Highly selective one-pot conversion of THP and MOM ethers to acetates by indium triiodide-catalysed deprotection and subsequent transesterification by ethyl acetate

Article abstract of DOI:10.1039/b104055n

The chemoselective one-pot conversion of tetrahydropyranyl (THP) and methoxymethyl (MOM) ethers of primary alcohols to the corresponding acetates was presented. It was done using indium triiodide-catalysed deprotection and subsequent acetylation by ethyl acetate through a transesterification process. The advantages offered by the method included operational simplicity, 'green' methodology involving no toxic or hazardous chemicals and high yield.

Full text of DOI:10.1039/b104055n

View Article Online / Journal Homepage / Table of Contents for this issue
Highly selective one-pot conversion of THP and MOM ethers to
acetates by indium triiodide-catalysed deprotection and subsequent
transesterification by ethyl acetate
1
Brindaban C. Ranu* and Alakananda Hajra
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur,
Calcutta – 70 0032, India. E-mail: ocbcr@mahendra.iacs.res.in; Fax: 91-33-4732805
Received (in Cambridge, UK) 4th May 2001, Accepted 3rd August 2001
First published as an Advance Article on the web 4th September 2001
A simple and efficient method is developed for the chemoselective one-pot conversion of tetrahydropyranyl (THP)
and methoxymethyl (MOM) ethers of primary alcohols to the corresponding acetates by indium triiodide-catalysed
deprotection and subsequent acetylation by ethyl acetate through a transesterification process.
by the reaction of indium metal and iodine7 (a small excess of
Introduction
either In or I2 does not make any difference to the normal
The protection and subsequent deprotection of a functional
course of reaction) for a certain period of time as required to
group is usual practice in a multistep synthetic strategy and a
complete the reaction. The reaction mixture was then quenched
switchover of one protective group to another is also often
with water and extracted with diethyl ether. Usual work-up and
required 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
column chromatography over silica gel furnished pure acetate.
A wide range of structurally different THP and MOM ethers
were subjected to this procedure to produce the corresponding
is becoming much more important in order to improve the
acetates. The results are summarised in Tables 1 and 2. It was
overall synthetic efficiency.1 Tetrahydropyranyl (THP) and
methoxymethyl (MOM) ethers are widely used in organic syn-
found that THP and MOM ethers of primary alcohols under-
went smooth conversion to acetates while those of secondary
thesis as hydroxy-protecting groups because they are stable
alcohols and phenols furnish only the parent hydroxy com-
under a variety of reaction conditions including strongly basic
pounds by simple deprotection. Obviously, the ethers first
undergo deprotection by Lewis acid (indium triiodide) and then
acetylation by ethyl acetate through transesterification. So, it is
media; however, they are not suitable for use in a relatively
strongly acidic environment.2 On the other hand, acetate,
another important hydroxy-protecting moiety, can tolerate
reasonable to assume that ethers of secondary alcohols and
acidic reagents. Thus, switchover of THP and MOM ethers
phenols after initial deprotection failed to proceed to acetyla-
to acetate is sometimes considered useful in certain steps.
tion with this reagent system. This is very much consistent with
Although only a limited number of methods have been reported
our earlier observation5 that secondary alcohols and phenols
recently for this purpose,3,4 they involve traditional reagents
do not undergo acetylation by indium triiodide-catalysed trans-
such as acetyl chloride,3a acetic anhydride4 and titanium
esterification by ethyl acetate. However, this chemoselective
tetrachloride,3b which being corrosive and hazardous need
conversion of THP and MOM ethers of primary hydroxy
replacement by ‘greener’ chemicals. In addition, the reported
groups to the corresponding acetates, in the presence of
procedure for the conversion of MOM ether to acetate lacks
secondary and phenolic ones which undergo deprotection only,
operational simplicity and is not free from side reactions.4
is of much synthetic utility. On the other hand, deprotection
Recently, we have discovered a unique use of ethyl acetate
of THP and MOM ethers of secondary alcohols and phenols
with a catalytic amount of indium triiodide for acetylation
by a mild Lewis acid (indium triiodide) provides a practical
of alcohols and amines through transesterification5 and we
alternative to many existing procedures using relatively strong
envisaged the potential of this combination for direct con-
acids.2 The present reaction conditions are tolerable to a
version of acid-labile hydroxy-protecting groups to acetates.
variety of sensitive functionalities and moieties such as nitro,
This prompted us to initiate a systematic investigation in this
chloro, iodo, methoxy, furan, thiophene, etc. Several hydroxy-
direction and we now report that THP and MOM ethers of
protecting groups including OTBDMS, O-allyl and O-benzyl
primary alcohols are converted to the corresponding acetates
also remained unaffected during this conversion. The reactions
are, in general, very clean and high-yielding and no side product
has been isolated in any reaction.
very efficiently through a one-pot indium triiodide-catalysed
reaction with ethyl acetate (Scheme 1).6
In conclusion, the present procedure using ethyl acetate and
a catalytic amount of indium triiodide provides a convenient
and efficient method for one-pot conversion of THP and
MOM ethers to acetates. The significant advantages offered
Scheme 1 Reagents and conditions: i, In, I2, EtOAc, reflux.
by this procedure are: (a) operational simplicity; (b) ‘green’
methodology involving no toxic or hazardous chemicals;
(c) remarkable chemoselectivity for THP and MOM ethers
of primary alcohols; (d) mild reaction conditions com-
Results and discussion
In a general experimental procedure, the THP or MOM ether
was heated at reflux in ethyl acetate in the presence of a cata-
lytic amount (20 mol%) of indium triiodide generate in situ
patible with several sensitive functional groups and hydroxy-
protecting ethers; and (e) high yield. We believe that this will
present a better and more viable alternative to the existing
2262
J. Chem. Soc., Perkin Trans. 1, 2001, 2262–2265
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b104055n

View Article Online
Table 1 Direct conversion of THP ether to acetate
Entry
Substrate
t/h
Product
Yields (%)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
PhCH2CH2CH2CH2OTHP
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
15
75
13
14
12
13
80
75
15
12
78
16
17
14
14
78
80
18
19
20
18
82
80
20
21
18
20
78
75
22
23
13
14
80
82
24
25
26
27
14
12
12
14
82
78
78
80
a Yields refer to those of pure isolated products fully characterised by spectral data.
J. Chem. Soc., Perkin Trans. 1, 2001, 2262–2265
2263

View Article Online
Table 2 Direct conversion of MOM ether to acetate
Entry
Substrate
t/h
Product
Yield (%)a
1
2
3
4
PhCH2OMOM
16
18
18
17
PhCH2OAc
82
85
84
82
PhCH2CH2OMOM
ClCH2CH2CH2OMOM
EtOCH2CH2OMOM
PhCH2CH2OAc
ClCH2CH2CH2OAc
EtOCH2CH2OAc
5
6
17
17
82
82
7
8
9
15
15
15
84
80
78
10
11
15
16
78
85
12
13
20
20
85
84
14
20
80
15
16
16
15
84
80
17
18
20
16
75
80
19
20
18
17
82
82
21
22
16
16
84
72
23
24
15
17
80
82
25
16
85
a Yields refer to those of pure isolated products fully characterised by spectral data.
2264
J. Chem. Soc., Perkin Trans. 1, 2001, 2262–2265

View Article Online
Table 3 IR, 1H and 13C NMR data of some selected acetates
Entry
νmax/cmϪ1
δH/ppm
δC/ppm
6 (Table 1)
7 (Table 1)
1739
1740
4.32 (t, 2H, J 5.6), 3.68 (t, 2H, J 5.6), 2.10 (s, 3H)
4.21 (t, 2H, J 6.1), 3.60 (t, 2H, J 6.3), 2.11–2.07 (m, 2H),
2.06 (s, 3H)
170.1, 63.7, 41.8, 20.9
170.9, 61.9, 41.3, 33.0, 19.5
10 (Table 1)
11 (Table 1)
1738
1744
3.95 (t, 4H, J 3.2), 1.90 (s, 6H), 1.57 (t, 4H, J 3.2)
4.12–4.01 (m, 2H), 1.97 (s, 3H), 1.46–0.79 (m, 19H)
171.2 (2), 64.1 (2), 22.5 (2), 21.0 (2)
171.3, 63.3, 38.5, 35.8, 28.9, 24.9, 22.8, 22.2, 22.1, 20.2,
20.0, 19.8
12 (Table 1)
14 (Table 1)
17 (Table 1)
1742
1743
1739
3.78 (q, 2H, J 10.6), 2.01 (s, 3H), 1.59–0.84 (m, 15H)
171.3, 72.0, 31.2, 30.3, 27.8, 25.4, 24.3, 23.7, 23.1, 22.3,
19.4
171.6, 133.1, 119.3, 72.2, 39.3, 34.4, 30.8, 27.0, 23.3,
22.7, 20.9
171.3, 119.3, 65.0, 64.9, 64.7, 45.3, 35.4, 30.7, 22.7, 20.9
5.23–5.22 (m, 1H), 3.79 (q, 2H, J 10.3), 2.01 (s, 3H),
1.89–1.34 (m, 9H), 0.87 (s, 3H)
4.12–4.05 (m, 2H), 3.89 (s, 4H), 2.10 (s, 3H) 1.89–1.38
(m, 7H)
19 (Table 1)
22 (Table 1)
3419, 1741
1739
4.15–4.12 (m, 3H), 2.03 (s, 3H), 1.96–0.85 (m, 8H)
7.27–7.22 (m, 1H), 6.92–6.81 (m, 3H), 5.05 (s, 2H), 3.79
(s, 3H), 2.08 (s, 3H)
171.1, 78.3, 64.6, 44.7, 32.1, 25.6, 22.9, 20.8
170.1, 159.9, 137.7, 133.7, 129.6, 122.0, 120.5, 66.2, 55.2,
21.0
25 (Table 1)
26 (Table 1)
1741
1736
7.01 (d, 2H, J 8.4), 6.60 (d, 2H, J 8.4), 4.81 (s, 2H), 1.87
(s, 3H), 0.78 (s, 9H), 0.03 (s, 6H)
7.24 (d, 2H, J 9.0), 6.85 (d, 2H, J 9.0), 6.06–5.96 (m, 1H),
5.41–5.23 (m, 2H), 5.01 (s, 2H), 4.50 (d, 2H, J 5.1), 2.04
(s, 3H)
169.1, 154.1, 128.8 (2), 127.0, 118.4 (2), 64.4, 24.1 (3),
19.4, 16.6, Ϫ6.0 (2)
170.5, 157.4, 132.0, 128.8 (2), 127.0, 116.3, 113.3 (2),
67.4, 64.7, 19.7
5 (Table 2)
1739
1743
7.31–7.14 (m, 5H), 4.13 (t, 2H, J 6.2), 2.94 (t, 2H, J 7.1),
2.01 (s, 3H), 1.95–1.87 (m, 2H)
4.15–3.77 (m, 5H), 1.99 (s, 3H), 1.97–1.88 (m, 3H), 1.63–
1.57 (m, 1H)
172.1, 136.4, 129.8, 129.6, 129.3, 126.5, 96.5, 63.1, 30.6,
28.6, 21.2
170.9, 76.7, 68.7, 66.7, 28.3, 25.9, 21.1
11 (Table 2)
16 (Table 2)
21 (Table 2)
1740
1745
7.28–6.93 (m, 3H), 5.22 (s, 2H), 2.03 (s, 3H)
7.83 (d, 1H, J 7.9), 7.37–7.32 (m, 2H), 7.00 (t, 1H, J 7.7),
5.1 (s, 2H), 2.13 (s, 3H)
170.9, 138.3, 128.6, 127.3, 127.2, 60.8, 21.2
170.6, 139.8, 138.7, 130.2, 130.1, 128.6, 96.5, 70.3, 21.2
24 (Table 2)
1737
7.38–7.22 (m, 7H), 6.90 (d, 2H, J 8.2), 5.05 (s, 2H), 4.99
(s, 2H), 1.99 (s, 3H)
171.0, 159.2, 137.3 (2), 130.9 (2), 129.0 (2), 128.8, 127.8,
127.3, 96.6 (2), 70.3, 66.4, 21.4
methodologies3,4 and thus it will find useful applications in the
synthesis of complex natural products where such conversions
are needed under mildly acidic conditions.
Acknowledgements
We are pleased to acknowledge financial support from CSIR,
New Delhi for this investigation. A. H. is also thankful to CSIR
for his fellowship.
Experimental
References
Indium metal (ingot from SRL Mumbai, India) was cut into
small slices, and used directly without any treatment. Iodine
crystals were used as obtained commercially. Ethyl acetate was
dried over CaCl2 and distilled before use. THP and MOM
ethers were prepared following reported procedures.8,9
1 (a) T. Oriyama, M. Oda, J. Gono and G. Koga, Tetrahedron Lett.,
1994, 35, 2027; (b) G. Yang, X. Ding and F. Kong, Tetrahedron Lett.,
1997, 38, 6725; (c) T. Oriyama, M. Kimura and G. Koga, Bull.
Chem. Soc. Jpn., 1994, 67, 885; (d ) T. Oriyama, K. Yatabe, S.
Sugauttra, Y. Machiguchi and G. Koga, Synlett, 1996, 523.
2 (a) T. W. Greene and P. G. M. Wuts, Protective Groups in Organic
Synthesis, Wiley, New York, 3rd edn., 1999; (b) P. J. Kocienski,
Protective Groups, Georg Thieme, Stuttgart, 1994.
General procedure for conversion of THP and MOM ethers to
acetates
3 THP ether to acetate: (a) S. Chandrasekhar, T. Ramachandar, M. V.
Reddy and M. Takhi, J. Org. Chem., 2000, 65, 4729; (b) M. Schwarz
and R. M. Waters, Synthesis, 1972, 567.
4 MOM ether to acetate: M. P. Bosch, I. Petschen and A. Guerrero,
Synthesis, 2000, 300.
5 B. C. Ranu, P. Dutta and A. Sarkar, J. Chem. Soc., Perkin Trans. 1,
2000, 2223.
6 A preliminary communication on the direct conversion of THP
ether to acetate has been made recently: B. C. Ranu and A. Hajra, J.
Chem. Soc., Perkin Trans. 1, 2001, 355.
7 Y. Han and Y.-Z. Huang, Tetrahedron Lett., 1995, 36, 7277.
8 For preparation of THP ethers: M. Miyashita, A. Yoshikoshi and
P. A. Grieco, J. Org. Chem., 1977, 42, 3772.
9 For preparation of MOM ethers: A. F. Kluge, K. G. Untch and J. H.
Fried, J. Am. Chem. Soc., 1972, 94, 7827.
10 C. J. Pouchert, The Aldrich Library of NMR Spectra, Aldrich
Chemical Co., Inc., Milwaukee, 2nd edn., 1983, vols. 1 and 2.
11 B. C. Ranu, S. K. Guchhait and M. Saha, J. Indian Chem. Soc., 1999,
76, 546.
A THP or MOM ether (2 mmol) as a solution in ethyl acetate
(2 cm3) was added to indium triiodide (20 mol%), prepared
in situ by refluxing indium metal and iodine in ethyl acetate
(3 cm3), and the mixture was then refluxed for a certain period
of time as required to complete the reaction (monitored by
TLC). The reaction mixture was then quenched with water and
extracted with diethyl ether (4 × 10 cm3). The combined extract
was washed successively with aq. sodium thiosulfate and brine,
and dried (Na2SO4). Evaporation of the solution and purifica-
tion by column chromatography over silica gel furnished the
corresponding acetate. The product acetates were easily charac-
1
terised by IR, H and 13C NMR data. The spectral data of
many of these acetates are already reported3a,5,10,11 and our
products have data in good agreement with those. The spectral
and analytical data of some selected acetates whose spectra are
not available for comparison are presented in Table 3.
J. Chem. Soc., Perkin Trans. 1, 2001, 2262–2265
2265