Order of reactivity of OH/NH groups of glucosamine hydrochloride and N -Acetyl glucosamine toward benzylation using NaH/BnBr in DMF

Article abstract of DOI:10.1080/07328303.2014.907907

The order of reactivity of OH and NH groups of glucosamine hydrochloride (GlcNH₂HCl) and N-acetyl glucosamine (GlcNAc) toward benzylation with NaH/BnBr in DMF was investigated. For GlcNH₂.HCl, benzyl groups were introduced in the order of N-Bn > N-Bn₂ > 1-O-Bn > 6-O-Bn > 4-O-Bn > 3-O-Bn; for GlcNAc, benzyl groups were introduced in the order of 1-O-Bn > 6-O-Bn > 4-O-Bn > 3-O-Bn > N-Bn. A range of partially benzylated 2-N,N′-dibenzyl glucopyranosides and GlcNAc derivatives were obtained in a single step. Taylor & Francis Group, LLC.

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Order of Reactivity of OH/NH Groups of
Glucosamine Hydrochloride and N-Acetyl
Glucosamine Toward Benzylation Using
NaH/BnBr in DMF
Stacy P. Alia & Nigel Kevin Jalsaa
a Department of Chemistry, The University of the West Indies, St.
Augustine, Trinidad and Tobago
Published online: 09 May 2014.
To cite this article: Stacy P. Ali & Nigel Kevin Jalsa (2014) Order of Reactivity of OH/NH Groups of
Glucosamine Hydrochloride and N-Acetyl Glucosamine Toward Benzylation Using NaH/BnBr in DMF,
Journal of Carbohydrate Chemistry, 33:4, 185-196, DOI: 10.1080/07328303.2014.907907
To link to this article: http://dx.doi.org/10.1080/07328303.2014.907907
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Journal of Carbohydrate Chemistry, 33:185–196, 2014
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Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2014.907907
Order of Reactivity of OH/NH
Groups of Glucosamine
Hydrochloride and N-Acetyl
Glucosamine Toward
Benzylation Using
NaH/BnBr in DMF
Stacy P. Ali and Nigel Kevin Jalsa
Department of Chemistry, The University of the West Indies, St. Augustine, Trinidad
and Tobago
The order of reactivity of OH and NH groups of glucosamine hydrochloride
.
(GlcNH2 HCl) and N-acetyl glucosamine (GlcNAc) toward benzylation with NaH/BnBr
.
in DMF was investigated. For GlcNH2 HCl, benzyl groups were introduced in the order
of N-Bn > N-Bn2 > 1-O-Bn > 6-O-Bn > 4-O-Bn > 3-O-Bn; for GlcNAc, benzyl groups
were introduced in the order of 1-O-Bn > 6-O-Bn > 4-O-Bn > 3-O-Bn > N-Bn. A range
of partially benzylated 2-N,Nꢁ-dibenzyl glucopyranosides and GlcNAc derivatives were
obtained in a single step.
Keywords Order of reactivity; Benzylation; Glucosamine hydrochloride; N-Acetyl glu-
cosamine
INTRODUCTION
Benzyl ethers are widely utilized as hydroxyl protecting groups in carbohy-
drate chemistry.[1] They are easily introduced under typical benzylating condi-
tions employing NaH and BnBr in DMF.[2] These conditions are strongly ba-
sic, and hence, base-labile protecting groups are generally not compatible with
such etherification reactions. In a synthetic route, benzyl groups are therefore
usually installed prior to the introduction of esters. Benzylation may also be ef-
fected under mildly basic conditions utilizing Ag2O and BnBr,[3] or under acidic
Received January 7, 2014; accepted March 20, 2014.
Address correspondence to Nigel Kevin Jalsa, Department of Chemistry, The University
of the West Indies, St. Augustine, Trinidad and Tobago. E-mail: nigel.jalsa@sta.uwi.edu
185

S. P. Ali and N. K. Jalsa
186
conditions, requiring a mixture of benzyl trichloroacetimidate (BnTCA) and tri-
flic acid (TfOH).[4] Regioselective benzylation may also be facilitated with the
use of stannylene acetals in moderate to good yields.[5,6]
Benzyl ethers can be easily removed in the presence of other com-
mon functionalities by hydrogenolysis, whether globally deprotected by di-
rect hydrogenation (H2/Pd/C, often in the presence of an acid)[7] or regioselec-
tively deprotected by catalytic transfer hydrogenation (NH4HCO2/Pd/Al2O3,
methanol).[8–10] They can also be cleaved under oxidative conditions[11,12] and
by various Lewis acids.[13,14] Unlike other common protections such as acyl or
silyl groups, which have a tendency to change their position on the carbohy-
drate ring under acidic[15] or basic[16,17] conditions, benzyl ethers are generally
stable to protecting group manipulations and therefore do not undergo this
migration process.
In this study, benzylations of the monosaccharides glucosamine hydrochlo-
.
ride (GlcNH2 HCl) and N-acetyl glucosamine (GlcNAc) were performed. These
sugars belong to the class of 2-amino-2-deoxy glucopyranoses, which are im-
portant constituents of glycoproteins,[18] glycolipids,[19] and glycosaminogly-
cans.[20] The most abundant of its class is GlcNAc, which is present in 1,2-
trans-glycosidic linkages in the pentasaccharide core of N-linked glycoproteins.
Though existing ubiquitously in nature, the synthesis of this β-(1-4) glycosidic
linkage is often very challenging for two reasons, both of which encompass the
fact that the 2-N center is functionalized with an acetyl group. If a suitably
protected GlcNAc derivative is used as a glycosyl donor, the formation of a
stable oxazolinium ion is inevitable.[21] This intermediate resists incoming nu-
cleophilic attack and is hence ineffective in glycosylation. If an appropriately
protected GlcNAc derivative is used as a glycosyl acceptor, it is relatively un-
reactive at the 4-OH position. This lack of reactivity is due to a combination of
steric hindrance, common to most pyranose 4-OH’s,[22] and the intramolecular
hydrogen-bonded network between the 2-N-Ac and the OH groups present.[23]
This increased steric bulk around the 4-OH reaction center hinders its nu-
cleophilicity, making GlcNAc a poor glycosyl acceptor at this position. It is
these two factors that make the synthesis of this linkage usually very diffi-
cult. Despite numerous accomplishments in synthesizing the β-(1-4) glycosidic
bond,[24–29] it still lacks a universally accepted approach. As such, non-acetate
protecting groups for the 2-amino functionality are of interest.[30] These should
possess the attributes of imparting stereoselective control, adequate reactivity,
high yields, and stability to further synthetic manipulations of the molecule
and must be easily removed under mild conditions. One example of a 2-amino
protection that offers these advantages is the 2-N,N’-dibenzylamino group in-
troduced by Hindsgaul and Jiao.[31] However, the effectiveness of this 2-N pro-
tecting group was examined in a galactosamine donor, not glucosamine. As
part of our ongoing efforts to develop a 2-N,N’-dibenzylamino glucosamine
donor system, we sought improved syntheses for such suitably functionalized
derivatives.

Reactivity Order Toward Benzylation
187
It is with this intention that we investigated the reactivity of OH and
.
NH groups of GlcNH2 HCl and GlcNAc under the benzylating conditions of
NaH/BnBr in DMF. Based on these relative reactivities, the orders of ben-
zyl group installation were determined, and consequently we have identified a
facile route for the synthesis of partially benzylated sugars via a single step.
To the best of our knowledge, this article is the first to report on the order of
functional group reactivity of these amino sugars.
RESULTS AND DISCUSSION
.
A series of benzylations were performed with GlcNH2 HCl and GlcNAc by grad-
ually increasing the ratio of NaH:BnBr equivalents. For all experimental pro-
tocols, after the removal of DMF from the benzylation step, immediate acetyla-
tion using pyridine and acetic anhydride was performed. This was done to ac-
count for the unreacted starting material that would have been preferentially
partitioned into the aqueous phase, and also to overcome difficulties associated
with purification by column chromatography of the partially protected sugars.
Benzylation of Glucosamine Hydrochloride
Table 1 shows that better yields were generally obtained when an extra
equivalent of NaH was used, compared to that of BnBr, to neutralize HCl
during the benzylation of glucosamine hydrochloride. Furthermore, the ma-
jor compounds produced by using these equivalents of NaH:BnBr (entries 1, 3,
5, 7, 9, and 11) gave the only discernible trend for the order of reactivity of the
.
OH and NH groups of GlcNH2 HCl.
As observed from the 2:1 equivalents of NaH:BnBr, the highest-yielding
compound obtained was acetyl 2-acetamido-2-N-benzyl-3,4,6-tri-O-acetyl-2-
deoxy-α-D-glucopyranoside (4); one benzyl group was installed at the 2-N posi-
tion. This compound appeared as rotamers, which was verified by a varying-
1
temperature NMR study that detected the H NMR chemical shifts of four
isomeric compounds. The 3:2 equivalents of NaH:BnBr yielded the major prod-
uct as acetyl 2-N,Nꢁ-di-benzyl-3,4,6-tri-O-acetyl-2-deoxy-α,β-D-glucopyranoside
(3); both benzyl groups were introduced at the 2-N center. Garegg and Das-
gupta obtained a small quantity of this compound in their synthesis of the
2-azido derivative.[32] It was expected that the anomeric OH would have ini-
tially reacted in preference to the NH, owing to the former’s greater acidity.[33]
However, the results suggest that the NH group was more reactive than the
.
anomeric OH of GlcNH2 HCl. A possible explanation for this can be due to the
lower electronegativity of nitrogen (compared to oxygen), allowing the more
nucleophilic NH to be benzylated in preference to the anomeric OH.
The major product obtained with the 4:3 equivalents of NaH:BnBr was
benzyl 2-N,N’-di-benzyl-3,4,6-tri-O-acetyl-2-deoxy-α,β-D-glucopyranoside (6);
three benzyl groups were installed, two at the 2-N center and the other at the

S. P. Ali and N. K. Jalsa
188
Table 1: Regioselective benzylation of GlcNH2.HCl (1) under varying equivalents of
NaH:BnBr
Entry NaH:BnBr equivalents used
Products
Yield [%]a
22
α:βb
1
2:1
1:2
3
4
33
30
α only
1:0.2
5
3
4
5
3
4
5
3
4
5
3
4
5
2
3
4
5
2:2
3:2
3:3
4:3
37
11
17
62
24
2
1:2
α only
1:0.2
1:2
1:0.5
1:0.1
1:2
56
15
10
26
12
1
1:0.3
1:0.2
1:1
α only
1:0.1
1:5
49
6
3
5
6
6
4:4
48
5
22
14
1:1
1:0.2
1:5
1:0.3
7
(Continued on next page)

Reactivity Order Toward Benzylation
189
Table 1: Regioselective benzylation of GlcNH2.HCl (1) under varying equivalents of
NaH:BnBr (Continued)
-
Entry NaH:BnBr equivalents used
Products
Yield [%]a
α:βb
7
5:4
3
5
7
18
11
4
1:2
1.0.2
1:0.3
1:2.5
35
8
0.8
β only
9
3
6
7
5
6
9
3
6
8c
9
5:5
6:5
6:6
6
60
19
7
1:3
1:4
1:0.35
1:0.2
1:4
32
44
5
1:3
10c
1:1
49
9
1:4
1:2
10
5
11
7:6
3
25
6
1:0.1
1:6
6
9
10
1:2
45
1:2
aYields were determined from chromatographically pure compounds.
bThe α:β ratio was calculated from the 1H NMR spectra of the purified product.
cComplex mixture of compounds was obtained in a small quantity for these entries.
anomeric position. The anomeric center reacted after the nitrogen, suggest-
ing that it is the most reactive of the OH groups under these conditions. The
5:4 equivalents of NaH:BnBr afforded benzyl 2-N,N’-di-benzyl-3,4-di-O-acetyl-
6-O-benzyl-2-deoxy-α,β-D-glucopyranoside (8) in the highest yield; four benzyl
groups were introduced, two at the 2-N center and one each at the anomeric

S. P. Ali and N. K. Jalsa
190
and 6-OH positions. This was expected since a primary hydroxyl is more reac-
tive than a secondary hydroxyl and therefore would react preferentially to the
3-OH and 4-OH groups.
The 6:5 equivalents of NaH:BnBr produced benzyl 2-N,N’-di-benzyl-3-
O-acetyl-4,6-di-O-benzyl-2-deoxy-α,β-D-glucopyranoside (9) as the major com-
pound; five benzyl groups were installed, two at the 2-N position and three at
the 1-OH, 6-OH, and 4-OH. The 4-OH site was the more reactive of the two sec-
ondary hydroxyl groups remaining. We postulate that the 4-OH is more steri-
cally accessible than the 3-OH; since the 3-OH group is adjacent to the 2-NBn2
center, steric factors hindered the 3-OH from reacting in preference to the 4-
OH. The reaction using 7:6 equivalents of NaH:BnBr afforded benzyl 2-N,N’-di-
benzyl-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranoside (10) as the main prod-
uct in a 45% yield. Ye and coworkers synthesized this compound as a precursor
for glucosamine-6-phosphate analogs in 89% starting from D-glucosamine.[34]
Their excellent yield was attributed to the portionwise additions of a total of
10 equivalents of NaH and a total of 7.4 equivalents of BnBr over a 3-h period.
For the majority of reactions performed, per-O-acetylated GlcNAc (5) was
obtained, which accounted for the unreacted starting material from the benzy-
lation step. For each entry, all benzylations proceeded in a total yield ranging
from 50% to 89%. From these results, the order of reactivity of NH and OH
groups of GlcNH2.HCl can be deduced as N-Bn > N-Bn2 > 1-O-Bn > 6-O-Bn
> 4-O-Bn > 3-O-Bn.
Benzylation of N-Acetyl Glucosamine
As shown in Table 2, better overall yields were obtained with an ex-
cess equivalent of BnBr in the benzylation of N-acetyl glucosamine; hence,
NaH:BnBr in these ratios (entries 2, 4, 6, 8, and 10) were considered in
determining the order of benzyl group installation for GlcNAc. The major
compounds produced for these entries were acetyl 2-acetamido-3,4,6-tri-O-
acetyl-2-deoxy-α,β-D-glucopyranoside (5, entry 2), benzyl 2-acetamido-3,4,6-
tri-O-acetyl-2-deoxy-α,β-D-glucopyranoside (11, entries 4, 6, 8), and benzyl
2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-α,β-D-glucopyranoside (15, entry 10).
From these results, the order of reactivity for GlcNAc was not identifiable.
However, the minor compounds produced by these equivalents of NaH:BnBr
gave the apparent trend in the order of reactivity of the NH and OH groups. It
should be noted that for any entry with more than one minor compound, the
highest yielding compound was used for the determination of the trend.
Benzyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside (11)
was obtained with the 1:2 equivalents of NaH:BnBr (entry 2) in a yield of
32%; one benzyl group was installed at the anomeric position. Therefore, un-
.
like GlcNH2 HCl, the anomeric OH of GlcNAc is more reactive than the 2-NH.
Crasto and Jones synthesized this compound in an overall yield of 75% in a

Reactivity Order Toward Benzylation
191
Table 2: Regioselective benzylation of GlcNAc (2) under varying equivalents of
NaH:BnBr
Entry NaH:BnBr equivalents used
Products
Yield [%]a α:βb
1
1:1
43
1 : 0.2
5
13
1 : 0.1
11
5
2
3
1:2
2:2
52
32
7
31
6
1 : 0.2
β only
1 : 0.2
β only
1:3
11
5
11
12
4
1:1
13
5
4
5
2:3
3:3
9
48
4
1 : 0.2
β only
1:2
11
12
21
β only
14
5
11
14
13
32
15
1 : 0.1
β only
β only
(Continued on next page)

S. P. Ali and N. K. Jalsa
192
Table 2: Regioselective benzylation of GlcNAc (2) under varying equivalents of
NaH:BnBr (Continued)
Entry NaH:BnBr equivalents used
Products
Yield [%]a α:βb
2
β only
15
5
6
3:4
7
1 : 0.2
β only
1:3
β only
β only
β only
β only
1 : 0.2
β only
1:2
11
12
14
15
11
15
5
25
23
18
5
7c
8
4:4
4:5
44
23
12
26
14
19
12
7
26
5
14
35
15
11
13
15
11
14
15
5
β only
β only
β only
1:5
9c
5:5
5:6
10
1 : 0.2
1:5
14
15
1:3
β only
16
aYields were isolated from chromatographically pure compounds.
bThe α:β ratio was calculated from the 1H NMR spectra of the purified product.
cComplex mixture of compounds was obtained in a small quantity for these entries.
two-step process, by initially per-acetylating GlcNAc for its subsequent use as
a glycosyl donor and refluxing in CH2Cl2 for 22 h with BnOH as the acceptor
and Yb(OTf)3 as the catalyst.[35]
The 2:3 equivalents of NaH:BnBr (entry 4) produced benzyl 2-acetamido-
3,4-di-O-acetyl-6-O-benzyl-2-deoxy-β-D-glucopyranoside (14) in 21% yield; two
benzyl groups were installed, one at the anomeric center and the other at the
.
primary hydroxyl position. As observed with GlcNH2 HCl, the 6-OH reacted
after the anomeric OH. The 3:4 equivalents of NaH:BnBr (entry 6) produced

Reactivity Order Toward Benzylation
193
benzyl 2-acetamido-3-O-acetyl-4,6-di-O-benzyl-2-deoxy-α,β-D-glucopyranoside
(12) in 23% yield; three benzyl groups were installed at the 1-OH, 6-OH, and 4-
OH positions. The reaction of the 4-OH group after the primary OH was due to
electronic factors. First, being adjacent to the 6-OBn allowed for an increased
nucleophilicity of the 4-OH due to the inductive effect. Second, the deactivation
of the 3-OH group because of its close proximity to the electron-withdrawing
N-Ac group would result in the 3-OH being less prone to benzylation.
The reaction using 4:5 equivalents of NaH:BnBr (entry 8) afforded benzyl
2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranoside (15) in 19% yield.
.
The 3-OH was the last of the hydroxyl groups to react. As with GlcNH2 HCl,
the adjacent 4-OBn enhanced the reactivity of the 3-OH. This compound
was previously synthesized by Harrison and Fletcher in 76% yield by benzy-
lating GlcNAc using BaO/Ba(OH)2.8H2O in DMF.[36] The 5:6 equivalents of
NaH:BnBr (entry 10) gave benzyl 2-acetamido-2-N-benzyl-3,4,6-tri-O-benzyl-
.
2-deoxy-β-D-glucopyranoside (16) in 15% yield. Unlike GlcNH2 HCl, the NH
of GlcNAc is less reactive than the OH groups. The presence of the electron-
withdrawing 2-N-acetyl group strongly reduces the nucleophilicity at the ni-
trogen atom, thus hindering benzylation from occurring at this position. Sim-
ilar to 4, compound 16 was also a rotameric mixture that was detected with
low-temperature NMR studies.
We also report a novel furanoside form for GlcNAc (13) produced in 4%
yield, with a benzyl group at its anomeric center. Fletcher and Inch previously
obtained the furanoside form of GlcNAc analogous to this derivative, but with
a benzoyl group at the anomeric center.[37] They achieved this from the rear-
rangement of 2-N-acetylbenzamido-2-deoxy-D-glucopyranose.
.
As with GlcNH2 HCl, compound 5 was also produced from the reactions
with GlcNAc. All benzylations proceeded in a total yield ranging from 30% to
71%. It should be noted that the overall yields for these reactions were signif-
.
icantly lower than those for GlcNH2 HCl, which indicates that the presence of
the acetyl group of GlcNAc has a considerable effect on its reactivity. Based
on the results, the order of reactivity of GlcNAc toward benzylation can be
deduced as 1-O-Bn > 6-O-Bn > 4-O-Bn > 3-O-Bn > N-Bn.
CONCLUSION
We have investigated the order of reactivity of OH and NH groups of
.
GlcNH2 HCl and GlcNAc toward benzylation using NaH/BnBr in DMF. The
.
NH2 group of GlcNH2 HCl was more reactive than all of the OH groups,
whereas for GlcNAc, the OH groups were more reactive than the NHAc group.
For both monosaccharides, the order of reactivity obtained for the hydroxyl
groups was identical, with the anomeric center being the most reactive, fol-
lowed by the primary OH and then the secondary hydroxyls, with the 3-OH

S. P. Ali and N. K. Jalsa
194
being the least reactive hydroxyl group. Such knowledge of the orders of re-
activity allows for a direct and facile route to the synthesis of novel partially
benzylated glucosamine and GlcNAc derivatives. Work is currently under way
for the investigation of these 2-N,N’-dibenzylamino glucopyranose derivatives
as glycosyl donors.
EXPERIMENTAL
For Table 1, reactions of entries 1–5 were performed on a 5-g scale GlcNH2.HCl
and all other reactions for both Tables 1 and 2 were carried out on a 2-g
scale.
.
GlcNH2 HCl or GlcNAc was dissolved in anhydrous DMF (100 mL for 5-
g scale and 60 mL for 2-g scale) under an inert atmosphere and stirred for
15 min. After this the reaction vessel was cooled to 0◦C and the required molar
equivalence of NaH was then slowly added. The reaction mixture was main-
tained at this temperature for an hour, after which the necessary molar equiv-
alence of BnBr was then added and allowed to warm to rt. The reaction was
monitored via TLC (EtOAc) then left overnight to ensure completion. It was
quenched with methanol (10 mL for 5-g scale and 5 mL for 2-g scale) and the
DMF was then removed under high vacuum. The crude residue was then dis-
solved in pyridine (Table 1: 100 mL for entry 1; 80 mL for entries 2, 3, and
4; 60 mL for entries 5–13; Table 2: 25 mL for entries 1–4; 20 mL for entries
5–12), followed by the addition of acetic anhydride (Table 1: 80 mL for entry
1; 60 mL for entries 2, 3, and 4; 45 mL for entries 5–13; Table 2: 20 mL for
entries 1–4; 15 mL for entries 5–12). The reaction was monitored via TLC (Pet
Ether:EtOAc, 1:1) and left overnight. Solvents were then removed under high
vacuum and the crude product was dissolved in CH2Cl2 (150 mL), washed with
2M HCl (3 × 100 mL), then washed with water (3 × 100 mL). The organic phase
was dried using anhydrous Na2SO4 and concentrated under reduced pressure.
The crude residue was then subjected to column chromatography for purifica-
tion.
ACKNOWLEDGMENTS
We are grateful to Mr. Franklyn Julien for the provision of high-resolution
mass spectral data; and many thanks to Mr. Keegan Dial and Dr. Nadia
Beepath-Singh for the provision of NMR spectroscopy data.
FUNDING
This work was supported by the University of the West Indies.

Reactivity Order Toward Benzylation
195
REFERENCES
1. Greene, T.W.; Wuts, P.G., Eds. Protective Groups in Organic Synthesis. Wiley-
Interscience, Hoboken, NJ: 2007, pp. 102–120.
2. Brimacombe, J.S. Methods in Carbohydrate Chemistry, R.L. Whistler and J.N. Be-
miller, Eds. Academic Press: New York and London, 1972, pp. 376–378.
3. Bouzide, A.; Sauve´, G. Highly selective silver (I) oxide mediated monoprotection of
symmetrical diols. Tetrahedron Lett. 1997, 38, 5945–5948.
4. Iversen, T.; Bundle, D. Benzyl trichloroacetimidate, a versatile reagent for acid-
catalysed benzylation of hydroxyl-groups. J. Chem. Soc. Chem. Comm. 1981, 23,
1240–1241.
5. Giordano, M.; Iadonisi, A. Tin-mediated regioselective benzylation and allylation
of polyols: applicability of a catalytic approach under solvent-free conditions. J. Org.
Chem. 2014, 79, 213–222.
6. Bieg, T.; Szeja, W.; Kral., K.; Paszkowska, J.; Wandzik, I. Microwave-assisted re-
gioselective benzylation: an access to glycal derivatives with a free hydroxyl group at
C4. J. Carb. Chem. 2012, 31, 593–601.
7. Mandal, P.K.; McMurray, J.S. Pd-C-Induced catalytic transfer hydrogenation with
triethylsilane. J. Org. Chem. 2007, 72, 6599–6601.
8. Bieg, T.; Szeja, W. Removal of O-benzyl protective groups by catalytic transfer
hydrogenation. Synthesis 1985, 76–77.
9. Jalsa, N.K. Regioselective removal of the anomeric O-benzyl from differentially
protected carbohydrates. Tetrahedron Lett. 2011, 52, 6587–6590.
10. Ram, S.; Ehrenkaufer, R.E. Ammonium formate in organic synthesis – a versatile
agent in catalytic hydrogen transfer reactions. Synthesis 1988, 91–95.
11. Rahim, M.A.; Matsumura, S.; Toshima, K. Deprotection of benzyl ethers using 2,3-
dichloro-5,6-dicyano-p-benzoquinone (DDQ) under photoirradiation. Tetrahedron Lett.
2005, 46, 7307–7309.
12. Pradhan, P.P.; Bobbitt, J.M.; Bailey, W.F. Oxidative cleavage of benzylic and re-
lated ethers using an oxoammonium salt. J. Org. Chem. 2009, 74, 9524–9527.
13. Hori, H.; Nishida, Y.; Ohrui, H.; Meguro, H. Regioselective de-O-benzylation with
Lewis acids. J. Org. Chem. 1989, 54, 1346–1353.
14. Pastore, A.; Valerio, S.; Adinolfi, M.; Iadonisi, A. An easy and versatile approach
for the reioselective de-O-benzylation of protected sugars based on the I2/Et3SiH com-
bined system. Chem. Eur. J. 2011, 17, 5881–5889.
15. Haines, A.H. Relative reactivities of hydroxyl groups in carbohydrates. Adv. Car-
bohydr. Chem. Biochem. 1976, 33, 11–109.
16. Mulzer, J.; Schollhorn, B. Multiple 1,2-O,O-shift of tert-butyldiphenylsilyl groups
in polyols. Angew. Chem. Int. Ed. 1990, 29, 431–432.
17. Arias-Perez, M.S.; Lopez, M.S.; Santos, M.J. Imidazole-promoted 1,4-migration of
the tert-butyldiphenysilyl group: influence on the selectivity control of the silylation
reactions of crbohydrate OH groups. J. Chem. Soc. Perkin Trans 2. 2002, 9, 1549–1552.
18. Schmidt, R.R.; Kinzy, W. Anomeric-oxygen activation for glycoside synthesis: the
trichloroacetimidate method. Adv. Carbohydr. Chem. Biochem. 1994, 50, 21–123.
19. Garg, H.G.; Von dem Bruch, K.; Kunz, H. Developments in the synthesis of gly-
copeptides containing glycosyl L-asparagine, L-serine, and L-threonine. Adv. Carbo-
hydr. Chem. Biochem. 1994, 50, 277–310.

S. P. Ali and N. K. Jalsa
196
20. Umezawa, S. Structures and synthesis of aminoglycoside antibiotics. Adv. Carbo-
hydr. Chem. Biochem. 1974, 30, 111–182.
21. Fairweather, J.K.; Stick, R.V.; Tilbrook, D.M.G. The asymmetric dihydroxylation of
some alkenyl 2-acetylamino-2-deoxy-β-D-glucopyranosides: the preparation of optically
pure epoxides as putative inhibitors of chitinases. Aust. J. Chem. 1998, 51, 471–482.
22. Paulsen, H. Advances in selective chemical syntheses of complex oligosaccharides.
Angew. Chem. Int. Ed. 1982, 21, 155–173.
23. Crich, D.; Dudkin, V. Why are the hydroxyl groups of partially protected N-
acetylglucosamine derivatives such poor glycosyl acceptors and what can be done
about it? A comparative study of the reactivity of N-acetyl-, N-phthalimido- and 2-
azido-2-deoxy-glucosamine derivatives in glycosylation. 2-Picolinyl ethers as reactivity-
enhancing replacements for benzyl ethers. J. Am. Chem. Soc. 2001, 123, 6819–6825.
24. Chang, K.-L.; Zuleta, M.M.L.; Lu, X.-A.; Zhong, Y.-Q.; Hung, S.-C. Regioselective
one-pot protection of D-glucosamine. J. Org. Chem. 2010, 75, 7424–7427.
25. Emmadi, M.; Kulkarni, S.S. Rapid transformation of D-mannose into orthogonally
protected D-glucosamine and D-galactosamine thioglycosides. J. Org. Chem. 2011, 76,
4703–4709.
26. Hernandez-Torres, J.M.; Liew, S.-T.; Achkar, J.; Wei, A. Optimised synthesis of an
orthogonally protected glucosamine. Synthesis 2002, 4, 487–490.
27. Cipolla, L.; Lay, L.; Nicotra, F. New and easy access to C-glycosides of glucosamine
and mannosamine. J. Org. Chem. 1997, 62, 6678–6681.
28. Bongat, A.F.G.; Demchenko, A.V. Recent trends in the synthesis of O-glycosides of
2-amino-2-deoxysugars. Carb. Res. 2007, 342, 374–406.
29. Banoub, J.; Boullanger, P.; Lafont, D. Synthesis of oligosaccharides of 2-amino-2-
deoxy sugars. Chem. Rev. 1992, 92, 1167–1195.
30. Debenham, J.; Rodebaugh, R.; Fraser-Reid, B. Recent advances in N-protection for
amino sugar synthesis. Liebigs Ann./Recueil 1997, 5, 791–802.
31. Jiao, H.; Hindsgaul, O. The 2-N,N-dibenylamino group as a participating group in
the synthesis of β-glycosides. Angew. Chem. Int. Ed. 1999, 38, 346–348.
32. Garegg, P.; Dasgupta, F. 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-β-D-glucopyranose
from D-glucosamine. J. Chem. Soc. Chem. Comm. 1989, 21, 1640–1641.
33. Sinnott, M.L., Ed. Carbohydrate Chemistry and Biochemistry. Cambridge, UK:
RSC Publishing, 2007, pp. 432–433.
34. Ye, X.-S.; Li, Y.; Lau, P.S.; Wang, G.-N. Synthesis and evaluation of glucosamine-
6-phosphate analogues as activators of glmS riboswitch. Tetrahedron 2012, 68,
9405–9412.
35. Crasto, C.F.; Jones, G.B. A practical method for preparation of β-glycosides of N-
acetylglucosamine. Tetrahedron Lett. 2004, 45, 4891–4894.
36. Harrison, R.; Fletcher, H.G. Syntheses with partially benzylated sugars. IV. A
rote to some 1-O-acyl-2-acylamido-2-deoxy-D-glucopyranoses and -D-galactopyranoses.
J. Org. Chem. 1965, 30, 2317–2321.
37. Inch, T.D.; Fletcher, H.G. N-acyl derivatives of 2-acylamino-2-deoxyhexoses. The
rearrangement of 2-(N-acetylbenzamido)-2-deoxy-D-glucose. J. Org. Chem. 1966, 31,
1821–1825.