ORGANIC
LETTERS
2
001
Vol. 3, No. 8
149-1151
A Highly Efficient, Mild, and Selective
1
Cleavage of â-Methoxyethoxymethyl
(
MEM) Ethers by Cerium(III) Chloride in
†
Acetonitrile
Gowravaram Sabitha,* R. Satheesh Babu, M. Rajkumar, R. Srividya, and
J. S. Yadav
Organic DiVision I, Indian Institute of Chemical Technology, Hyderabad 500007, India
Received January 19, 2001
ABSTRACT
3 2
A highly selective cleavage of MEM ethers has been achieved in high yields using CeCl ‚7H O in refluxing acetonitrile under mild and neutral
reaction conditions. The method is very rapid and compatible with other hydroxyl protecting groups such as Bn, TBDPS, Ac, Me, Tr, PMB,
benzylidene, THP, MOM, BOM, and NHAc present in the substrate.
8
The selective protection and deprotection of hydroxyl groups
has occupied a unique position on the stage of chemical
synthesis because of the fundamental importance of hy-
droxyl groups and their role in multistep synthesis of complex
natural products. In recent years the â-methoxyethoxymethyl
Alternatively, two boron reagents6,7 and TMSCl/NaI have
been reported for MEM group removal. Many of these
methods suffer from some drawbacks, which include use of
1
5
toxic and/or hazardous materials, strongly acidic conditions,
unsatisfactory yields, expensive reagents, longer reaction
times, lack of selectivity, and necessity of anhydrous
conditions. In this context there is a need to develop a mild
and efficient method for the selective cleavage of MEM
ethers in the presence of acid-sensitive protecting groups.
Recently, cerium(III) chloride has been used for several
4
6,7
7
(
MEM) group has been introduced as a suitable protection
2
3
for alcohols in organic synthesis. This protecting group
provides a number of significant advantages such as ease of
introduction and stability toward a wide variety of conditions
including many organometallic reagents, reducing conditions,
and oxidizing agents and introduces no stereochemical
ambiguities. Even though MEM ethers are widely used in a
multistep synthesis of functionally complex organic mol-
ecules, difficulties are encountered in its cleavage. As a
consequence, several reagents have been introduced in order
to facilitate the cleavage of MEM ethers. These include the
9
regio- and chemoselective transformations, since this com-
pound is a very cheap and water-tolerant reagent.10 The
activity of CeCl
3
was increased in combination with NaI.11
Herein, we report an exceedingly mild and efficient
protocol (Scheme 1) for the cleavage of MEM ethers by
using cerium(III) chloride heptahydrate in refluxing aceto-
3
3
4
2 4
use of anhydrous ZnBr , TiCl , fluoroboric acid, and
(
5) (a) Anderson, R. J; Adams, K. G.; Chinn, H. R.; Hendrick, C. A. J.
5
n-BuLi followed by treatment with mercuric acetate.
Org. Chem. 1980, 45, 2229. (b) Ireland, R. E.; Wuts, P. G. M.; Ernst, B. J.
Am. Chem. Soc. 1981, 103, 3205. (c) Martinez, G. R.; Grieco, P. A.;
Williams, E.; Kanai, K. Srinivasan, C. V. J. Am. Chem. Soc. 1982, 104,
1436.
(6) Williams, D. R.; Sakdarat, S. Tetrahedron Lett. 1983, 3965.
(7) Guindon, Y.; Morton, H. E.; Yoakim, C. Tetrahedron Lett. 1983,
3969.
†
IICT Communication 4709.
(
(
1) Kocienski, P. J. In Protecting Groups; Thieme: Stuttgart, 1994.
2) Greene, T. W.; Wuts, P. G. M. In ProtectiVe Groups in Organic
Chemistry, 3rd ed.; John Wiley & Sons: New York, 1999.
(
(
3) Corey, E. J. Gras, J.-L.; Ulrich, P. Tetrahedron Lett. 1976, 809.
4) Ikota, N.; Ganem, B. J. Chem. Soc., Chem. Commun. 1978, 869.
(8) Rigby, J. H.; Wilson, J. Z. Tetrahedron Lett. 1984, 1429.
1
0.1021/ol015585w CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/21/2001