Preferential hydrolysis of benzylic/allylic dithianes and dithiolanes using o-iodoxybenzoic acid (IBX) in DMSO containing traces of water

Article abstract of DOI:10.1016/S0040-4039(02)01346-1

Dithianes and dithiolanes at benzylic or allylic carbons can easily be hydrolyzed by IBX in DMSO, whereas non-activated dithianes/dithiolanes are much more stable under these conditions.

Full text of DOI:10.1016/S0040-4039(02)01346-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6443–6445
Preferential hydrolysis of benzylic/allylic dithianes and
dithiolanes using o-iodoxybenzoic acid (IBX) in DMSO
containing traces of water
Yikang Wu,* Xin Shen, Jia-Hui Huang, Chao-Jun Tang, He-Hua Liu and Qi Hu
State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
Received 20 May 2002; revised 21 June 2002; accepted 3 July 2002
Abstract—Dithianes and dithiolanes at benzylic or allylic carbons can easily be hydrolyzed by IBX in DMSO, whereas
non-activated dithianes/dithiolanes are much more stable under these conditions. © 2002 Elsevier Science Ltd. All rights reserved.
Compared with their oxygen-counterparts, thioacetals/
thioketals, especially dithianes/dithiolanes, are much
easier to form and remarkably more stable under acidic
as well as basic conditions.1 Nevertheless, they can still
be cleaved cleanly to release free carbonyl groups under
essentially neutral conditions by using e.g. a proper
oxidant2 or visible light.3 Thus, it is possible to cleave
selectively4 thioacetals/thioketals in the presence of
acetals/ketals and vice versa. These properties make
thioacetals/thioketals excellent protecting groups in
synthesis. In addition, the 1,3-dithianes formed from
aldehydes can form carbanions on treatment with a
strong base, which easily react with various elec-
trophiles to afford thioketals, representing a useful
means of carbon–carbon bond formation.5 It is there-
fore not surprising that dithianes/dithiolanes are of
great importance in synthesis. However, the deprotec-
tion of thioacetals/thioketals is not always facile. In
some cases it can be an extremely difficult task. This is
presumably the main impetus for the lasting efforts to
develop new deprotection protocols, which had resulted
in more than 60 procedures6 in the literature by the
mid-1990s.
ferent types of dithianes/dithiolanes. To our knowledge
only one7 procedure, which uses Tl(NO3)2·3H2O as the
reagent, has been reported to be able to cleave selec-
tively an allylic dithiolane in the presence of another
dithiolane at a non-allylic position. However, the reac-
tions using Tl(NO3)2·3H2O proceed rather fast, which
inevitably makes it difficult to control the reaction and
thus greatly discourages further exploration of this
reagent in selective deprotection. Throughout the 20
years since this first report,7 only one8 among the
numerous documented applications has involved selec-
tive deprotection. No one seems to have exploited the
effects of subtle structural differences between different
types of dithianes/ditholanes on their cleavage/hydroly-
sis. Herein, we wish to report the first systematic study
on the type-selective dithianes/ditholanes cleavage and
the first reagent that shows large differences in reaction
rates for different types of dithianes/ditholanes.
Our deprotection of ‘activated’ dithianes/ditholanes
(e.g. those at benzylic and allylic positions) was realized
by treatment of the substrate with o-iodoxybenzoic
acid9,10 (IBX) in DMSO containing traces of added
water. At ambient temperatures, the dithianes/
ditholanes at benzylic, or allylic positions were easily
cleaved to give the corresponding carbonyl compounds
whereas those at non-activated positions remained
intact unless subjected to prolonged exposure to the
cleaving conditions.11 The yields are generally high for
activated substrates. As shown in Table 1, the activated
thioacetals are rather liable to the IBX cleavage condi-
tions. In most cases, the sulfur protecting groups at
benzylic and allylic positions can be removed cleanly
within 30 minutes, whilst non-activated ones remained
It is interesting to note that amongst the numerous
methods6 for converting thioacetals/thioketals to the
corresponding carbonyl compounds documented over
the last half-century, there is essentially none that
shows a substantial difference in cleavage rate for dif-
Keywords: activated dithianes; activated dithiolanes; selective hydroly-
sis; IBX.
* Corresponding author. E-mail: yikangwu@pub.sioc.ac.cn
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01346-1

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Y. Wu et al. / Tetrahedron Letters 43 (2002) 6443–6445
Table 1. IBX mediated cleavage of thioketals/thioacetals into the corresponding carbonyl compoundsa
unreacted starting 22 in 70% and 86% yields (with some
intact under the same conditions for many hours, even
days. The deprotection of dithianes prepared from aro-
matic ketones proceeds more slowly, often requiring a
few hours to drive the reaction to completion. How-
ever, the large rate difference between activated (benzy-
lic/allylic) and non-activated ketone-derived dithianes
remains. Dithiolanes appear to be more difficult to
cleave than the corresponding dithianes, as observed
under other dethioacetalization conditions.
loss of material during the work-up), respectively. Simi-
lar selectivity was also found between dithianes pre-
pared from aldehydes (Scheme 1, Box B).
It is noteworthy that pollution of the reaction mixture
by traces12 of an iron salt could dramatically speed up
the cleavage processes and lead to drastic decreases in
the rate differences between the activated and the non-
activated species. Further investigation into this unex-
plained phenomenon is still ongoing in our group.
To have a closer comparison of the selectivity between
the activated and non-activated substrates we carried
out competition tests. Thus, an equimolar mixture of 17
and 22 was treated with 1.5 molar equiv. of IBX at
22–26°C (ambient temperature)11 for 9 h (Scheme 1,
Box A). The resulting reaction mixture was worked up
and further treated with NaBH4 to reduce the resulting
aromatic ketone (because 22a had the same Rf as that
of 22 on TLC) into the corresponding alcohol 23.
Column chromatographic separation gave 23 and the
Acknowledgements
This work was supported by the National Natural
Science Foundation of China (20025207, 29832020), the
Major State Basic Research Development Program
(G2000077502), the Chinese Academy of Sciences

Y. Wu et al. / Tetrahedron Letters 43 (2002) 6443–6445
6445
17
CHO
17
86% recovered
1
IBX
O
(93%)
O
DMSO
IBX
O
22a
NaBH4
H2O
DMSO
H2O
OMe
OH
1 h/25°C
24
(90% recovery)
24
22
23
>70%
OMe
B
A
Scheme 1.
(CAS), and the Life Science Special Fund of CAS
Supported by the Ministry of Finance (Stz 98-3-03).
8. Jones, P. S.; Ley, S. V.; Simpkins, N. S.; Whittle, A. J.
Tetrahedron 1986, 42, 6519–6534.
9. Frigerio, M.; Santagostino, M. Tetrahedron Lett. 1994,
35, 8019–8022.
10. See, e.g.: Wirth, T. Angew. Chem., Int. Ed. 2001, 40,
2812–2814.
References
11. General experimental procedure. The dithiane or dithio-
lane (1.0 mmol) was dissolved in DMSO (5.0 mL) con-
taining a small amount (ca. 0.09 mL) of added H2O. IBX
(1.5 mmol) was then introduced. The mixture was stirred
(preferably under N2 or argon) at ambient temperature
for 15 min–12 h (depending on the structure of the
substrate). When TLC showed completion of the reac-
tion, water (10 mL) was added. The white precipitates
were filtered off (washing with ether). The combined
filtrate/washings were washed with water and brine, and
dried over Na2SO4. The residue after removal of the
solvent was chromatographed on silica gel (eluting with
petroleum ether/ethyl acetate) to give the pure product.
12. For a rapid yet indiscriminate thioketal/thioacetal cleav-
age using 6 molar equiv. of FeCl3, see: Kamal, A.;
Laxman, E.; Reddy, P. S. M. M. Synlett 2000, 1476–
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1. See, e.g.: Gro¨bel, B.-T.; Seebach, D. Synthesis 1977,
357–402 and references cited therein.
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