Aza-Ferrier rearrangement of glycals with amides promoted by molecular iodine

Article abstract of DOI:10.1016/j.tetlet.2014.09.023

Amidoglycosidation of tri-O-acetyl-d-glucal with different N-nucleophiles such as t-butyl carbamate, N-benzyl carbamate, N-ethyl carbamate, tosyl amide, and mesyl amide has been achieved using an equimolar amount of molecular iodine under mild and neutral

Full text of DOI:10.1016/j.tetlet.2014.09.023

Tetrahedron Letters 55 (2014) 6048–6050
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Aza-Ferrier rearrangement of glycals with amides promoted
by molecular iodine
⇑
Zubeda Begum, Ch. Kishore, V. Veerabhadra Reddy, B. V. Subba Reddy
Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Amidoglycosidation of tri-O-acetyl-D-glucal with different N-nucleophiles such as t-butyl carbamate,
Received 20 January 2014
Revised 5 September 2014
Accepted 6 September 2014
Available online 20 September 2014
N-benzyl carbamate, N-ethyl carbamate, tosyl amide, and mesyl amide has been achieved using an
equimolar amount of molecular iodine under mild and neutral conditions to afford the corresponding
N-glycosyl amides in good yields with a preferential a-anomeric selectivity. The use of iodine makes this
method simple, convenient, and cost-effective. This is the first report on aza-Ferrier rearrangement using
molecular iodine.
Keywords:
Ó 2014 Published by Elsevier Ltd.
Aza-Ferrier rearrangement
Glycals
N-glycosyl amides and sulfonamides
The sulfonamides continue to play an important role in chemo-
therapy. They are known to display a broad range of biological
activities like diuretic, antiglaucoma, antiepileptic, and antidiabetic
and hypoglycemic behavior.1,2 In particular, 2,3-unsaturated
N-glycosyl sulfonamides are very useful as human carbonic
anhydrase inhibitors3 and antiproliferative agents.4 Generally,
2,3-unsaturated glycosides are prepared via the Ferrier rearrange-
ment of glycals with various nucleophiles such as alcohols and
thiols.5–13 Despite a large number of methods reported for the
synthesis of 2,3-unsaturated O-glycosides and thioglycosides, only
a few methods are reported for the preparation of N-glycosyl sul-
fonamides.14–18 On the other hand, 2-iodo-sulfonamidohexoses
are prepared from glycals using iodonium di-sym-collidine
perchlorate.19 However, the development of a simple and metal-
Accordingly, we first attempted the amidoglycosidation of 3,4,
6-tri-O-acetyl- -glucal (1) with t-butyl carbamate (2) using a
catalytic amount of iodine (10 mol %) in dichloromethane at room
temperature (Table 1).
The desired 2,3-unsaturated-N-pseudoglycal 3a was obtained in
very low yield (20%) even after a long reaction time (12 h). By
D
Table 1
Screening the catalysts and solvents in the formation of 3a
O
O
NHBoc
AcO
AcO
I2
AcO
H2NBoc
+
Solvent, 25 oC
AcO
free approach for the conversion of 3,4,6-tri-O-acetyl-D-glucal into
OAc
2
N-pseudoglycals with carbamates and sulfonamides using
3a
1
inexpensive and readily available reagents is desirable.
Entry
Catalyst
Amounta
10 mol %
50 mol %
1 equiv
1 equiv
1 equiv
10 mol%
1 equiv
0.5 g/mmol
0.5 g/mmol
0.5 g/mmol
0.5 g/mmol
Solvent
Time
Yieldb (%)
Recently, molecular iodine has received
a considerable
attention in organic synthesis because of its low cost and ready
availability.20 The mild Lewis acidity associated with iodine has
enhanced its use in organic synthesis to perform several organic
transformations using stoichiometric levels to catalytic amounts.21
Following our interest in the catalytic application of molecular
iodine,22 we herein report a metal-free approach for the prepara-
tion of N-glycosyl amides from glycals and N-nucleophiles such
as t-butyl carbamate, N-benzyl carbamate, N-ethyl carbamate,
tosyl amide, and mesyl amide by means of the aza-Ferrier reaction.
a
b
c
d
e
f
g
h
i
Iodine
Iodine
Iodine
Iodine
Iodine
InCl3
InCl3
K10 clay
Amberlyst-15
PMA
TPA
DCM
DCM
DCM
CH3CN
THF
DCM
DCM
DCM
DCM
DCM
DCM
12 h
8 h
30 min
40 min
60 min
8 h
3 h
6 h
4 h
3 h
20
40
89
85
65
10
70
50
45
55
60
j
k
3 h
a
The reactions are carried out at 25 °C.
Isolated yields after column chromatography.
b
⇑
Corresponding author. Fax: +91 40 27160512.
E-mail address: basireddy@iict.res.in (B.V.S. Reddy).
http://dx.doi.org/10.1016/j.tetlet.2014.09.023
0040-4039/Ó 2014 Published by Elsevier Ltd.

Z. Begum et al. / Tetrahedron Letters 55 (2014) 6048–6050
6049
increasing the amount of molecular iodine to an equimolar ratio,
the corresponding N-pseudoglycal 3a was formed in 89% yield with
2:1 anomeric selectivity (Table 1). The efficiency of other catalysts
such as InCl3, K10 clay, acidic ion-exchange resin, and heteropoly
acids was studied. Among them, molecular iodine was found to
be superior to other catalysts tested (Table 1). Furthermore, the
deprotection of Boc was observed when the reaction was
performed in acetonitrile using strong acids such as K10 clay,
Amberlyst-15, phosphomolybdic acid (PMA), and tungstophos-
phoric acid (TPA) (Table 1, entries h–k). As solvent, dichlorometh-
ane gave the best results. In all the cases, the reactions proceeded
rapidly at room temperature under mild conditions. The reactions
were clean and no side products were detected under these
conditions.
high to excellent yields with good
a
-anomeric selectivity.
Furthermore, sulfonamides were found to be excellent nucleophiles
providing the corresponding glycosyl sulfonamides in high yields
with good selectivity (Table 2, entries d and e). Next we examined
the reactivity of O-benzyl derivative of glucal with various
N-nucleophiles. Interestingly, carbamates such as t-butyl, N-benzyl,
and N-ethyl carbamates furnished the corresponding N-pseudogly-
cals in good yields (Table 2, entries f, g, and h). However, urethane
was found to be less reactive than t-butyl carbamate and N-benzyl
carbamate (Table 2, entries c and h). Furthermore, methanesulfon-
amide also gave the respective 2,3-unsaturated N-glycosyl sulfon-
amide in 79% yield (Table 2, entry i). The end products could
easily be transformed into the corresponding N-glycosyl amines
by the removal of amine protecting groups. However, benzyl amine
This result provided the incentive for further study with different
substrates. Interestingly, other carbamates such as N-benzyl and
failed to react either with tri-O-acetyl-D-glucal or with tri-O-benzyl-
D
-glucal (Table 2, entry j). The products were characterized by 1H,
N-ethyl carbamates also reacted well with 3,4,6-tri-O-acetyl-
D-glucal
13C NMR, IR spectra, and mass spectrometry and also by comparison
under similar conditions. In all cases, the products were obtained in
with known samples.14–18 In the absence of iodine, no reaction was
Table 2
Iodine catalyzed aza-Ferrier rearrangement of glycals with amides
Entry
a
Glycal (1)
Amide (2)
Producta (3)
Time (min)
30
Yieldb
89
Ratioc
2:1
(a/b)
O
O
NHBoc
NHCbz
NHCO2Et
NHTs
AcO
AcO
AcO
BocNH2
AcO
OAc
O
O
AcO
AcO
AcO
b
c
d
e
f
CbzNH2
EtCO2NH2
TsNH2
30
30
20
30
40
40
40
40
86
78
85
83
86
84
72
79
3:1
2:1
3:1
1:1
3:1
7:3
7:3
3:1
AcO
OAc
O
O
AcO
AcO
AcO
AcO
OAc
O
O
AcO
AcO
AcO
AcO
OAc
O
O
NHMs
AcO
AcO
AcO
MsNH2
AcO
OAc
O
O
NHBoc
NHCbz
NHCO2Et
NHMs
BnO
BnO
BnO
BocNH2
CbzNH2
EtCO2NH2
MsNH2
BnO
OBn
O
O
BnO
BnO
BnO
g
h
i
BnO
OBn
O
O
BnO
BnO
BnO
BnO
OBn
O
O
BnO
BnO
BnO
BnO
OBn
O
O
NHBn
RO
RO
RO
RO
j
BnNH2
60
0
—
OR
R= benzyl or acetyl
R= benzyl or acetyl
a
b
c
All products were characterized by NMR, mass, and IR spectroscopy.
Yield refers to pure products after chromatography.
Ratio was determined by 1H NMR spectrum of the product.

6050
Z. Begum et al. / Tetrahedron Letters 55 (2014) 6048–6050
..
Supplementary data
O
O
O
NHCOR
AcO
RCONH2
AcO
AcO
AcO
AcO
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.09.
023.
AcO
O
O
I2
Scheme 1. A plausible reaction mechanism.
References and notes
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times, and good
a-selectivity. In addition, this method avoids the
use of expensive reagents and does not require any additives or
stringent reaction conditions. This method is quite simple and con-
venient affording the desired products in good to excellent yields.
The scope and generality of this process are illustrated with respect
to glucal and amides/sulfonamides and the results are presented in
Table 2.24
Mechanistically, the reaction was expected to proceed via the
formation of oxocarbenium ion through the activation of allylic
acetate of the glucal by molecular iodine. A subsequent axial attack
of the amide on oxocarbenium ion would give the desired glycosyl
amide (Scheme 1).
Alternatively, iodine may react initially with amides to generate
HI which may be responsible for the activation of glucal to facili-
tate the reaction.
Unlike amides, aniline failed to give the desired product under
similar conditions, which may be due to an intrinsic low reactivity
of aryl amines. Another reason would be the trapping or quenching
of iodine by aryl amine.
21. (a) Ren, Y. M.; Cai, C.; Yang, R. C. RSC Adv. 2013, 3, 7182; (b) Hojat, V. Curr. Org.
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aza-Ferrier rearrangement for the synthesis of 2,3-unsaturated
N-pseudoglycals from glycals and amides under mild and neutral
conditions. This method provides good yields of N-glycosyl amides/
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1638; (b) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K.; Swamy, T. Tetrahedron
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24. Experimental procedure: To a stirred solution of amide (0.5 mmol) and iodine
(0.5 mmol) in dichloromethane (2 mL) was added glucal (0.5 mmol). The
resulting mixture was stirred at room temperature for the specified time
(Table 1). After complete conversion as indicated by TLC, the mixture was
quenched with hypo solution and extracted with dichloromethane (3 Â 10 mL)
and dried over anhydrous Na2SO4. Removal of the solvent in vacuo, followed by
purification on silica gel using hexane–ethyl acetate (3:1) afforded the pure C-
glycosyl amide. (Spectral data for the products see Supporting information).
sulfonamides in a short reaction time with good
selectivity, which makes it an attractive process.
a-anomeric
Acknowledgments
Z.B. thanks CSIR, New Delhi, and C.K. thanks UGC, New Delhi for
the award of fellowships. B.V.S. thanks CSIR, New Delhi for finan-
cial support as a part of XII five year plan under title DENOVA
(CSC-0205).