Facile oxidative cleavage of benzylidene acetals using molecular oxygen catalyzed by N-hydroxyphthalimide/Co(OAc)2

Article abstract of DOI:10.1016/S0040-4039(01)00905-4

Benzylidene acetals derived from 1,2- and 1,3-diols undergo facile oxidative cleavage to give hydroxy benzoate esters with molecular oxygen in the presence of catalytic amount of N-hydroxyphthalimide/Co(OAc)₂.

Full text of DOI:10.1016/S0040-4039(01)00905-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4955–4958
Facile oxidative cleavage of benzylidene acetals using molecular
oxygen catalyzed by N-hydroxyphthalimide/Co(OAc)2
Yongsheng Chen and Peng George Wang*
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA
Received 7 May 2001; accepted 25 May 2001
Abstract—Benzylidene acetals derived from 1,2- and 1,3-diols undergo facile oxidative cleavage to give hydroxy benzoate esters
with molecular oxygen in the presence of catalytic amount of N-hydroxyphthalimide/Co(OAc) . © 2001 Elsevier Science Ltd. All
2
rights reserved.
A benzylidene acetal is a widely used protective group
for 1,2- and 1,3-diols in organic synthesis due to its
were isolated in 82% combined yield in a ratio of 2:1
(Scheme 1).
1
tolerance to a variety of chemical conditions. As it
provides selective protection of the 4- and 6-hydroxyl
moieties of the pyranoses of common monosaccharides
such as glucose, galactose, and mannose, the benzyli-
dene acetal group has found extensive applications in
oligosaccharide and glycoconjugate synthesis. Adding
greatly to the utility of this group are methodologies for
the selective cleavage of the benzylidene acetal, allowing
formation of a benzyl ether (under reductive condition)
or a benzoate ester (under oxidative condition) at either
the C4 or C6 hydroxyl group.
A survey of the literature revealed that oxidative cleav-
age of benzylidene acetals to hydroxyesters has been in
place since 1973. Various reagents, such as trityl
+
−
5
6
fluoroborate (Ph C BF ), ozone, t-butyl hydroperox-
3
4
2,3
7
8
9
ide,
NBS/H O,
NaBO ,
2,2%-bipyridinium
2
3
1
0
11
chlorochromate/m-CPBA,
and NaBrO /Na S O ,
3 2 2 4
have been employed for this transformation with vary-
ing degrees of regioselectivity. However, most of these
procedures suffer from the use of a toxic reagent, or
rather harsh or environmentally unfriendly conditions.
An interesting approach for the oxidation of alcohols
to carbonyl compounds using molecular oxygen (O2)
catalyzed by N-hydroxyphthalimide (NHPI) combined
with a Co species has recently appeared in the litera-
To examine the generality of the current oxidative
cleavage system, the benzylidene acetals of a couple of
1,2- and 1,3-diols, including several sugar substrates,
were subjected to the oxidation conditions (Table 1). In
each instance except for entry 5, the benzylidene acetal
was smoothly cleaved to give the hydroxy benzoate
ester(s) in good to excellent yields. Under the reaction
conditions, compound 6 gave a complex mixture. While
symmetrical substrates 2 and 4 yielded only one
4
ture. In the course of our studies towards bicyclic
sugars, we carried out the oxidation of glucoside 1 with
the reported NHPI/Co(OAc) /O system. Instead of the
2
2
desired ketone 1c, the corresponding 4-hydroxy-6-O-
benzoate ester 1a and 6-hydroxy-4-O-benzoate ester 1b
O
N
OH (NHPI), 10 mol%
Co(OAc)2, 0.5 mol%
OBz
O
OH
O
Ph
O
Ph
O
O
O
O
O
HO
BzO
+ BzO
BzO
O
BzO
BzO
HO
mCPBA, 5 mol%
O2, EtOAc
HO
HO
O
OMe
OMe
OMe
OMe
1
1a
1b
1c
Scheme 1. Oxidative cleavage of 4,6-O-benzylidene acetal 1.
*
0
Corresponding author. Tel.: 313-993-6759; fax: 313-577-2554; e-mail: pwang@chem.wayne.edu
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00905-4

4
956
Y. Chen, P. G. Wang / Tetrahedron Letters 42 (2001) 4955–4958
Table 1. Oxidative cleavage of benzylidene acetals
product, the other benzylidenes gave a roughly 1:1
mixture of regioisomers. The deprotection of sugar
substrates 1, 7–9 (entries 6–9) showed functional group
tolerance of this NHPI/Co(OAc) /O system towards
and that the Co(III)–dioxygen complex assists the for-
mation of a phthalimide N-oxyl radical (PINO) from
4,12
NHPI.
The PINO radical thus generated abstracts a
hydrogen atom from 3 to form a,a%-dialkoxy benzyl
radical A, which is eventually converted into hydroxy-
esters 3a and 3b through the formation of a,a%-
dialkoxy benzyl hydroperoxide B. This mechanism
explains the complexation with substrates 6 and 9,
where the formation of an a-alkoxy benzyl radical at
another carbon is highly possible and competes with
the main deprotection reaction. Because the collapse of
hydroperoxide B to form hydroxyesters has little bias
toward either side of the molecule, this mechanism also
accounts for the low regioselectivities observed for all
the substrates.
2
2
esters and glycosidic methyl acetals. However, in the
case of 9, oxidation of the O-benzyl group to O-ben-
zoyl and accompanying O-debenzoylation were
7
b
observed, giving rise to products with a free C2 or C3
hydroxyl group in addition to the two major products
shown. The reactions with simple substrates (entries
1
–4) usually took place within 1–2 h. In fact, if the
reaction with 3 was run for 5 h, the only product
isolated was the ketone corresponding to 3a in quanti-
tative yield.
A plausible reaction path for the aerobic oxidative
cleavage of 3 by the present catalytic system is illus-
trated in Scheme 2. Ishii et al. showed that the genera-
tion of a Co(III)–dioxygen complex, derived from
Co(OAc) and O , is important to initiate the oxidation
In a typical procedure, methyl 3-O-benzoyl-4,6-O-ben-
zylidene-a- -glucopyranoside 1 (247 mg, 0.64 mmol),
D
NHPI (10 mg, 10 mol%), Co(OAc) (0.8 mg, 0.5 mol%),
2
and m-CPBA (5 mg, 5 mol%) in EtOAc (5 mL) were
2
2

Y. Chen, P. G. Wang / Tetrahedron Letters 42 (2001) 4955–4958
4957
O
HO
OBz
BzO
OH
3b
N OH
3a
NHPI
O
O2
AcO)2CoII
AcO)2CoIII
(AcO)2Co OO
III
(
III
(
(AcO)2Co OOH
O
Ph
OOH
Ph
O
O
NO
O
O
PINO
O
B
3
NHPI
Ph
Ph
OO
O
O
O
O
A
O2
Scheme 2. A plausible reaction path for the aerobic oxidative cleavage of benzylidene acetal 3.
placed in a flask equipped with a balloon filled with O2.
The mixture was stirred at ambient temperature for 15
h. Removal of the solvent under reduced pressure,
followed by silica-gel chromatography (EtOAc:Hexanes
Acknowledgements
This work was supported by a grant from the NIH
GM 54074).
1
:1 to 5:3) provided 1a (140 mg, 54%) as a solid and 1b
(
†
(
70 mg, 27%) as a liquid.
In conclusion, we have reported a facile procedure for
the oxidative cleavage of benzylidene acetals to the
corresponding hydroxy benzoate ester(s). The method-
ology is environmentally benign and experimentally
simple, and utilizes mild reaction conditions compatible
with common carbohydrate protecting groups.
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