Selective cleavage of sugar anomeric O-acyl groups using FeCl3·6H2O

Article abstract of DOI:10.1016/j.tetlet.2008.07.035

A convenient method has been developed for regioselective anomeric deacylation of carbohydrate derivatives using FeCl₃·6H₂O in CH₃CN. Operational simplicity, economic consideration, high yield, and low toxicity are key features associated with this protocol.

Full text of DOI:10.1016/j.tetlet.2008.07.035

Tetrahedron Letters 49 (2008) 5488–5491
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Tetrahedron Letters
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Selective cleavage of sugar anomeric O-acyl groups using FeCl3Á6H2O
*
Guohua Wei, Lei Zhang, Chao Cai, Shuihong Cheng, Yuguo Du
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Scienece, Chinese Academy of Sciences, Beijing 100085, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient method has been developed for regioselective anomeric deacylation of carbohydrate deriv-
atives using FeCl3Á6H2O in CH3CN. Operational simplicity, economic consideration, high yield, and low
toxicity are key features associated with this protocol.
Received 6 April 2008
Revised 28 June 2008
Accepted 4 July 2008
Available online 9 July 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Carbohydrates
Regioselective deacylation
FeCl3
Anomeric center
Selective deacylation on C-1 of carbohydrate residue often plays
an important role in anomeric functional group transformations,
especially in the preparation of glycosyl trichloroacetimidates1
and glycosyl halide.2,3 A great number of reagents have been sug-
gested for this purpose, such as hydrazine acetate,4 bis(tributyl-
tin)oxide,5 tributyltin methoxide,6 mercuric chloride/mercuric
oxide7 benzylamine,8 ammonium salts,9 piperidine,10 HClO4–
SiO2,11 and lanthanide triflates.12 Some of these methods, however,
suffered from either highly toxic, expensive, harsh reaction condi-
tions, low regioselectivity, or low general applications. Therefore,
providing alternatively less toxic, high regioselective, and environ-
mentally benign protocols for anomeric deacylation of carbohy-
drates would be very necessary and valuable.
conditions. Literature search suggested that ferric chloride has
been applied in O-isopropylidenation, acetylation, anomerization,
detritylation, debenzylation, deprotection of acetals, and coupling
reactions.14 Here we would like to report our findings in anomeric
deacylation using ferric chloride hexahydrate.
The exploration started from per-O-acetylated D-glucose and
anhydrous ferric chloride, combining with commercial 1,2-dichlo-
roethane (DCE) or water-containing DCE (Table 1, entries 1–3). The
experiments suggested that a good yield of 1-OH derivative, that is,
2,3,4,6-tetra-O-acetyl-D-glucopyranose, could be obtained in the
presence of certain amount of water under reflux. To test the reac-
tion conditions, the same procedure was thus carried out in com-
mercial acetonitrile and water-containing acetonitrile (Table 1,
entries 4–6). The results indicated that both water content and
reaction temperature were key elements for this reaction. Further
optimization of the reaction conditions suggested that the best
result could be obtained using FeCl3Á6H2O in CH3CN at 70 °C.
In conversion of 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-b-
D
-glucopyranose into its corresponding oxazoline using ferric chlo-
ride as catalyst,13 the anomeric deacetylated derivative was sur-
prisingly obtained as the major product under our reaction
Table 1
Optimization of the reaction conditions for the preparation of 2,3,4,6-tetra-O-acetyl-D-glucopyranose
Entry
Solvent
Temp (°C)
Time (h)
Yield (%)
(1) Anhydrous FeCl3 (1–2 equiv)
(2) Anhydrous FeCl3 (1–2 equiv)
(3) Anhydrous FeCl3 (1 equiv)
(4) Anhydrous FeCl3 (1 equiv)
(5) Anhydrous FeCl3 (1 equiv)
(6) Anhydrous FeCl3 (1–2 equiv)
(7) FeCl3Á6H2O (1 equiv)
Commercial DCE
DCE–H2O = 19:1
DCE–H2O > 20:1
Commercial CH3CN
CH3CN–H2O = 19:1
CH3CN–H2O = 19:1
CH3CN
Reflux
Reflux
Reflux
Reflux
Reflux
rt
7–10
5–8
7
10
1
60–80
60–80
Complex
Complex
85
12
0.5
<5%
92
70
* Corresponding author.
E-mail address: duyuguo@rcees.ac.cn (Y. Du).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.035

G. Wei et al. / Tetrahedron Letters 49 (2008) 5488–5491
5489
Table 2
Anomeric deacylation of sugar derivatives using FeCl3Á6H2O in CH3CN
Entry
Substrate
FeCl3Á6H2O (equiv)
Temp (°C)
Time (h)
0.5
Yielda,b (%)
OAc
O
1
AcO
AcO
1
70
92
OAc
OAc
OAc
OAc
OAc
O
2
3
4
5
6
1
1
1
2
2
70
0.5
0.5
0.5
1.5
1.5
91
89
85
90
83
AcO
OAc
AcO
AcO
AcO
OAc
O
70
OAc
OAc
OAc
O
40
OAc
OAc
AcO
OAc
O
Reflux
Reflux
OAc
AcO
NHAc
OAc
OAc
OAc
O
O
O
AcO
AcO
OAc
AcO
OAc
OAc
OAc
O
OAc
O
OAc
O
7
8
2
2
Reflux
Reflux
2.5
80
86
AcO
AcO
O
AcO
OAc
AcO
O
AcO
AcO
OBz
O
BzO
BzO
3
BzO
OBz
OBz
OBz
O
OBz
OBz
O
9
2
Reflux
5
78
O
BzO
OBz
OBz
OBz
OBz OFmoc
O
10
11
12
2
2
2
Reflux
Reflux
Reflux
3
85
88
86
BzO
AcO
OBz
OBz
OAc
O
2
AcO
OAc
NPhth
OAc
O
1.5
AcO
AcO
OAc
NHTroc

5490
G. Wei et al. / Tetrahedron Letters 49 (2008) 5488–5491
Table 2 (continued)
Entry
Substrate
FeCl3Á6H2O (equiv)
Temp (°C)
Time (h)
2.5
Yielda,b (%)
OAc
O
AcO
AcO
13
14
15
2
2
2
Reflux
81
ONO2
N3
O
MeOOC
AcO
AcO
Reflux
Reflux
2.5
2.5
83
86
OAc
OAc
OAc
OAc
MeOOC
O
OLev
OAc
OBz
O
BzO
BzO
O
OBz
AcO
O
16
2
Reflux
9
80
OBz
O
O
OAc
BzO
BzO
OAc
OBz
OPiv
O
PivO
PivO
PivO
17
18
19
20
4
1
2
1
1
Reflux
20
70
OPiv
BnO
BnO
O
50
0.5
2.5
0.5
0.5
78c
53c
n.d.c
n.d.c
BnO
OAc
OAc
TBDPSO
AcO
O
50
AcO
OAc
OAc
TBSO
BnO
O
40
BnO
OAc
OAc
Ph
O
O
21
40
O
OAc
AcO
OAc
a
Isolated yields as average.
b
c
The a
,b ratios, based on TLC or 1H NMR spectra, were variable from batch to batch.
Higher temperature causes decomposition.
To investigate the scope and the limitation of this reaction,
applied considering both yield and time consumption. Moreover,
anomeric benzoate (entries 8–10) and nitrate groups (entry 1315
more protected sugar derivatives were subjected to this reaction
system and the results are summarized in Table 2. All of the exam-
ined reactions proceeded smoothly under indicated reaction condi-
tions, and the products were obtained in good to excellent yields
(entries 1–19). The reaction was equally effective for the removal
of both a- and b-acetates (entries 1–5). For L-fucose acetate (entry
4), lower temperature (optimized as 40 °C) significantly shrunk
)
could also be removed under the similar reaction conditions. For
di- and trisaccharides (entries 6, 7, 9, and 16), interglycosidic
linkage remained unaffected under this mild condition. A variety
of hydroxyl protecting groups, such as Fmoc (entry 1016), Phth
(entry 11), Troc (entry 1217), COOMe (entries 14 and 1518), Piv
(entry 17), Bn (entry 1819), and even TBDPS (entry 19) under lower
reaction temperature, are compatible to the conditions. However,
side products. In some cases (entries 5–17), reflux conditions were

G. Wei et al. / Tetrahedron Letters 49 (2008) 5488–5491
5491
acid labile TBS group (entry 2020) and benzylidene group (entry 21)
References and notes
cannot be survive under this condition. More impressively, the
yield for removal of anomeric acetate from trisaccharide derivative
(entry 16) was significantly improved using FeCl3Á6H2O in CH3CN,
comparing to that of using NH3 in MeOH and THF co-solvent.21 No
significant amount of required products was observed using Fe2(S-
O4)3ÁxH2O in CH3CN or other apolar solvents (CH2Cl2, THF, etc.).
A typical experimental procedure is depicted as follows: To a
solution of 1-O-acyl protected sugar (1.0 mmol) in CH3CN (5 mL)
was added FeCl3Á6H2O (1–2 mmol), and the reaction mixture was
stirred under the appropriate conditions as mentioned in Table 2.
After reaction completion (monitored by TLC), the reaction mixture
was concentrated directly under diminished pressure, in case of
small-scale reaction, and the corresponding residue was further
purified on column chromatography. For large-scale preparation,
the reaction mixture was neutralized with saturated aqueous NaH-
CO3 first, and then centrifuged. The liquid phase was collected and
extracted with CH2Cl2 three times. The combined organic phase
was evaporated to dryness, and the residue was purified by column
chromatography to gain desired product.
In summary, we have demonstrated that FeCl3Á6H2O–CH3CN
system is highly efficient toward regioselective anomeric deacyl-
ation of carbohydrate derivatives. The mild reaction conditions,
experimental simplicity, low cost, excellent yield, convenience in
large scale preparation, and the environmental benign nature are
major advantages of this new approach. Most commonly used pro-
tecting groups are matching with current chemistry, and some
highly toxic and expensive reagents can be avoided. We expected
that this green complimentary method would provide a general
application in organic synthesis.
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Acknowledgment
This work was supported by NNSF of China (Projects 30701043,
20572128, 20621703, and 20732001).
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