An exceptionally simple and catalytic method for regeneration of carbonyl functionality from the corresponding 1,3-oxathiolanes

Article abstract of DOI:10.1039/b110305a

A wide variety of 1,3-oxathiolanes 1 can be chemo-selectively deprotected to the corresponding carbonyl compounds 2 in good yields by employing V₂O₅-H₂O₂ catalyzed oxidation of ammonium bromide in a CH₂Cl₂- H₂O mixture at 0-5°C. Some of the major advantages of this procedure are its mild conditions, and that it is highly selective and efficient, high yielding, and cost-effective. Furthermore, no brominations occur at the double bond or allylic position or α to the keto position or aromatic ring.

Full text of DOI:10.1039/b110305a

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An exceptionally simple and catalytic method for regeneration of
carbonyl functionality from the corresponding 1,3-oxathiolanes
Ejabul Mondal, Priti Rani Sahu, Gopal Bose and Abu T. Khan*
1
Department of Chemistry, Indian Institute of Technology, North Guwahati, Guwahati-781 039,
India. E-mail: atk@postmark.net; Fax: ϩ 91 361 690 762
Received (in Cambridge, UK) 12th November 2001, Accepted 14th February 2002
First published as an Advance Article on the web 22nd March 2002
A wide variety of 1,3-oxathiolanes 1 can be chemo-
selectively deprotected to the corresponding carbonyl
compounds 2 in good yields by employing V2O5–H2O2
catalyzed oxidation of ammonium bromide in a CH2Cl2–
H2O mixture at 0–5 ЊC. Some of the major advantages of
this procedure are its mild conditions, and that it is highly
selective and efficient, high yielding, and cost-effective.
Furthermore, no brominations occur at the double bond or
allylic position or ꢀ to the keto position or aromatic ring.
various 1,3-oxathiolanes to the parent carbonyl compounds.
In this communication, we would like to report a catalytic
and environmentally favorable protocol for the deprotection
of various oxathioacetals by employing V2O5, H2O2 and NH4Br
(Scheme 1). The catalyst V2O5 is used for oxidation of
Introduction
The protection and deprotection strategy is a common tactic in
multistep organic synthesis. Among the various functional
groups, the protection of carbonyl groups as 1,3-oxathiolanes
has attracted much considerable interest owing to their many
important applications. They are usually used as acyl carbanion
equivalents1 for carbon–carbon bond forming reactions. The
most remarkable application is the use of chiral 1,3-oxa-
thiolanes for the synthesis of optically active tertiary alcohols
bearing a carbonyl functionality at the α-position, first demon-
strated2 by Eliel and Lynch. Later on, these protected com-
pounds were further utilized by Utimoto’s group in organic
synthesis.3 In addition, the use of oxathioacetals is much more
convenient than the corresponding O,O-acetals or S,S-acetals
because they are comparatively more stable than O,O-acetals
under acidic conditions and easier to remove than the corre-
sponding S,S-acetals. Although a large number of methods
have been developed for the deprotection of 1,3-dithiolanes4 to
the corresponding carbonyl compounds, only a few methods
are known in the literature for the deprotection of 1,3-
oxathiolanes.5 The usual procedures for the deprotection of
1,3-oxathiolanes are as follows: i) by using isoamyl nitrite,6a and
chloramine-T,6b ii) by employing TMSOTf alone,7a iii) by using
TMSOTf in the presence of p-nitrobenzaldehyde,7b,c or polymer
supported p-nitrobenzaldehyde,7d iv) by utilizing halonium ion
sources in the presence of expensive silver salts8a,b or by using
NBS in acetone.8c Unfortunately, some of these methods have
serious drawbacks such as the removal of the by-product 1,3-
oxathiolanes derived from p-nitrobenzaldehyde,7b,c or the use of
an expensive polymer-supported reagent,7d and sometimes the
failure to deprotect non-benzylic oxathioacetals7a and also their
much longer reaction times.7d Other drawbacks related to halo-
nium ion sources include the need for a large molar excess of
reagents such as expensive silver salts8a,b and again much longer
reaction times.8c Recently, a further method was reported9 by
Kirihara et al. using a catalytic amount of trichlorooxy-
vanadium, which requires drastic reaction conditions. Con-
sequently, it seems to us that there is still a great need for better
alternatives that might proceed under reaction conditions that
are mild, clean, environmentally benign, efficient, site-selective,
operationally simple, and economically much cheaper.
Scheme 1
ammonium bromide by H2O2 and all these chemicals are
environmentally acceptable.
Results and discussion
A wide variety of structurally different 1,3-oxathiolanes 1a–1p
were prepared by treatment with the appropriate carbonyl
compound and 2-mercaptoethanol in the presence of a catalytic
amount of n-tetrabutylammonium tribromide (TBATB).13
Next, we attempted to optimize the reaction conditions for
cleavage of 1,3-oxathiolanes to obtain the desired parent
carbonyl compounds. We found that a mixture of substrate–
ammonium bromide–vanadium pentaoxide–hydrogen peroxide
(1 : 1 : 0.1 : 10) in dichloromethane–water solvent (5 : 1, 6 ml
mmolϪ1 substrate) gave the best results. We also observed that
the same reaction was completed within a much shorter period
if the amount of V2O5 was increased from 0.1 to 0.25 equiv-
alents and the amount of ammonium bromide from 1 to 3
equivalents. By following the above typical reaction procedure,
the substrate 2-(p-methoxyphenyl)-1,3-oxathiolane (1a) reacted
smoothly to provide the desired compound p-methoxy-
benzaldehyde (2a) in 85% yield. The compound 2a was char-
1
acterized by comparison of its IR and H-NMR spectra with
those of an authentic sample. Similarly, compounds 1b–1e
were smoothly converted to the desired carbonyl compounds
2b–2e in good yields under identical reaction conditions.
Likewise, 2-(p-nitrophenyl)-1,3-oxathiolane (1f ) was also
converted directly into the p-nitrobenzaldehyde (2f ) within
2.5 h in 90% yield. It is important to highlight that the same
compound 2f was obtained from compound 1f on treatment
with NBS8c but only after 6 h, which shows that our protocol
is much more effective in comparison to this earlier reported
method. Subsequently, various protected compounds 1g–1p
were transformed into their corresponding carbonyl com-
pounds 2g–2p without any difficulty under identical reaction
conditions. The results summarized in Table 1 clearly demon-
strate that the method is equally efficient for a wide variety
of oxathioacetals. It is noteworthy that no brominations (for
entries 1i–1k) take place at either the double bond or the
allylic positions, a result that would be very difficult to
achieve by using NBS. It is also important to mention that
other protecting groups such as Bn, Ac, TBDMS (for
entries 1b, 1c and 1h) were unaffected under the experimental
The discovery of vanadium bromoperoxidase (VBrPO),10
a
vanadium enzyme that catalyzes the oxidation of bromide by
hydrogen peroxide,11 as well as our ongoing research to develop
a new methodology,12 prompted us to use a V2O5–H2O2
catalyzed oxidation of ammonium bromide for the cleavage of
1026
J. Chem. Soc., Perkin Trans. 1, 2002, 1026–1028
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b110305a

View Article Online
Table 1 Cleavage of various oxathioacetals 1 to the parent carbonyl compounds 2 by ammonium bromide in the presence of V2O5 and H2O2
Entry
Substrate (1)
Reaction time/h
0.75
Product (2)a
Yieldb (%)
a
85
b
c
d
1.25
1.0
88
84
82
1.25
e
1.25
85
f
2.5
90
90
g
0.75
h
i
0.75
1.0
85
73
j
1.0
1.0
68
70
k
l
1.5
CH3(CH2)10CHO
CH3(CH2)6CHO
76
86
96
m
n
1.25
1.25
o
p
1.5
1.0
90
92
a Products were characterized by IR, 1H-NMR and 13C-NMR, by comparison with the spectra of authentic samples, as well as by elemental analyses.
b Isolated yield.
conditions. All the deprotected compounds were fully charac-
Conclusions
1
terized14 by IR, H-NMR and 13C-NMR, by comparison with
the spectra of authentic samples, as well as by elemental
analyses.
In summary, we have demonstrated a useful and catalytic
method for the chemoselective deprotection of various 1,3-
oxathiolanes to the corresponding carbonyl compounds in
presence of other protecting groups using V2O5–H2O2 oxidation
of ammonium bromide under very mild reaction conditions.
In addition, all of these reagents are environmentally accept-
able and easy to handle; maintaining the stoichiometric ratio
while carrying out the reaction is also possible. It is noteworthy
that no brominations take place at the double bond, allylic
positions, aromatic ring or α to the keto position. Due to its
operational simplicity, generality and efficacy, this method is
expected to have a wide applicability for the cleavage of various
The deprotection of various 1,3-oxathiolanes into the
corresponding carbonyl compounds can be explained as fol-
lows. Vanadium pentaoxide reacts with hydrogen peroxide to
generate reactive peroxovanadate() intermediates,15 which
oxidize BrϪ to Brϩ. The reactive bromonium ion can undergo
further oxidation to Br2 or Br3Ϫ, which might exist in solu-
tion. Then the reactive species Brϩ reacts with sulfur to form
a bromosulfonium complex, which is finally hydrolyzed by
water to yield the parent carbonyl compounds, as depicted in
Scheme 2.
J. Chem. Soc., Perkin Trans. 1, 2002, 1026–1028
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Scheme 2
oxathioacetals. Other alkali bromides can also be used for
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Experimental
To a suspension of V2O5 (0.018 g, 0.1 mmol) in water (1.0 ml)
was added 30% H2O2 solution (1.2 ml, 10 mmol) at ice-bath
temperature with continued stirring. After 25 min, the colour
of the solution changed into a clear brown–red, and then
ammonium bromide (0.098 g, 1 mmol) was added. The sub-
strate 2-(p-nitrophenyl)-1,3-oxathiolane (1f ) (0.211 g, 1 mmol)
was added after 10 min in solution in CH2Cl2 (5 ml) with
further stirring. The reaction was complete within 1 h and
55 min of stirring as monitored by TLC. The reaction mixture
was then extracted with CH2Cl2 (2 × 15 ml), washed with water
(1 × 15 ml) and finally washed with brine solution (1 × 10 ml).
The organic layer was dried over anhydrous Na2SO4 and con-
centrated in vacuo. Evaporation of the solvent gave the crude
residue, which was finally purified by column chromatography
on silica gel (eluent: hexane–EtOAc, 9 : 1). The product 2f was
obtained as a light yellow solid 0.136 g (90%), mp 105–106 ЊC
(lit.16 mp 104–106 ЊC).
10 H. Vitler, Phytochemistry, 1984, 23, 1387.
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1
14 Spectroscopic data for compound 1j: H-NMR (300 MHz, CDCl3)
δ 1.85–2.09 (m, 6H, cyclohexyl CH2-), 3.16–3.32 (m, 2H, -SCH2-),
3.87–3.95 (m, 1H, -OCH2-), 4.48–4.54 (m, 1H, -OCH2-), 4.79–4.91
(m, 1H, -OCH-), 5.83–5.99 (m, 3H, olefinic H, -O-CH-S), 6.89
(d, 2H, J = 8.5 Hz, ArH), 7.39 (d, 2H, J = 8.5 Hz). Anal. calcd. for
C15H18O2S: C 68.67, H 6.91. Found C 68.52, H 6.88%. Spectroscopic
data for compound 1j: 1H-NMR (400 MHz, CDCl3) δ 1.63–2.18 (m,
6H, cyclohexyl CH2-), 4.91 (s, 1H, -ArOCH-), 5.84–5.87 (m, 1H,
olefinic H), 6.00–6.04 (m, 1H, olefinic H), 7.01 (d, 2H, J = 8.8 Hz,
ArH), 7.82 (d, 2H, J = 9.0 Hz, ArH), 9.87 (s, 1H, -CHO); 13C-NMR
(100 MHz, CDCl3) δ 18.76, 24.95, 28.11, 71.10, 115.59 (2C), 125.16,
129.59, 131.99 (2C), 133.05, 163.09, 190.70. Anal. calcd. for
C13H14O2: C 77.20, H 6.98. Found C 77.01, H 6.94%.
Acknowledgements
We are pleased to acknowledge financial support from the
Department of Science and Technology (DST), New Delhi
(Grant No. SP/S1/G-35/98 to A.T.K.). E. M. and G. B. are
thankful to the CSIR for their research fellowships. P. R. S. is
also grateful to the DST for her fellowship. The authors are also
thankful to the Director, I.I.T. Guwahati for providing general
facilities to carry out this research work and to the referees for
their valuable comments and suggestions.
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J. Chem. Soc., Perkin Trans. 1, 2002, 1026–1028