Reactivity, Selectivity, and Synthesis of 4-C-Silylated Glycosyl Donors and 4-Deoxy Analogues

Article abstract of DOI:10.1002/anie.202009209

A method for introducing dimethylphenylsilyl at the 4-position in carbohydrates has been developed. Two C-silylated glycosyl donors were prepared via levoglucosenone, starting from cellulose. The glycosylation properties were studied using three glucoside

Full text of DOI:10.1002/anie.202009209

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Reactivity, Selectivity and Synthesis of 4-C-Silylated Glycosyl
Donors and 4-Deoxy Analogues
Authors: Martin Jæger Pedersen and Christian Marcus Pedersen
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202009209
Link to VoR: https://doi.org/10.1002/anie.202009209

10.1002/anie.202009209
Angewandte Chemie International Edition
COMMUNICATION
Reactivity, Selectivity and Synthesis of 4-C-Silylated Glycosyl
Donors and 4-Deoxy Analogues
Martin Jæger Pedersen[a],[b] and Christian Marcus Pedersen*[a]
[a]
*Associate Professor, PhD, Christian Marcus Pedersen, CMP
Department of Chemistry
University of Copenhagen
Universitetsparken 5, 2100 Copenhagen Ø, Denmark
E-mail: cmp@chem.ku.dk
[b]
Currently: PhD, Martin Jæger Pedersen, MJP
School of Chemistry
University College Dublin
Belfield, Dublin 4, Ireland
Supporting information for this article is given via a link at the end of the document.
Abstract:
A
method for introducing dimethylphenylsilyl at the
Despite the perspectives of having silicon on a sugar scaffold,
only a few sporadic examples have been reported. Pegram and
Anderson introduced a C6-(dimethylphenylsilyl) via hydrosilation
of the 5,6-unsaturated hexopyranoside.[12] Sinaÿ and coworkers
observed a silyl-migration of a 2-O-TMS group to C-1 under basic
conditions giving the α-D-glycopyranosyltrimethylsilane.[13] The
same group later reported the use of silylmethylene radical
cyclization, followed by a Tamao oxidation, for the synthesis of
4-position in carbohydrates has been developed. Two C-silylated
glycosyl donors were prepared via levoglucosenone, starting from
cellulose. The glycosylation properties were studied using three
glucoside acceptors, a 3-OH, 4-OH and 6-OH. Compared with the
4-deoxy variant, it was found that the anomeric selectivity was
influenced more by the C-2 substituents orientation than the silyl in
the 4-position. In general, the reactivity of these donors was higher
than the corresponding 4-deoxy-analogue, albeit a competition
experiment showed that the introduction of a C-Si increases the
relative reactivity by a modest factor of around two.
branched
carbohydrates.[14]
Grignard
reactions
using
(phenyldimethylsilyl)methylmagnesium chloride were introduced
by van Boom and coworkers for the elongation of
carbohydrates.[15] This approach was later followed up by
Stepowska and Zamojski.[16] Boulineay and Wei used the same
reagent for epoxide-opening to yield L-hexopyranosides from
pentoses.[17] Zhu and Vogel used the nucleophilic silyl reagent
(phenyldimethylsilyl)dimethylzinc lithium for the conjugated
addition to a carbohydrate derived enone.[18] Cen and Sauve
Introduction
All functional groups found on a sugar ring in the biosphere are
electron withdrawing (relative to carbon), and deoxy-glycosides
are therefore considered the upper limit in terms of reactivity for
glycosyl donors. When the deoxy position is next to the anomeric
center (on C2), the resulting donor is often uncontrollable,
unstable and less selective in glycosylation reactions,[1,2] as a
non-functionalized position does not have a steric influence and
only little conformational influence. Consequently, it is interesting
to study how electron donating groups with steric bulk can
influence a glycosyl donors’ reactivity and selectivity. Comparably
few functional groups are electron donating relative to carbon and
even fewer would be practical for use in glycosylation chemistry.
Boron and silicon however are both electropositive relative to H
and C, and form stable bonds with carbon.[3] Particularly, alkylated
or arylated silicon are popular as O-protective groups because
they are easily installed and removed with high degree of
orthogonality. Contrary to this, the direct introduction of Si on the
sugar scaffold would reverse the stereoelectronic effects
compared to a protected alcohol and increase the steric rigidity
from having a tetravalent group directly attached to the pyrane
ring.[4] Additionally, silicon is well known to stabilize the formation
of carbocations, especially in, but not limited to, their β-position.[5]
Beside these interesting properties, the C-Si can be reductively
cleaved to a C-H, or oxidatively cleaved to the corresponding
alcohol. Hence, a silicon functions as a masked alcohol, offering
the hydroxyl group with retention of stereochemistry using
Fleming-Tamao oxidation[6–10] or related methods.[11]
synthesized
a
2-deoxy-2-fluororibolactone via
a
C2-TMS
intermediate, which was obtained from the silylation of the α-
carbon (C-2) under basic conditions with TMSOTf as
electrophile.[19] Recently, Frihed et al. used C-H activation to
synthesize L-sugars from the corresponding 6-deoxy-L-sugars via
a cyclic silyl intermediate.[20,21] Lastly, Álvarez and Pedersen
synthesized C-6 silylated glycosyl donors for the study of
glycosylation properties in terms of selectivity and reactivity.[22]
A common factor for most of the examples above is that the
obtained silylated carbohydrate derivative are intermediates and
further investigation of having a silyl incorporated has only been
studied in one case.[22] No one has studied the impact of a silicon,
on glycosylation reactivity and selectivity, when directly attached
to the pyranose.
The lack of studies of C-silylated carbohydrates are striking as
C-Si bond formation has received considerable attention in other
natural product classes, e.g. peptide chemistry, and other areas
of bio- and medicinal chemistry, examples of this are
metalloprotease inhibitors[23] and pseudo-peptides.[24,25]
Results and Discussion
For the synthesis of 4-C-silylated glycosyl donors a broad variety
of methods for introducing silicon has been tested, i.e. addition of
1
This article is protected by copyright. All rights reserved.

10.1002/anie.202009209
Angewandte Chemie International Edition
COMMUNICATION
silyl lithium and metal- and Lewis-acid catalyzed silylation of
double bonds.[12,14,18] However, none of these reactions
successfully provided a satisfactory yield of the C-silylated
products. The breakthrough was the use of an α,β-unsaturated
ketone, D-levoglucosenone 1, as a precursor for the C-silylated
compounds. This compound is commercially available, but also
easily synthesized via thermolytic decomposition of cellulose.[26,27]
We obtained 1 from cellulose, using soybean oil as reaction
medium. The product was isolated in high purity by vacuum
distillation giving a yield of 18 % (Scheme 1).
Nucleophilic addition of silane to 1, using dimethylphenylsilyl
lithium in THF at -78 °C, gave both 1,2- and 1,4-addition in 34 %
and 29 % yield, respectively. Exchanging the lithiated silyl
nucleophile for the softer silylcuprate[28] exclusively yielded the
desired 1,4-addition as a single diastereoisomer 2. The following
reduction of the ketone 2 with L-selectride delivered selectively
With the C-silylated carbohydrate scaffold, the glycosyl donor
synthesis was continued. First, the hydroxyl group was
benzylated to give a fully protected 1,6-anhydro sugar with the
manno-isomer giving a high yield of 90% and the gluco-isomer a
more modest yield of 65%. The 1,6-anhydro bridge was opened
and a thiophenyl ether installed using TMSSPh in combination
with ZnI2 giving the thioglycosides in high yields and with good
α-selectivity; exclusively α for 5a and an anomeric mixture of 5:2
(α/β) for 5b. Finally, the 6-OH were protected by TIPS groups in
high yields, giving the glycosyl donors 6a and 6b on a gram scale.
Even though 3-deoxy-glucoside donor 6b was obtained as
mixture of anomers we evaluated that their reactivity difference
would be negligible. It was demonstrated by Heuckendorff et al.
that there can be reactivity differences between restricted α- and
β-thioglycosides.[31] However, this difference does not influence
the stereochemical outcome of the glycosylation, because the
the hydride to the re-face yielding 3a as the sole product. However, reaction intermediate, glycosyl iodides and triflates, readily
a divergent synthesis strategy was desirable and reduction of 2
with NaBH4 resulted in separable 2:1 mixture of
anomerizes and the initial stereochemical information is lost in the
reaction.[32]
a
diastereoisomers. In this way, we accessed both 3-deoxy-
mannose, 3a and 3-deoxy-glucose, 3b configurated donors.
Starting from ketone 2 the 3-position could be functionalized with
a benzoate ester 28 (not shown), by a protocol developed by
Tomkinson and coworkers.[29,30] An example of a Fleming-Tamao
oxidation was performed on the reduced 4-C-silylated substrate
29 to give allosan 30 (see supporting information, Scheme S1).
For simplicity, we chose to continue with the 3-deoxy structures,
accessing two configurations of C-silylated donors.
To investigate the influence of the silyl group on reactivity and
selectivity in glycosylation reactions, we wished to compare the
equivalent deoxy analogue. This 3,4-di-deoxy glycosyl donor 11
was synthesized from levoglucosenone 1 in five steps (Scheme
3).
Scheme 1. Synthesis of 4-C-silylated carbohydrate derivatives.
Scheme 3. The 3,4-dideoxy donor 11 was successfully synthesized starting
from levoglucosenone 1.
The properties of the three donors were studied by glycosylating
three model glycosyl acceptors. Glucosyl acceptor 12 being more
accessible and reactive, while acceptor 13 with the 4-OH acceptor
site is less nucleophilic (more electron poor[33]
) and less
accessible as studied by Codée and co-workers.[34,35] Acceptor 14
has the 3-OH even more sterically hindered. Three methods of
activation; A, B, and C, were used (details in Table 1)
Scheme 2. Synthesis of 3-deoxy-mannoside 6a and 3-deoxy-glucoside 6b
donors from their respective 1,6-anhydro derivative.
2
This article is protected by copyright. All rights reserved.

10.1002/anie.202009209
Angewandte Chemie International Edition
COMMUNICATION
Figure 1. The three different glucoside-based acceptors allowed for coupling to
three different positions.
secondary acceptors 13 and 14, delivering the disaccharides 17
and 18 in decent yields with good α-selectivity.
The addition of LiOTf also lowered the reaction time between 3-
deoxy-glucoside 6b and primary acceptor 12 (Table 1, entry 5),
however the selectivity in this case had changed compared to
entry 2. Glycosylations with donor 6b and the secondary
acceptors 13 and 14 performed much better under these
conditions, increasing the β-selectivity. Glycosylation of acceptor
12 with the 3,4-dideoxy donor 11 (entry 6) resulted in disaccharide
22 in 88 % yield and high α-selectivity. The secondary acceptors
13 and 14, were successfully glycosylated to give 23 and 24 with
similarly good α-selectivity.
Though LiOTf was a significant improvement and minimized side
reactions under the glycosylation conditions, we investigated the
effects of other Brønsted and Lewis acids. At room temperature
weak Brønsted acids did not affect the outcome of the reactions,
however addition of TfOH resulted in decomposition. Likewise,
TMSOTf also led to some degradation, albeit to a lesser degree.
This indicated that the 4-C-silylated saccharides possessed a
decent Lewis acid stability at ambient temperature, while strong
Brønsted acid degraded them. Whether the positive effect of
LiOTf originated from the weak Lewis acidity of lithium or the
counter ion, triflate is not clear from these results, but triflates are
known to be beneficial for substitution reactions.[36]
A simple model alcohol mimicking a sugar alcohol, 2-methoxy
ethanol, was used to study the reactivity and selectivity of glycosyl
donor 6b to give glycoside 15 (Table 1, entry 1). Immediately after
addition of N-iodosuccinimide (NIS) at ambient temperature, the
characteristic color change was observed, and TLC analysis
showed full conversion of the donor material in less than 5
minutes. Glycosylation of 12 with 6b gave disaccharide 19 in
similar reaction times both in CH2Cl2 and CH3CN (entries 2 and 3).
Activation and glycosylation with only NIS was best for primary
acceptors, such as methoxyethanol and 12. However, couplings
between the sterically demanding acceptors 13 and 14 was low
yielding (see SI and Table S2).
Adding a mild Lewis or Brønsted acid and/or having a non-
participating anion present could improve the reaction outcome in
terms of yield or selectivity by stabilizing glycosylation
intermediates after the activation by NIS. Introducing LiOTf as a
mild Lewis acid (glycosylation method B) improved the outcome
without affecting reaction time. Glycosylation between 3-deoxy-
mannoside donor 6a and 6-OH acceptor 12 gave 16 in 76 % yield
(entry 4), compared to 55 % without the addition of LiOTf. These
conditions also let donor 6a successfully glycosylate both the
Table 1. Reaction results from glycosylation between C-silylated donors and the different carbohydrate acceptors (for full table, see supporting information
Table S2).
Entry
1[e]
Conditions[a]
Donor
Acceptor
Reaction time[b]
Product
Anomeric ratio
Yield
(%)[d]
(α/β)[c]
61 (α)
39 (β)
66
methoxy-
ethanol
A
6b
5 min
15
61:39
19
19
16
19
22
16
17
2
3
4
5
6
7
8
A
A[f]
B
6b
6b
6a
6b
11
6a
6a
12
12
12
12
12
12
13
<9 min
<3 min
<30 sec
<3 min
<3min
6 h
76:24
71:29
93:7
80
76
B
60:40
91:9
72
B
74
C
>95:<5
>95:<5
88
C
3 h
73
54 (α)
27 (β)
79
9[e]
C
6b
13
1.8 h
20
71:29
21
24
10
11
C
C
6b
11
14
14
50 min
35 min
63:37
92:8
81
[a] Glycosylation conditions: A: Acceptor (1.5 equiv.), donor (1.0 equiv.), CH2Cl2, 3Å MS, ambient temperature, then NIS (1.1 equiv.); B: Acceptor (1.5 equiv.),
donor (1.0 equiv.), CH2Cl2, 3Å MS, ambient temperature, LiOTf (15 mol%), then NIS (1.1 equiv.), C: Acceptor (1.5 equiv.), donor (1.0 equiv.), CH2Cl2, 3Å MS, -
78 °C, then NIS (1.1 equiv.) and TMSOTf (10 mol%). [b] Based on color change of the reaction mixture and confirmed by TLC analysis. [c] Based on 1H and 13
NMR of the crude mixture. [d] Isolated yield. [e] The respective anomers were separable. [f] CH3CN as reaction solvent.
C
3
This article is protected by copyright. All rights reserved.

10.1002/anie.202009209
Angewandte Chemie International Edition
COMMUNICATION
Glycosylation of less acid-stabile donors are preferably performed
at low temperature (−78 °C with TMSOTf and NIS as,
glycosylation conditions C, Table 1, entries 7-11).
Glycosylating using 6a under conditions C led to higher yields,
and better selectivity. Coupling primary acceptor 12 gave 88 % of
16 (entry 7) and the secondary acceptors 13 and 14, gave 73 %
of 17 (entry 8) and 66 % of 18 with high anomeric selectivity
(>20:1 α/β). 3-Deoxy-glucoside 6b and the secondary acceptors
13 and 14 (entries 9 and 10) showed similar good yields around
80 % and anomeric selectivity comparable to those observed with
method B. Reactions between 3,4-dideoxy donor 11 and acceptor
12 and 13 were slow, and increasing the temperature to -40 °C
was beneficial. Hence, acceptor 13 gave disaccharide 23 in 41 %,
compared to 23 % (see SI Table S2, entries 28 and 29). Coupling
to 14 was generally found to be faster and gave good yield of
glycoside 24 (Table 1, entry 11). Strikingly, acceptors 12 – 14
showed a reverse tendency of reaction time contradictory to their
expected nucleophilicity.
The anomeric selectivity for donor 6a and 11 in the glycosylation
reactions (Table 1) were primarily influenced by the orientation of
the benzyl ether in the neighboring 2-position in line with the
general observation for α-selectivity of any mannosylations. An
intermediate oxocarbenium ion is expected to mainly adopt a 4H3-
conformation for compound 6a and 11, placing the silyl and the
methylene substituents in sterically more favorable pseudo-
equatorial positions (figure 2). Nucleophilic attack from the “α-side”
on the 4H3-conformation is favored and leads to the lowest energy
transition state, according to Woerpel and co-workers
observations.[37,38]
Figure 2. Suggested equilibria states of different oxocarbenium ions for the
reaction between the three donors and a nucleophile.
Surprised by the small reactivity differences between a silicon
group and hydrogen in the 4-position, a competition experiment
using method C was performed (SI, Figure S4 and S5). This
experiment showed
a
relative reactivity difference of
approximately 1:2.5 between the 3,4-dideoxy donor 11 and 4-silyl
donor 6a. Although smaller than expected it is interesting that the
bulky silyl group in the 4-position – furthest away from the reactive
center – is more activating compared to the 4-deoxy analogue.
The 3-deoxy-glucoside 6b, was found to be α-selective, but to a
lesser degree than in 6a and 11, with their axial 2-benzyloxy
substituent. This suggest that the oxocarbenium also adopt the
4H3-conformation, placing all substituents in a sterically more
favorable pseudo-equatorial position (Figure 2). The
3H4-conformation suffers from a 1,3-diaxial interaction between
2-benzyloxy and 4-silyl. Nucleophilic attack from the α-face leads
Curiously, our less successful attempts to perform the competition
study directly in an NMR-tube at room temperature led us to
discover and determine the major side-product pathway. The 13
C
NMR measurements indicated the characteristics of vinylic
signals around 115 ppm (SI Figure S6), originating from the
rearrangement of the donor and/or products. This was not unlike
vinyl furanoside 25, L-threo-hex-5-enofuranoside[39,40] observed
by glycosylating acceptor 12 directly with 1,6-anhydro compound
4b (Scheme 4). This vinyl furanoside was also the sole isolated
product when 3-deoxy-glucoside donor 6b was activated with
iodine and base. Oddly, when 1,6-anhydro 4b was opened using
TMSOTf instead of ZnI2, two minor side-products, a vinyl
furanoside 26 and the 6,6-bis(phenylthio)hex-2-en-1-ol 27 were
isolated (SI Figure S2). This suggest that the formation of the
double bond goes through a stabilized cation, allowing for
isomerization of this bond into the energetically favored E-
conformation. It also indicates that the glycosylation must occur
prior to the elimination.
4
to a destabilizing 1,2-gauche interaction in the H3-conformation
and attack from the β–face a destabilizing 1,3-diaxial interaction
between the nucleophile and the C5-methyleneoxy. Together with
the observed lower selectivity therefore indicates a near equal
contribution of steric influences in the transition state. Surprisingly,
the bulky silyl group in the 4-position seems not to influence the
glycosylation out-come much.
4
This article is protected by copyright. All rights reserved.

10.1002/anie.202009209
Angewandte Chemie International Edition
COMMUNICATION
[1]
[2]
[3]
[4]
A. Veyrières, Carbohydrates Chem. Biol. 2000, 367–405.
C. H. Marzabadi, R. W. Franck, Tetrahedron 2000, 56, 8385–8417.
I. J. Wilk, J. Chem. Educ. 1957, 34, 463.
W. Kitching, H. A. Olszowy, G. M. Drew, W. Adcock, J. Org. Chem.
1982, 47, 5153–5156.
[5]
[6]
L. H. Sommer, E. Dorfman, G. M. Goldberg, F. C. Whitmore, J. Am.
Chem. Soc. 1946, 68, 488–489.
I. Fleming, R. Henning, D. C. Parker, H. E. Plaut, P. E. J.
Sanderson, J. Chem. Soc. Perkin Trans. 1 1995, 317–337.
G. R. Jones, Y. Landais, Tetrahedron 1996, 52, 7599–7662.
I. Fleming, R. Henning, H. Plaut, J. Chem. Soc. Chem. Commun.
1984, 29–31.
[7]
[8]
Scheme 4. Vinyl furanoside 25 was observed as the major product under some
glycosylation conditions. For the glycosylation reactions of 12 with 1,6-anhydro
donor 4b the following two catalysts were used; BF3·Et2O (0.6 equiv), 87 %
(1:7.3 α/β); TfOH (0.1 equiv), 75 % (1:13 α/β).
[9]
K. Tamao, N. Ishida, M. Kumada, J. Org. Chem. 1983, 48, 2120–
2122.
[10]
[11]
K. Tamao, N. Ishida, T. Tanaka, M. Kumada, Organometallics 1983,
2, 1694–1696.
T. Torigoe, T. Ohmura, M. Suginome, J. Org. Chem. 2017, 82,
2943–2956.
The mechanistic background for the formation of vinyl furanosides
was not investigated in-depth. Nevertheless, our observations
suggest that the β-cationic stabilization from the silyl-group results
in the electrophilic substitution of an unsaturated allylic
silane[5,41,42] through a two-step mechanism related to a 1,2-silyl
migration or 1,3-silyl rearrangement followed by anti-elimination,
not unlike a Peterson-olefination.[13,43,44] This would explain why
inversion of the 4-position was observed. It is noteworthy that the
formation of vinyl furanosides also was observed by Imperio et al.
during their synthesis of 6-boronic acid sugar derivatives.[45] The
similarity in side-product formation reveals a reduced stability of
polyols containing weaker electronegative elements, both in
terms of acid and base lability.
[12]
[13]
[14]
J. J. Pegram, C. B. Anderson, Carbohydr. Res. 1988, 184, 276–278.
V. Pedretti, A. Veyrières, P. Sinaÿ, Tetrahedron 1990, 46, 77–88.
V. Pedretti, J.-M. Mallet, P. Sinaÿ, Carbohydr. Res. 1993, 244, 247–
257.
[15]
P. Smid, F. J. M. Schipper, H. J. G. Broxterman, G. J. P. H. Boons,
G. A. van der Marel, J. H. van Boom, Recl. des Trav. Chim. des
Pays-Bas 1993, 112, 451–456.
[16]
[17]
[18]
[19]
[20]
H. Stpowska, A. Zamojski, Tetrahedron 1999, 55, 5519–5538.
F. P. Boulineau, A. Wei, Org. Lett. 2002, 4, 2281–2283.
Y.-H. Zhu, P. Vogel, Synlett 2001, 2001, 82–86.
Y. Cen, A. A. Sauve, J. Org. Chem. 2009, 74, 5779–5789.
T. G. T. G. Frihed, M. Heuckendorff, C. M. C. M. Pedersen, M. Bols,
Angew. Chemie - Int. Ed. 2012, 51, 12285–12288.
T. G. Frihed, C. M. Pedersen, M. Bols, European J. Org. Chem.
2014, 2014, 7924–7939.
Conclusion
[21]
[22]
[23]
[24]
[25]
[26]
A method for introducing a silyl substituent in the 4-position of a
carbohydrate scaffold has been developed. This mitigated the
synthesis of silylated glycosides, where two thioglycosides were
used as donors to investigate the reactivity and selectivity of this
previously unknown class of carbohydrates. Comparing
glycosylation reactions with these and a 3,4-di-deoxy donor
showed that the 4-C-silylated donors had surprisingly similar
properties in terms of selectivity. Although the relative reactivity
difference was small, it is appreciably different. The introduction
of C-Si bonds increased the donor reactivity outside the current
limits. The silylated glycosides have good shelf-life with little to no
alteration after several months of storage at room temperature.
Yet, under reaction conditions, at room temperature, this
compound class were shown to have a limited tolerance to strong
acids and bases.
I. Álvarez-Martínez, C. M. Pedersen, European J. Org. Chem. 2020,
2020, 4621–4634.
M. wa Mutahi, T. Nittoli, L. Guo, S. M. Sieburth, J. Am. Chem. Soc.
2002, 124, 7363–7375.
J. L. H. Madsen, C. U. Hjørringgaard, B. S. Vad, D. Otzen, T.
Skrydstrup, Chem. – A Eur. J. 2016, 22, 8358–8367.
G. K. Min, D. Hernández, T. Skrydstrup, Acc. Chem. Res. 2013, 46,
457–470.
W. S. Trahanovsky, J. M. Ochaoda, C. Wang, K. D. Revell, K. B.
Arvidson, Y. Wang, H. Zhao, S. Chung, S. Chang, in Carbohydr.
Synthons Nat. Prod. Chem., American Chemical Society, 2002, pp.
2–21.
[27]
[28]
[29]
T. Taniguchi, K. Nakamura, K. Ogasawara, Synlett 1996, 1996,
971–972.
M. Lautens, R. K. Belter, A. J. Lough, J. Org. Chem. 1992, 57, 422–
424.
Acknowledgements
C. S. Beshara, A. Hall, R. L. Jenkins, K. L. Jones, T. C. Jones, N. M.
Killeen, P. H. Taylor, S. P. Thomas, N. C. O. Tomkinson, Org. Lett.
2005, 7, 5729–5732.
The Villum Foundation is acknowledged for a block stipend for
MJP.
[30]
[31]
[32]
A. Hall, K. Jones, T. Jones, N. Killeen, R. Pörzig, P. Taylor, S. Yau,
N. Tomkinson, Synlett 2006, 2006, 3435–3438.
M. Heuckendorff, L. T. Poulsen, C. Hedberg, H. H. Jensen, Org.
Biomol. Chem. 2018, 16, 2277–2288.
Keywords: Silylation • Carbohydrates • Glycosylation •
Reactivity • Selectivity • Levoglucosenone • Functionalization
C. W. Chang, C. H. Wu, M. H. Lin, P. H. Liao, C. C. Chang, H. H.
5
This article is protected by copyright. All rights reserved.

10.1002/anie.202009209
Angewandte Chemie International Edition
COMMUNICATION
Chuang, S. C. Lin, S. Lam, V. P. Verma, C. P. Hsu, C. C. Wang,
Angew. Chemie - Int. Ed. 2019, 58, 16775–16779.
[33]
[34]
P. C. M., O. Jacob, B. A. B., B. Mikael, Chem. – A Eur. J. 2011, 17,
7080–7086.
S. van der Vorm, J. M. A. van Hengst, M. Bakker, H. S. Overkleeft,
G. A. van der Marel, J. D. C. Codée, Angew. Chemie 2018, 130,
8372–8376.
[35]
S. Van der Vorm, T. Hansen, H. S. Overkleeft, G. A. Van der Marel,
J. D. C. Codée, Chem. Sci. 2017, 8, 1867–1875.
B. Dhakal, L. Bohé, D. Crich, J. Org. Chem. 2017, 82, 9263–9269.
C. G. G. Lucero, K. A. A. Woerpel, J. Org. Chem. 2006, 71, 2641–
2647.
[36]
[37]
[38]
[39]
[40]
L. Ayala, C. G. Lucero, J. A. C. Romero, S. A. Tabacco, K. A.
Woerpel, J. Am. Chem. Soc. 2003, 125, 15521–15528.
J. Petrignet, I. Prathap, S. Chandrasekhar, J. S. Yadav, R. Grée,
Angew. Chemie - Int. Ed. 2007, 46, 6297–6300.
E. G. Gioti, T. V Koftis, E. Neokosmidis, E. Vastardi, S. S. Kotoulas,
S. Trakossas, T. Tsatsas, E. E. Anagnostaki, T. D. Panagiotidis, C.
Zacharis, E. P. Tolika, A.-A. Varvogli, T. Andreou, J. K. Gallos,
Tetrahedron 2018, 74, 519–527.
[41]
[42]
[43]
[44]
[45]
F. C. Whitmore, L. H. Sommer, J. Am. Chem. Soc. 1946, 68, 481–
484.
L. H. Sommer, F. C. Whitmore, J. Am. Chem. Soc. 1946, 68, 485–
487.
K. Miura, T. Takahashi, T. Hondo, A. Hosomi, Chirality 2003, 15,
41–52.
K. Miura, T. Hondo, S. Okajima, T. Nakagawa, T. Takahashi, A.
Hosomi, J. Org. Chem. 2002, 67, 6082–6090.
D. Imperio, E. Del Grosso, S. Fallarini, G. Lombardi, L. Panza, Org.
Lett. 2017, 19, 1678–1681.
6
This article is protected by copyright. All rights reserved.

10.1002/anie.202009209
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
Insert graphic for Table of Contents here. ((Please ensure your graphic is in one of following formats))
Two 4-C-silylated glycosyl donors have been synthesized starting from cellulose. This new class of donors showed remarkably
similar selectivity to and modestly more reactivity than their 4-C-deoxy analogue. Allowing for very mild glycosylation reaction
conditions and short reaction times.
7
This article is protected by copyright. All rights reserved.