Montmorillonite K-10 clay as an efficient solid catalyst for chemoselective protection of carbonyl compounds as oxathiolanes with 2-mercaptoethanol

Article abstract of DOI:10.1055/s-2004-829054

Montmorillonite K-10 clay has been found to be a mild and efficient solid catalyst for the protection of a variety of carbonyl compounds, such as oxathiolanes, with 2-mercaptoethanol in good to excellent yields. In addition, by using this catalyst, high chemoselective protection of aldehydes in presence of ketones has been achieved.

Full text of DOI:10.1055/s-2004-829054

1
592
LETTER
Montmorillonite K-10 Clay as an Efficient Solid Catalyst for Chemoselective
Protection of Carbonyl Compounds as Oxathiolanes with 2-Mercaptoethanol
M
S
ontmorillon
i
ite K-1
d
y
as an
dE fficient Sol
h
idCatalyst
f
a
or Chemose
r
lective
P
t
rotecti
h
on a Gogoi, Jagat C. Borah, Nabin C. Barua*
Natural Products Chemistry Division, Regional Research Laboratory (CSIR), Jorhat-785006, Assam, India
Fax +91(376)2370011; E-mail: ncbarua2000@yahoo.co.in
Received 9 March 2004
mand further searches for better catalysts that are superior
to the existing ones especially with regard to toxicity and
selectivity. In recent years, there has been a tremendous
Abstract: Montmorillonite K-10 clay has been found to be a mild
and efficient solid catalyst for the protection of a variety of carbonyl
compounds, such as oxathiolanes, with 2-mercaptoethanol in good
to excellent yields. In addition, by using this catalyst, high chemose- upsurge of interest in the use of different clays as hetero-
lective protection of aldehydes in presence of ketones has been geneous and environment friendly catalysts for different
achieved.
organic transformations. In this context, we have devel-
Key words: carbonyl compounds, 2-mercaptoethanol, montmoril- oped a mild and efficient method for the protection of al-
lonite K-10, chemoselective, oxathiolanes
dehydes and ketones with 2-mercaptoethanol in the
presence of montmorillonite K-10 clay. Due to strong cat-
alytic activity as Brønsted acid, montmorillonite K-10
clay has been most frequently used in fine organic synthe-
sis. Although montmorillonite K-10 has been used exten-
sively as a catalyst for the protection of carbonyl and
The protection-deprotection sequence is probably the
most recurrent functional group interconversion in multi-
step organic synthesis. Amongst the numerous protecting
groups employed to protect aldehydes and ketones from
nucleophilic attack, 1,3-oxathioacetals have long been
18
hydroxyl groups with trimethylorthoformate and 3,4-di-
19
hydro-2H-pyran, as a Lewis acid in aldol condensa-
used as a protective group and an acyl anion equivalent tion,20 Diels–Alder and Friedel–Crafts reaction,
21
22
a
1
2
3
in C-C bond forming reactions. Moreover, the use of literature search clearly shows that there has been no in-
oxathiolanes is much more convenient than the corre- vestigation into the protection of carbonyl groups with 2-
sponding O,O-acetals or S,S-acetals because they are mercaptoethanol in the presence of this clay. Herein we
comparatively more stable than O,O-acetals under acidic report a mild and efficient method for the 1,3-oxathioace-
conditions and easier to remove than the corresponding talization of carbonyl compounds in good to high yields as
4
5
well as the chemoselective protection of various alde-
hydes in the presence of ketones by using montmorillonite
S,S-acetals. On the other hand, Eliel and the others have
clearly established the use of chiral 1,3-oxathioacetals as
chiral auxiliaries for the enantioselective synthesis of a-
hydroxy acids and glycols in organic synthesis. In the lit-
erature there are several methods reported for the prepara-
tion of oxathiolanes from carbonyl compounds employing
K-10 clay in CH Cl at room temperature (Scheme 1).
2
2
O
O
S
HOCH2
CH SH (1.5–2 equiv)
2
6
R1
R2
R1
R2
acid catalysts such as dry hydrogen chloride or HCl,
Montmorillonite K-10, CH2Cl2, r.t.
7
8
9
10
HClO , refluxing with TsOH, BF ·OEt , Bu NBr ,
4
3
2
4
3
1
1
12
13
14
1
R = aryl, alkyl, allyl, heterocyclic
TMSOTf,
i-Pr SiOTf,
SO ,
ZrCl4,
ZnCl2–
3
2
2
1
5
16
17
R = alkyl, H
Na SO , ion-exchange resins and Sc(OTf)3 as cata-
2
4
lyst or as stoichiometric reagents. Unfortunately, most of
the reported procedures have certain drawbacks such as
long reaction times, low yields of the products, reflux-
ing of the reaction mixture, formation of unwanted side
products, use of expensive reagents and tedious work up
procedure. Therefore, the developments in this area de-
Scheme 1
1
4
10
23
As shown in Table 1, various types of aliphatic, aromat-
ic and heterocyclic aldehydes are efficiently and rapidly
converted to their corresponding 1,3-oxathiolanes in the
presence of 2-mercaptoethanol (1.5–2 equiv) under the
O
O
O
CHO
2 2
HOCH CH SH (1.5–2 equiv)
S
X
X
Montmorillonite K-10, CH2Cl2, 3 h, r.t.
X
X
89–91%
98%
X = H, Br, Cl
Scheme 2
influence of montmorillonite K-10 (two times the mass of
the substrate) at room temperature. It has been observed
that in the case of both activated and weakly activated ar-
SYNLETT 2004, No. 9, pp 1592–1594
2
2.
0
7.
2
0
0
4
Advanced online publication: 29.06.2004
DOI: 10.1055/s-2004-829054; Art ID: G07304ST
Georg Thieme Verlag Stuttgart · New York
©

LETTER
Montmorillonite K-10 Clay as an Efficient Solid Catalyst for Chemoselective Protection
1593
Table 1 Montmorillonite K-10 Catalyzed Preparation of 1,3-Oxa-
thiolanes
omatic aldehydes, the yields of the products (entries 4, 5
and 10) were slightly higher than the recent protocols.7
,10
Aliphatic ketones also react efficiently to produce the cor-
responding oxathiolanes (entries 1, 2 and 7) in good
yields. It is interesting to note that aromatic ketones did
not produce the corresponding oxathiolanes under the
same reaction conditions. This result indicates that the
present protocol is potentially applicable for the chemose-
lective protection of aldehydes in the presence of ketones
in multi-functional compounds. With this objective, as a
representative example we have conducted some compet-
itive protection reactions with equimolar mixtures of alde-
hydes and ketones (Scheme 2). It was observed that in this
mixture, only aldehydes formed the oxathiolanes and ke-
tones were almost completely recovered.
Entry Substrates
O
Productsa
Reaction Yields
time (h) (%)
b
O
O
S
S
1
1
90
O
2
1
2
85
82
O
S
CHO
O
O
3
4
S
This experiment has also been extended for the intra-
molecular chemoselectivity between keto and aldehyde
functionalities in b-ketoaldehydes (Scheme 3). It was ob-
served that deactivated aromatic b-ketoaldehydes such as
CHO
O
0.5
86
b-ketoaldehyde of p-NO -benzene when subjected to the
2
MeO
MeO
CHO
O
same reaction conditions, could be converted to oxathio-
lanes selectively at aldehyde position after long reaction
time (9–10 h) and in moderate yield (65–75%). The alde-
hyde group of benzylic b-ketoaldehyde also formed oxa-
thiolane selectively in good yield (85%).
MeO
MeO
S
OMe
CHO
5
6
1.5
3
88
70
OMe
O
S
O
O
O
HOCH2CH2SH (2 equiv)
O
S
O
H
H
CHO
R
Montmorillonite K-10, CH Cl , 2–10 h, r.t.
R
2
2
7
3.5
73
S
65–85%
R = p-ClC6H5-, p-CH3OC6H5-, CH3C6H5-, 2-thiophene, 2-furan,
C6H5-, PhCH2-, p-NO2C6H5-
O
O
S
S
Scheme 3 Chemoselective protection of aldehyde functionalities
using clay
8
9
0
4
69
89
91
MeO
MeO
MeO
MeO
Cl
CHO
O
In conclusion, we have developed a mild and efficient
method for the protection of aliphatic, heterocyclic and
aromatic aldehydes as well as aliphatic ketones as the
corresponding oxathiolane derivatives with 2-mercapto-
ethanol by using montmorillonite K-10 clay in good to ex-
cellent yields. Moreover the demonstration of the
chemoselectivity between the keto and aldehyde groups
makes the present method an efficient method for oxathio-
acetalization.
2
CHO
O
S
Cl
1
1.5
CHO
O
S
1
1
1
2
3
1.5
5
89
–
Acknowledgment
O
The authors gratefully acknowledge the Director, Regional
Research Laboratory (CSIR), Jorhat, Assam, India for providing
facilities for this work. SG thanks CSIR, New Delhi for the award
of Junior Research Fellowship.
No reaction
O
1
No reaction
5
–
HO
a
1
All products were characterized by H NMR, IR and mass spectros-
copy.
b
Isolated yields after purification by thin layer chromatography on sil-
ica gel.
Synlett 2004, No. 9, 1592–1594 © Thieme Stuttgart · New York

1
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S. Gogoi et al.
LETTER
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1
(
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Synlett 2004, No. 9, 1592–1594 © Thieme Stuttgart · New York