Synthesis of glycosyl fluorides from (phenylthio)glycosides using IF5-pyridine-HF

Article abstract of DOI:10.1016/j.carres.2015.08.005

IF₅-pyridine-HF, an air- and moisture-stable fluorinating reagent, was applied to the synthesis of glycosyl fluorides from (phenylthio)glycosides. Common protecting groups of alcohol and diol can tolerate the reaction conditions performed, and therefore, the present method is applicable to the synthesis of various glycosyl fluorides.

Full text of DOI:10.1016/j.carres.2015.08.005

Accepted Manuscript
Title: Synthesis of glycosyl fluorides from (phenylthio)glycosides using IF5-
pyridine-HF
Author: Masataka Kunigami, Shoji Hara
PII:
S0008-6215(15)00227-X
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.carres.2015.08.005
CAR 7049
To appear in:
Carbohydrate Research
Received date: 24-4-2015
Revised date: 15-6-2015
Accepted date: 12-8-2015
Please cite this article as: Masataka Kunigami, Shoji Hara, Synthesis of glycosyl fluorides from
(phenylthio)glycosides using IF5-pyridine-HF, Carbohydrate Research (2015),
http://dx.doi.org/doi:10.1016/j.carres.2015.08.005.
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Synthesis of glycosyl fluorides from (phenylthio)glycosides using IF5-pyridine-HF
Masataka Kunigami, Shoji Hara*
Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
*Corresponding author. Tel: +81 11 706 6556.
E-mail address: shara@eng.hokudai.ac.jp
Highlights
Glycosyl fluorides were synthesized from (phenylthio)glycosides.> IF5-pyridine-HF was used for the
synthesis. > IF5-pyridine-HF is air- and moisture stable, and easy to use. > Various kinds of glycosyl
fluorides were synthesized.
Graphical Abstract
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ABSTRACT
IF5-pyridine-HF, an air- and moisture-stable fluorinating reagent, was applied to the
synthesis of glycosyl fluorides from (phenylthio)glycosides. Common protecting groups
of alcohol and diol can tolerate the reaction conditions performed, and therefore, the
present method is applicable to the synthesis of various glycosyl fluorides.
keywords:
glycosyl fluorides
(phenylthio)glycosides
IF5-pyridine-HF
air- and moisture-stable
1. Introduction
Glycosyl fluorides have been successfully used as glycosyl donors in C-glycosydation
and O-glycosylation, because of their exceptional stability and ease of handling
compared to other halogen derivatives.1-4 Glycosyl fluorides are also known to have
considerable importance as substrates and inhibitors in enzymatic reactions,5,6 and so
their synthesis is becoming increasingly important.
Glycosyl fluorides were generally prepared from the corresponding thioglycosides by
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the reaction with fluorinating reagent such as IPy2BF4,7,8 IF,9,10 ArIF2,11 Xtalfluor,12
amine-HF with NIS,13 and most commonly DAST with an oxidant such as NBS.14
However, DAST is moisture sensitive and thermally unstable,15 and NBS can cause the
formation of by-products.16 Therefore, a safer and more reliable method for the
synthesis of glycosyl fluorides is desired. Recently, we reported synthesis of a new
fluorinating reagent, IF5-pyridine-HF, and its application to fluorination reactions.17,18
As IF5-pyridine-HF is an air- and moisture-stable fluorinating reagent, we applied IF5-
pyridine-HF for the synthesis of glycosyl fluorides from (phenylthio)glycosides.
2. Results and discussion
The reaction of phenyl 2,3,4,6-tetra-O-acetyl--D-1-thioglucopyranoside (1a) with
IF5-pyridine-HF was carried out in CH2Cl2 at room temperature, and the reaction
progress was followed by GC. Although the reaction was completed with less than 1 eq
of IF5-pyridine-HF to 1a, a long reaction time was required (Entry 1 in Table 1). When
1.1 eq of IF5-pyridine-HF was used, the reaction was completed in a shorter time and
2,3,4,6-tetra-O-acetyl-D-glucopyranosyl fluoride (2a) was obtained in good yield (Entry
2). The use of 2 eq of IF5-pyridine-HF resulted in a slight improvement in yield (Entry
3). The ratio of - and -isomers in 2a was found to be in the range of 1.0 : 2.0-2.3, and
was independent of the reaction conditions examined (Entries 1-3).
We applied IF5-pyridine-HF for the synthesis of various glycosyl fluorides as shown in
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Table 2. Various protecting groups of alcohol and diol such as acetate (Entries 1, 2, 7,
and 8), benzyl ether (Entry 3), acetonide (Entries 4-6), and benzoate (Entry 5), tolerate
the reaction conditions. Silyl ethers, also widely used as the protecting group of alcohols,
are sensitivity to fluoride and fluorinating reagents. Therefore, we used IF5-pyridine-HF
to the reaction with a substrate bearing the silyl protecting group. A ribose derivative
bearing a tert-butyldimethylsilyl group (1f) was treated with 1.1 eq of IF5-pyridine-HF,
and the reaction was followed by NMR. After 30 min, 1f was consumed completely and
the desired glycosyl fluoride (2f) was formed in 80% yield. However, the desilylated
product was also formed in 20% yield. In contrast, when 0.55 eq of IF5-pyridine-HF
was used, the reaction was completed in 30 min and 2f was formed in 88% yield (Entry
5). Under these conditions, only 7% of the desilylated product was formed. It was also
found that IF5-pyridine-HF could be applied to the synthesis of the 2-amino-2-
deoxyglycosyl fluoride derivative (2g) (Entry 7) and the disaccharide derivative (2h)
(Entry 8). In addition to pyranosyl fluorides (2a,b,g,h), furanosyl fluorides (2c-f) could
be prepared from the corresponding (phenylthio)glycosides by reaction with IF5-
pyridine-HF.
3. Conclusion
We applied IF5-pyridine-HF, which is air- and moisture-stable, and easy to use, for the
preparation of glycosyl fluorides from corresponding (phenylthio)glycosides. It was
found that IF5-pyridine-HF is suitable for the synthesis of various glycosyl fluorides,
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and common protecting groups of alcohol tolerate the fluorination conditions.
4. Experimental
4.1. General methods
IF5 in a cyclinder was supplied by Daikin industries, Ltd. Anhydrous HF in a cyclider
was purchaed from Stella Chemifa Corporation. IF5-pyridine-HF was prepared from IF5
and pyridine-HF by the previously reported method.17 (Phenylthio)glycosides 1a,b,19
1c,20 1d-f,21 and 1g,h19 were prepared according to the literatures. Glassware can be
used for the reaction, but use of Teflon™ or polyethylene ware is recommended.
•
4.2. A typical procedure for transformation of (phenylthio)glycoside into glycosyl
fluoride using IF5-pyridine-HF
4.2.1. 2,3,4,6-Tetra-O-acetyl-D-glucopyranosyl fluoride (2a)
To a CH2Cl2 solution (2 mL) of IF5-pyridine-HF (321 mg, 1.0 mmol) was added 1a
(220 mg, 0.5 mmol) at room temperature and the mixture was stirred at room
temperature for 18 h. After confirmation of complete consumption of 1a by GC, the
mixture was poured into water (20 mL) and extracted with ether (20 mL X 3). The
combined organic layer was washed with aq NaHCO3 and aq Na2S2O3, and dried over
MgSO4. After concentration, 2a was isolated by column chromatography (silica
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gel/hexane:Et2O = 1:1~1:2) in 81% yield as a mixture of - and -isomer (1:2.2
determined by 19FNMR).
-isomer22): White solid. Mp 104-106 °C.
(-isomer23): White solid. Mp 79-80 °C.
2,3,4-Tri-O-acetyl-D-xylopyranosyl fluoride (2b)
-isomer24): Yellow solid. Mp 84-85 °C.
(-isomer24): Yellow solid. Mp 54-55 °C.
2,3,5-Tri-O-benzyl--D-arabinofuranosyl fluoride (2c) 25
Clear liquid.
2,3:5,6-Bis-O-( isopropylidene)--D-mannofuranosyl fluoride (2d) 11
Clear liquid.
2,3-Di-O-isopropylidene-5-O-benzoyl--D-ribofuranosyl fluoride (2e) 26
Clear liquid.
2,3-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)--D-ribofuranosyl fluoride (2f)
23
Clear liquid.
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3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido--D-glucosyl fluoride (2g) 27
White solid. Mp. 166-167 °C.
2,3,6-Tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl--D-glucopyranosyl)--D-
glucopyranosyl fluoride (2h) 28
White solid. Mp 167-168 °C.
Acknowledgment
We are grateful to Daikin industries, Ltd. for their donation of IF5.
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•
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•
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Table 1 Synthesis of glycosyl fluoride 2a by the reaction of (phenylthio)glycoside 1a
with IF5-pyridine-HFa
Entry
IF5-pyridine-HF
React time, h
Yield of 2a, %b
1a
1
2
3
0.55
1.1
2.0
33
20
18
85 (1:2.0)
94 (1:2.2)
98 (1:2.2)
a The reaction was carried out in CH2Cl2 at room temperature.
b 19F NMR yield. In prentheses, ratio of α- and β-isomer.
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Table 2 Synthesis of glycosyl fluorides from (phenylthio)glycosides by the reaction with
IF5-pyridine-HFa
Entr Substrate 1
y
Reac Product 2
t.
Yield,
%
b
Time
h
18
1c
81(98)
(α:β
=
1.0:2.2)
2
3
2
76
(α:β
1.0:1.5)
=
6.5
77
(β only)
4
2
90
(α only)
5
4
89
(β only)
6d
0.5
65 (88e)
(β only)
7
8
2
3
96
(β only)
73
(β only)
a
If otherwise not mentioned, the reaction was carried out in CH2Cl2 at room
temperature using 1.1 eq of IF5-pyridine-HF.
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b Isolated yield. In parentheses, 19F-NMR yield.
c 2.0 eq. of IF5-pyridine-HF was used.
d 0.55 eq. of IF5-pyridine-HF was used.
e 7% of desilylated product was also formed.
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