A one-pot tandem oxidation-reduction protocol for the synthesis of cyclic ethers from their diols

Article abstract of DOI:10.1016/j.tetlet.2008.09.046

A novel and an efficient one-pot cyclization method for the preparation of cyclic ethers from their diols via a tandem oxidation-reduction protocol using a cocktail of MnO₂/Et₃SiH/CF₃COOH is reported.

Full text of DOI:10.1016/j.tetlet.2008.09.046

Tetrahedron Letters 49 (2008) 6701–6703
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Tetrahedron Letters
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A one-pot tandem oxidation–reduction protocol for
the synthesis of cyclic ethers from their diols
*
Biswajit Panda, Tarun K. Sarkar
Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 July 2008
Revised 6 September 2008
Accepted 10 September 2008
Available online 13 September 2008
A novel and an efficient one-pot cyclization method for the preparation of cyclic ethers from their diols
via a tandem oxidation–reduction protocol using a cocktail of MnO2/Et3SiH/CF3COOH is reported.
Ó 2008 Elsevier Ltd. All rights reserved.
In conjunction with a project underway in our laboratory, we
faced the problem of synthesizing, in quantity, the halogeno-
substituted heterocyclic ether 2a from the corresponding diol 1a
under non-basic conditions (Scheme 1). To date, four main ap-
proaches have been reported for such a transformation: (i) acid
catalyzed cyclodehydration using HCl1,2/H3PO43/PTSA,4 etc. (ii)
CF3COOH. Our choice of the oxidant was dictated by a literature re-
port which indicated that MnO2 oxidation of ortho diols to lactols
proceeds faster than the corresponding oxidation of lactols to lac-
tones.9 Furthermore, MnO2 should be compatible with the use of
the reductant, Et3SiH, in the presence of CF3COOH.
In this Letter, we report the successful development of a new
methodology for efficient one-pot transformation of ortho diols,
for example, 3 to the cyclic ethers 5 based on the above concept.
Thus, exposure of the diol 1a in DCM to active MnO213 (5 equiv)
followed by addition of Et3SiH (4.5 equiv) and CF3CO2H (15 equiv)
at À5?0 °C for 1 h and then 1 h at rt gave 2a in 93% isolated yield.
We then applied this methodology to a series of ortho diols, and the
5
TPP-CCl4 promoted cyclodehydration of diols via intramolecular
displacement of TPPO, (iii) base promoted6 mono-tosylate forma-
tion and elimination7 and (iv) intramolecular cyclization of diols
via a Mitsunobu reaction.8
Unfortunately, none of the above conditions proved useful in
the transformation of 1a–2a (Table 1). Thus, we deemed it neces-
sary to develop a new methodology that would allow ready one-
pot conversion of 1a–2a.
Our strategy to effect this transformation is summarized in
Scheme 2. The success of this protocol hinges on clean monoxida-
tion of the ortho diols 3 to the corresponding lactols 4 unaccompa-
nied by any of the over-oxidized products, for example, lactones 6,
and further transformation of the lactols 4 to the cyclic ethers 5 via
reduction of the corresponding oxonium ion intermediates. Active
MnO2 appeared to be the oxidant of choice in this protocol, and for
the reduction step, we selected a combination of Et3SiH and
Table 1
Preparation of ether 2a from diol 1a according to the literature conditions
Conditions
Yield (%)
Recovery (%) of diol 1a
HCl-MeOH, heat
H3PO4, PhMe, heat
PTSA, C6H6, reflux
PPh3-CCl4, reflux
TsCl, py
0
0
0
25
0
0
0
0
<5
0
PPh3, DEAD
17a
62
a
The product was obtained after a reaction time of 12 h at rt.
Cl
Cl
N
OH
OH
O
O
O
Cl
N
Cl
R
5
OH
O
OH
R
1a
2a
R
4
3
OH
Scheme 1.
R
6
O
* Corresponding author. Tel.: +91 03222283330; fax: +91 03222255303.
E-mail address: tksr@chem.iitkgp.ernet.in (T. K. Sarkar).
Scheme 2.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.09.046

6702
B. Panda, T. K. Sarkar / Tetrahedron Letters 49 (2008) 6701–6703
Table 3
results are presented in Table 2. As can be seen from Table 2, the
yields of the cyclic ethers in almost all the cases are excellent. Only
in the case of 1g did we isolate some staring material (16%). Fur-
thermore, in the absence of both MnO2 and Et3SiH, addition of
CF3COOH in DCM did not lead to the cyclic ethers even after a reac-
tion time of over 30 h at rt, only starting materials were recovered.
This methodology is also applicable to the synthesis of acyclic
ethers14 7–9 (Table 3). For example, while benzyl alcohol gave
dibenzyl ether 7 (93%), a mixture of benzyl alcohol and 3-phenyl-
propan-1-ol (1:1.2, respectively) gave only the mixed ether 8 in
high yield (88%); no dibenzyl ether could be detected (TLC) in
the latter case in the crude reaction product. Furthermore, this
Synthesis of acyclic ethers from alcohols10,11
Alcohol
Ether
Yield (%)
93
O
OH
OH
7
(
)
3
+
O
88
()3
HO
8
Table 2
Synthesis of cyclic ethers from their diols10–12
Cl
Me
Diola
Ether
Yieldb (%)
Me
N
Cl
N
N
OH
Cl
N
(
)
3
O
Cl
OH
OH
86
O
93
+
()3
Cl
Cl
Cl
Cl
HO
9
2a
1a
OMe
OMe
OH
OH
reaction could also be carried out by addition of a mixture of
benzyl alcohol and 3-phenylpropan-1-ol (1:1.2, respectively) to a
cocktail of active MnO2 (5 equiv), Et3SiH (4.5 equiv) and CF3COOH
(15 equiv) in DCM, but with a lower yield of 8 (60%); in this case
also, no dibenzyl ether could be detected in the crude reaction
product by TLC. As can be seen from Table 3 this protocol is also
applicable to the synthesis of the heterocyclic ether 9.
In conclusion, we have developed a tandem oxidation–reduc-
tion protocol for the highly effective etherification of diols and
alcohols using a combination of active MnO2/Et3SiH/CF3COOH.
Typical experimental procedure: To diol 1a 208 mg (1 mmol) in
7 ml of dry DCM was added 435 mg of active MnO2 (5 mmol) in
one portion at À5?0 °C (ice-salt bath). Then, triethylsilane
(0.72 ml, 4.5 mmol) was added dropwise followed by trifluoroace-
tic acid (1.2 ml, 15 mmol) over a period of 15 min. The reaction
mixture was stirred at the same temperature for 1 h, and for 1 h
at room temperature. Water (5 ml) was added and the reaction
mixture was filtered through a sintered funnel over a celite-450
bed. The organic layer was separated from the filtrate and the
aqueous layer was extracted with DCM (3 Â 5 ml). The combined
organic layer was dried over anhydrous Na2SO4, concentrated in
vacuo and the crude product was purified by chromatography over
silica gel to afford 2a (176 mg, 93%).
O
O
88
91
Cl
Cl
N
Cl
Cl
N
1b
2b
OH
OH
N
N
N
Cl
2c
Cl
1c
Cl
Cl
OH
OH
O
N
89
91
86
OMe
OMe
2d
1d
OH
OH
O
1e
2e
OH
OH
Acknowledgements
O
This work was supported by DST and CSIR, Government of India.
B.P. is grateful to CSIR, Government of India for a Junior Research
Fellowship.
OMe
OMe
1f
2f
Cl
Supplementary data
( )2
Cl
OH
OH
N
O
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.09.046.
N
73c
Cl
Cl
References and notes
2g
1g
a
The preparation of the diols will be published elsewhere.
Isolated yield of purified product.
16% of 1 g was isolated after a 3 h reaction period at rt.
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b
c

B. Panda, T. K. Sarkar / Tetrahedron Letters 49 (2008) 6701–6703
6703
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s), 4.87 (2H, s), 4.81 (2H, s), 3.80 (1H, s), 2.61 (1H, s). 13C NMR (CDCl3, 50 MHz) d
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200 MHz) d 7.26 (1H, s), 5.18 (2H, s), 5.1 (2H, s). 13C NMR(CDCl3, 50 MHz) d
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14. Publications on the synthesis of acyclic ethers via reductive etherification of
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11. All reactions were carried out on a 1 mmol scale.