Y(OTf)3 as a highly efficient catalyst in Ferrier Rearrangement for the synthesis of O- and S-2,3-unsaturated glycopyranosides

Article abstract of DOI:10.1016/j.tetlet.2014.08.092

By using Y(OTf)₃ as the catalyst, a series of 2,3-unsaturated-glucosides have been synthesized from 3,4,6-tri-O-acetyl-d-glucal, 3,4-di-O-acetyl-l-rhamnal, and 3,4,6-tri-O-benzyl-d-glucal under mild reaction conditions in good yields with high anomeric selectivities. It was found that, in this reaction, 3,4,6-tri-O-benzyl-d-glucal behaved differently from the other two glucals when it was reacted with phenol, O-benzyl glucoside instead of O-phenyl glucoside formed as the sole product. An explanation is given for this phenomenon.

Full text of DOI:10.1016/j.tetlet.2014.08.092

Tetrahedron Letters 55 (2014) 5813–5816
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Tetrahedron Letters
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Y(OTf)3 as a highly efficient catalyst in Ferrier Rearrangement for the
synthesis of O- and S-2,3-unsaturated glycopyranosides
a
Peiran Chen a,b, , Shan Li
⇑
a Key Lab of Eco-Textile, The Ministry of Education, Donghua University, 2999 Renmin Road North, Songjiang District, Shanghai 201620, China
b Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, CAS, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
By using Y(OTf)3 as the catalyst, a series of 2,3-unsaturated-glucosides have been synthesized from
Received 13 July 2014
Revised 13 August 2014
Accepted 22 August 2014
Available online 29 August 2014
3,4,6-tri-O-acetyl-
tion conditions in good yields with high anomeric selectivities. It was found that, in this reaction,
3,4,6-tri-O-benzyl- -glucal behaved differently from the other two glucals when it was reacted with
phenol, O-benzyl glucoside instead of O-phenyl glucoside formed as the sole product. An explanation
is given for this phenomenon.
D-glucal, 3,4-di-O-acetyl-L-rhamnal, and 3,4,6-tri-O-benzyl-D-glucal under mild reac-
D
Keywords:
Y(OTf)3
Ó 2014 Elsevier Ltd. All rights reserved.
3,4,6-Tri-O-acetyl-
3,4,6-Tri-O-benzyl-
3,4-Di-O-acetyl- -rhamnal
D-glucal
D-glucal
L
2,3-Unsaturated glycoside
Ferrier Rearrangement
Owing to their versatile chemical transformations, alkyl and
aryl 2,3-unsaturated glycosides are important chiral intermediates
in the synthesis of biologically active molecules1 and new func-
tional materials.2 Ferrier Rearrangement is an efficient and facile
highest yield were obtained at 40 °C. Therefore, the established
reaction conditions are mild.
Under the established reaction conditions, 2,3-unsaturated
glycosides were synthesized from three glycals and various nucle-
ophiles. Hereinafter we will discuss our results based on the glycals
used.
reaction for the synthesis of 2,3-unsaturated glycopyranosides.3
A
variety of reagents have been used to promote this reaction,
including Bronsted acids,4 Lewis acids,5 as well as other reagents
such as oxidants.6 Due to their special properties and high catalytic
activity, rare earth metal salts as catalyst have recently gained
more and more applications. Among them, Sc(OTf)3, CeCl3,
Dy(OTf)3, Er(OTf)3, and Yb(OTf)3 have been employed as the cata-
lysts in Ferrier Rearrangement.7 In our continuing effort to search
for more efficient catalyst for Ferrier Rearrangement, we found
Y(OTf)3 is a highly efficient catalyst for the transformation of vari-
ous glucals to the O- and S-2,3-unsaturated glucosides. Here we
reported our result.
First of all, reaction condition optimization was performed.
Among YF3, Y2O3, Y2(SO4)3, and Y(OTf)3, we found Y(OTf)3 to be
the most efficient. For the reaction solvent, among the tested
acetonitrile, methylene dichloride, tetrahydrofuran, and toluene,
acetonitrile gave the highest conversion under the catalysis of
Y(OTf)3. For the reaction temperature, shortest reaction time and
Table 1 shows the result of 3,4,6-tri-O-acetyl-D-glucal (1). We
can see that when alcohols were used as nucleophile, the expected
products were obtained in high yields with good anomeric selec-
tivities. Phenols and thiols needed longer time to give good to
moderate yields with high selectivities.
A report mentioned that when 3,4,6-tri-O-acetyl-D-glucal was
treated with p-methoxyphenol in CH2Cl2 with BF3ÁOEt2 as the cat-
alyst, C-glycoside was obtained exclusively.8 However, in our case,
no such phenomenon occurred. Phenol, p-methoxyphenol, and
2-naphthol gave the normal O-glucoside products in good yields
(entries 7–9), which can be confirmed by the two ortho aromatic
signals in the 1H NMR spectra of the products (3g, 3h, and 3i).
Table 2 shows the results of 3,4-di-O-acetyl-L-rhamnal (4),
which appeared to be similar to the results given in Table 1. The
anomeric selectivities were high but the yields were slightly lower
than those of 3,4,6-tri-O-acetyl-D-glucal (1). Phenols as the nucleo-
phile again afforded the normal O-glycoside products (entries 6
and 7).
Results in Table 3 show that 3,4,6-tri-O-benzyl-D-glucal (6) was
⇑
less active than the former two glycals. In the case of alcohols
(entries 1–4) as the nucleophiles, the reaction needed longer time
Corresponding author. Tel.: +86 21 67792594.
E-mail address: prchen@dhu.edu.cn (P. Chen).
http://dx.doi.org/10.1016/j.tetlet.2014.08.092
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

5814
P. Chen, S. Li / Tetrahedron Letters 55 (2014) 5813–5816
Table 1
Table 2 (continued)
Y(OTf)3 catalyzed Ferrier Rearrangement of 3,4,6-tri-O-acetyl-D-glucal (1) with
Reaction time (min) Yieldb (%)/( :b)c
a
nucleophiles (2)a
Entry Nucleophile (2)
AcO
AcO
OH
2
18
5b: 85% (
a
only)
Y(OTf)3
O
O
(10 mol%)
OAc
Nu
+
Nucleophile
MeCN, 40oC
HO
OAc
AcO
3
10
5c: 81% (a
only)
3
1
2
Entry
1
Nucleophile (2)
Reaction time (min)
15
Yieldb (%)/(
a
:b)c
O
EtOH
3a: 91% (17:1)
OH
4
8
5d: 79% (
a
only)
2
3
18
10
3b: 90% (11:1)
HO
OH
3c: 85% (9:1)
3d: 77% (8:1)
OH
5
120
120
5e: 70% (3:1)
OH
HO
4
5
8
6
5f: 75% (2.5:1)
MeO
SH
7
90
5g: 75% (a only)
20
3e: 77% (11:1)
N
SH
OH
O
8
100
5h: 75% (21:1)
N
a
O
O
General reaction conditions: 3,4-di-O-acetyl-
L
-rhamnal (4) (177 mg, 0.7 mmol),
6
20
3f: 82% (
a
only)
nucleophile (2) (1.5 equiv), Y(OTf)3 (10 mol %), MeCN (5 mL), 40 °C.
b
O
Isolated yield.
HO
O
c
The anomeric ratio was determined by integration of the anomeric hydrogen in
the 1H NMR spectra.
OH
7
8
120
90
3g: 65% (
a
only)
only)
only)
only)
only)
OH
3h: 75% (
a
MeO
Table 3
OH
Y(OTf)3 catalyzed Ferrier Rearrangement of 3,4,6-tri-O-benzyl-D-glucal (6) with
9
100
30
3i: 61% (
3j: 82% (
3k: 70% (
a
nucleophiles (2)a
SH
BnO
BnO
Y(OTf)
3
O
10
11
a
O
(10 mol%)
OBn
Nu
Me
N
+
Nucleophile
o
MeCN, 40 C
SH
OBn
BnO
180
a
7
6
2
N
a
General reaction conditions: tri-O-acetyl-D-glucal (1) (188 mg, 0.7 mmol),
Entry
Nucleophile (2)
Reaction time (min)
120
Yieldb (%)/( :b)c
a
nucleophile (2) (1.5 equiv), Y(OTf)3 (10 mol %), MeCN (5 mL), 40 °C.
b
Isolated yield.
OH
c
The anomeric ratio was determined by integration of the anomeric hydrogen in
1
2
7a: 70% (10:1)
7b: 65% (4:1)
the 1H NMR spectra.
OH
90
Table 2
HO
Y(OTf)3 catalyzed Ferrier Rearrangement of 3,4-di-O-acetyl-L-rhamnal (4) with
3
180
7c: 62% (a only)
nucleophiles (2)a
OAc
Y(OTf)
AcO
Me
3
O
O
(10 mol%)
Nu
Me
+
Nucleophile
o
4
5
180
48h
7d: 40% (13:1)
MeCN, 40 C
OH
OH
OAc
4
5
2
7b: 46% (8:1)
Entry Nucleophile (2)
Reaction time (min) Yieldb (%)/( :b)c
a
a
General reaction conditions: 3,4,6-tri-O-benzyl-
0.7 mmol), nucleophile (2) (1.5 equiv), Y(OTf)3 (10 mol %), MeCN (5 mL), 40 °C.
D
-glucal (6) (292 mg,
OH
b
1
10
5a: 86% (a only)
Isolated yield.
c
The anomeric ratio was determined by integration of the anomeric hydrogen in
the 1H NMR spectra.

P. Chen, S. Li / Tetrahedron Letters 55 (2014) 5813–5816
5815
..
..
O
O
Nu
O
R2
R2
R2
1
:Nu
2
2
R1
allyloxycarbeniumion
R1
R1
3
LG
3
LA
:
LG = leaving group
LA = Lewis acid catalyst
Scheme 1. Mechanism of Ferrier Rearrangement proposed by Ferrier.
BnO
BnO
BnO
Y(OTf)3
O
O
O
(10mol%)
+
OBn
OBn
7b
OBn
MeCN, 40oC
OBn
BnO
BnO
6
Scheme 2. A proposed 3,1-migration of BnO-group in 3,4,6-tri-O-benzyl-D-glucal promoted by Y(OTf)3.
to give products in moderate yields. Moreover, when phenol was
used as the nucleophile (entry 5), the reaction gave an unexpected
product of O-benzyl glucoside (7b) instead of the expected O-phe-
nyl glucoside in 46% yield.
References and notes
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Ferrier gave a mechanism9 for his Rearrangement reaction
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To explain the phenomenon in Table 3, entry 5, we assumed the
leaving group from C3 (in this case, benzyloxy anion) to be existing
in free form to compete the added nucleophile (in this case, phe-
nol). Because benzyloxy anion was much more nucleophilic than
phenol, O-benzyl glucoside (7b) formed as a sole product. Treat-
ment of 3,4,6-tri-O-benzyl-D-glucal (6) alone with Y(OTf)3 under
the same reaction conditions without the addition of nucleophile,
we also obtained O-benzyl glucoside (7b) in 70% yield. The
proposed procedure is shown in Scheme 2.
While hydron donor (such as phenol in entry 5, Table 3) pre-
sented in the reaction, the nucleophilic activity of BnO would be
lowered since the formation of BnOH, which led to the relative
low yield (46%) in entry 5, Table 3.
In summary, Y(OTf)3 is a highly efficient catalyst for the synthesis
of O- and S-2,3-unsaturated glycosides. Under our reaction condi-
tions, 3,4,6-tri-O-acetyl-
afforded O- and S-productsin high togood yields with high anomeric
selectivities, while 3,4,6-tri-O-benzyl- -glucal gave O-alkyl
products in moderate yields with good selectivities. Interestingly,
reaction of 3,4,6-tri-O-benzyl- -glucal with phenol did not give
D-glucal and 3,4-di-O-acetyl-L-rhamnal
D
D
the expected O-phenyl 2,3-unsaturated glucoside. Instead, O-benzyl
2,3-unsaturated glucoside was formed as the sole product.
Acknowledgments
This work is financially supported by a Grant of The National
Natural Science Foundation of China (NSFC, Grant No. 21272305),
The Natural Science Foundation of Shanghai Municipality (Grant
No. 12ZR1400200), and The Fundamental Research Funds for the
Central Universities.
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.08.
092.

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P. Chen, S. Li / Tetrahedron Letters 55 (2014) 5813–5816
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