A useful and convenient synthetic protocol for interconversion of carbonyl compounds to the corresponding 1,3-oxathiolanes and vice versa employing organic ammonium tribromide (OATB)

Article abstract of DOI:10.1016/S0040-4039(02)00345-3

A wide variety of carbonyl compounds 1 can be easily protected selectively as the corresponding 1,3-oxathiolanes 2 in good yields using a catalytic amount (0.01-0.1 equiv.) of n-tetrabutylammonium tribromide in dry CH₂Cl₂ at 0-5°C. O

Full text of DOI:10.1016/S0040-4039(02)00345-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2843–2846
A useful and convenient synthetic protocol for interconversion of
carbonyl compounds to the corresponding 1,3-oxathiolanes and
vice versa employing organic ammonium tribromide (OATB)†
Ejabul Mondal,a Priti Rani Sahu,a Gopal Bosea and Abu T. Khana,b,
*
aDepartment of Chemistry, Indian Institute of Technology, North Guwahati, Guwahati 781 039, India
bDepartment of Chemistry, Visva-Bharati, Santiniketan, West Bengal 731 235, India
Received 3 December 2001; revised 22 January 2002; accepted 15 February 2002
Abstract—A wide variety of carbonyl compounds 1 can be easily protected selectively as the corresponding 1,3-oxathiolanes 2 in
good yields using a catalytic amount (0.01–0.1 equiv.) of n-tetrabutylammonium tribromide in dry CH2Cl2 at 0–5 °C. On the other
hand, various 1,3-oxathiolanes 2 can be deprotected chemoselectively to the parent carbonyl compounds 1 employing 0.5
equivalents of organic ammonium tribromides under identical conditions in very high yields. Mild conditions, high selectivity and
yield, highly efficient, less expensive, and no brominations either at the double bond or allylic position and even a- to the keto
position or aromatic ring are some of the major advantages of the protocol. © 2002 Elsevier Science Ltd. All rights reserved.
Protection and deprotection strategies are very com-
monly used techniques for complex natural and non-
natural product synthesis. Among various functional
groups, protection of the carbonyl group as a 1,3-
oxathiolane is important for the following reasons.
Firstly, they can be used as acyl carbanion equivalents1
for carbon–carbon bond forming reactions. Secondly,
the chiral 1,3-oxathiolanes are valuable synthons for
enantioselective synthesis of a-hydroxyaldehydes, first
demonstrated by Eliel and his co-workers.2 Later on,
these compounds were further utilized by Utimoto et
al.3 for studying diastereoselective reactions. Thirdly,
the use of oxathioacetals is more convenient than the
corresponding O,O-acetals or S,S-acetals because they
are comparatively more stable than O,O-acetals in
acidic conditions and much easier to remove than S,S-
acetals. Though a large number of methods have been
developed for the protection and deprotection of car-
bonyl compounds as 1,3-dithiolanes,4 only a few meth-
ods are available for oxathioacetals.5 The usual
procedures for the formation of oxathioacetals from
their corresponding carbonyl compounds are as fol-
lows: (i) using HCl,6a (ii) refluxing with p-TSA,6b (iii)
treating with BF3-OEt2,6c (iv) using ZnCl2, and (v)
6d
utilizing catalytic amounts of TMSOTf.6e All these
methods have certain drawbacks such as low yield,6a
relatively harsh reaction conditions,6b,c relatively long
reaction times,6c and expensive reagents6e (TMSOTf) as
well as inconvenience of use. Similarly, a few methods
are also reported for the deprotection of 1,3-oxathio-
lanes using (i) isoamyl nitrite7a and chloramine-T,7b
(ii) TMSOTf alone,6e or in the presence of p-nitrobenz-
aldehyde,7c,d and polymer supported p-nitrobenzalde-
hyde.7e Some of these methods have serious drawbacks
such as difficult to remove by-product 1,3-oxathiolanes
derived from p-nitrobenzaldehyde,7c,d or the use of
expensive polymer supported reagents.7e Another
important drawback is the deprotection of non-benzylic
oxathioacetals which requires much longer reaction
times.6e Some methods also known in the literature are
based on halonium ion sources such as NCS-
AgNO3,8a,b I2-AgNO2
and NBS in acetone8e for the
8c,d
deprotection of a wide variety of oxathioacetals. Unfor-
tunately, these methods suffer from the requirement of
a large molar excess of reagents such as expensive silver
salts8a–d as well as much longer reaction times.8e Very
recently, another method has appeared9 for deprotec-
tion of various oxathioacetals by using glyoxylic acid in
the presence of Amberlyst 15 in a microwave oven,
which is relatively expensive. Consequently, what is
needed is a methodology that is mild, clean, environ-
Keywords: protection; deprotection; 1,3-oxathiolanes; n-tetra-
butylammonium tribromide (TBATB); cetyltrimethylammonium tri-
bromide (CetTMATB).
* Corresponding author. Fax: +91-361-690762; e-mail: atk@
postmark.net
†
This work is dedicated to Professor D. N. Buragohain, Director,
IIT Guwahati for setting up this new institute and giving us the
opportunity to carry out our research work.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00345-3

2844
E. Mondal et al. / Tetrahedron Letters 43 (2002) 2843–2846
TBATB can be used for deprotection of silyl ethers.13a
All the protected compounds were fully characterized
by 1H NMR spectroscopy and elemental analyses.15
The formation of the products can be explained as
follows. It has been shown that OATB such as ben-
zyltrimethyl ammonium tribromide generates HBr and
MeOBr in methanol.16 We suggest that HBr is forming
slowly from the reaction of TBATB with 2-mercapto-
ethanol, which catalyzes the conversion of the carbonyl
compounds into the corresponding 1,3-oxathiolanes.
We noted that the pH of the solution was ꢀ2–3 while
carrying out the reaction.
mentally benign and yet efficient, site selective, opera-
tionally simple, and cost effective.
In an endeavor to gradually change the current working
practices to greener alternatives and environmental
demands,10 an environmentally favorable protocol for
the preparation of various organic ammonium tribro-
mides (OATB) and some of its applications was dis-
closed recently.11 We have also shown that these
reagents are extremely useful in organic synthesis par-
ticularly for deprotection of dithioacetals,12a and in
natural product synthesis.12b Some other valuable appli-
cations were also reported recently for deprotection of
TBDMS ethers13a and protection/deprotection of THP
ethers.13b Knowing the unique behavior and properties
of the reagents and as part of our ongoing research
project to develop a newer methodology,14 we con-
ceived the idea that OATBs might further be applied
for interconversion of various carbonyl compounds to
1,3-oxathiolanes and vice versa. We would like to
report our successful results in this communication, as
depicted in Scheme 1.
Next, we looked for suitable reaction conditions for
deprotection of 1,3-oxathiolanes to the parent carbonyl
compounds. The compound 2-(4-methoxyphenyl)-1,3-
oxathiolane 2a was deprotected smoothly to the parent
carbonyl compound 4-methoxybenzaldehyde 1a within
5 min on treatment with 0.5 equivalents of CetTMATB
or TBATB in dichloromethane at 0–5 °C. Similarly, we
have successfully converted various substituted 1,3-
oxathiolanes 2b–2n to the parent compounds 1b–1n
employing either CetTMATB or TBATB under identi-
cal reaction conditions, respectively. The results are
shown in Table 1 and the products were characterized
We have attempted optimization of the reaction condi-
tions for protection of a wide variety of carbonyl
compounds giving the corresponding 1,3-oxathiolanes.
The substrate p-methoxybenzaldehyde 1a was con-
verted to the protected compound 2a using 0.01 equiva-
lents of n-tetrabutylammonium tribromide (TBATB) in
dichloromethane at ice-bath temperature within 5 min
and in 65% yield. Similarly, compound 2a can also be
prepared from compound 1a using 0.01 equivalents of
acetyltrimethylammonium tribromide (CetTMATB)
under identical reaction conditions in 30 min. Using
TBATB, the reaction is faster in comparison to
CetTMATB. Likewise, we have successfully converted
various carbonyl compounds 1b–1n to the correspond-
ing 1,3-oxathiolanes 2b–2n, on treating the carbonyl
compound with 2-mercaptoethanol in the presence of a
catalytic amount of TBATB depending upon the
amount of reagent and reaction conditions, as shown in
Table 1. The results summarized in Table 1 clearly
demonstrate that the method is equally efficient for
various substrates.
1
by IR, H NMR spectroscopy and elemental analyses
as well as by comparison with the authentic com-
pounds.17 Our protocol is very effective, for instance,
oxathioacetal 2d was deprotected more rapidly than by
the earlier reported procedure.8e It is pertinent to men-
tion that the substrate 2g gives an undesired compound
instead of expected 1g at ice-bath temperature reaction
conditions. However, the compound 1g can be obtained
from the compound 2g if the reaction is carried out at
a lower temperature (−20°C), implying that the selectiv-
ity can be achieved by controlling reaction temperature.
The formation of the deprotected compound can be
rationalized as follows. TBATB generates Br+ ions,
which react with sulfur to form a bromosulfonium
complex, which is finally hydrolyzed to the correspond-
ing carbonyl compound.
In summary, we have devised a simple and convenient
method for the protection of various carbonyl com-
pounds as the corresponding 1,3-oxathiolanes as well as
deprotection to the parent carbonyl compounds,
chemoselectively, using OATBs and by tuning the
amount of the reagents, under very mild reaction condi-
tions. In addition, these reagents are environmentally
It is significant that no brominations take place either
at the double bond or allylic positions, for instance 1f,
1g and 1i. More interestingly, the TBDMS group is also
unaffected under the experimental conditions although
HOCH2CH2SH/TBATB (0.01-0.1 equiv.), dry CH2Cl2, 0-5 oC
R1
R1
O
O
S
R2
R2
2
1
CetTMATB or TBATB (0.5 equiv.), CH2Cl2, 0-5 oC
R1 = alkyl or aryl, R2 = H or alkyl or aryl
Scheme 1.

E. Mondal et al. / Tetrahedron Letters 43 (2002) 2843–2846
2845
Table 1. Protection of various carbonyl compounds 1 as the corresponding 1,3-oxathiolanes 2 and deprotection of com-
pounds 2 to the parent carbonyl compounds 1 using OATB
interconversion of various carbonyl compounds to the
corresponding oxathioacetals and vice versa. Other
OATBs can also be used for similar transformations,
which are under investigation and will be reported in
due course.
benign and are easy to handle. It is noteworthy that no
brominations take place either at the double bond or
allylic position, or in the aromatic rings. Due to its
operational simplicity, generality and efficacy, this
method is expected to have wider applicability for

2846
E. Mondal et al. / Tetrahedron Letters 43 (2002) 2843–2846
Heterocycles 1997, 44, 393; (e) Karimi, B.; Seradj, H.;
Acknowledgements
Tabaei, M. H. Synlett 2000, 1798.
9. Chavan, S. P.; Soni, P.; Kamat, S. K. Synlett 2001, 1251.
10. Clark, J. H. (Ed.) Chemistry of Waste Minimization,
Chapman and Hall: London, 1995.
11. (a) Chaudhuri, M. K.; Khan, A. T.; Patel, B. K.; Dey,
D.; Kharmawophlang, W.; Lakshmiprabha, T. R.; Man-
dal, G. C. Tetrahedron Lett. 1998, 39, 8163; (b) Bose, G.;
Bujar Barua, P. M.; Chaudhuri, M. K.; Kalita, D.; Khan,
A. T. Chem. Lett. 2001, 290.
A.T.K. acknowledges the Department of Science and
Technology (DST), New Delhi for financial grant
(Grant No. SP/S1/G-35/98). E.M. and G.B. are thank-
ful to the CSIR for their research fellowships. P.R.S.
thanks the DST for her fellowship. The authors are also
grateful to Professor M. K. Chaudhuri, I.I.T. Guwahati
for the reagents and to the referees for valuable com-
ments and suggestions.
12. (a) Mondal, E.; Bose, G.; Khan, A. T. Synlett 2001, 785;
(b) Bose, G.; Mondal, E.; Khan, A. T.; Bordoloi, M. J.
Tetrahedron Lett. 2001, 42, 8907.
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(b) Naik, S.; Gopinath, R.; Patel, B. K. Tetrahedron Lett.
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15. Spectroscopic data for compound 2f: H NMR (300 MHz,
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H, 6.31. Compound 2g: H NMR (300 MHz, CDCl3): l
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ꢀSCH2ꢀ), 3.87–3.95 (m, 1H, ꢀOCH2ꢀ), 4.48–4.54 (m, 1H,
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1
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ArH), 7.83 (d, 2H, J=8.6 Hz, ArH), 9.88 (s, 1H, ꢀCHO).
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73.89; H, 6.19. Compound 1g: 1H NMR (300 MHz,
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1H, ꢀOCHꢀ), 5.84–6.04 (m, 2H, CHꢁCH), 7.01 (d, 2H,
J=8.5 Hz, ArH), 7.82 (d, 2H, J=8.6 Hz, ArH), 9.87 (s,
1H, ꢀCHO). Anal. calcd for C13H14O2: C, 77.20; H, 6.98.
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