A first example using o-iodoxybenzoic acid (IBX) in combination with tetraethylammonium bromide (TEAB) for ring expansion of 1,3-dithiolanes and 1,3-dithianes

Article abstract of DOI:10.1055/s-2005-868496

A novel one-pot procedure for the synthesis of dihydro-1,4-dithiins and dihydro-1,4-dithiepines from the corresponding 1,3-dithiolanes and 1,3-dithianes using o-iodoxybenzoic acid (IBX) in combination with tetraethylammonium bromide (TEAB) is described. T

Full text of DOI:10.1055/s-2005-868496

LETTER
1483
A First Example Using o-Iodoxybenzoic Acid (IBX) in Combination with
Tetraethylammonium Bromide (TEAB) for Ring Expansion of 1,3-Dithiolanes
and 1,3-Dithianes
R
ing Expansion of
i
1, 3-D
i
d
thiolane
s
an
y
1,3-Dithian
a
es nand G. Shukla, Paresh D. Salgaonkar, Krishnacharya G. Akamanchi*
Department of Pharmaceutical Sciences & Technology, University Institute of Chemical Technology, Matunga, Mumbai-400 019, India
E-mail: kgap@rediffmail.com
Received 31 December 2004
IBX in combination with catalytic amounts of b-cyclo-
Abstract: A novel one-pot procedure for the synthesis of dihydro-
dextrin (b-CD) by supramolecular catalysis. Other exam-
1,4-dithiins and dihydro-1,4-dithiepines from the corresponding
ples for effective deprotection of dithiolanes and dithianes
using hypervalent iodine reagents are also documented in
1,3-dithiolanes and 1,3-dithianes using o-iodoxybenzoic acid (IBX)
in combination with tetraethylammonium bromide (TEAB) is de-
scribed. The salient features of the protocol include mild reaction the current literature.6c,d
conditions, short reaction times and high yields.
The ring enlargement of 1,3-dithiolanes and 1,3-dithianes
Key words: o-iodoxybenzoic acid (IBX), dithiins, dithiepines,
tetraethylammonium bromide (TEAB)
can be successfully applied as a tool for the construction
of larger sulfur-containing heterocyclic rings and also for
1,2-transposition of carbonyl compounds.7 Very few
methods are reported for the synthesis of dihydro-1,4-
dithiins and dihydro-1,4-dithiepines. The majority of
these methods involve neutral or acid-catalyzed thermal
rearrangement of 1,3-dithiolan-1-oxide.8 Direct ring en-
largement of thioketals using different reagents such as
ethyl N-chlorocarbamate,9 2,4,6-trichloro-1,3,5-triazine
(TT),10 tungsten hexachloride (WCl6) in the presence of
The organic chemistry of polyvalent iodine compounds
has experienced intense development during the last de-
cade. Hypervalent iodine reagents have found widespread
applications in organic synthesis because of their selectiv-
ity and simplicity in use.1
The chemistry of IBX and DMP has been confined mainly
to simple oxidation of alcohols. However, recent reports
from Nicolaou et al.2 have opened up the development of
a number of novel pentavalent iodine mediated reactions.
The reactivity at the iodine nucleus of IBX and DMP can
be tuned by using a variety of ligands.3 Our group has
been working extensively on development of novel meth-
odologies using the pentavalent iodine reagents o-iodoxy-
benzoic acid (IBX) and Dess–Martin periodinane
(DMP).4 We have introduced for the first time the use of
tetraethylammonium bromide (TEAB) in combination
with pentavalent iodine compounds, mainly IBX and
DMP.4a,d,5 We were able to tune the reactivity at the iodine
nucleus of IBX by using TEAB, and hence could develop
a mild room temperature method for chemoselective oxi-
dation of sulfides to sulfoxides.5 In continuation of these
studies, we wish to report an efficient and highly regiose-
lective method for the ring expansion of 1,3-dithiolanes
and 1,3-dithianes to dihydro-1,4-dithiins and dihydro-1,4-
dithiepines using IBX in combination with stoichometric
amounts of TEAB.
12
dimethyl sulfoxide,7b phenyl selenyl chloride,11 TeCl4
have also been reported.
In an initial experiment, 2-methyl-2-phenyl-1,3-dithi-
olane was treated with IBX and TEAB in dry chloroform.
It was observed that the starting material was consumed
within 30 minutes. Much to our interest, deprotection to
acetophenone did not occur as indicated by thin layer
chromatography (TLC) analysis. Purification by silica gel
column chromatography (60–120 mesh) using EtOAc–
hexane (1:9) as eluants indicated the formation of 2-phe-
nyl-5,6-dihydro-1,4-dithiin, a ring expansion product in
89% yield (Scheme 1).
S
S
IBX, TEAB
CHCl3, r.t.
S
S
CH3
H
Scheme 1 Ring expansion of 2-methyl-2-phenyl-1,3-dithiolane
using IBX and TEAB
Wu et al.6a reported on the use of IBX in DMSO contain-
ing trace amounts of water for deprotection of ‘activated’
dithiolanes and dithianes at ambient temperature. In a
separate communication, Rama Rao et al.6b reported on
the regeneration of carbonyl compounds from the corre-
sponding 1,3-dithiolanes and 1,3-dithianes with the use of
Encouraged by the above-mentioned result, further devel-
opment work was undertaken. A variety of dithiolanes
and dithianes was prepared using the procedure developed
by Ong.13 The synthesized 1,3-dithiolanes and 1,3-
dithianes were then subjected to the reaction with IBX and
TEAB in dry chloroform and the results are recorded in
Table 1.
SYNLETT 2005, No. 9, pp 1483–1485
0
1.
0
6.
2
0
0
5
Advanced online publication: 27.04.2005
DOI: 10.1055/s-2005-868496; Art ID: D39404ST
© Georg Thieme Verlag Stuttgart · New York

1484
V. G. Shukla et al.
LETTER
Table 1 Ring Expansion of 1,3-Dithiolanes and 1,3-Dithianesa
As is illustrated in Table 1, a variety of 1,3-dithiolanes
and 1,3-dithianes was converted smoothly and rapidly to
the corresponding dihydro-1,4-dithiins and dihydro-1,4-
dithiepines. As expected, the rate of reaction was compar-
atively slow with benzyloxycarbonyl (entry 3) and chloro
substituents (entries 4 and 8). In the case of nitro-substi-
tuted 1,3-dithiolane (entry 5) the reaction did not go to
completion even after 12 hours. In the case of aliphatic
dithiolanes, cyclohexen-1,3-dithiolane (entry 9) was also
converted to the corresponding 2,3,5,6,7,8-hexahydro-
1,4-benzodithiin within 45 minutes. However, in the case
of open chain aliphatic dithiolane (entry 10), the reaction
was not found to be of general utility and a mixture com-
prising of rearranged product with unreacted starting ma-
terial and traces of 2-tert-butyl-2-methyl-1,3-dithiolane-
1-oxide was obtained. Silica gel column chromatographic
purification afforded the corresponding dihydro-1,4-dithi-
in in ca. 20% yield. In the case of 1-phenyl-1,3-dithiolane
(entry 11) deprotection occurred rapidly, and benzalde-
hyde was recovered in more than 85% yield.
R
n
S
S
S
S
IBX, TEAB
CH3
CHCl3, r.t.
n = 1, 2
n
H
R
Entry Substrate
Product
Time Yield
(h)
(%)b
1
0.5
89
S
S
S
S
CH3
H
2
0.5
1
85
84
85
65c
H3CO
S
S
S
S
CH3
H3CO
H
3
PhOOC
S
S
S
S
S
CH3
PhOOC
H
To indicate the role of TEAB, control experiments were
performed on 2-methyl-2-phenyl-1,3-dithiolane with
IBX, in the absence of TEAB and in the presence of cata-
lytic amounts of TEAB (10 mol%). In the former case a
small amount of deprotection to acetophenone was ob-
served with unreacted starting material remaining in
>90% even after 12 hours, which is in accordance with
observations of Rama Rao et al.6b In the latter case, forma-
tion of a polar compound was noticed with >70% starting
material remaining unreacted after 12 hours. Purification
by silica gel column chromatography using EtOAc–hex-
ane (1:1) as eluants afforded this polar compound in ca.
20% yield and this was identified as 3-phenyl-5,6-dihy-
dro-1,4-dithin-1-oxide by spectroscopic analysis. Further
development work is in progress to prepare these com-
pounds (Scheme 2).
4
1.5
Cl
S
S
S
CH3
Cl
H
5
6
12
S
S
O2N
S
S
CH3
O2N
H
0.75 85
S
S
S
S
S
H3C
7
8
0.5
1.5
72
69
S
S
S
H
Cl
S
S
S
S
S
S
S
IBX, TEAB (cat.)
CHCl3, r.t.
CH3
H
Cl
H
S
9
0.75 84
S
S
S
O
S
Scheme 2 Formation of 3-phenyl-5,6-dihydro-1,4-dithiin-1-oxide
10
1
20d
A plausible mechanism for ring expansion of 1,3-di-
thiolanes and 1,3-dithianes is proposed in Scheme 3.
S
S
S
CH3
H
S
As depicted in Scheme 3, the addition of TEAB to IBX
causes the polarization of I=O bond, thus increasing the
electrophilicity at the central iodine atom of IBX. Conse-
quently, the nucleophilic attack by the sulfur atom of 1,3-
dithiolane on the central iodine of IBX is enhanced, with
bromide ion as a leaving group.
11
0.5 >85
O
S
S
H
H
a Reaction at r.t. using 1.0 equiv of substrate, 1.1 equiv of IBX and 1.1
equiv of TEAB in 10 mL CHCl3.
b Isolated yield after column chromatography.
c Reaction incomplete.
We expected that DMP in combination with TEAB would
serve as an alternative reagent system to the developed
IBX/TEAB system for conversion of 1,3-dithiolanes and
1,3-dithianes to the corresponding dihydro-1,4-dithiins
and dihydro-1,4-dithiepines.14 As a study oriented in this
d Reaction not chemoselective; mixture of compounds obtained with
starting material remaining unreacted.
Synlett 2005, No. 9, 1483–1485 © Thieme Stuttgart · New York

LETTER
Ring Expansion of 1,3-Dithiolanes and 1,3-Dithianes
1485
O–Q+
References
O
HO
HO
Br
:
I
I
:
:S
S:
(1) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523.
(2) (a) Nicolaou, K. C.; Zhong, Y.-L.; Baran, P. S. J. Am. Chem.
Soc. 2000, 122, 7596. (b) Nicolaou, K. C.; Montagnon, T.;
Baran, P. S.; Zhong, Y.-L. J. Am. Chem. Soc. 2002, 124,
2245. (c) Ref. 1 and references cited therein.
O
+ Q+Br–
O
O
Ph
CH3
O
Q+ = N+(CH2CH3)4
(3) Nicolaou, K. C.; Montagnon, T.; Baran, P. S. Angew. Chem.
Int. Ed. 2002, 41, 1386.
OH
S
+Q–O
OH
I
O
+Q–O
:
S
(4) (a) Ramanarayanan, G. V.; Shukla, V. G.; Akamanchi, K. G.
Synlett 2002, 2059. (b) Chaudhari, S. S.; Akamanchi, K. G.
Synthesis 1999, 760. (c) Chaudhari, S. S.; Akamanchi, K. G.
Tetrahedron Lett. 1998, 39, 3209. (d) Salgaonkar, P. D.;
Shukla, V. G., Akamanchi, K. G. Aust. J. Chem.,
communicated.
:
S+
:
S
:
I
H C
2
CH2
H
O
Ph
Ph
O
:Br–
O
OH
I
(5) Shukla, V. G.; Salgaonkar, P. D.; Akamanchi, K. G. J. Org.
Chem. 2003, 68, 5422.
O–Q+
S
H
S+
O–
(6) (a) Wu, Y.; Shen, X.; Huang, J.-H.; Tang, C.-J.; Liu, H.-H.;
Hu, Q. Tetrahedron Lett. 2002, 43, 6443. (b) Srilakshmi
Krishnaveni, N.; Surendra, K.; Nageswar, Y. V. D.; Rama
Rao, K. Synthesis 2003, 2295. (c) Barton, D. H. R.;
Godfrey, C. R. A.; Morzycki, J. W.; Motherwell, W. B.;
Stobie, A. Tetrahedron Lett. 1982, 23, 957. (d) Stork, G.;
Zhao, K. Tetrahedron Lett. 1989, 30, 287.
(7) (a) Larsen, L.; Garner, D. C.; Joule, J. A. J. Chem. Soc.,
Perkin Trans. 1 1989, 2311. (b) Firouzabadi, H.; Iranpoor,
N.; Karimi, B. Synlett 1999, 413; and references cited
therein.
H
Ph
O
S
S
H
Scheme 3 Mechanism for ring expansion of 1,3-dithiolanes and
1,3-dithianes using IBX/TEAB
(8) (a) Chen, C. H. Tetrahedron Lett. 1976, 1, 25. (b) Chen, C.
H.; Donatelli, B. A. J. Org. Chem. 1976, 41, 3053.
(c) Janssen, J. W. A. M.; Kwart, H. J. Org. Chem. 1977, 42,
1530.
(9) Yoshino, H.; Kawazoe, Y.; Taguchi, T. Synthesis 1974, 713.
(10) Karimi, B.; Hazarkhani, H. Synthesis 2003, 2547.
(11) Francisco, C. G.; Freire, R.; Hernandez, R.; Salazar, J. A.;
Suarez, E. Tetrahedron Lett. 1984, 25, 1621.
(12) (a) Tani, H.; Inamasu, T.; Tamura, R.; Suzuki, H. Chem.
Lett. 1990, 1323. (b) Tani, H.; Inamasu, T.; Masumoto, K.;
Tamura, R.; Shimizu, H.; Suzuki, H. Phosphorus, Sulfur
Silicon Relat. Elem. 1992, 67, 261.
(13) Ong, B. S. Tetrahedron Lett. 1980, 21, 4225.
(14) General Experimental Procedure.
direction, a reaction was carried out on 2-methyl-2-phe-
nyl-1,3-dithiolane using DMP in combination with TEAB
in dry chloroform. Indeed, rearrangement occurred in 30
minutes and 2-phenyl-5,6-dihydro-1,4-dithiin was isolat-
ed in ca. 81% yield after silica gel column chromatogra-
phy. Further work is in progress in this direction.
Despite the widespread use of hypervalent iodine reagents
in oxidative transformations, to the best of our knowledge,
the present IBX protocol is the first example for the oxi-
dative ring expansion of 1,3-dithiolanes and 1,3-dithianes
to the corresponding dihydro-1,4-dithiins and dihydro-
1,4-dithiepines using hypervalent iodine reagents.
To a stirred suspension of IBX (1.1 equiv) in 10 mL dry
CHCl3 was added TEAB (1.1 equiv) in one portion. The
mixture was stirred at r.t. for 5 min followed by the addition
of 1,3-dithiolane/1,3-dithiane (1.0 equiv) and stirring
continued at r.t. until complete consumption of starting
material as observed by TLC. The reaction mixture was
diluted with CHCl3 and the organic layer was washed
successively with 10% Na2S2O5 solution (2 × 15 mL), sat.
NaHCO3 solution (2 × 15 mL), H2O (2 × 15 mL), and brine
(1 × 15 mL). The organic layer was dried over Na2SO4 and
concentrated in vacuo. Purification by silica gel column
chromatography (10% EtOAc–hexane) afforded the pure
dihydro-1,4-dithiins and dihydro-1,4-dithianes.
The salient features of the developed method are short
reaction times, mild reaction conditions and high yields.
The most notable feature of the method is absence of
deprotection to the corresponding carbonyl compounds.
Acknowledgment
The authors thank CSIR, New Delhi for financial support.
Synlett 2005, No. 9, 1483–1485 © Thieme Stuttgart · New York