An eco-friendly tandem tosylation/Ferrier N-glycosylation of amines catalyzed by Er(OTf)3 in 2-MeTHF

Article abstract of DOI:10.1016/j.tetlet.2017.03.047

Er(OTf)₃ in 2-MeTHF provides a new and eco-friendly process for Ferrier glycosylation of sulfonamides and amino acids with various N-nucleophiles. The stereoselective synthesis of 2,3-unsaturated-N-pseudoglycals was carried out with 3,4,6-tri-O-acetyl-D-glucal and different nucleophiles affording good results in a short time.

Full text of DOI:10.1016/j.tetlet.2017.03.047

Accepted Manuscript
An eco-friendly tandem tosylation/Ferrier N-glycosylation of amines catalyzed
by Er(OTf) in 2-MeTHF
3
Monica Nardi, Natividad Herrera Cano, Antonio De Nino, Maria Luisa Di Gioia,
Loredana Maiuolo, Manuela Oliverio, Ana Santiago, Diletta Sorrentino,
Antonio Procopio
PII:
S0040-4039(17)30349-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.03.047
TETL 48748
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
20 January 2017
9 March 2017
13 March 2017
Please cite this article as: Nardi, M., Cano, N.H., De Nino, A., Di Gioia, M.L., Maiuolo, L., Oliverio, M., Santiago,
A., Sorrentino, D., Procopio, A., An eco-friendly tandem tosylation/Ferrier N-glycosylation of amines catalyzed by
Er(OTf) in 2-MeTHF, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.03.047
3
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Graphical Abstract
An eco-friendly tandem tosylation/Ferrier N-
glycosylation of amines catalyzed by
Leave this area blank for abstract info.
3
Er(OTf) in 2-MeTHF.
Monica Nardi, Natividad Herrera Cano, Antonio De Nino, Maria Luisa Di Gioia, Loredana Maiuolo, Manuela
Oliverio, Ana Santiago, Diletta Sorrentino and Antonio Procopio
O
O
O
O
O
O
O
O
NH2
O
O
O
Cl
S
O
O
O
S
N
O
O
O
O
O
O
O
O
S
O
NH
O

1
Tetrahedron Letters
journal homepage: www.els evier.com
An eco-friendly tandem tosylation/Ferrier N-glycosylation of amines catalyzed by
Er(OTf) in 2-MeTHF.
3
a,b
c
a
Monica Nardi,* Natividad Herrera Cano, Antonio De Nino, Maria Luisa Di Gioia, Loredana
d
a
Maiuolo, Manuela Oliverio, Ana Santiago, Diletta Sorrentino and Antonio Procopio
e
c
a
e
a
Dipartimento di Chimica, Università della Calabria, Cubo 12C, 87036, Arcavacata di Rende (CS), Italy
b
Dipartimento di Agraria, Università Telematica San Raffaele, Via di Val Cannuta, 00166,247, Rome, Italy
c
INFIQC, Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, 5000,
Córdoba, Argentina
d
Dipartimento di Farmacia e Scienze della Salute e della Nutrizione, Università della Calabria, Arcavacata di Rende (CS), 87036, Italy
Dipartimento di Scienze della Salute, Università Magna Graecia, Viale Europa, 88100, Germaneto (CZ), Italia.
e
ARTICLE INFO
ABSTRACT
Article history:
Received
3
Er(OTf) in 2-MeTHF provides a new and eco-friendly process for Ferrier glycosylation of
sulfonamides and amino acids with various N-nucleophiles.
The stereoselective synthesis of 2,3-unsaturated-N-pseudoglycals was carried out with 3,4,6-
tri-O-acetyl-D-glucal and different nucleophiles affording good results in a short time.
Received in revised form
Accepted
Available online
Keywords:
2
009 Elsevier Ltd. All rights reserved.
2
-MeTHF
Glycosydation
Green chemistry
Sulfonamidoglycosides.
1
. Introduction
Sulfonamides continue playing an important role in
On the other hand, the classical method for the synthesis of
sulfonamides involves the nucleophilic attack of amines to
sulfonyl chlorides in the presence of bases or other catalysts in
chemotherapy despite their discontinued use as antibiotics. It is
known that several sulfonamides inhibit the carbonic anhydrase
enzyme and are also used as diuretics, antiepileptics or used to
7
,8
organic solvents at high temperature and pressure.
Furthermore the subsequent N-alkylation of sulfonamides
1-3
reduce intraocular pressure in the treatment of glaucoma.
Other sulfonamides such as E7010, E7070, ER-67865 and ER-
9
-11
requires the use of strong reaction conditions.
The
4
,5
6
8487 show anticancer properties
(Figure 1) whereas some
sulfonamidoglycosides show antiproliferative action against
environmental pollution caused by the use of non-green
solvents and catalysts as well as tedious work-up makes these
1
2
6
methods inappropriate for the synthesis of azaglycosides.
human hepatocellular carcinoma.
The synthesis of 2,3-unsaturated glycosides has become of
great interest and importance since they are basic building
blocks for the production of molecules with biological activity.
One of these methods is the Ferrier reaction, which involves an
acid catalysis in the presence of nucleophiles (OH-, S-, etc).
1
3,14
Nitrogen nucleophiles have not been extensively used in
the Ferrier rearrangement, azide being the typical nucleophile
1
5-18
used to afford N-pseudoglycals.
However, several protocols have been developed for the
1
9
synthesis of N-pseudoglycals with sulfonamides, carbamates,
amides and azides from 3,4,6-tri-O-acetyl-D-glucal using
Figure 1. Sulfonamide use as Antitumor Agent

2
Tetrahedron
1
9
20
boron trifluoride etherate Amberlyst 15, ZnCl
21
2
/Al
2
O ,
3
2. Results and Discussion
2
ruthenium trichloride, iodine catalysis and Mitsunobu
2
23
2
4
Very recently, we developed a new aqueous MW-assisted
protocol for the rapid and efficient N-protection of amino acids
and amines using carbonate and sulfonyl chlorides as
reaction conditions.
We previously studied the synthesis of O-, C-, N- and S-
glycal derivatives, describing a highly efficient and simple
procedure for the synthesis of O- and S-alkyl and aryl 2,3-
5
1
protecting groups.
This sustainable protection method has stimulated the
development of a synthetic way for the synthesis of 2,3-
unsaturated-N-pseudoglycals. Thus, we investigated the Ferrier
azaglycosylation reaction for providing 2,3-unsaturated-N-
pseudoglycals using the N-protected amines obtained according
to our previous protocol (Scheme 1).
unsaturated
glycosides
using
trifluoromethanesulfonate as a Lewis acid catalyst.
erbium(III)
5-27
Erbium
2
(III) is a water-tolerant Lewis acid, used as catalyst for the
29
synthesis of Acetonides and ring opening of epoxides.
2
8
We have successfully applied microwave heating to the
addition of different organic moieties on the surface of the
mesoporous silica to obtain a new hybrid mesoporous silica–
O
O
H
Cl
conditions
solvent
N
S
S
R
+
R NH2
O
O
3
0
supported Er III catalyst. This catalyst has proved to be very
efficient in a series of frequent organic reactions such as the C-
1
.2 eq.
1 eq.
3
C bond formation, protection and de-protection of alcohols
1
32
OAc
3
3
and carbonyl compounds, the synthesis of benzodiazepines
3
and trans-4,5-diaminocyclopent-2-enones.
O
1
eq.
4,35
36
AcO
O
N S
O
2
R
1
OAc
In the last decade, some considerable interest has developed
around the innovative synthetic protocols in organic synthesis
AcO6
O
5
AcO
3
7,38
adopting a more eco-sustainable approach.
Based on these results and in view of the numerous
4
3
3
9,40
Scheme 1: One-pot synthesis of azaglycosilated sulfonamides.
biological properties of glycosides,
we proposed the
development of a low-cost environmentally friendly procedure
for N-glycosylation of tri-O-acetyl-D-glucal with different N-
nucleophiles employing 2-MeTHF as solvent.
The same method was extended to the synthesis of L-amino
acid-glycosides
and
N-tosyl-L-amino
acid-glycosides,
According to Anastas and Warner's 12 Principles of Green
considered potential drugs, and to the preparation of
azidotrimethyl-silanes used as precursors for the synthesis of
glycosyl amines (N-glycosides), N-glycopeptides and N-
glycoproteins.
4
1,42
Chemistry,
to toxic solvents. Tetrahydrofuran (THF) and diethyl ether
DEE) as a reaction solvent can be substituted in some
reactions by 2-MeTHF. This is of great importance since it
this solvent can be considered a real alternative
(
4
3
This study takes the best reaction condition for the MW-
51
assisted N-protection of amines recently published which are
comes from renewable resources like corncobs and bagasse.
-MeTHF improves extraction yields by reducing the number
of extraction steps as it forms a water-rich azeotrope at
2
evaluated in the Ferrier azaglycosylation with the aim of
developing a one-pot methodology.
4
4-46
atmospheric pressure.
N-glycosylation of O-methyl alanine (2.0 mmol) with 3,4,6-
tri-O-acetyl-D-glucal (2.0 mmol) was chosen as a model
reaction (Table 1). Opposite to what happens for the simple
tosylation reactions, in tosylation/Ferrier glycosylation reaction
Furthermore, 2-MeTHF is recognized by GSK
46
(
considered negative for genotoxicity and mutagenicity.
GlaxoSmithKline) as a new “green” alternative solvent and
4
7
Lanthanides (III) prove as environmentally friendly
4
oxophilic Lewis acids for activation of glycosyl donors.
2 2
poor yields were obtained using CH Cl (entries 1-3, Table 1).
8
The result found was the same, increasing reaction time
entry 4, Table 1). By contrast, good product yields were
In recent years a number of important contributions to
the chemistry of Ferrier N-glycosidation have appeared. In
many cases, these catalysts are used in traditional organic
(
obtained when the reaction was performed in EL (ethyl lactate)
and 2-MeTHF (entries 5-10, Table 1). The reaction carried out
in the absence of Er (III) did not lead to the formation of the
product which means that the Lewis acid catalyst, not involved
in the tosylation reaction of amine, is essential for the Ferrier
azaglycosylation reaction to occur (entry 11, Table 1). Thus, in
order to decrease reaction time, we carried out the same
reaction under microwave activation, but lower yields were
observed due to decomposition of glucal (entry 12, Table 1).
The reaction carried out in water did not lead to the formation
of the product, not even when the reaction system was
subjected to microwave irradiation (entries 13 - 20, Table 1).
4
9
solvents or under dry conditions.
We studied the system Er(OTf)
3
/2-MeTHF for the reduction
reaction of α,β-unsaturated carbonyl compounds. We proposed
this protocol as a cheap, efficient, and environmentally
sustainable reduction system for the synthesis of allylic
5
0
alcohols.
The results reported here are comparable to those of the
classical Ferrier azaglycosylation; however, the proposed
method involves a significant greening of the whole process
compared to several previous protocols that required the use of
toxic solvents. In addition, the protocol is applicable to
biologically important products such as amino acids, showing
good yields and high stereoselectivity.
3
The reaction carried out in 2-MeTHF with Er(OTf) under
reflux showed the best results (entry 9, Table 1, only α) as
described in the references section.
52

3
a
Table 1. Tosylation/Azaglycosidation reactions of O-methyl alanine with 3,4,6-tri-O-acetyl-D-glucal.
c
Entry
Lewis acid
Solvent
b
Yield (%)
T °C
Time (min)
1
2
3
4
5
6
7
8
9
ErCl
3
·6H
2
O
CH
2
Cl
Cl
Cl
Cl
2
2
2
2
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
80
110
60
150
150
150
240
150
150
150
240
240
240
240
15
40
40
40
40
60
60
60
70
80
73
0
Er(OTf)
3
CH
2
ErCl
3
CH
2
ErCl
ErCl
3
3
·6H
2
O
O
CH
2
·6H
2
EL
EL
EL
Er(OTf)
3
ErCl
3
ErCl
3
·6H
2
O
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
Er(OTf)
3
1
1
1
1
1
1
1
0
1
2
3
4
5
6
ErCl
-
3
Er(OTf)
Er(OTf)
3
20
trace
trace
10
0
3
H
2
O
O
O
O
O
O
O
O
150
150
150
150
15
ErCl
-
3
H
2
H
2
ErCl
3
·6H
2
O
H
2
d
1
7
8
9
0
Er(OTf)
3
H
2
0
d
d
d
1
1
2
ErCl
-
3
H
2
15
0
H
2
15
0
ErCl
3
·6H
2
O
H
2
15
0
a
Reaction conditions: O-methyl alanine (2 mmol), tosyl chloride (2.2 mmol) and the Lewis acid (0.2 mmol) were dissolved in the solvent (3 mL). After the
formation of N-tosyl alanine, 3,4,6-tri-O-acetyl-D-glucal (2 mmol) was added to the mixture.
b
After the addition of 3,4,6-tri-O-acetyl-D-glucal.
Isolated yield. α only product is formed.
The reactions were conducted in a Synthos 3000 microwave oven (Anton-Paar).
c
d
Therefore we decided to test a series of amines in the one-pot
synthesis of 2,3-unsaturated-N-pseudoglycals (Table 2).
alanine/methyl 2-(4 methylphenylsulfonamido)propanoate
methyl ester and N- amino acid sulfonamides which could be
potential anticancer drugs. However, no amino acid tested was
useful for this type of reaction (entries 10-11, Table 2). This is
probably due to amino acids that act as zwitterions, decreasing
the nucleophilicity on nitrogen atom.
Glycal and various sulfonamides were coupled in the presence
of Er(OTf)
3
(10 mol%) in 2-MeTHF affording the
corresponding N-glycosyl sulfonamides (1a-10a). In good
yields with high anomeric selectivity, N-(phenyl)-4
methylbenzene
sulfonamide,
N-(phenyl)-2-
Methylbenzenesulfonamide reacted smoothly to afford 2,3-
unsaturated-N-glycosides (entries 3, 4 and 6, Table 2).
methylbenzenesulfonamide and N-(4-chlorophenyl)-4- Ts-L-
phenylalanine methyl ester (2) gave new N-glycosyl N-Ts-L-

4
Tetrahedron
a
Table 2: One pot tosylation/Azaglycosidation of amine reactions with 3,4,6-tri-O-acetyl-D-glucal.
b
Entry
Substrate
Product
Yield (%)
α:β
7
3
2
2a
90:10
1
9
0
3
3a
90:10
2
9
8
4
4a
α only
3
9
1
4
5
5a
α only
8
5
5
6
7
8
6a
7a
8a
75:25
8
3
α only
6
8
7
7
90:10

5
9
0
9
9a
8
87:13
8
6
1
0
10a
9
α only
1
1
11a
1
0
NR
1
2
12a
1
1
NR
a
3
General reaction conditions: the N-nucleophile (2.0 mmol) and Er(OTf) (0.2 mmol) were added to a stirred solution of tosyl chloride (2.2 mmol) in 2-
MeTHF (3 mL). The reaction was conducted in a two neck round bottom flask using reflux system. After 2 hours tri-O-acetyl-D-glucal (2.0 mmol) was
added.
b
1
Anomeric selectivity was determined by H-NMR.
The reaction mechanism proposed is shown in Scheme 2.
The Ferrier process starts with the coordination of Er and
one of the oxygen atom lone pairs of the glycal molecule
producing the release of a glycoxil group. A delocalized cation
is formed and then attacked by a nucleophile affording a
product.
Due to the extensive use of fluorenylmethyloxycarbonyl
chloride (Fmoc-Cl) and tert-butyloxycarbonyl (Boc) as amino-
5
3
protecting groups and their significant synthetic utility, we
examined the scope of the present reagent system with series of
Fmoc- and Boc-protected amines, exploring the generality of
this azaglycosylation method (Table 3). Unfortunately, we
observed that N-Fmoc and N-Boc amines failed to react in the
usual reaction conditions (Table 3).
Scheme 2: Mechanism hypothesized for Ferrier glycosylation

6
Tetrahedron
a
Table 3: Azaglycosidation reactions of N-Boc and N-Fmoc protected amines
b
Entry
Substrate
Product
Yield (%)
1
13
13a
NR
2
14
14a
NR
3
1
5
15a
NR
NR
4
16
16a
a
General reaction conditions: the N-nucleophile (2.0 mmol) and Er(OTf)
3
(0.2 mmol) were added to a stirred solution of tri-O-acetyl-D-glucal
(2.0 mmol), in 2-MeTHF (3 mL). The reaction was performed in a two neck round bottom flask using reflux system.
b
Substrate recovered.
We then decided to test the efficiency of sulfonamides,
carbamates and primary amines, using the same protocol
2
two methyl groups (Me NH, N =17.12), a small increase in
55
proposed for Ferrier azaglycosylation. Excellent results were
obtained for primary sulfonamides (entries 1-4, Table 4). The
reaction with benzylamide gave moderate yields (entry 5, Table
nucleophilicity was observed. Thus, a secondary amine is
more nucleophilic than a primary amine. This could explain the
fact that N- Benzyl benzene sulfonamide (8) is more reactive
than N- benzylamine (24). Conversely, Fmoc- and Boc-
protected amines did not react to afford the corresponding
pseudoglycals, probably due to high steric hindering (Table 3,
entries 1-4).
Even though the reaction did not perform well on amino
acids without methyl group, probably because amino acids
behave like zwitterions reducing nucleophilicity, the reaction
provided good yields for azaglycosylation using amino acids
with methyl group.
54
4
). This result encouraged us to further exploit Ferrier
azaglycosylation with benzyl carbamate, t-butyl carbamate and
trimethylsilyl azide (TMSN ) (entries 6, 7 and 9, Table 4) as
3
nucleophiles. Reaction of carbamates with glucal provided the
corresponding pseudoglycals (22a and 23a), in good yields and
selectivities. These products can be transformed into the
corresponding amines by elimination of the protecting moiety.
In contrast, reaction of benzylamine was unsuccessful (entry 8,
3
Table 4). Likewise, glycosylation of glucal with TMSN gave
the corresponding α- and β-1-azido-3-deoxy (25a) and a- and
b-3-azido-3-deoxy (26a) glycoside in 90% yield (entry 9, Table
The results reported here are comparable to those of the
classical Ferrier azaglycosylation; however, the proposed
method involves a significant greening of the whole process
compared to several previous protocols that required the use of
toxic solvents. In addition, the protocol is applicable to
biologically important products such as amino acids, showing
good yields and high stereoselectivity.
4).
Although the nucleophilicity (N) of the amines studied is
difficult to predict in our systems, we could make estimates of
the trend. For instance, when the hydrogens of ammonia (N =
2
9.48) are successively replaced by one (MeNH , N = 13.85) and

7
a
Table 4: Ferrier azaglycosylation of tri-O-acetyl-D-glucal with sulfonamides and carbamates primary
b
Entry
Substrate
Product
Yield (%)
α:β)
(
8
9
1
17
17a
92:8
9
3
2
18
18a
85:15
NO2
O
S
NH
O
AcO
O
OAc
83
3
4
19
20
19a
90:10
9
5
20a
72:28
6
0
5
6
21
22
21a
22a
70:30
9
0
90:10
8
5
7
8
23
24
23a
24a
80:20
c]
N.R
9
0
(25a) 70:30
9
25
25a
26a
(26a) 80:20.
a
3
General reaction conditions: the N-nucleophile (2.0 mmol) and Er(OTf) (0.2 mmol) were added to a stirred solution of tri-O-acetyl-D-glucal (2.0 mmol), in
2
-MeTHF (3 mL). The reaction was performed in a two neck round bottom flask using reflux system.
b
1
The anomeric ratio was determined by integration of the anomeric hydrogen in the H NMR spectrum.
c
Substrate recovered.

8
Tetrahedron
Conclusion
23. Procopio A, Dalpozzo R, De Nino A, Nardi M, Tagarelli A, Russo
B. Synthesis, 2006; 2: 332- 338.
2
4. Procopio A, Dalpozzo R, De Nino A, Nardi M, Oliverio M, Russo
B. Synthesis, 2006; 15: 2608 -2612.
25. Procopio A, Dalpozzo R, De Nino A, Maiuolo L, Nardi M, Oliverio
In summary, we describe an efficient, eco-friendly and
simple procedure for the synthesis of sulfonamides and 2,3-
unsaturated-N-pseudoglycals. The application of erbium (III)
trifluoromethanesulfonate as a Lewis acid catalyst in 2-MeTHF
shows good results. Although this new protocol does not
perform well on N-Cbz and N-Boc amines, the same method
affords good yields and excellent selectivity for
azaglycosylation using primary amine carbamates.
M, Russo B. Carbohydr Res. 2007; 342: 2125 -2131.
6. Procopio A, Gaspari M, Nardi M, Oliverio M, Rosati O.
Tetrahedron Lett. 2008; 49, 14: 2289-2293
2
2
2
2
3
3
7. Procopio A, Dalpozzo R, De Nino A, Maiuolo L, Nardi M, Russo B.
Adv Synth Catal. 2005; 347: 1447-1450.
8. Procopio A, Das G, Nardi M, Oliverio M, Pasqua L. ChemSusChem,
2008; 1: 916.
9. Procopio A, Cravotto G, Oliverio M, Costanzo P, Nardi M, Paonessa
R. Green Chem. 2011; 13: 436-443.
0. Nardi M, Cozza A, De Nino A, Oliverio M, Procopio A. Synthesis,
Compared to the classical procedures, the present protocol
(
Er(OTf)
of green solvent, use of water alone for the work-up (use of
O and 2-MeTHF as an organic solvent), recovery and
3
/2-MeTHF) offers several advantages including use
2
1. Procopio A, Das G, Nardi M, Oliverio M, Pasqua L, ChemSusChem,
012; 44: 800-804.
H
2
2008; 1: 916- 919.
32. Procopio A, Cravotto G, Oliverio M, Costanzo P, Nardi M, Paonessa
reusability of the catalyst, use of mild reaction conditions and
wide range of applicability.
R. Green Chem. 2011; 13: 436-443.
3. Nardi M, Cozza A, Maiuolo L, Oliverio M, Procopio A. Tetrahedron
Lett. 2011; 52: 4827–4834.
3
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RJ.
Topics in Current
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5
5
5
6
1.
Nardi M, Herrera Cano N, Costanzo P, Oliverio M, Sindona G,
Procopio A. RSC Adv. 2015; 5: 18751- 18760.
5
2.
General Procedure one pot tosylation/azaglycosidation reaction
of amine with 3,4,5-tri-O-acetyl- D-glucal, exemplified with 1a:
To a stirred solution of tosyl chloride (2.2 mmol), in 2-MeTHF (3
9. (a) Chandrasekhar S, Reddy CR, Chandrashekar G, Tetrahedron
Lett. 2004, 45, 6481–6484. (b) Ding F, William R, Kishan Gorityala
BJ, Wang S, Wei Liu X. Tetrahedron Lett. 2010; 51: 3146.
mL) was added the O-methyl alanine (2.0 mmol) and Er(OTf)
0.2 mmol). The reaction was conducted in a two neck round
3
2
0. (a) Colinas PA, Bravo RD. Carbohydr Res. 2007; 342: 2297-2302.
(
(
b) Témpera CA, Colinas PA, Bravo RD, Tetrahedron Lett. 2010,
1, 5372–5374.
bottom flask using a reflux system. The reaction process was
monitored by TLC using ultraviolet illumination at 254 nm or
staining with ninhydrin solution. After 2 hours is added 2 mmol of
tri-O-acetyl-D-glucal and it is left in the same conditions for
5
2
2
1. Houston TA, Chervin SM, Koreeda M. ITE Lett. 2002; 3: 23.
2. Michigami K, Hayashi M. Tetrahedron, 2012; 68: 1092.

9
another 2 hours. The reaction mixture was extracted with H
the organic phase (2-MeTHF as solvent), then dried over Na
The crude material was dried under vacuum (~1 mmHg) and
purified by flash chromatography on silicagel (CHCl /EtOH
.5/0.5) to isolate the desired product 1a. α−Methyl-2-(4,6-Di-O-
acetyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranosyl-N-p-
toluenesulfonamide)-propanoate (1a). yellow oil obtained in 80 %
2
O and
54.
General Procedure Ferrier azaglycosylation of tri-O-acetyl-D-
glucal with sulfonamides and carbamates primary, exemplified
with 17a . To a stirred solution of tri-O-acetyl-D-glucal (2 mmol),
in 2-MeTHF (3 mL) was added the benzenesulfonamide (2.0
2
SO
4
.
3
9
3
mmol) and Er(OTf) (0.2 mmol). The reaction was conducted in a
two neck round bottom flask using a reflux system for 2 hours.
The reaction process was monitored by TLC using ultraviolet
illumination at 254 nm allowed for visualization for UV active
materials or staining with ninhydrin solution allowed for further
1
yield; H NMR (300 MHz, CDCl
7
3
): δ =7.76 (d, 2H, J = 8.2, Ar),
.32 (d, 2H, J = 8.2, Ar), 5.94 (dd, 1H, J=9.3, 6.1 Hz, H-3), 5.82
visualization. The reaction mixture was extracted with H
the organic phase (2-MeTHF as solvent), then dried over Na
The crude material was dried under vacuum (~1 mmHg) and
purified by flash chromatography on silica gel (CHCl /EtOH
2
O and
(
ddd, J=9.3, J=8.1, 1.7 Hz, 1H, H-2), 5.47-5.45 (m, 1H, H-4), 5.28
d, J=8.1, Hz, 1H, H-1), 4.24-4.22 (m, 2H, H-6), 4.19-4.17 (m,
SO .
4
(
2
1
H, H-5), 3.99-4.01 (m, J=7.1 Hz, 1H, CH-N), 3.55 (s, 3H,
CH COO), 2.43 (s, 3H, CH Ph), 2.10 (s, 3H, CH COO), 2.07 (s,
COO). C NMR (75 MHz, CDCl ): δ =172.7 (C=O),
3
3
3
3
1
3
9.5/0.5) to isolate the desired product 17a. 4,6-Di-O-acetyl-2,3-
dideoxy- α-D-erythro-hex-2-enopyranosyl-N-benzenesulfonamide
3
1
1
6
2
H, CH
3
3
70.4 (C=O), 170.0 (C=O), 143.6 (C), 138.1 (H), 130.2 (CH),
33.9 (CH), 127.5 (CH), 127.5 (2 CH), 68.0 (CH-1), 63.9 (CH-5),
(
17a). Straw yellow oil obtained in 89 % yield; Spectroscopic data
19b
compared to those reported in the literature.
Brotzel F, Chu YC, Mayr H. J Org Chem. 2007; 72: 3679-3688.
3.4 (CH-4), 63.2 (CH
2
-6), 52.4 (CH
3
), 51.8 (CH), 21.4 (CH
3
),
5
5.
0.8 (CH COO), 20.6 (CH
3
3
COO), 19.9 (CH
3
).
IR (neat) : 3440, 3019, 2400, 1741, 1216, 1045, 749, 669.
Anal. Calcd for C21 S: C 53.72, H 4.80, N 2.98. Found
3.80, H 4.76, N 2.95.
H
27NO
9
C
Supplementary Material
5
5
3.
Di Gioia ML, Gagliardi A, Leggio A, Leotta V, Romio E, Liguori
A. RSC Adv. 2015; 5: 63407-63420.
Supplementary data associated with this article are
available.

10
Tetrahedron
RESEARCH HIGHLIGHTS
•
convenient
synthesis
of
sulfonamides and 2,3-unsaturated-
N-pseudoglycals
•
•
green procedure in 2-MeTHF
application of erbium (III)
trifluoromethanesulfonate as
Lewis acid catalyst
a