5), 75.3 (C-4), 73.8 (CH2, Bn-3),
71.8 (C-2), 21.1 (CH3CO), 21.1 (CH3CO), 19.1 (C-6), −1.6 (CH3Si), −2.5
(CH3Si). HR-MS: [M+Na]+ calcd for C31H36NaO6SSi: 587.1900; found:
587.1900.
Phenyl 2,3,4-tri-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-α-D-
glucopyranoside (5a). Rf 0.27 (PE/EtOAc, 19:1); 1H NMR (500 MHz,
CDCl3) δ 7.59 – 7.17 (m, 25H; HCAr), 5.62 (d, J = 5.3 Hz, 1H; H-1), 4.24
(ddd, J = 10.5, 9.3, 2.7 Hz, 1H; H-5), 3.85 (dd, J = 9.8, 5.3 Hz, 1H; H-2),
3.79 (dd, J = 9.8, 8.6 Hz, 1H; H-3), 3.16 (dd, J = 9.3, 8.6 Hz, 1H; H-4), 1.44
(dd, J = 14.9, 2.7 Hz, 1H; H-6a), 0.92 (dd, J = 14.9, 10.5 Hz, 1H; H-6b),
0.15 (s, 3H; CH3Si), 0.10 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ
140.0 – 126.3 [aromatic C atoms], 87.0 (C-1), 84.6 (C-4), 82.5 (C-3), 80.2
(C-2), 75.9 (CH2, Bn), 75.6 (CH2, Bn), 72.7 (CH2, Bn), 70.8 (C-5), 19.3
(C-6), −1.8 (CH3Si), −2.5 (CH3Si). HR-MS: [M+Na]+ calcd for
C41H44NaO4SSi: 683.2627; found: 683.2645.
Phenyl 3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-D-glucopy-
ranosides (4a, 4b). To a 50-mL flask, phenyl 2,4-di-O-acetyl-3-O-benzyl-
6-deoxy-6-dimethylphenylsilyl-1-thio-D-glucopyranoside (3) (0.62 g, 1.10
mmol) and dry MeOH (25 mL) were added. To the solution, NaOH (4.4 mg,
0.11 mmol) was added. The mixture was stirred overnight at room temper-
ature. To quench the reaction, acidic ion-exchange resin was rinsed in
methanol and added in small portions to the reaction mixture until neutral
pH was observed. After filtration, the solution was concentrated under re-
duced pressure, yielding a colourless syrup that was used directly in the
next reaction.
Phenyl 2,3,4-tri-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-β-D-
glucopyranoside (5b). Rf 0.32 (PE/EtOAc, 19:1); [α]D +44.8° (c 1.4,
25
CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.56 – 7.51 (m, 2H; HCAr), 7.41 –
7.37 (m, 3H; HCAr), 7.36 – 7.23 (m, 20H; HCAr), 4.90 (d, J = 10.3 Hz, 1H;
CHH, Bn-a), 4.87 (d, J = 10.9 Hz, 1H; CHH, Bn-b), 4.86 (d, J = 10.9 Hz,
1H; CHH, Bn-c), 4.82 (d, J = 10.9 Hz, 1H; CHH, Bn-b), 4.74 (d, J = 10.3
Hz, 1H; CHH, Bn-a), 4.67 (d, J = 10.9 Hz, 1H; CHH, Bn-c), 4.59 (d, J = 9.8
Hz, 1H; H-1), 3.59 (dd, J = 8.8, 8.8 Hz, 1H; H-3), 3.47 (dd, J = 9.8, 8.8 Hz,
1H; H-2), 3.26 (dd, J = 11.0, 9.1, 2.5 Hz, 1H; H-5), 3.20 (dd, J = 9.1, 8.8
Hz, 1H; H-4), 1.37 (dd, J = 14.7, 2.5 Hz, 1H; H-6a), 0.93 (dd, J = 14.7, 11.0
Hz, 1H; H-6b), 0.22 (s, 3H; CH3Si), 0.20 (s, 3H; CH3Si). 13C NMR (126
MHz, CDCl3) δ 139.0 (CAr,q), 138.6 (CAr,q), 138.3 (CAr,q), 138.2 (CAr,q), 133.8
(2×CArH), 133.6 (CAr,q-S), 132.9 (2×CArH), 129.1 (2×CArH), 128.9 (CArH),
128.6 (4×CArH), 128.5 (2×CArH), 128.3 (2×CArH), 128.1 (2×CArH), 128.0
(2×CArH), 128.0 (CArH), 128.0 (CArH), 127.9 (CArH), 127.8 (CArH), 127.8
(2×CArH), 88.6 (C-1), 86.7 (C-3), 84.4 (C-4), 81.4 (C-2), 78.0 (C-5), 75.9
(CH2, Bn), 75.6 (CH2, Bn), 75.6 (CH2, Bn), 19.5 (C-6), −1.6 (CH3Si), −2.5
(CH3Si). HR-MS: [M+Na]+ calcd for C41H44NaO4SSi: 683.2627; found:
683.2645.
Phenyl 3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-α-D-gluco-
pyranoside (4a). 1H NMR (500 MHz, CDCl3) δ 7.51 – 7.47 (m, 2H; HCAr),
7.42 – 7.23 (m, 16H; HCAr), 5.54 (d, J = 5.4 Hz, 1H; H-1), 5.02 (d, J = 11.4
Hz, 1H; CHH, Bn), 4.76 (d, J = 11.4 Hz, 1H; CHH, Bn), 4.12 (ddd, J = 10.2,
9.0, 3.2 Hz, 1H; H-5), 3.96 (ddd, J = 9.6, 8.6, 5.4 Hz, 1H; H-2), 3.34 (dd, J
= 9.6, 8.9 Hz, 1H; H-3), 3.24 (ddd, J = 9.0, 8.9, 2.5 Hz, 1H; H-4), 2.35 (d,
J = 8.6 Hz, 1H; OH-2), 2.19 (d, J = 2.5 Hz, 1H; OH-4), 1.47 (dd, J = 14.9,
3.2 Hz, 1H; H-6a), 1.04 (dd, J = 14.9, 10.2 Hz, 1H; H-6b), 0.27 (s, 3H;
CH3Si), 0.26 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 139.6 (CAr,q),
138.5 (CAr,q), 135.0 (CAr,q-S), 133.7 (2×CArH), 130.9 (2×CArH), 129.3
(2×CArH), 129.0 (CArH), 128.9 (2×CArH), 128.2 (CArH), 128.2 (2×CArH),
127.8 (2×CArH), 127.3 (CArH), 91.8 (C-1), 83.4 (C-3), 76.1 (C-4), 75.2 (CH2,
Bn), 72.7 (C-2), 72.0 (C-5), 19.3 (C-6), −1.7 (CH3Si), −2.2 (CH3Si).
Benzyl 2,3-di-O-benzyl-5,6-dideoxy-β-D-xylo-hex-5-enofuranoside (6).
1H NMR (500 MHz, CDCl3) δ 7.60 – 7.54 (m, 1H; HCAr), 7.48 – 7.20 (m,
28H; HCAr), 6.04 (ddd, J = 17.2, 10.3, 7.8 Hz, 1H; H-5), 5.39 (ddd, J = 17.2,
1.6, 1.1 Hz, 1H; H-6a), 5.32 (ddd, J = 10.3, 1.6, 0.8 Hz, 1H; H-6b), 5.07 (d,
J = 4.3 Hz, 1H; H-1), 4.85 (d, J = 12.3 Hz, 1H; CHH, Bn), 4.74 – 4.68 (m,
1H; H-4), 4.66 – 4.54 (m, 5H; 5×CHH Bn), 4.38 (dd, J = 6.9, 6.0 Hz, 1H;
H-3), 4.06 (dd, J = 6.0, 4.3 Hz, 1H; H-2). 13C NMR (126 MHz, CDCl3) δ
138.2 (CAr,q), 137.9 (CAr,q), 137.8 (CAr,q), 134.3 (C-5), 133.7, 133.1, 129.2,
128.5, 128.5, 128.5, 128.4, 128.4, 128.3, 128.0, 127.9, 127.8, 127.7 [aro-
matic C atoms], 118.7 (C-6), 98.2 (C-1), 83.8 (C-2), 82.7 (C-3), 78.9 (C-4),
72.5 (CH2 Bn), 72.4 (CH2 Bn), 69.1 (CH2 Bn). HR-MS: [M+Na]+ calcd for
C27H28NaO4: 439.1885; found: 439.1889.
Phenyl 3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-β-D-gluco-
pyranoside (4b). 1H NMR (500 MHz, CDCl3) δ 7.52 – 7.44 (m, 6H; HCAr),
7.37 – 7.15 (m, 18H; HCAr), 4.98 (d, J = 11.6 Hz, 1H; CHH, Bn), 4.71 (d, J
= 11.6 Hz, 1H; CHH, Bn), 4.40 (d, J = 9.7 Hz, 1H; H-1), 3.46 (ddd, J = 9.7,
8.6, 1.9 Hz, 1H; H-2), 3.30 (dd, J = 8.7, 8.6 Hz, 1H; H-3), 3.25 (ddd, J =
10.5, 9.0, 3.0 Hz, 1H; H-5), 3.19 (ddd, J = 9.0, 8.7, 2.4 Hz, 1H; H-4), 2.48
(d, J = 1.9 Hz, 1H; OH-2), 2.17 (d, J = 2.4 Hz, 1H; OH-4), 1.39 (dd, J =
14.9, 3.0 Hz, 1H; H-6a), 1.00 (dd, J = 14.9, 10.5 Hz, 1H; H-6b), 0.30 (s,
3H; CH3Si), 0.30 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 139.1 (CAr,q),
138.6 (CAr,q), 133.8 (2×CArH), 133.8 (2×CArH), 131.5 (CAr,q-S), 129.2
(2×CArH), 129.0 (CArH), 128.8 (2×CArH), 128.5 (CArH), 128.2 (2×CArH),
128.1 (CArH), 127.8 (2×CArH), 89.3 (C-1), 85.1 (C-3), 78.4 (C-5), 75.6 (C-4),
74.9 (CH2, Bn), 73.0 (C-2), 19.6 (C-6), −1.6 (CH3Si), −2.2 (CH3Si).
3-O-Benzyl-6-deoxy-1,2-O-isopropylidene-6-dimethylphenylsilyl-α-L-
idofuranose (7). To a 1-L flask, 3-O-benzyl-1,2-O-isopropylidene-α-D-glu-
cofuranose (10.81 g, 34.83 mmol), tetrabutylammonium chloride (0.97 g,
3.48 mmol) and DCM/H2O (1:1, 400 mL) were added. In order to prevent
periodate decomposition, the mixture was excluded from light by covering
the flask with aluminium foil. After cooling down the mixture to 0°C in a
7
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
water-ice bath, sodium periodate (8.96 g, 41.80 mmol) was added in three
portions over 30 min. The mixture was stirred for 150 min. After this, the
aqueous layer was extracted with DCM (3 × 100 mL). The organic layers
were combined, washed with water (2 × 80 mL) and brine (80 mL) and
dried over MgSO4. After concentration over reduced pressure, the residue
was stored at 0°C and used in the next reaction without further purification.
(CH3CO), −1.8 (CH3Si), −2.5 (CH3Si). HR-MS: [M+Na]+ calcd for
C23H28NaO5Si: 435.1604; found: 435.1615.
Phenyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-
25
thio-α-L-idopyranoside (10a). Rf 0.29 (PE/EtOAc, 5:1); [α]D −99.6° (c
0.7, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.50 – 7.17 (m, 15H; HCAr), 5.56
(bs, 1H; H-1), 5.17 (ddd, J = 2.6, 1.2, 1.0 Hz, 1H; H-2), 4.82 (ddd, J = 8.7,
6.0, 1.3 Hz, 1H; H-5), 4.80 (d, J = 12.1 Hz, 1H; CHH, Bn), 4.65 (d, J = 12.1
Hz, 1H; CHH, Bn), 4.64 – 4.62 (m, 1H; H-4), 3.75 (ddd, J = 3.0, 2.6, 1.2
Hz, 1H; H-3), 2.07 (s, 3H; CH3CO), 2.07 (s, 3H; CH3CO), 1.27 (dd, J = 14.8,
8.7 Hz, 1H; H-6a), 1.03 (dd, J = 14.8, 6.0 Hz, 1H; H-6b), 0.28 (s, 3H; CH3Si),
0.27 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 170.4 (C=O), 169.7
(C=O), 138.8 (CAr,q), 137.5 (CAr,q), 137.0 (CAr,q), 133.7 (2×CArH), 129.9
(2×CArH), 129.2 (CArH), 129.0 (2×CArH), 128.6 (2×CArH), 128.0 (2×CArH),
127.9 (CArH), 127.6 (2×CArH), 126.8 (CArH), 85.9 (C-1; 1JC1-H1 = 165.0 Hz,
characteristic of an axially oriented group on C-1), 72.4 (CH2, Bn), 72.0
(C-3), 70.4 (C-4), 69.2 (C-2), 65.0 (C-5), 21.2 (CH3CO), 21.0 (CH3CO),
18.1 (C-6), −2.0 (CH3Si), −2.7 (CH3Si). HR-MS: [M+Na]+ calcd for
C31H36NaO6SSi: 587.1900; found: 587.1890.
To a 50-mL flask, dry magnesium (119 mg, 4.81 mmol) was added and it
was mechanically activated overnight by dry stirring under an argon at-
mosphere. To the dry metal, dry THF (10.5 mL) was added and then
(chloromethyl)dimethylphenylsilane (855 mg, 4.49 mmol) was added drop-
wise. The reaction mixture was refluxed for 90 min, allowed to cool down
to room temperature and then to 0°C in an ice-water bath. 3-O-Benzyl-1,2-
O-isopropylidene-α-D-xylo-pentodialdo-1,4-furanose (0.5 g, 4.492 mmol)
in THF (7.30 mL) was added dropwise over 45 min. Once the addition was
done, the mixture was stirred for 2 h. To quench the reaction, water (1 mL)
was added. After filtration over a pad of diatomite, NH4Cl(aq) (25 mL) was
added, the mixture was extracted with DCM (3 × 30 mL). The organic lay-
ers were combined, washed with brine (3 × 30 mL) dried over MgSO4(s)
and concentrated under reduced pressure. The residue was purified by
column chromatography (toluene/acetone, 24:1) yielding a yellowish syrup
(546 mg, 1.27 mmol; 71 %; L-ido/D-gluco, 97:3). Rf 0.17 (toluene/acetone,
24:1); 1H NMR (500 MHz, CDCl3) δ 7.53 – 7.47 (m, 2H; HCAr), 7.37 – 7.20
(m, 8H; HCAr), 5.96 (d, J = 3.8 Hz, 1H; H-1), 4.67 (d, J = 11.8 Hz, 1H; CHH,
Bn), 4.63 (d, J = 3.8 Hz, 1H; H-2), 4.40 (d, J = 11.8 Hz, 1H; CHH, Bn), 4.11
(ddd, J = 11.0, 6.4, 3.3, 1.9 Hz, 1H; H-5), 3.97 (dd, J = 6.4, 3.4 Hz, 1H;
H-4), 3.90 (d, J = 3.4 Hz, 1H; H-3), 2.54 (dd, J = 2.2, 1.9 Hz, 1H; OH), 1.47
(s, 3H; CH3C), 1.32 (s, 3H; CH3C), 1.05 (dd, J = 14.4, 11.0 Hz, 1H; H-6a),
0.83 (ddd, J = 14.4, 3.3, 2.2 Hz, 1H; H-6b), 0.35 (s, 3H; CH3Si), 0.33 (s,
3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 139.6 (CAr,q), 136.9 (CAr,q), 133.8
(2×CArH), 128.9 (CArH), 128.7 (2×CArH), 128.3 (CArH), 128.1 (2×CArH),
127.8 (2×CArH), 111.9 (C(CH3)2), 105.1 (C-1), 85.6 (C-4), 82.3 (C-3, C-2),
71.9 (CH2, Bn), 68.1 (C-5), 26.9 (CH3CO), 26.5 (CH3CO), 20.2 (C-6), −1.5
(CH3Si), −2.3 (CH3Si).
Phenyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-
thio-β-L-idopyranoside (10b). Rf 0.33 (PE/EtOAc, 5:1); 1H NMR (500
MHz, CDCl3) δ 7.53 – 7.49 (m, 2H; HCAr), 7.39 – 7.23 (m, 13H; HCAr), 5.16
(d, J = 1.8 Hz, 1H; H-1), 5.06 (ddd, J = 2.4, 1.8, 1.0 Hz, 1H; H-2), 4.67 (d,
J = 12.0 Hz, 1H; CHH, Bn), 4.63 (d, J = 12.0 Hz, 1H; CHH, Bn), 4.57 (ddd,
J = 2.8, 1.5, 1.0 Hz, 1H; H-4), 3.95 (ddd, J = 9.1, 5.5, 1.5 Hz, 1H; H-5),
3.78 (dd, J = 2.8, 2.4 Hz, 1H; H-3), 2.13 (s, 3H; CH3CO), 2.07 (s, 3H;
CH3CO), 1.33 (dd, J = 14.8, 9.1 Hz, 1H; H-6a), 0.97 (dd, J = 14.8, 5.5 Hz,
1H; H-6b), 0.22 (s, 3H; CH3Si), 0.19 (s, 3H; CH3Si). 13C NMR (126 MHz,
CDCl3) δ 170.5 (C=O), 170.3 (C=O), 138.5 (CAr,q), 137.4 (CAr,q), 134.1
(CAr,q-S), 133.6 (2×CArH), 132.3 (2×CArH), 129.2 (CArH), 129.2 (2×CArH),
128.6 (2×CArH), 128.1 (CArH), 128.0 (2×CArH), 127.9 (CArH), 127.8
1
(2×CArH), 84.7 (C-1; JC1-H1 = 155.2 Hz, characteristic of an equatorially
oriented group on C-1), 73.4 (C-5), 73.3 (C-3), 72.7 (CH2, Bn), 69.6 (C-2),
69.4 (C-4), 21.1 (CH3CO), 21.0 (CH3CO), 18.5 (C-6), −1.8 (CH3Si), −2.7
(CH3Si). HR-MS: [M+Na]+ calcd for C31H36NaO6SSi: 587.1900; found:
587.1891.
Phenyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-
thio-L-idopyranosides (10a, 10b). This product was synthesised as mix-
ture of anomers in a 3-step procedure equivalent to the one used to obtain
the D-gluco isomers (3a, 3b) from 2. In this case, using 7 as a starting
material.
Phenyl
2,3-di-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-α-L-
idopyranoside (12).1H NMR (500 MHz, CDCl3) δ 7.55 – 7.50 (m, 2H;
HCAr), 7.46 – 7.14 (m, 22H; HCAr), 5.59 (bs, 1H; H-1), 4.69 (ddd, J = 8.3,
6.6, 1.2 Hz, 1H; H-5), 4.64 – 4.60 (m, 2H; 2×CHH Bn), 4.53 (d, J = 11.8
Hz, 1H; CHH, Bn), 4.48 (d, J = 12.2 Hz, 1H; CHH, Bn), 3.87 (ddd, J = 2.9,
1.4, 1.2 Hz, 1H; H-3), 3.81 (ddd, J = 3.1, 3.1, 1.3 Hz, 1H; H-2), 3.41 (dddd,
J = 11.7, 3.4, 1.9, 1.5 Hz, 1H; H-4), 3.21 (d, J = 11.7 Hz, 1H; OH), 1.42
(dd, J = 14.8, 8.3 Hz, 1H; H-6a), 1.19 (dd, J = 14.8, 6.5 Hz, 1H; H-6b), 0.31
(s, 3H; CH3Si), 0.29 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 139.6
(CAr,q), 138.0 (CAr,q), 137.8 (CAr,q), 136.9 (CAr,q), 133.7 (2×CArH), 129.6
(2×CArH), 129.0 (2×CArH), 128.9 (CArH), 128.7 (2×CArH), 128.6 (2×CArH),
128.3 (CArH), 128.0 (2×CArH), 127.9 (CArH), 127.8 (2×CArH), 127.7
(2×CArH), 126.5 (CArH), 85.9 (C-1), 76.0 (C-3), 73.8 (C-2), 72.4 (CH2, Bn),
72.0 (CH2, Bn), 70.0 (C-4), 67.0 (C-5), 17.9 (C-6), −1.9 (CH3Si), −2.2
(CH3Si).
Acetyl 2,4-di-O-Acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-α-L-
idopyranoside (8). 1H NMR (500 MHz, CDCl3) δ 7.55 – 7.47 (m, 2H; HCAr),
7.40 – 7.22 (m, 12H; HCAr), 5.99 (d, J = 1.8 Hz, 1H; H-1), 4.97 (ddd, J =
2.8, 1.8, 0.9 Hz, 1H; H-2), 4.65 (d, J = 11.8 Hz, 1H; CHH, Bn), 4.62 (d, J =
11.8 Hz, 1H; CHH, Bn), 4.57 (ddd, J = 2.6, 1.7, 0.9 Hz, 1H; H-4), 4.19 (ddd,
J = 9.3, 5.3, 1.7 Hz, 1H; H-5), 3.80 (dd, J = 2.8 Hz, 1H; H-3), 2.12 (s, 3H;
CH3CO), 2.10 (s, 3H; CH3CO), 2.06 (s, 3H; CH3CO), 1.33 (dd, J = 14.8,
9.3 Hz, 1H), 0.96 (dd, J = 14.8, 5.3 Hz, 1H), 0.34 (s, 3H; CH3Si), 0.31 (s,
3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 170.4 (C=O), 170.1 (C=O),
168.9 (C=O), 138.5 (CAr,q), 137.2 (CAr,q), 133.7 (2×CArH), 129.2 (CArH),
128.6 (2×CArH), 128.2 (CArH), 128.0 (2×CArH), 127.8 (2×CArH), 90.2 (C-1),
73.9 (C-3), 72.7 (CH2, Bn), 72.0 (C-5), 69.5 (C-4), 66.6 (C-2), 21.1
(CH3CO), 21.0 (CH3CO), 21.0 (CH3CO), 18.1 (C-6), −2.0 (CH3Si), −2.8
(CH3Si).
Phenyl 2,3,4-tri-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-α-L-
idopyranoside (13).1H NMR (500 MHz, CDCl3) δ 7.49 – 7.44 (m, 4H;
HCAr), 7.41 – 7.17 (m, 25H; HCAr), 5.35 (d, J = 4.8 Hz, 1H; H-1), 4.74 (d, J
= 11.5 Hz, 1H; Bn-a), 4.64 (d, J = 11.7 Hz, 1H; Bn-b), 4.59 (d, J = 11.5 Hz,
1H; Bn-a), 4.54 (d, J = 11.9 Hz, 1H; Bn-c), 4.52 (d, J = 11.7 Hz, 1H; Bn-b),
4.46 (ddd, J = 10.5, 4.3, 3.4 Hz, 1H; H-5), 4.37 (d, J = 11.9 Hz, 1H; Bn-c),
3.74 (dd, J = 5.7, 5.4 Hz, 1H; H-3), 3.59 (dd, J = 5.4, 4.8 Hz, 1H; H-2), 3.31
(dd, J = 5.7, 3.4 Hz, 1H; H-4), 1.38 (dd, J = 15.2, 10.5 Hz, 1H; H-6a), 1.07
(dd, J = 15.2, 4.3 Hz, 1H; H-6b), 0.20 (s, 3H; CH3Si), 0.20 (s, 3H; CH3Si).
13C NMR (126 MHz, CDCl3) δ 139.5 (CAr,q), 138.3 (CAr,q), 138.2 (CAr,q),
138.1 (CAr,q), 135.8 (CAr,q-S), 133.8 (2×CArH), 130.9 (2×CArH), 129.0, 128.6,
128.4, 128.3, 128.0, 128.0, 127.9, 127.9, 127.9, 127.8, 127.7, 126.9 [aro-
matic C atoms], 84.6 (C-1), 78.1 (C-4), 77.7 (C-2), 76.2 (C-3), 73.8 (CH2,
1,4-Anhydro-2-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-β-
L-idopyranose (9).1H NMR (500 MHz, CDCl3) δ 7.55 – 7.49 (m, 2H; HCAr),
7.39 – 7.22 (m, 12H; HCAr), 5.35 (d, J = 1.2 Hz, 1H; H-1), 4.62 (d, J = 11.9
Hz, 1H; CHH Bn), 4.61 (d, J = 1.7 Hz, 1H; H-4), 4.47 (dd, J = 7.9, 7.0 Hz,
1H; H-5), 4.44 (d, J = 11.9 Hz, 1H; CHH Bn), 4.18 (d, J = 4.9 Hz, 1H; H-3),
3.78 (ddd, J = 4.9, 1.7, 1.2 Hz, 1H; H-2), 1.55 (s, 3H; CH3CO), 1.14 (dd, J
= 14.4, 7.9 Hz, 1H; H-6a), 0.96 (dd, J = 14.4, 7.0 Hz, 1H; H-6b), 0.35 (s,
3H; CH3Si), 0.32 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 170.2 (C=O),
138.9 (CAr,q), 137.5 (CAr,q), 133.8 (2×CArH), 129.2 (CArH), 128.6 (2×CArH),
128.1 (CArH), 128.0 (2×CArH), 127.9 (2×CArH), 102.5 (C-1), 82.6 (C-2),
80.2 (C-3), 79.0 (C-4), 73.0 (CH2, Bn), 71.4 (C-5), 22.0 (C-6), 21.1
8
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
Bn), 73.6 (CH2, Bn), 72.8 (CH2, Bn), 69.3 (C-5), 15.4 (C-6), −1.9 (CH3Si),
−2.9 (CH3Si).
129.0 (CArH), 128.5 (2×CArH), 127.9 (2×CArH), 127.7 (CArH), 127.5
(2×CArH), 93.0 (C-1), 77.3 (C-3), 76.7 (C-4), 74.7 (OCH, Cy), 74.7 (CH2,
Bn-3), 74.2 (C-2), 67.6 (C-5), 33.1 (CH2, Cy), 30.9 (CH2, Cy), 25.7 (CH2,
Cy), 24.0 (CH2, Cy), 23.6 (CH2, Cy), 21.2 (CH3CO), 21.0 (CH3CO), 19.2
(C-6), −1.0 (CH3Si), −2.5 (CH3Si). HR-MS: [M+Na]+ calcd for
C31H42NaO7Si: 577.2598; found: 577.2586.
2-Methoxyethyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphen-
ylsilyl-D-glucopyranosides (18a, 18b). General procedure A with phenyl
2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-D-gluco-
pyranoside (3) (100 mg, 0.178 mmol), 2-methoxyethanol (14) (21 μL,
0.266 mmol), NIS (46 mg, 0.195 mmol) and TfOH (1.6 μL, 0.017 mmol).
After the work-up and before the column chromatography, overnight acet-
ylation of the crude mixture with Ac2O/pyridine (1:1, v/v). The procedure
afforded 77 mg (82%; α/β, 16:84) of 18a and 18b after flash silica column
chromatography (toluene/acetone, 30:1 to 15:1).
Cyclohexyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsi-
25
lyl-β-D-glucopyranoside (19b).Rf 0.24 (toluene/acetone, 30:1); [α]D
1
−3.0° (c 1.1, CHCl3); H NMR (500 MHz, CDCl3) δ 7.52 – 7.20 (m, 10H;
HCAr), 5.00 (dd, J = 9.8, 8.0 Hz, 1H; H-2), 4.91 (dd, J = 9.6, 9.3 Hz, 1H; H-
4), 4.55 (s, 2H, CH2, Bn-3), 4.28 (d, J = 8.0 Hz, 1H; H-1), 3.57 (dd, J = 9.8,
9.3 Hz, 1H; H-3), 3.55 – 3.44 (m, 1H, OCH, Cy), 3.36 (ddd, J = 11.0, 9.6,
2.9 Hz, 1H; H-5), 1.98 (s, 3H; CH3CO), 1.97 (s, 3H; CH3CO), 1.79 – 1.35
(m, 10H; CH2, Cy), 1.10 (dd, J = 14.9, 11.0 Hz, 1H; H-6a), 1.02 (dd, J =
14.9, 2.9 Hz, 1H; H-6b), 0.35 (s, 3H; CH3Si), 0.29 (s, 3H; CH3Si). 13C NMR
(126 MHz, CDCl3) δ 169.8 (C=O), 169.2 (C=O), 138.9 (CAr,q), 138.2 (CAr,q),
133.7 (2×CArH), 129.1 (CArH), 128.5 (2×CArH), 128.0 (2×CArH), 127.9
(2×CArH), 127.8 (CArH), 99.2 (C-1), 80.1 (C-3), 76.7 (OCH, Cy), 75.5 (C-4),
73.1 (C-2; CH2, Bn-3), 72.1 (C-5), 33.2 (CH2, Cy), 31.3 (CH2, Cy), 25.7
(CH2, Cy), 23.8 (CH2, Cy), 23.5 (CH2, Cy), 21.2 (CH3CO), 21.0 (CH3CO),
18.6 (C-6), −1.3 (CH3Si), −2.4 (CH3Si). HR-MS: [M+Na]+ calcd for
C31H42NaO7Si: 577.2598; found: 577.2586.
2-Methoxyethyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphen-
ylsilyl-α-D-glucopyranoside (18a). Rf 0.39 (toluene/acetone, 9:1); 1H
NMR (500 MHz, CDCl3) δ 7.51 – 7.21 (m, 10H; HCAr), 4.99 (d, J = 3.8 Hz,
1H; H-1), 4.84 (dd, J = 9.6, 9.4 Hz, 1H; H-4), 4.76 (dd, J = 10.0, 3.8 Hz,
1H; H-2), 4.69 (d, J = 11.8 Hz, 1H; CHH, Bn-3), 4.57 (d, J = 11.8 Hz, 1H;
CHH, Bn-3), 3.90 (dd, J = 10.0, 9.6, 1H; H-3), 3.87 (ddd, J = 10.5, 9.4, 3.5
Hz, 1H; H-5), 3.44 – 3.33 (m, 4H; 4×CH, aglyc.), 3.32 (s, 3H; CH3O), 2.03
(s, 3H; CH3CO), 1.96 (s, 3H; CH3CO), 1.08 (dd, J = 14.9, 3.5 Hz, 1H; H-
6a), 1.02 (dd, J = 14.9, 10.5 Hz, 1H; H-6b), 0.35 (s, 3H; CH3Si), 0.28 (s,
3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 170.3 (C=O), 170.0 (C=O),
139.1 (CAr,q), 138.7 (CAr,q), 133.7 (2×CArH), 129.1 (CArH), 128.5 (2×CArH),
127.9 (2×CArH), 127.7 (CArH), 127.5 (2×CArH), 95.9 (C-1), 77.3 (C-3), 76.4
(C-4), 74.8 (CH2, Bn-3), 73.9 (C-2), 71.5 (CH2), 67.6 (C-5), 67.5 (CH2),
59.1 (CH3O), 21.2 (CH3CO), 21.0 (CH3CO), 19.0 (C-6), −0.9 (CH3Si), −2.4
(CH3Si). HR-MS: [M+Na]+ calcd for C28H38NaO8Si: 553.2234; found:
553.2219.
Methyl 2’,4’-di-O-acetyl-3’-O-benzyl-6’-deoxy-6’-dimethylphenylsilyl-
β-D-glucopyranosyl-(1’→4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside
(20). General procedure A with phenyl 2,4-di-O-acetyl-3-O-benzyl-6-de-
oxy-6-dimethylphenylsilyl-1-thio-D-glucopyranoside (3) (101 mg, 0.178
mmol), methyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside (16) (124 mg, 0.267
mmol), NIS (46 mg, 0.196 mmol) and TfOH (1.6 μL, 0.018 mmol). The
procedure afforded 116 mg (71%) of 20 after flash silica column chroma-
tography (PE/EtOAc, 2:1). Rf 0.28 (PE/EtOAc, 2:1); 1H NMR (500 MHz,
CDCl3) δ 7.46 – 7.20 (m, 25H, HCAr), 4.95 (d, J = 10.9 Hz, 1H; CHH, Bn),
4.92 (dd, J = 9.6, 8.0 Hz, 1H; H-2’), 4.84 (dd, J = 9.5, 9.4 Hz, 1H; H-4’),
4.83 (d, J = 11.9 Hz, 1H; CHH, Bn), 4.75 – 4.69 (m, 3H; CHH, Bn), 4.59 (d,
J = 3.7 Hz, 1H; H-1), 4.52 (d, J = 11.5 Hz, 1H; CHH, Bn), 4.48 (d, J = 11.5
Hz, 1H; CHH, Bn), 4.35 (d, J = 12.1 Hz, 1H; CHH, Bn), 4.15 (d, J = 8.0 Hz,
1H; H-1’), 3.82 – 3.76 (m, 2H; H-3; H-4), 3.68 (dd, J = 10.6, 2.6 Hz, 1H;
H-6a), 3.55 (ddd, J = 7.2, 2.6, 2.1 Hz, 1H; H-5), 3.50 (dd, J = 10.6, 2.1 Hz,
1H, H-6b), 3.45 – 3.41 (m, 1H; H-2), 3.38 (s, 3H; CH3O), 3.23 (dd, J = 9.5,
9.5 Hz, 1H; H-3’), 3.19 (dd, J = 10.5, 9.5 2.5 Hz, 1H; H-5’), 2.01 (s, 3H;
CH3CO), 1.89 (s, 3H; CH3CO), 0.89 (dd, J = 15.1, 2.5 Hz, 1H; H-6a’), 0.83
(dd, J = 15.1, 10.5 Hz, 1H; H-6b’), 0.29 (s, 3H; CH3Si), 0.19 (s, 3H; CH3Si).
13C NMR (126 MHz, CDCl3) δ 169.8 (C=O), 168.9 (C=O), 139.4 (CAr,q),
139.3 (CAr,q), 138.5 (CAr,q), 138.2 (CAr,q), 137.5 (CAr,q), 133.7 (2×CArH),
129.1 (CArH), 129.0 (2×CArH), 128.7 (2×CArH), 128.6 (2×CArH), 128.5
(2×CArH), 128.5 (2×CArH), 128.3 (2×CArH), 128.2 (CArH), 128.1 (2×CArH),
128.0 (2×CArH), 127.9 (CArH), 127.8 (CArH), 127.7 (2×CArH), 127.3 (CArH),
99.6 (C-1’), 99.0 (C-1), 80.4 (C-3’), 80.1 (C-3), 78.1 (C-2), 75.9 (CH2, Bn),
75.7 (C-4), 75.4 (C-4’), 74.0 (CH2, Bn), 73.7 (CH2, Bn), 73.5 (C-2’), 73.4
(CH2, Bn), 71.7 (C-5’), 70.2 (C-5), 67.4 (C-6), 55.5 (CH3O), 21.2 (CH3CO),
21.0 (CH3CO), 17.9 (C-6’), −1.2 (CH3Si), −2.9 (CH3Si). HR-MS: [M+Na]+
calcd for C53H62NaO12Si: 941.3908; found: 941.3882.
2-Methoxyethyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphen-
25
ylsilyl-β-D-glucopyranoside (18b). Rf 0.35 (toluene/acetone, 9:1); [α]D
1
−7.3° (c 1.4, CHCl3); H NMR (500 MHz, CDCl3) δ 7.52 – 7.19 (m, 10H,
HCAr), 5.02 (dd, J = 9.6, 8.0 Hz, 1H; H-2), 4.90 (dd, J = 9.4, 9.4 Hz, 1H; H-
4), 4.57 (d, J = 11.7 Hz, 1H; CHH, Bn-3) , 4.54 (d, J = 11.7 Hz, 1H; CHH,
Bn-3), 4.29 (d, J = 8.0 Hz, 1H; H-1), 3.82 – 3.76 (m, 1H; CH, aglyc.), 3.58
(dd, J = 9.6, 9.4 Hz, 1H; H-3), 3.51 – 3.45 (m, 3H; 3×CH, aglyc.), 3.39 (ddd,
J = 10.9, 9.4, 3.2 Hz, 1H; H-5), 3.33 (s, 3H; CH3O), 1.98 (s, 3H; CH3CO),
1.98 (s, 3H; CH3CO), 1.09 (dd, J = 14.9, 10.9 Hz, 1H; H-6a), 1.01 (dd, J =
14.9, 3.2 Hz, 1H; H-6b), 0.35 (s, 3H; CH3Si), 0.31 (s, 3H; CH3Si). 13C NMR
(126 MHz, CDCl3) δ 169.8 (C=O), 169.4 (C=O), 138.9 (CAr,q), 138.1 (CAr,q),
133.7 (2×CArH), 129.1 (CArH), 128.5 (2×CArH) , 128.0 (2×CArH) , 128.0
(2×CArH), 127.9, (CArH), 101.3 (C-1), 80.0 (C-3), 75.5 (C-4), 73.4 (CH2, Bn-
3), 72.9 (C-2), 72.3 (C-5) , 71.7 (CH2) , 68.8 (CH2) , 59.2 (CH3O), 21.1
(CH3CO) , 21.0 (CH3CO), 18.6 (C-6), −1.4 (CH3Si), −2.3 (CH3Si). HR-MS:
[M+Na]+ calcd for C28H38NaO8Si: 553.2234; found: 553.2236.
Cyclohexyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsi-
lyl-D-glucopyranosides (19a, 19b). General procedure A with phenyl 2,4-
di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-D-glucopyra-
noside (3) (101 mg, 0.178 mmol), cyclohexanol (15) (29 μL, 0.267 mmol),
NIS (46 mg, 0.196 mmol) and TfOH (1.6 μL, 0.018 mmol). After the work-
up and before the column chromatography, overnight acetylation of the
crude mixture with Ac2O/pyridine (1:1, v/v). The procedure afforded 79 mg
(80%; α/β, 14:86) of 19a and 19b after flash silica column chromatography
(toluene/acetone, 40:1 to 30:1).
Methyl 2’,4’-di-O-acetyl-3’-O-benzyl-6’-deoxy-6’-dimethylphenylsilyl-
β-D-glucopyranosyl-(1’→4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-α-
D-glucopyranoside (21). General procedure B with phenyl 2,4-di-O-ace-
tyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-D-glucopyranoside (3)
(41 mg, 0.073 mmol), methyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-
glucopyranoside (17) (20 mg, 0.049 mmol), NIS (19 mg, 0.080 mmol) and
TfOH (0.7 μL, 0.007 mmol). The procedure afforded 16 mg (38%) of 21
after flash silica column chromatography (toluene/acetone, 2:1). Rf 0.25
(toluene/acetone, 3:1); 1H NMR (500 MHz, CDCl3) δ 7.49 – 7.44 (m, 2H,
HCAr), 7.38 – 7.24 (m, 16H, HCAr), 7.24 – 7.19 (m, 2H, HCAr), 5.12 (d, J =
8.4 Hz, 1H; NH), 4.96 (dd, J = 9.6, 8.0 Hz, 1H; H-2’), 4.89 (d, J = 12.5 Hz,
1H; CHH, Bn), 4.84 (dd, J = 9.4, 9.4 Hz, 1H; H-4’), 4.77 (d, J = 3.6 Hz, 1H;
H-1), 4.74 (d, J = 12.1 Hz, 1H; CHH, Bn), 4.55 – 4.50 (m, 3H; 3×CHH, Bn),
4.41 (d, J = 12.1 Hz, 1H; CHH, Bn), 4.21 (d, J = 8.0 Hz, 1H; H-1’), 4.10
Cyclohexyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsi-
25
lyl-α-D-glucopyranoside (19a). Rf 0.28 (toluene/acetone, 30:1); [α]D
+19.2° (c 0.6, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.53 – 7.20 (m, 10H,
HCAr), 5.07 (d, J = 3.8 Hz, 1H; H-1), 4.83 (dd, J = 9.5, 9.5 Hz, 1H; H-4),
4.73 (dd, J = 10.1, 3.8 Hz, 1H; H-2), 4.71 (d, J = 11.9 Hz, 1H; CHH, Bn-3),
4.58 (d, J = 11.9 Hz, 1H; CHH, Bn-3), 3.93 (ddd, J = 10.6, 9.6, 3.5 Hz, 1H;
H-5), 3.90 (dd, J = 10.1, 9.4 Hz, 1H; H-3), 3.38 – 3.31 (m, 1H; OCH, Cy),
2.03 (s, 3H; CH3CO), 1.96 (s, 3H; CH3CO), 1.71 – 1.12 (m, 10H; CH2, Cy),
1.07 (dd, J = 14.9, 3.5 Hz, 1H; H-6a), 1.01 (dd, J = 14.9, 10.6 Hz, 1H; H6-
b), 0.33 (s, 3H; CH3Si), 0.27 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ
170.4 (C=O), 170.0 (C=O), 139.3 (CAr,q), 138.7 (CAr,q), 133.6 (2×CArH),
9
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
(ddd, J = 10.4, 8.4, 3.6 Hz, 1H; H-2), 3.88 (dd, J = 9.6, 8.6 Hz, 1H; H-4),
3.71 (dd, J = 10.7, 3.2 Hz, 1H; H-6a), 3.55 (dd, J = 10.7, 2.0 Hz, 1H; H-6b),
3.51 (ddd, J = 9.6, 3.2, 2.0 Hz, 1H; H-5), 3.44 (dd, J = 10.4, 8.6 Hz, 1H;
H-3), 3.30 (dd, J = 9.6, 9.4 Hz; H-3’), 3.29 (s, 3H; CH3O), 3.22 (ddd, J =
10.6, 9.4, 2.2 Hz, 1H; H-5’), 1.99 (s, 3H; CH3CO), 1.92 (s, 3H; CH3CO),
1.83 (s, 3H; CH3CON), 0.93 (dd, J = 15.1, 2.2 Hz, 1H; H-6a’), 0.84 (dd, J
2-Methoxyethyl 2,3,4-tri-O-benzyl-6-deoxy-6-dimethylphenylsilyl-β-D-
glucopyranoside (26b). Rf 0.32 (PE/EtOAc, 7:1); [α]D +3.1° (c 0.6,
25
CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.49 – 7.46 (m, 2H; HCAr), 7.35 –
7.21 (m, 18H; HCAr), 4.94 (d, J = 10.9 Hz, 1H; CHH, Bn-a), 4.87 (d, J =
10.9 Hz, 1H; CHH, Bn-b), 4.85 (d, J = 11.0 Hz, 1H; CHH, Bn-c), 4.73 (d, J
= 10.9 Hz, 1H; CHH, Bn-b), 4.66 (d, J = 10.9 Hz, 1H; CHH, Bn-a), 4.63 (d,
J = 11.0 Hz, 1H; CHH, Bn-c), 4.26 (d, J = 7.7 Hz, 1H; H-1), 3.86 (ddd, J =
9.5, 5.1, 2.8 Hz, 1H; CHHCH2, aglyc.), 3.57 – 3.49 (m, 4H; 3×CH, aglyc.;
H-3), 3.42 (dd, J = 9.3, 7.7 Hz, 1H; H-2), 3.34 (s, 3H; CH3O), 3.33 (ddd, J
= 11.2, 9.2, 2.5 Hz, 1H; H-5), 3.17 (dd, J = 9.2, 8.9 Hz, 1H; H-4), 1.41 (dd,
J = 14.8, 2.5 Hz, 1H; H-6a), 0.93 (dd, J = 14.8, 11.2 Hz, 1H; H-6b), 0.31
(s, 3H; CH3Si), 0.29 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 139.3
(CAr,q), 138.8 (CAr,q), 138.8 (CAr,q), 138.4 (CAr,q), 133.7, 129.0, 128.5, 128.5,
128.4, 128.3, 128.1, 128.1, 127.9, 127.7 [aromatic C atoms], 103.9 (C-1),
84.5 (C-3), 84.3 (C-4), 82.6 (C-2), 75.8 (CH2, Bn-b), 75.5 (CH2, Bn-c), 74.8
(CH2, Bn-a), 73.2 (C-5), 71.8 (CH2, aglyc.), 69.2 (CH2, aglyc.), 59.1 (CH3O),
18.9 (C-6), −1.3 (CH3Si), −2.2 (CH3Si). HR-MS: [M+Na]+ calcd for
C38H46NaO6Si: 649.2961; found: 649.2964.
= 15.1, 10.6 Hz, 1H; H-6b’), 0.34 (s, 3H; CH3Si), 0.25 (s, 3H; CH3Si). 13
C
NMR (126 MHz, CDCl3) δ 170.0 (C=O), 169.8 (C=O), 169.2 (C=O), 139.3
(CAr,q), 139.1 (CAr,q), 138.2 (CAr,q), 137.8 (CAr,q), 133.7 (2×CArH), 129.1
(CArH), 128.7 (2×CArH), 128.7 (2×CArH), 128.5 (2×CArH), 128.4 (2×CArH),
128.4 (2×CArH), 128.1 (CArH), 128.0 (2×CArH), 127.9 (CArH), 127.7
(2×CArH), 127.6 (CArH), 126.1, 99.8 (C-1’), 98.3 (C-1), 80.3 (C-3’), 77.5 –
76.8 (C-3), 76.5 (C-4), 75.6 (C-4’), 74.6 (CH2, Bn), 73.9 (CH2, Bn), 73.7
(C-2’; CH2, Bn), 71.9 (C-5’), 70.9 (C-5), 67.5 (C-6), 55.3 (CH3O), 52.6 (C-2),
23.5 (CH3CON), 21.2 (CH3CO), 21.0 (CH3CO), 18.2 (C-6’), −1.3 (CH3Si),
−2.9 (CH3Si).
Acetyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-α-D-
glucopyranoside (24). 1H NMR (500 MHz, CDCl3) δ 7.54 – 7.42 (m, 2H;
HCAr), 7.39 – 7.18 (m, 8H; HCAr), 6.23 (d, J = 3.8 Hz, 1H; H-1), 5.00 (dd, J
= 10.0, 3.8 Hz, 1H; H-2), 4.90 (dd, J = 9.7, 9.5 Hz, 1H; H-4), 4.66 (d, J =
11.8 Hz, 1H; Bn), 4.57 (d, J = 11.8 Hz, 1H; Bn), 3.85 – 3.79 (m, 1H; H-5),
3.82 (dd, J = 10.0, 9.5 Hz, 1H; H-3), 1.98 (s, 3H; CH3CO), 1.97 (s, 3H;
CH3CO), 1.97 (s, 3H; CH3CO), 1.01 – 0.98 (m, 2H; H-6a, H-6b), 0.31 (s,
3H; CH3Si), 0.25 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 169.8 (C=O),
169.7 (C=O), 169.1 (C=O), 138.7 (CAr,q), 138.3 (CAr,q), 133.8 (2×CArH),
129.0 (CArH), 128.5 (2×CArH), 127.9 (2×CArH), 127.9 (CArH), 127.6
(2×CArH), 89.3 (C-1), 75.6 (C-4), 74.6 [one out of C-3, C-5], 72.0 (C-2),
70.4 [one out of C-5, C-3], 21.1 (CH3CO), 20.9 (CH3CO), 20.8 (CH3CO),
19.0 (C-6), −1.4 (CH3Si), −2.8 (CH3Si).
Cyclohexyl 2,3,4-tri-O-benzyl-6-deoxy-6-dimethylphenylsilyl-D-gluco-
pyranosides (27a, 27b). General procedure A with phenyl 2,3,4-tri-O-ben-
zyl-6-deoxy-6-dimethylphenylsilyl-1-thio-D-glucopyranoside (5) (100 mg,
0.152 mmol), cyclohexanol (15) (24 μL, 0.227 mmol), NIS (40 mg, 0.167
mmol) and TfOH (1.4 μL, 0.015 mmol). The procedure afforded 82 mg
(83%; α/β, 57:43) of 27a and 27b after flash silica column chromatography
(toluene/acetone, 40:1). Rf 0.50 (PE/EtOAc, 10:1); 1H NMR (500 MHz,
CDCl3) δ 7.52 – 7.25 (m, 20H, HCAr–α; 20H, HCAr–β), 4.99 – 4.63 (m, 6H,
Bn–α; 6H, Bn–β), 4.87 (d, J = 3.6 Hz, 1H; H-1–α), 4.37 (d, J = 7.8 Hz, 1H;
H-1–β), 3.96 (dd, J = 9.8, 8.9 Hz, 1H; H-3–α), 3.89 (ddd, J = 11.2 Hz, 9.3
Hz, 2.4 Hz, 1H; H-5–α), 3.59 (dddd, J = 9.2 Hz, 9.2 Hz, 3.8 Hz, 3.8 Hz, 1H;
OCH, Cy–β), 3.53 (dd, J = 9.3, 8.9 Hz, 1H; H-3–β), 3.50 (dd, J = 9.8, 3.6
Hz, 1H; H-2–α), 3.43 (m, 1H; OCH, Cy–α), 3.42 (dd, J = 9.3, 7.8 Hz; H-2–
β), 3.33 (ddd, J = 11.3 Hz, 9.2 Hz, 2.5 Hz, 1H; H-5–β), 3.21 (dd, J = 9.2,
8.9 Hz, 1H; H-4–β), 3.12 (dd, J = 9.3, 8.9 Hz, 1H; H-4–α), 1.47 (dd, J =
14.8, 2.4 Hz; H-6a–α), 1.44 (dd, J = 14.8, 2.5 Hz; H-6a–β), 1.94 – 1.12 (m,
20H; CH2, Cy–α; CH2, Cy–β), 0.96 (dd, J = 14.8, 11.3, Hz, 1H; H-6b–β),
0.84 (dd, J = 14.8, 11.2, 1H; H-6b–α), 0.33 (s, 3H; CH3Si), 0.31 (s, 3H;
CH3Si), 0.31 (s, 3H; CH3Si), 0.28 (s, 3H; CH3Si). 13C NMR (126 MHz,
CDCl3) δ 139.6 (CAr,q), 139.3 (CAr,q), 139.1 (CAr,q), 138.9 (CAr,q), 138.8
(CAr,q), 138.6 (CAr,q), 138.5 (CAr,q), 138.5 (CAr,q), 133.7 (CArH), 133.6 (CArH),
129.0 (CArH), 128.9 (CArH), 128.6 (CArH), 128.5 (CArH), 128.5 (CArH), 128.5
(CArH), 128.3 (CArH), 128.2 (CArH), 128.2 (CArH), 128.2 (CArH), 128.1
(CArH), 127.9 (CArH), 127.7 (CArH), 127.7 (CArH) [aromatic C atoms], 101.1
(C-1–β), 93.4 (C-1–α), 85.7 (C-4–α), 84.7 (C-3–β), 84.4 (C-4–β), 82.7 (C-
2–β), 81.8 (C-3–α), 80.4 (C-2–α), 76.6 (OCH, Cy–β), 75.8 (Bn), 75.6 (Bn),
75.7 (Bn), 75.5 (Bn), 75.0 (Bn), 73.9 (OCH, Cy–α), 73.1 (C-5–β), 73.0 (Bn),
68.8 (C-5–α), 33.8 (CH2, Cy), 33.2 (CH2, Cy), 31.6 (CH2, Cy), 31.0 (CH2,
Cy), 25.8 (CH2, Cy), 25.8 (CH2, Cy), 24.6 (CH2, Cy), 24.3 (CH2, Cy), 24.2
(CH2, Cy), 24.0 (CH2, Cy), 19.8 (C-6–α), 18.9 (C-6–β), −1.1 (CH3Si–α),
−1.3 (CH3Si–β), −2.3 (CH3Si–β), −2.4 (CH3Si–α).
Methyl 2-acetamido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-α-D-glu-
copyranoside (25). 1H NMR (500 MHz, CDCl3) δ 7.53 – 7.12 (m, 10H;
HCAr), 5.60 (s, 1H; CHO2Ph), 5.32 (d, J = 9.2 Hz, 1H; NH), 4.91 (d, J =
12.2 Hz, 1H; CHH, Bn), 4.70 (d, J = 3.8 Hz, 1H; H-1), 4.66 – 4.61 (m, 1H,
CHH, Bn), 4.30 – 4.27 (m, 1H; H-6a), 4.27 (ddd, J = 10.1, 9.2, 3.8 Hz, 1H;
H-2), 3.81 – 3.62 (m, 4H; H-3; H-4; H-5; H-6b), 3.35 (s, 3H; CH3O). 13C
NMR (126 MHz, CDCl3) δ 169.9 (C=O), 138.7 (CAr,q), 137.5 (CAr,q), 129.1,
128.5, 128.4, 128.2, 127.8, 126.1 [aromatic C atoms], 101.4 (CHO2Ph),
99.3 (C-1), 82.9, 76.0 [two out of C-3, C-4, C-5], 74.1 (CH2, Bn), 69.2 (C-6),
62.8 [one out of C-3, C-4, C-5], 55.3 (CH3O), 52.6 (C-2), 23.6 (CH3CO).
2-Methoxyethyl 2,3,4-tri-O-benzyl-6-deoxy-6-dimethylphenylsilyl-D-
glucopyranosides (26a, 26b). General procedure A with phenyl 2,3,4-tri-
O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-D-glucopyranoside (5) (101
mg, 0.152 mmol), 2-methoxyethanol (14) (18 μL, 0.228 mmol), NIS (40 mg,
0.167 mmol) and TfOH (1.4 μL, 0.015 mmol). The procedure afforded 84
mg (88%; α/β, 52:48) of 26a and 26b after flash silica column chromatog-
raphy (petroleum ether/EtOAc, 7:1 to 4:1).
2-Methoxyethyl 2,3,4-tri-O-benzyl-6-deoxy-6-dimethylphenylsilyl-α-D-
glucopyranoside (26a). Rf 0.24 (PE/EtOAc, 7:1); [α]D +37.2° (c 0.6,
Methyl 2’,3’,4’-tri-O-benzyl-6’-deoxy-6’-dimethylphenylsilyl-D-gluco-
pyranosyl-(1’→4)-2,3,6-tri-O-benzyl-α-D-glucopyranosides (28a, 28b).
25
CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.43 – 7.15 (m, 20H; HCAr), 4.90 (d,
J = 10.8 Hz, 1H; CHH, Bn-a), 4.84 (d, J = 11.0 Hz, 1H; CHH, Bn-b), 4.71
(d, J = 10.8 Hz, 1H; CHH, Bn-a), 4.71 (d, J = 3.6 Hz, 1H; H-1), 4.65 (d, J =
12.0 Hz, 1H; CHH, Bn-c), 4.61 (d, J = 12.0 Hz, 1H; CHH, Bn-c), 4.58 (d, J
= 11.0 Hz, 1H; CHH, Bn-b), 3.86 (dd, J = 9.8, 8.9 Hz, 1H; H-3), 3.76 (ddd,
J = 11.0, 9.4, 2.6 Hz, 1H; H-5), 3.45 – 3.30 (m, 4H; 4×CHH, aglyc.), 3.43
(dd, J = 9.8, 3.6 Hz, 1H; H-2), 3.26 (s, 3H; CH3O), 3.04 (dd, J = 9.4, 8.9
Hz, 1H; H-4), 1.40 (dd, J = 14.8, 2.6 Hz, 1H; H-6a), 0.78 (dd, J = 14.8, 11.0
Hz, 1H; H-6b), 0.26 (s, 3H; CH3Si), 0.21 (s, 3H; CH3Si). 13C NMR (126
MHz, CDCl3) δ 139.5 (CAr,q), 139.1 (CAr,q), 138.6 (CAr,q), 138.6 (CAr,q), 133.7,
128.9, 128.5, 128.5, 128.5, 128.1, 128.1, 128.0, 127.9, 127.8, 127.6 [11
peaks; 4 signals CArH, 8 signals 2×CArH], 97.0 (C-1), 85.3 (C-4), 81.7 (C-3),
80.4 (C-2), 75.7 (CH2, Bn), 75.5 (CH2, Bn), 72.7 (CH2, Bn), 71.9 (CH2,
aglyc.), 68.8 (C-5), 67.0 (CH2, aglyc.), 59.1 (CH3O), 19.7 (C-6), −1.0
(CH3Si), −2.3 (CH3Si). HR-MS: [M+Na]+ calcd for C38H46NaO6Si:
649.2961; found: 649.2958.
General procedure
A with phenyl 2,3,4-tri-O-benzyl-6-deoxy-6-dime-
thylphenylsilyl-1-thio-D-glucopyranoside (5) (74 mg, 0.112 mmol), methyl
2,3,6-tri-O-benzyl-α-D-glucopyranoside (16) (78 mg, 0.168 mmol), NIS (29
mg, 0.132 mmol) and TfOH (1.0 μL, 0.011 mmol). The procedure afforded
76 mg (67%; α/β, 65:35) of 28a and 28b after flash silica column chroma-
tography (PE/EtOAc, 4:1).
Methyl 2’,3’,4’-tri-O-benzyl-6’-deoxy-6’-dimethylphenylsilyl-α-D-glu-
copyranosyl-(1’→4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (28a). Rf
0.33 (PE/EtOAc, 4:1); [α]D +34.2° (c 0.6, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 7.51 – 7.27 (m, 35H; HCAr), 5.55 (d, J = 3.4 Hz, 1H; H-1’), 5.09
(d, J = 11.9 Hz, 1H; CHH, Bn), 4.94 (d, J = 11.2 Hz, 1H; CHH, Bn), 4.85 –
4.63 (m, 5H; CHH, Bn), 4.76 (d, J = 12.1 Hz, 1H; CHH, Bn), 4.67 – 4.65
(m, 1H; H-1), 4.60 (d, J = 11.9 Hz, 1H; CHH, Bn), 4.57 (d, J = 11.9 Hz, 1H;
CHH, Bn), 4.54 (d, J = 12.2 Hz, 1H; CHH, Bn), 4.46 (d, J = 12.1 Hz, 1H;
25
10
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
CHH, Bn), 4.04 (dd, J = 9.5, 8.5 Hz, 1H; H-3), 3.87 – 3.79 (m, 2H; H-5;
H-5’), 3.83 (dd, J = 9.9, 8.8 Hz; H-3’), 3.75 (dd, J = 10.0, 8.5 Hz, 1H; H-4),
3.63 (dd, J = 10.4, 2.0 Hz, 1H; H-6a), 3.57 (dd, J = 9.5, 3.5 Hz, 1H; H-2),
3.45 – 3.41 (m, 1H; H6b), 3.44 (s, 3H; CH3O), 3.38 (dd, J = 9.9, 3.5 Hz,
1H; H-2’), 3.12 (dd, J = 9.5, 8.8 Hz, 1H; H-4’), 1.44 (dd, J = 14.9, 4.0 Hz,
1H; H-6a’), 0.97 (dd, J = 14.9, 9.1 Hz, 1H; H-6b’), 0.35 (s, 3H; CH3Si), 0.32
(s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 139.8 (CAr,q), 139.2 (CAr,q),
138.9 (CAr,q), 138.8 (CAr,q), 138.2 (CAr,q), 138.2 (CAr,q), 138.2 (CAr,q), 133.8,
129.0, 128.6, 128.5, 128.4, 128.4, 128.4, 128.3, 128.1, 128.0, 128.0, 127.9,
127.7, 127.6, 127.6, 127.1, 126.8 [aromatic C atoms], 97.7 (C-1), 95.1
(C-1’), 85.0 (C-4’), 82.2 (C-3), 81.5 (C-3’), 80.3 (C-2’), 80.1 (C-2), 75.5
(CH2, Bn), 75.3 (CH2, Bn), 74.3 (CH2, Bn), 73.4 (CH2, Bn), 73.4 (CH2, Bn),
73.0 (CH2, Bn), 72.0 (C-4), 70.0, 69.6 [C-5, C-5’], 69.4 (C-6), 55.2 (CH3O),
20.1 (C-6’), −0.8 (CH3Si), −1.6 (CH3Si). HR-MS: [M+Na]+ calcd for
C63H70NaO10Si: 1037.4636; found: 1037.4627.
Bn], 70.3 [one out of C-3, C-4, C-3’, C-5’], 69.2 (C-6), 55.1 (CH3O), 51.0
(C-2), 23.6 (CH3CO), 19.9 (C-6’), −0.9 (CH3Si), −1.5 (CH3Si).
Methyl 2’,3’,4’-tri-O-benzyl-6’-deoxy-6’-dimethylphenylsilyl-β-D-glu-
copyranosyl-(1’→4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-gluco-
pyranoside (29b). Rf 0.22 (PE/acetone, 7:3); 1H NMR (500 MHz, CDCl3)
δ 7.49 – 7.44 (m, 2H; HCAr), 7.39 – 7.18 (m, 28H; HCAr), 5.18 (d, J = 8.3
Hz, 1H; NH), 4.95 (d, J = 12.4 Hz, 1H; CHH, Bn), 4.88 (d, J = 11.1 Hz, 1H;
CHH, Bn), 4.86 – 4.82 (m, 2H; 2×CHH, Bn), 4.80 (d, J = 3.7 Hz, 1H; H-1),
4.79 – 4.73 (m, 2H; 2×CHH, Bn), 4.66 (d, J = 11.2 Hz, 1H; CHH, Bn), 4.62
(d, J = 12.1 Hz, 1H; CHH, Bn), 4.55 (d, J = 12.4 Hz, 1H; CHH, Bn), 4.40
(d, J = 12.1 Hz, 1H; CHH, Bn), 4.28 (d, J = 7.5 Hz, 1H; H-1’), 4.14 (ddd, J
= 10.8, 8.3, 3.7 Hz, 1H; H-2), 3.98 (dd, J = 10.1, 8.8 Hz, 1H; H-4), 3.82 (dd,
J = 10.9, 3.2 Hz, 1H; H-6a), 3.53 (ddd, J = 10.1, 3.2, 2.4 Hz, 1H; H-5), 3.51
– 3.47 (m, 1H; H-6b), 3.46 (dd, J = 10.8, 8.8 Hz, 1H; H-3), 3.42 – 3.34 (m,
2H; H-3’; H-2’), 3.32 (s, 3H; CH3O), 3.23 (ddd, J = 10.9, 9.0, 1.7 Hz, 1H;
H-5’), 3.13 (dd, J = 9.0, 8.7 Hz, 1H; H-4’), 1.86 (s, 3H; CH3CO), 1.38 (dd,
J = 14.9, 1.7 Hz, 1H; H-6a’), 0.72 (dd, J = 14.9, 10.9 Hz, 1H; H-6b’), 0.31
(s, 3H; CH3Si), 0.26 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 169.8
(C=O), 139.6 (CAr,q), 139.5 (CAr,q), 138.8 (CAr,q), 138.7 (CAr,q), 138.6 (CAr,q),
138.0 (CAr,q), 133.8 (2×CArH), 128.9 (CArH), 128.6 (2×CArH), 128.5 (CArH),
128.5 (2×CArH), 128.5 (2×CArH), 128.4 (2×CArH), 128.4 (2×CArH), 128.3
(2×CArH), 128.2 (2×CArH), 128.0 (2×CArH), 127.9 (2×CArH), 127.9 (2×CArH),
127.8 (2×CArH), 127.8 (CArH), 127.7 (CArH), 127.7 (CArH), 127.5 (CArH),
102.0 (C-1’), 98.4 (C-1), 84.7, 84.6 [2 peaks: C-3’; C-4’], 83.6 (C-2’), 77.8
(C-3), 76.4 (C-4), 75.7 (CH2, Bn), 75.3 (CH2, Bn), 75.1 (CH2, Bn), 74.4
(CH2, Bn), 73.6 (CH2, Bn), 72.9 (C-5’), 70.8 (C-5), 67.7 (C-6), 55.3 (CH3O),
52.8 (C-2), 23.5 (CH3CO), 18.5 (C-6’), −1.4 (CH3Si), −2.7 (CH3Si).
Methyl 2’,3’,4’-tri-O-benzyl-6’-deoxy-6’-dimethylphenylsilyl-β-D-glu-
copyranosyl-(1’→4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (28b). Rf
0.43 (PE/EtOAc, 4:1); 1H NMR (500 MHz, CDCl3) δ 7.53 – 7.20 (m, 35H;
HCAr), 5.03 (d, J = 11.0 Hz, 1H; CHH, Bn), 4.93 (d, J = 11.2 Hz, 1H; CHH,
Bn), 4.88 – 4.69 (m, 8H; CHH, Bn), 4.63 (d, J = 3.7 Hz, 1H; H-1), 4.62 (d,
J = 11.9 Hz; CHH, Bn), 4.38 (d, J = 12.1 Hz, 1H; CHH, Bn), 4.23 (d, J =
7.0 Hz, 1H; H-1’), 3.91 (dd, J = 10.1, 9.1 Hz, 1H; H-4), 3.81 (dd, J = 9.7,
9.1 Hz, 1H; H-3), 3.77 (dd, J = 10.8, 2.9 Hz, 1H; H-6a), 3.54 (ddd, J = 10.1,
2.9, 1.6 Hz, 1H; H-5), 3.49 (dd, J = 9.7, 3.7 Hz, 1H; H-2), 3.45 – 3.40 (m,
1H; H-6b), 3.41 (s, 3H; CH3O), 3.38 – 3.30 (m, 2H; H-2’; H-4’), 3.24 (ddd,
J = 11.1, 9.1, 1.5 Hz, 1H; H-5’), 3.16 (dd, J = 8.8 Hz, 1H; H-3’), 1.40 (dd, J
= 14.8, 1.5 Hz, 1H; H-6a’), 0.78 (dd, J = 14.8, 11.1 Hz, 1H; H-6b’), 0.31 (s,
3H; CH3Si), 0.24 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ 139.8 (CAr,q),
139.7 (CAr,q), 138.9 (CAr,q), 138.8 (CAr,q), 138.7 (CAr,q), 138.6 (CAr,q), 137.6
(CAr,q), 133.8 (2×CArH), 128.9 (CArH), 128.7 (2×CArH), 128.6 (2×CArH),
128.6 (2×CArH), 128.5 (2×CArH), 128.5 (2×CArH), 128.5 (2×CArH), 128.3
(2×CArH), 128.0 (CArH), 128.0 (2×CArH), 128.0 (2×CArH), 127.9 (2×CArH),
127.9 (2×CArH), 127.8 (CArH), 127.8 (2×CArH), 127.8 (CArH), 127.7 (CArH),
127.6 (CArH), 127.2 (CArH), 101.8 (C-1’), 98.8 (C-1), 84.6, 84.5, 83.5 [C-2’;
C-3’; C-4’], 80.6 (C-3), 78.2 (C-2), 75.8, 75.7, 75.5, 75.3 [3×CH2, Bn; C-4],
74.9 (CH2, Bn), 73.8 (CH2, Bn), 73.7 (CH2, Bn), 72.8 (C-5’), 70.3 (C-5),
67.6 (C-6), 55.4 (CH3O), 18.4 (C-6’), −1.2 (CH3Si), −2.7 (CH3Si). HR-MS:
[M+Na]+ calcd for C63H70NaO10Si: 1037.4636; found: 1037.4627.
2-Methoxyethyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphen-
ylsilyl-L-idopyranosides (30a, 30b). General procedure A with phenyl
2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphenylsilyl-1-thio-L-
idopyranoside (10) (68 mg, 0.120 mmol), 2-methoxyethanol (14) (14 μL,
0.181 mmol), NIS (31 mg, 0.132 mmol) and TfOH (1.1 μL, 0.012 mmol).
The procedure afforded 51 mg (81%; α/β, 93:7) of 30a and 30b after flash
silica column chromatography (PE/EtOAc, 7:3).
2-Methoxyethyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphen-
ylsilyl-α-L-idopyranoside (30a). Rf 0.22 (PE/EtOAc, 3:1); [α]D25 −64.1° (c
0.8, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.51 – 7.47 (m, 2H; HCAr), 7.37
– 7.25 (m, 8H; HCAr), 4.93 (ddd, J = 2.9, 1.6, 0.9 Hz, 1H; H-2), 4.79 (bs,
1H; H-1), 4.71 (d, J = 12.0 Hz, 1H; CHH, Bn), 4.66 – 4.65 (m, 1H; H-4),
4.60 (d, J = 12.0 Hz, 1H; CHH, Bn), 4.45 (ddd, J = 8.5, 6.4, 1.8 Hz, 1H;
H-5), 3.68 (ddd, J = 11.0, 4.6, 4.5 Hz, 1H; CH, aglyc.), 3.66 – 3.64 (m, 1H;
H-3), 3.52 (ddd, J = 11.0, 5.8, 4.4 Hz, 1H; CH, aglyc.), 3.46 – 3.43 (m, 2H;
2×CH, aglyc.), 3.32 (s, 3H; CH3O), 2.07 (s, 3H; CH3CO), 2.05 (s, 3H;
CH3CO), 1.22 (dd, J = 14.8, 8.5 Hz, 1H; H-6a), 1.04 (dd, J = 14.8, 6.4 Hz,
1H; H-6b), 0.34 (s, 3H; CH3Si), 0.33 (s, 3H; CH3Si). 13C NMR (126 MHz,
CDCl3) δ 170.4 (C=O), 169.7 (C=O), 138.6 (CAr,q), 138.1 (CAr,q), 133.7
(2×CArH), 129.2 (CArH), 128.4 (2×CArH), 128.0 (2×CArH), 127.7 (CArH),
127.5 (2×CArH), 98.6 (C-1; 1JC1-H1 = 168.2 Hz, characteristic of an axially
oriented group on C-1), 73.1 (C-3), 71.9 (CH2, Bn), 71.7 (CH2, aglyc.), 70.9
(C-4), 67.6 (CH2, aglyc.), 67.4 (C-2), 63.6 (C-5), 59.3 (CH3O), 21.2
(CH3CO), 21.1 (CH3CO), 18.0 (C-6), −1.7 (CH3Si), −2.6 (CH3Si). HR-MS:
[M+Na]+ calcd for C28H38NaO8Si: 553.2234; found: 553.2220.
Methyl 2’,3’,4’-tri-O-benzyl-6’-deoxy-6’-dimethylphenylsilyl-D-gluco-
pyranosyl-(1’→4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopy-
ranosides (29a, 29b). General procedure B with phenyl 2,3,4-tri-O-ben-
zyl-6-deoxy-6-dimethylphenylsilyl-1-thio-D-glucopyranoside (5) (48 mg,
0.072 mmol), methyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopy-
ranoside (17) (20 mg, 0.048 mmol), NIS (19 mg, 0.079 mmol) and TfOH
(0.7 μL, 0.007 mmol). The procedure afforded 30 mg (60%; α/β, 35:65) of
29a and 29b after flash silica column chromatography (PE/acetone, 7:3).
Methyl 2’,3’,4’-tri-O-benzyl-6’-deoxy-6’-dimethylphenylsilyl-α-D-glu-
copyranosyl-(1’→4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-gluco-
pyranoside (29a). Rf 0.28 (PE/acetone, 7:3); 1H NMR (500 MHz, CDCl3)
δ 7.50 – 7.44 (m, 2H; HCAr), 7.40 – 7.17 (m, 28H; HCAr), 5.47 (d, J = 9.3
Hz, 1H; NH), 5.41 (d, J = 3.5 Hz, 1H; H-1’), 4.91 (d, J = 11.2 Hz, 1H; CHH,
Bn), 4.84 (d, J = 10.8 Hz, 1H; CHH, Bn), 4.73 (d, J = 3.6 Hz, 1H; H-1), 4.71
– 4.43 (m, 8H; CHH, Bn), 4.37 (ddd, J = 10.2, 9.3, 3.6 Hz, 1H; H-2), 3.87
– 3.75 (m, 5H; H-3; H-4; H-5; H-3’; H-5’), 3.61 (dd, J = 10.5, 2.3 Hz, 1H;
H-6a), 3.54 (dd, J = 10.5, 5.6 Hz, 1H; H-6b), 3.40 – 3.36 (m, 1H; H-2’), 3.36
(s, 3H; CH3O), 3.09 (dd, J = 9.1 Hz, 1H; H-4’), 1.87 (s, 3H; CH3CO), 1.42
(dd, J = 15.0, 4.0 Hz, 1H; H-6a’), 0.96 (dd, J = 15.0, 8.7 Hz, 1H; H-6b’),
0.29 (s, 3H; CH3Si), 0.26 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ
169.9 (C=O), 139.5 (CAr,q), 138.9 (CAr,q), 138.7 (CAr,q), 138.4 (CAr,q), 138.3
(CAr,q), 138.0 (CAr,q), 133.8, 129.2, 128.5, 128.5, 128.5, 128.5, 128.1, 128.0,
128.0, 128.0, 127.9, 127.8, 127.8, 127.8, 127.7, 127.7, 127.6 [aromatic C
atoms], 98.1 (C-1), 95.7 (C-1’), 84.8 (C-4’), 81.4, 80.0, 79.9 [C-2’; two out
of C-3, C-4, C-3’, C-5’], 75.5 (CH2, Bn), 75.4 (CH2, Bn), 73.4 (CH2, Bn),
72.7 (CH2, Bn), 71.8 [one out of C-3, C-4, C-3’, C-5’], 70.8, 70.7 [C-5; CH2,
2-Methoxyethyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-dimethylphen-
1
ylsilyl-β-L-idopyranoside (30b). Rf 0.14 (PE/EtOAc, 3:1); H NMR (500
MHz, CDCl3) δ 7.53 – 7.48 (m, 2H; HCAr), 7.38 – 7.24 (m, 8H; HCAr), 4.95
(ddd, J = 2.9, 1.6, 0.9 Hz, 1H; H-2), 4.77 (d, J = 1.6 Hz, 1H; H-1), 4.66 (d,
J = 11.8 Hz, 1H; CHH, Bn), 4.62 (d, J = 11.8 Hz, 1H; CHH, Bn), 4.57 (ddd,
J = 2.5, 1.6, 0.9 Hz, 1H; H-4), 4.03 (ddd, J = 9.4, 5.0, 1.6 Hz, 1H; H-5),
3.95 (ddd, J = 10.6, 4.7, 3.6 Hz, 1H; CHHCH2, aglyc.), 3.78 (dd, J = 2.9,
2.5 Hz, 1H; H-3), 3.62 (ddd, J = 10.6, 7.2, 3.9 Hz, 1H; CHHCH2, aglyc.),
3.64 – 3.48 (m, 2H; 2×CH, aglyc.), 3.35 (s, 3H; CH3O), 2.09 (s, 3H;
CH3CO), 2.05 (s, 3H; CH3CO), 1.35 (dd, J = 14.9, 9.4 Hz, 1H; H-6a), 0.98
(dd, J = 14.9, 5.0 Hz, 1H; H-6b), 0.35 (s, 3H; CH3Si), 0.33 (s, 3H; CH3Si).
13C NMR (126 MHz, CDCl3) δ 170.6 (C=O), 170.4 (C=O), 138.6 (CAr,q),
11
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000708
European Journal of Organic Chemistry
FULL PAPER
137.5 (CAr,q), 133.7 (2×CArH), 129.3 (CArH), 128.6 (2×CArH), 128.1 (CArH),
128.1 (2×CArH), 127.7 (2×CArH), 98.0 (C-1; 1JC1-H1 = 158.1 Hz, character-
istic of an equatorially oriented group on C-1), 74.1 (C-3), 72.7 (CH2, Bn),
71.7 (CH2, aglyc.), 70.8 (C-5), 70.0 (C-4), 69.0 (CH2, aglyc.), 67.3 (C-2),
59.3 (CH3O), 21.3 (CH3CO), 21.0 (CH3CO), 18.0 (C-6), −1.7 (CH3Si), −2.4
(CH3Si). HR-MS: [M+Na]+ calcd for C28H38NaO8Si: 553.2234; found:
553.2220.
2-Methoxyethyl 2,3,4-tri-O-benzyl-6-deoxy-α-D-glucopyranoside (35).
To a 10-mL flask, 2-methoxyethyl 2,3,4-tri-O-benzyl-6-deoxy-6-dime-
thylphenylsilyl-α-D-glucopyranoside (26a) (35 mg, 0.056 mmol) and dry
DMF (2 mL) were added. To this solution, 1 M TBAF in THF (0.39 mL, 0.90
mmol) was added. The mixture was stirred at 80°C overnight. After cooling
down to room temperature, 1 M HCl(aq) (10 mL) was added and extracted
with EtOAc (3 × 10 mL). The organic layers were combined and washed
with water, 1 M HCl(aq) and brine. After drying over MgSO4(s), the mixture
was concentrated to dryness over reduced pressure. The desired product
was obtained pure as a colourless syrup without further purification (22
mg; 79%). Rf 0.27 (PE/EtOAc, 5:1); [α]D25 +31.3° (c 0.6, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.40 – 7.25 (m, 18H), 5.00 (d, J = 10.8 Hz, 1H; CHH,
Bn-a), 4.90 (d, J = 10.9 Hz, 1H; CHH, Bn-b), 4.82 (d, J = 10.8 Hz, 1H; CHH,
Bn-a), 4.78 (d, J = 12.0 Hz, 1H; CHH, Bn-c), 4.77 (d, J = 3.6 Hz; H-1), 4.69
(d, J = 12.0 Hz, 1H; CHH, Bn-c), 4.63 (d, J = 10.9 Hz, 1H; CHH, Bn-b),
3.98 (dd, J = 9.6, 9.0 Hz, 1H; H-3), 3.82 (dq, J = 9.6, 6.2 Hz, 1H; H-5), 3.75
(ddd, J = 11.2, 5.5, 4.2 Hz, 1H; CHH, aglyc.), 3.66 (ddd, J = 11.2, 5.1, 5.1
Hz, 1H; CHH, aglyc.), 3.60 (m, 2H; 2×CH, aglyc.), 3.54 (dd, J = 9.6, 3.6
Hz, 1H; H-2), 3.39 (d, J = 1.5 Hz, 3H; CH3O), 3.13 (dd, J = 9.6, 9.0 Hz, 1H;
H-4), 1.24 (d, J = 6.2 Hz, 3H; CH3). 13C NMR (126 MHz, CDCl3) δ 139.1
(CAr,q), 138.5 (CAr,q), 138.5 (CAr,q), 128.5 (4×CArH), 128.5 (2×CArH), 128.2
(2×CArH), 128.1 (4×CArH), 127.9 (CArH), 127.9 (CArH), 127.7 (CArH), 97.1
(C-1), 84.0, 81.9, 80.5, 75.8, 75.5, 73.0, 71.9, 66.9, 66.8 [9 peaks: C-2;
C-3; C-4; C-5; 3×CH2, Bn; 2×CH2, aglyc.], 59.1 (CH3O), 18.0 (C-6).
HR-MS: [M+Na]+ calcd for C30H36NaO6: 515.2410; found: 515.2398.
Methyl 2’,4’-di-O-acetyl-3’-O-benzyl-6’-deoxy-6’-dimethylphenylsilyl-
α-L-idopyranosyl-(1’→4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (31).
General procedure A with phenyl 2,4-di-O-acetyl-3-O-benzyl-6-deoxy-6-
dimethylphenylsilyl-1-thio-L-idopyranoside (10) (102 mg, 0.180 mmol), me-
thyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside (17) (126 mg, 0.270 mmol),
NIS (47 mg, 0.198 mmol) and TfOH (1.6 μL, 0.018 mmol). The procedure
afforded 95 mg (58%) of 31 after flash silica column chromatography (tol-
uene/acetone, 19:1). Rf 0.27 (PE/EtOAc, 3:1); 1H NMR (500 MHz, CDCl3)
δ 7.39 (m, 2H; HCAr), 7.35 – 7.19 (m, 23H; HCAr), 5.05 (m, 1H; H-1’), 4.85
– 4.81 (m, 2H; H3’; CHH, Bn-a), 4.78 (d, J = 11.1 Hz, 1H; CHH, Bn-a), 4.67
(d, J = 12.0 Hz, 1H; CHH, Bn-b), 4.62 (d, J = 11.9 Hz, 1H; CHH, Bn-c),
4.59 (d, J = 11.9 Hz, 1H; CHH, Bn-c), 4.58 – 4.53 (m, 4H; H-1; H-2’; H-5’;
CHH, Bn-b), 4.44 (s, 2H; 2×CH, Bn-d), 3.86 (dd, J = 9.1, 9.0 Hz, 1H; H-4),
3.82 (dd, J = 9.2, 9.0 Hz, 1H; H-3), 3.72 (dd, J = 10.7, 3.7 Hz, 1H; H-6a),
3.69 (ddd, J = 9.1, 3.7, 1.7 Hz, 1H; H-5), 3.64 (ddd, J = 3.0, 1.1, 1.1 Hz,
1H; H-4’), 3.59 (dd, J = 10.7, 1.7 Hz, 1H; H-6b), 3.49 (dd, J = 9.2, 3.6 Hz,
1H; H-2), 3.36 (s, 3H; CH3O), 1.94 (s, 3H; CH3CO), 1.91 (s, 3H; CH3CO),
1.03 (dd, J = 14.7, 7.3 Hz, 1H; H-6a’), 0.87 (dd, J = 14.7, 8.1 Hz, 1H; H-6b’),
0.20 (s, 3H; CH3Si), 0.19 (s, 3H; CH3Si). 13C NMR (126 MHz, CDCl3) δ
170.5 (C=O), 169.7 (C=O), 139.4 (CAr,q), 139.3 (CAr,q), 138.3 (CAr,q), 138.2
(CAr,q), 137.9 (CAr,q), 133.7, 129.2, 129.0, 128.5, 128.5, 128.4, 128.3, 128.2,
128.0, 127.9, 127.8, 127.8, 127.7, 127.6, 127.5, 127.2 [aromatic C atoms],
98.2 (C-1), 97.7 (C-1’), 80.8 (C-4), 80.0 (C-2), 75.1 (CH2, Bn), 74.6 (C-3),
73.6, 73.3, 73.3 [C-4’; 2×CH2, Bn], 72.4 (CH2, Bn), 70.2, 70.2 [C-5; C-2’
or C-5’], 68.9 (C-6), 67.8 (C-3’), 64.3 [C-2’ or C-5’], 55.4 (CH3O), 21.1
(CH3CO), 21.0 (CH3CO), 17.7 (C-6), −1.5 (CH3Si), −2.2 (CH3Si). HR-MS:
[M+Na]+ calcd for C53H62NaO12Si: 941.3908; found: 941.3878.
Acknowledgements
Villum Foundation are acknowledged for financial support.
Keywords: Silylated sugars • Glycosylation • Stereoelectronic
effects • Reactivity • Selectivity
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Methyl 2’,4’-di-O-acetyl-3’-O-benzyl-6’-deoxy-6’-dimethylphenylsilyl-
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HCAr), 7.35 – 7.21 (m, 16H; HCAr), 7.17 – 7.12 (m, 2H; HCAr), 5.02 (d, J =
9.0 Hz, 1H; NH), 5.01 – 5.00 (m, 1H; H-1’), 4.91 – 4.89 (m, 1H; H-2’), 4.67
(d, J = 3.7 Hz, 1H; H-1), 4.65 – 4.61 (m, 2H; H-4’; CHH, Bn-b), 4.64 (d, J
= 12.2 Hz, 1H; CHH, Bn-a), 4.61 (d, J = 11.8 Hz, 1H; CHH, Bn-b), 4.56
(ddd, J = 8.5, 6.9, 1.8 Hz, 1H; H-5’), 4.54 (d, J = 12.1 Hz, 1H; CHH, Bn-c),
4.50 (d, J = 12.1 Hz, 1H; CHH, Bn-c), 4.40 (d, J = 12.2 Hz, 1H; CHH, Bn-a),
4.15 (ddd, J = 10.5, 9.0, 3.7 Hz, 1H; H-2), 3.93 (dd, J = 9.5, 8.9 Hz, 1H;
H-4), 3.76 (dd, J = 10.8, 3.6 Hz, 1H; H-6a), 3.71 – 3.65 (m, 2H; H-3’; H-5),
3.64 (dd, J = 10.8, 1.9 Hz, 1H; H-6b), 3.54 (dd, J = 10.5, 8.9 Hz, 1H; H-3),
3.30 (s, 3H; CH3O), 1.98 (s, 3H; CH3CO), 1.97 (s, 3H; CH3CO), 1.69 (s,
3H; CH3CON), 1.16 (dd, J = 14.6, 6.9 Hz, 1H; H-6b’), 1.09 (dd, J = 14.6,
8.5 Hz, 1H; H-6b’), 0.27 (s, 3H; CH3Si), 0.26 (s, 3H; CH3Si). 13C NMR (126
MHz, CDCl3) δ 170.4 (C=O), 169.8 (C=O), 169.7 (C=O), 138.9 (CAr,q),
138.8 (CAr,q), 138.4 (CAr,q), 137.8 (CAr,q), 133.7 (2×CArH), 129.1 (CArH),
128.5 (6×CArH), 128.4 (2×CArH), 128.0 (2×CArH), 127.9 (CArH), 127.8
(2×CArH), 127.7 (CArH), 127.6 (2×CArH), 127.5 (CArH), 98.4 (C-1), 97.6
(C-1’), 78.4 (C-3), 75.1 (C-4), 74.3 (CH2, Bn-a), 73.4 (C-3’), 73.3 (CH2,
Bn-c), 72.6 (CH2, Bn-b), 71.1 (C-5), 70.2 (C-4’), 68.7 (C-6), 68.3 (C-2’),
64.6 (C-5’), 55.2 (CH3O), 52.4 (C-2), 23.4 (CH3CON), 21.1 (CH3CO), 21.0
(CH3CO), 17.8 (C-6'), −1.7 (CH3Si), −2.4 (CH3Si). HR-MS: [M+Na]+ calcd
for C53H62NaO12Si: 941.3908; found: 941.3878.
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13
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FULL PAPER
Entry for the Table of Contents
To study the influence of a silyl group on the reactivity and selectivity of glycosyl donors, two
synthetic routes have been developed to obtain both D-glucosyl and L-idosyl donors with a silyl
group attach to C6. The glycosylation and competition studies show that it enhances reactivity
beyond what an O-benzyl group on C6 would do. In order to access C6-deoxy sugars, an
efficient protodesilylation methodology is also described.
Si Ph
O
Reactivity
RO
BnO
SPh
OR
= Ac, Bn
R
Selectivity
Ph
SPh
Si
OBn
O
Ph
Si
H
OAc OAc
D-Glucose
14
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