A one-pot selective deprotective acetylation of benzyl ethers and OTBDMS ethers using the BF3·Et2O-NaI-Ac2O reagent system

Article abstract of DOI:10.1016/j.tetlet.2006.05.016

An efficient selective deprotection followed by acetylation of several benzyl ethers, including 6-OBn ethers of monosaccharides, and -OTBDMS ethers has been developed by using the BF₃·Et₂O-NaI-Ac₂O reagent system. In addition, both benzylidene and isopropylidene groups are deprotected to form the corresponding diacetates.

Full text of DOI:10.1016/j.tetlet.2006.05.016

Tetrahedron Letters 47 (2006) 5207–5210
A one-pot selective deprotective acetylation of benzyl ethers and
OTBDMS ethers using the BF ÆEt O–NaI–Ac O reagent system
3
2
2
Anita Brar and Yashwant D. Vankar*
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India
Received 30 January 2006; revised 21 April 2006; accepted 4 May 2006
Abstract—An efficient selective deprotection followed by acetylation of several benzyl ethers, including 6-OBn ethers of monosac-
charides, and -OTBDMS ethers has been developed by using the BF
and isopropylidene groups are deprotected to form the corresponding diacetates.
2006 Elsevier Ltd. All rights reserved.
3 2 2
ÆEt O–NaI–Ac O reagent system. In addition, both benzylidene
ꢀ
The importance of the selective introduction and
removal of protecting groups in organic synthesis is well
known and the suitability of a particular method largely
depends on the stability of the protecting groups
towards different reaction conditions in a given synthetic
endeavor. Protection of hydroxy groups as ethers, espe-
cially as benzyl ethers has long been recognized as a
valuable reaction. This is mainly because benzyl ethers
are stable under basic and acidic reaction conditions
and are relatively insensitive to various oxidizing and
reducing agents. Furthermore, the wide use of benzyl
ethers as protecting groups in organic synthesis is
because of the easy deprotection by hydrogenolysis with
recently with the K/t-BuNH /t-BuOH/18-crown-6
reagent system. Deprotection of a benzyl ether is often
2
6
followed by the conversion of the released alcohol to
another functionality. Hence, attempts have been made
in carbohydrate chemistry to convert 6-O-benzyl ethers
into the corresponding acetates using reagents like
7
ZnCl –Ac O–AcOH. However, this procedure requires
2
2
the use of a large amount of ZnCl and subsequent
2
work-up becomes tedious. There are, however, a few
8
other Lewis acids and acidic catalysts such as FeCl ,
3
9
10
11
ZnI2, H SO
and TMSOTf that have been em-
2
4
ployed along with Ac O to effect this transformation,
2
but either the selectivity or yield is not satisfactory.
1
11
palladium catalysts, under essentially neutral condi-
Further, in some cases the temperature needs to be
tions. Selective cleavage of a benzylic ether derived from
a primary alcohol in the presence of other benzylic
ethers, derived from secondary alcohols, as well as other
protecting groups is equally useful. From the carbohy-
drate point of view, various bio-active natural products
controlled to observe selectivity.
In connection with another project, where we attempted
to make use of the ZnCl –Ac O–AcOH procedure for
2
2
converting a 6-O-benzyl ether to the corresponding ace-
tate, we decided that a new procedure was required that
would utilize smaller amounts of a Lewis acid to avoid a
tedious work-up. Several years ago, we reported a sim-
ple procedure for the selective deprotection of benzylic,
phenolic methyl and aliphatic methyl ethers using NaI–
2
contain 1!6-O-glycosidic linkages. Hence, selective
deprotection of 6-OBn ethers of methyl glycoside deriv-
atives is a useful procedure for the synthesis of 1 ! 6-O-
linked oligosaccharides.
1
2
13
In addition to the use of catalytic hydrogenolysis,
cleavage of benzylic ethers has also been reported with
BF ÆEt O which has been well utilized in organic
3 2
1
4
synthesis. Our current interest in carbohydrate chemis-
try has led us to make use of this combination along
3
4
5
reagents such as Na/liq. NH , O , TMSI, and more
3
3
with Ac O to convert benzyl ethers to the corresponding
2
acetates. Our results are shown in Table 1.
Keywords: Selective deprotection; Acetylation; Benzylidene; Aceto-
nide; TBDMS ethers.
Thus, methyl 2,3,4,6-tetra-O-benzyl-a-D-mannopyrano-
*
Corresponding author. Tel.: +91 512 2597169; fax: +91 512
597436; e-mail: vankar@iitk.ac.in
side (Table 1, entry 1) upon treatment with the BF Æ
3
1
5
2
Et O–NaI–Ac O reagent system
gave 6-O-acetyl
2
2
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.05.016

5208
A. Brar, Y. D. Vankar / Tetrahedron Letters 47 (2006) 5207–5210
Table 1. Selective deprotective acetylation of –OBn and –OTBDMS ethers using the BF
3
ÆEt
2
2
O–NaI–Ac O reagent system
a
Entry
Substrate
Product
Time (h)
Yield (%)
a/b
OBn
OBn
OAc
OBn
O
O
BnO
BnO
BnO
BnO
1
1.5
75
—
OMe
OMe
OMe
1
1a
2a
OBn
OAc
O
O
BnO
BnO
BnO
BnO
b
2
3
4
1.0
1.5
1.0
78
—
BnO
BnO
OMe
2
BnO
BnO
OBn
BnO
BnO
OAc
O
O
82
80
a
BnO
BnO
OMe
OAc
O
3
3a
OAc
Ph
O
O
O
AcO
BnO
BnO
—
BnO
OMe
BnO
OMe
4
4
a
O
O
BnO
AcO
BnO
O
OAc
5
6
7
2
68
77
72
—
—
—
OAc
BnO
O
5
5a
OBn
OAc
O
O
BnO
BnO
BnO
BnO
1.5
1.5
OBn
OBn
6
6
a
OAc
O
OBn
O
BnO
BnO
BnO
SPh
SPh
BnO
OBn
OBn
7
7
a
OAc
OBn
O
O
BnO
BnO
BnO
BnO
8
9
SPh
1.5
76
a
BnO
OBn
OAc
8
8
a
OBn
OAc
OAc
1.5
1.5
70
70
—
—
9
9a
OTBDMS
1
0
1
0
10a

A. Brar, Y. D. Vankar / Tetrahedron Letters 47 (2006) 5207–5210
5209
Table 1 (continued)
a
Entry
Substrate
Product
Time (h)
1.5
Yield (%)
a/b
OBn
OAc
OAc
1
1
2
69
68
—
—
1
1
11a
OTBDMS
1
1.2
1.5
1.5
1
2
1
2a
OBn
OAc
1
1
3
4
69
65
—
—
1
3
13a
14a
OTBDMS
OAc
1
4
a
Isolated yields.
Yield after the recovery of starting material.
b
7
product 1a in 75% yield in 1.5 h. Likewise, the acetate
sponding acetate, however, the reactions were generally
slow and not clean. The reactions using the InCl /Ac O
reagent system, with or without NaI, were also not clean
and were generally slow.
1
6
2
a
was obtained in 78% yield (entry 2). However,
methyl 2,3,4,6-tetra-O-benzyl-a-D-galactopyranoside 3
entry 3) produced the diacetate 3a17 in 82% yield where
3
2
(
the anomeric –OMe ether was also replaced with an ace-
tate group when the reaction was allowed to proceed to
In conclusion, we have developed an efficient and selec-
tive deprotective acetylation of benzylic ethers using the
BF ÆEt O–NaI–Ac O reagent system. We believe that
since this method involves the use of inexpensive
reagents and the work-up is relatively easy, it will find
further use in organic synthesis.
1
8
completion. The stereochemistry at the anomeric cen-
tre was found to be a. It is likely that in this case since
the 6-OBn and the 4-OBn groups are cis to each other,
steric hindrance makes debenzylation of the 6-OBn
group somewhat slower and hence the methoxy group
from the anomeric position is also cleaved in competi-
tion eventually forming the diacetate 3a. Further, as
expected, both benzylidene and isopropylidene groups
were found to undergo cleavage followed by acetylation
of the released alcohols. Thus, methyl 2,3-O-dibenzyl-
3
2
2
Acknowledgements
We thank the Council of Scientific and Industrial
Research, New Delhi for financial support through a
project [01(1892)/03/EMR-II]. One of us (A.B.) thanks
the Centre for Development of Technical Education,
IIT Kanpur for a Research Scholarship.
4
,6-O-benzylidene-a-D-glucopyranoside 4 (entry 4) led
1
9
to product 4a in 80% yield and 3,5-di-O-benzyl-1,2-
O-isopropylidine-a-D-xylo-furanoside 5 (entry 5) gave
2
0
3
-O-benzyl-1,2,5-triacetyl-a-D-xylo-furanoside 5a
in
6
8% yield. The use of a smaller amount of the Lewis acid
did not alter the reactivity. 3-C-(2,3,4,6-tetra-O-benzyl-
b-D-glucopyranosyl)-1-propene 6 and phenyl 2,3,4,6-tet-
ra-O-benzyl-1-thio-b-D-galactopyranoside 7 (entry 7)
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2
1
22
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1
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20. Data for 5a: R = 0.65 (8:2 hexanes/EtOAc); yield = 68%;
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25
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ꢀ1
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½aꢁ +40.0 (c 0.75, CHCl
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127.4–128.3, 137.9, 168.9, 169.6. MS (ESI): m/z = 389
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–OBn or –OTBDMS ether (1 mmol) in dry acetic anhy-
+
dride (1.5 mL) at 0 ꢁC was added dropwise a solution of
NaI (1 mmol) in acetonitrile (0.5 mL) followed by
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