Indium triiodide catalysed one-step conversion of tetrahydropyranyl ethers to acetates with high selectivity

Article abstract of DOI:10.1039/b100014b

Chemoselective one-step conversion of tetrahydropyranyl ethers of primary alcohols to corresponding acetates was carried out. The reaction occurred through an indium triiodide catalyzed transesterification process in ethyl acetate. The method provided advantages such as operational simplicity, acceptable reaction conditions to acid-sensitive functional groups and good yield.

Full text of DOI:10.1039/b100014b

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Indium triiodide catalysed one-step conversion of tetrahydropyranyl
ethers to acetates with high selectivity
Brindaban C. Ranu* and Alakananda Hajra
1
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur,
Calcutta 700 032, India
Received (in Cambridge, UK) 2nd January 2001, Accepted 15th January 2001
First published as an Advance Article on the web 24th January 2001
A very simple and efficient method has been developed for
the chemoselective one-step conversion of tetrahydro-
pyranyl ethers of primary alcohols to the corresponding
acetates through an indium triiodide catalysed trans-
esterification process in ethyl acetate.
to the corresponding acetates very efficiently through a one-
step indium triiodide catalysed reaction in ethyl acetate
(Scheme 1).
i
RCH2OTHP
RCH2OAc
Scheme 1 Reagents and conditions: (i) In, I2, EtOAc, reflux.
The conversion of one protective group to another is often
required in a multistep organic synthesis as demanded by the
reaction conditions in subsequent steps. Thus, a direct method
for this transformation bypassing the intermediate step of
going back to the parent functionality is becoming much more
important in order to improve the overall synthetic efficiency.1
Tetrahydropyranyl (THP) ether is one of the most useful pro-
tective groups for the hydroxy functionality as it is stable under
a variety of reaction conditions including strong basic media;
however it is not suitable for use in an acidic environment. On
the other hand, acetate, another important hydroxy protecting
moiety, can tolerate acidic reagents. Thus, switch-over of a THP
ether to an acetate is sometimes considered useful in organic
synthesis. Although a couple of methods are available in the
literature for this purpose,2 these involve corrosive and hazard-
ous reagents such as acetyl chloride,2a acetic anhydride and
titanium tetrachloride.2b Our recent experience with indium
triiodide3 thus prompted us to explore the utility of this Lewis
acid catalyst for this useful transformation and we have dis-
covered that THP ethers of primary alcohols are converted
In a simple experimental procedure, the THP ether was
heated at reflux in ethyl acetate in the presence of a catalytic
amount (20 mol%) of indium triiodide generated in situ (a small
excess of either In or I2 does not affect the reaction) for a
certain period of time as required to complete the reaction. The
reaction mixture was then quenched with water and extracted
with ether. Usual workup and column chromatography over
silica gel furnished pure acetate.
A wide range of structurally varied THP ethers were sub-
jected to this procedure to give the corresponding acetates in
high yields. The results are reported in Table 1. It was found
that this direct conversion method proceeds very efficiently with
the THP ethers of primary alcohols, whereas THP ethers from
secondary alcohol (entry 18) and phenol (entry 21) undergo
simple deprotection to produce the parent hydroxy compound.
Obviously, the THP ethers first undergo deprotection and then
acetylation through transesterification with ethyl acetate in the
presence of the Lewis acid catalyst, indium triiodide. The THP
Table 1 One-step conversion of THP ether to acetate
Entry
Substrate
Time/h
Product
Yield (%)a
1
2
3
4
5
6
7
8
9
PhCH2OTHP
15
12
12
14
14
12
13
12
12
15
PhCH2OAc
80
82
82
78
78
75
82
76
78
78
PhCH2CH2OTHP
PhCH2CH2CH2OTHP
n-BuOTHP
PhCH2CH2OAc
PhCH2CH2CH2OAc
n-BuOAc
n-HexOTHP
n-HexOAc
ClCH2CH2OTHP
ClCH2CH2CH2OTHP
MeOCH2CH2OTHP
EtOCH2CH2OTHP
THPO(CH2)4OTHP
ClCH2CH2OAc
ClCH2CH2CH2OAc
MeOCH2CH2OAc
EtOCH2CH2OAc
AcO(CH2)4OAc
10
11
13
78
12
13
15
12
13
75
80
75
14
DOI: 10.1039/b100014b
J. Chem. Soc., Perkin Trans. 1, 2001, 355–357
This journal is © The Royal Society of Chemistry 2001
355

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Table 1 (Contd.)
Entry
15
Substrate
Time/h
12
Product
Yield (%)a
78
᎐
᎐
16
17
H᎐᎐᎐CH2OTHP
14
14
H᎐᎐᎐CH2OAc
78
80
᎐
᎐
18
19
20
18
82
80
20
21
18
20
78
75
22
23
13
14
80
82
24
25
14
12
82
78
26
27
12
14
78
80
a Yields refer to those of pure isolated products fully characterised by spectral data.
ethers of secondary alcohol and phenol after initial depro-
tection remained inert under the present reaction conditions,
which is consistent with our earlier observation3b of no acetyl-
ation of secondary alcohols and phenol by this indium triiodide
catalysed transesterification process.
Thus, chemoselective conversion of the THP ether of a
primary hydroxy group to the corresponding acetate in the
presence of a secondary one which undergoes only depro-
tection, is achieved with high efficiency (entries 19, 20). Never-
theless, this selectivity is of considerable synthetic potential.
The reaction conditions are mild enough not to induce any
isomerisation of the double (entries 13–15) and triple bonds
(entry 16). Most significantly, acid-sensitive functionalities such
as ketal (entry 17) and TBDMS ether (entry 25) remained
356
J. Chem. Soc., Perkin Trans. 1, 2001, 355–357

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unaffected. In addition, a variety of other functionalities
like Cl, OMe, OEt, O–allyl and NO2, also survived under the
present reaction conditions.
column chromatography over silica gel furnished the corre-
sponding acetate (269 mg, 82%), the identity of which was
established by comparison with the spectra (IR and NMR) of
an authentic sample.
This procedure was followed for all the substrates included in
Table 1.
In conclusion, the present procedure using indium triiodide
provides a simple and efficient method for direct conversion of
THP ethers to acetates. The significant advantages of this pro-
cedure are: (a) operational simplicity; (b) no involvement of
toxic or hazardous chemicals; (c) excellent selectivity for THP
ethers of primary alcohols; (d) reaction conditions acceptable
to several acid-sensitive functional groups including acetal and
TBDMS ether; and (e) good yield. We believe this will present a
better and more practical alternative to the existing method-
ologies and thus will find useful applications in the synthesis of
complex natural products where such a conversion is needed.
Acknowledgements
This investigation has enjoyed financial support from CSIR,
New Delhi [Grant No. 01(1504)/98]. A. H. is also grateful to
CSIR for his fellowship.
References
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Experimental
Indium triiodide was first prepared by refluxing indium metal
slices (46 mg, 0.4 mmol) and iodine (152 mg, 0.6 mmol) in ethyl
acetate (3 cm3) for half an hour. Then the THP ether of
2-phenylethyl alcohol (412 mg, 2.0 mmol) (entry 2) in ethyl
acetate (2 cm3) was added and refluxed for 12 h (monitored by
TLC). The reaction mixture was then quenched with water and
extracted with ether (4 × 10 cm3). The ether extract was washed
successively with sodium thiosulfate solution and brine, and
dried (Na2SO4). Evaporation of solvent and purification by
J. Chem. Soc., Perkin Trans. 1, 2001, 355–357
357