Highly Efficient and Convenient Deprotection of Methoxymethyl Ethers and Esters Using Bismuth Triflate in an Aqueous Medium

Article abstract of DOI:10.1246/cl.2003.1038

A simple and efficient method has been developed for the hydrolysis of methoxymethyl (MOM) ethers and esters to the corresponding alcohols and acids employing a catalytic amount of bismuth triflate in an aqueous medium. The conversions occur at ambient temperature and the yields of the deprotected alcohols are very good. The reaction was highly selective in the presence of other protecting groups such as TBDMS, TBDPS, benzyl, and allyl ethers.

Full text of DOI:10.1246/cl.2003.1038

1038
Chemistry Letters Vol.32, No.11 (2003)
Highly Efficient and Convenient Deprotection of Methoxymethyl Ethers
and Esters Using Bismuth Triflate in an Aqueous Medium
S. Venkat Reddy, R. Jagadeeshwar Rao, U. Sampath Kumar, and J. Madhusudana RaoÃ
Natural Product Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology,
Hyderabad-500 007, India
(Received July 17, 2003; CL-030646)
A simple and efficient method has been developed for the
anhydrous THF. The reaction went to completion within 30–
40 min. In order to reduce the use of organic solvents, the reac-
tion was carried out in the presence of minor amounts of water.
To our surprise, the yields of the deprotected alcohols were high-
er with reduced reaction times. Optimal results were observed
when the reaction was carried out with equal volumes of THF
and water.
hydrolysis of methoxymethyl (MOM) ethers and esters to the
corresponding alcohols and acids employing a catalytic amount
of bismuth triflate in an aqueous medium. The conversions occur
at ambient temperature and the yields of the deprotected alcohols
are very good. The reaction was highly selective in the presence
of other protecting groups such as TBDMS, TBDPS, benzyl, and
allyl ethers.
A series of aromatic MOM ethers were deprotected under
the similar conditions (Table 1). The reaction was extended to
Selective protection and deprotection of hydroxy and car-
boxyl groups is often a challenging task in multistep synthesis
of complex natural products.1,2 Among various methods availa-
ble for the protection of hydroxy groups most widely used is
transformation into methoxymethyl ethers as they can easily
be introduced and are stable under a variety of reaction condi-
tions including strongly basic and weakly acidic media.3,4 De-
protection is usually effected under acidic conditions. Normally
the reaction is carried out in protic solvents and is catalyzed by
acids such as HCl5 and pyridinium p-toluenesulfonate.6 Several
Lewis acids have also been used for this purpose such as,
LiBF4,7 Me2BBr,8 Ph2BBr,9 catechol boron bromide,10 ZnBr2,11
and TiCl4. These methods suffer drawbacks such as harsh reac-
tion conditions including the use of mineral acids, high reaction
temperatures, and reaction times. There was a report recently on
the deprotection of MOM ethers with CBr412 whose use is toxic
and not environmentally friendly.
Table 1. Deprotection of MOM ethers and esters using
Bi(OTf)3
Herein we wish to report a new method for the deprotection
of MOM ethers and esters using bismuth triflate in a biphasic
aqueous medium (THF and water) (Scheme 1). The method
takes advantage of the highly stable, cheap, and environmen-
tal-friendly nature of Bi(OTf)3. Bismuth triflate has been em-
ployed, as an efficient catalyst in organic synthesis in a variety
of reactions13 and is known to exhibit stronger activity than other
known corresponding Bi(III) Lewis acids14 as well as Lantha-
nide metal triflates.15 Lewis acids like, TiCl4, ZnBr2 requires
aprotic solvents11 whereas the reactions with Bi(OTf)3 can be
carried out effectively in aqueous media. Although bismuth tri-
flate is not commercially available, it can be easily prepared in
the laboratory in large quantities at relatively low cost.16
Initially we attempted to hydrolyze aromatic MOM ethers in
aAll the products were characterrized by 1HNMR and
mass spectroscopy. Isolated yields.
b
Scheme 1.
Copyright Ó 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.11 (2003)
1039
aliphatic MOM ethers and esters, which required slightly higher
reaction temperatures and time.
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2
3
4
5
6
Finally we examined the chemoselective deprotection of ali-
phatic MOM ethers and esters in the presence of other protecting
groups such as phenolic TBDMS, TBDPS, and benzyl ethers
(Entries 7–9). The results were very satisfactory as shown in
Table 1. Similar chemoselective deprotection was also achieved
in the presence of aliphatic TBDPS, benzyl, and allyl ethers (En-
tries 13–15).
Typical procedure: To a stirred solution of the methoxy-
methyl ether of ferulic acid methyl ester (100 mg, 0.44 mmol,
Entry 1) in THF and water (1:1) was added Bi(OTf)3 (1–2 mol
%) at room temperature. The progress of the reaction was moni-
tored by TLC. After the completion of the reaction, the reaction
mixture was filtered, and the filtrate concentrated and subjected
to column chromatography on silica gel using hexane:ethyl ace-
tate (97:3) to afford the pure product.
H. Monti, G. Leandri, M. Klos-Rinquet, and C. Corriol,
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(1986).
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8
9
In summary the present procedure of deprotection of MOM
ethers and esters offers salient features such as ease of operation,
high efficiency, environmental-friendly and chemoselectivity.
The deprotection described here adds a new and convenient
method, which may find extensive application in organic synthe-
sis where selective deprotection of MOM ethers is required at
ambient conditions in large scale.
10 R. K. Boeckman Jr. and J. C. Potenza, Tetrahedron Lett., 26,
1407(1985).
11 E. J. Corey, J.-L. Gras, and P. Ulrich, Tetrahedron Lett., 17,
809 (1976).
12 A. S.-Y. Lee, Y.-J. Hu, and S. F. Chu, Tetrahedron, 57, 2121
(2001).
13 A. Kamal, P. S. M. M. Reddy, and D. R. Reddy, Tetrahedron
Lett., 44, 2857(2003) and references cited therein.
14 H. Firouzabadi, I. Mohammadpoor-Baltork, and S. Kolagar,
Synth. Commun., 31, 905 (2001).
The authors are thankful to the Director IICT and Head
Organic Chemistry Division-I for their constant encouragement.
R. J. R thank UGC for providing financial support.
15 T. Oriyama, T. Watahiki, Y. Kobayashi, H. Hirano, and T.
Suzuki, Synth. Commun., 31, 2305 (2001).
16 S. Repichet, A. Zwick, L. Vendier, C. Le Roux, and J.
Dubac, Tetrahedron Lett., 43, 993 (2002).
References
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Published on the web (Advance View) October 13, 2003; DOI 10.1246/cl.2003.1038