Cleavage of 2-methoxyethoxymethyl ethers catalyzed by cerium(IV) ammonium nitrate (CAN) in acetic anhydride

Article abstract of DOI:10.1246/cl.2001.1012

The reactions of 2-methoxyethoxymethyl (MEM) ethers 1 with a catalytic amount of cerium(IV) ammonium nitrate (CAN) in acetic anhydride gave the corresponding mixed acetal esters 2 and acetates 3.

Full text of DOI:10.1246/cl.2001.1012

1012
Chemistry Letters 2001
Cleavage of 2-Methoxyethoxymethyl Ethers Catalyzed by Cerium(IV) Ammonium Nitrate (CAN)
in Acetic Anhydride
Kiyoshi Tanemura,* Tsuneo Suzuki, Yoko Nishida, Koko Satsumabayashi, and Takaaki Horaguchi†
School of Dentistry at Niigata, The Nippon Dental University, Hamaura-cho, Niigata 951-8580
†Department of Chemistry, Faculty of Science, Niigata University, Ikarashi, Niigata 950-2181
(Received July 9, 2001; CL-010633)
The reactions of 2-methoxyethoxymethyl (MEM) ethers 1
with a catalytic amount of cerium(IV) ammonium nitrate
(CAN) in acetic anhydride gave the corresponding mixed acetal
esters 2 and acetates 3.
MEM ethers are one of the most important protecting
groups in synthetic organic chemistry.1 The special feature of
this protecting group is comparative stability for protic acids
and easy removal by Lewis acids such as ZnBr2 and TiCl4.
Recently, some mild reagents for deprotection such as CeCl3,2a
2c
CBr4/i-PrOH,2b and MgBr2 have been devised. MEM ethers
are also converted into the corresponding acetates by treatment
with FeCl3 in Ac2O.3
CAN is a representative oxidizing reagent and many reac-
tions such as oxidation of alcohols, deprotection of dithioac-
etals, conversion of hydroquinones into quinones, and ligand
dissociation from iron carbonyl complexes have been known.4
In this paper, we wish to report that MEM ethers 1 react with
a catalytic amount of CAN in Ac2O to give the corresponding
mixed acetal esters 2 and acetates 3 which are easily converted
into the corresponding alcohols 13 by alkaline hydrolysis.
First, we examined the reactions of a variety of MEM
ethers. The results are summarized in Table 1. Cyclododecyl
MEM ether (1a) was treated with 10 mol% of CAN in Ac2O at
room temperature for 24 h under N2 to give cyclododecy-
loxymethyl acetate (2a) in 82% yield (Run 1). When 40 mol%
of CAN was employed, the reaction time was reduced (Run 2).
In CH3CN, the reaction did not proceed. The reactions of the
other secondary and tertiary MEM ethers 1b–f gave acetal
esters 2b–f (Runs 3–7). The reactions of primary MEM ethers
1 gave mixed acetal esters 2 together with small amounts of
acetates 3 except for 1k which afforded only 2k (Runs 8–12).
In the cases of MEM ethers involving triple bond, enone, ben-
zyl methylene, and acetonide, the products were obtained in
good yields (Runs 4, 5, 11, and 12), whereas, MEM ethers 1e
and 1f possessing double bonds gave acetal esters 2e and 2f in
low yields because CAN oxidized the double bonds (Runs 6
and 7).5 Acetal esters 2 were the main products in CAN-cat-
alyzed reactions although the products were acetates 3 in
FeCl3–Ac2O.3 Acetal esters 2 and acetates 3 were converted
into the corresponding alcohols 13 quantitatively by treatment
with NaOMe in MeOH.3b,6
The reactions of methoxymethyl (MOM) and silyl ethers
with CAN in Ac2O were investigated. The results are given in
Table 2. MOM ethers were also cleaved by a catalytic amount
of CAN in Ac2O at room temperature (Runs 1 and 2). t-
Butyldimethylsilyl (TBDMS) and t-butyldiphenylsilyl
(TBDPS) ethers were stable under these conditions (Runs 3–6).
Next, we examined the mechanism of CAN-mediated
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
1013
for the deprotection of MEM ethers 1. Path a leads to acetal
esters 2, on the other hand, acetates 3 were produced by path b.
The fact that silyl ethers are stable under these conditions indi-
cates that the reactions are not catalyzed by protic acids result-
ing from the hydrolysis of CAN.
A typical procedure is as follows: A mixture of MEM ether
1a (272 mg, 1.0 mmol) and CAN (55 mg, 0.1 mmol) in Ac2O
(1.32 mL) was stirred at room temperature for 24 h under N2.
The mixture was poured into 10% potassium carbonate (20 mL)
and extracted with ether. The extracts were washed with water,
dried, and evaporated. The residue was purified by column
chromatography with 20:1 hexane–EtOAc on silica gel to give
2a (209 mg, 82%).
The crude 2a (without purification by column chromatog-
raphy) was added to a solution of NaOMe (21 mg, 0.4 mmol) in
MeOH (4.2 mL) at room temperature. After being stirred for 1
h, Dowex 50 WX2 ion-exchange resin (ca. 0.3 g) was added
until the solution becomes neutral. The mixture was filtered
and the filtrate was evaporated. The residue was chro-
matographed with 5:1 hexane–acetone to give cyclododecanol
13a (148 mg, 80%).
cleavage of MEM ethers. The generation of CH3CO+ is sup-
posed in the reactions using Lewis acids such as FeCl3, TMSCl,
and BF3·OEt2 in Ac2O.7 Benzene rings were acetylated during
the reactions using FeCl3–Ac2O.2a Interestingly, o-nitrotoluene
(59%) and p-nitrotoluene (37%) were obtained from the reac-
tions of CAN with toluene in Ac2O. We propose that the reac-
+
tions might be catalyzed by NO2 . In order to confirm the
+
intermediacy of NO2 in CAN-mediated reactions, we exam-
ined the reaction of MEM ether 1a with NO2BF4 (40 mol%) in
Ac2O. Acetal ester 2a (16%) and acetate 3a (40%) were
obtained from the reaction catalyzed by NO2BF4 although only
2a (82%) was formed by the CAN–Ac2O system. The reason
for the difference of the products is not clear now.
In conclusion, MEM ethers are converted into mixed acetal
esters and acetates by a catalytic amount of CAN in Ac2O. A
difference of the positions of cleavage between CAN and the
other Lewis acids is interesting.
References and Notes
1
2
T. W. Greene and P. G. M. Wuts, “Protective Groups in
Organic Synthesis,” John Wiley and Sons, New York
(1999), pp 41–44.
a) G. Sabitha, R. S. Babu, M. Rajkumar, R. Srividya, and J.
S. Yadav, Org. Lett., 3, 1149 (2001). b) A.S. -Y. Lee, Y. -J.
Hu, and S. -F. Chu, Tetrahedron, 57, 2121 (2001). c) S.
Kim, Y. H. Park, and I. S. Kee, Tetrahedron Lett., 26, 3099
(1991).
3
a) R. S. Gross and D. S. Watt, Synth. Commun., 17, 1749
(1987). b) R. A. Holton, R. R. Juo, H. B. Kim, A. D.
Williams, S. Harusawa, R. E. Lowenthal, and S. Yogai, J.
Am. Chem. Soc., 110, 6558 (1988).
A plausible mechanism for the formation of NO2+ is shown
4
5
6
T. -L. Ho, Synthesis, 1973, 347.
in Scheme 1. CAN would cleave Ac2O to produce 9 and acetyl
T. Sugiyama, Nippon Kagaku Kaishi, 1993, 493.
F. M. Menger and B. N. A. Mbadugha, J. Am. Chem. Soc.,
123, 875 (2001).
N. C. Barua, R. P. Sharma, and J. N. Baruah, Tetrahedron
Lett., 24, 1189 (1983).
+
nitrate 10. In this process, CAN acts as a Lewis acid. NO2 is
formed by the dissociation of acetyl nitrate 10. Because of the
high positive charge of Ce atom, CAN could behave as an
effective Lewis acid. Scheme 2 shows the plausible mechanism
7