5696
J . Org. Chem. 1999, 64, 5696-5699
Sch em e 1
A Sim p le Meth od for th e Selective
Dep r otection of p-Meth oxyben zyl Eth er s by
Cer iu m (III) Ch lor id e Hep ta h yd r a te a n d
Sod iu m Iod id e
either electrolytically,8 or chemically by means of 2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ)9,10 or ceric am-
monium nitrate (CAN),11 have been reported. Also, the
cleavage of the PMB ether has been accomplished using
a 10% solution of trifluoroacetic acid12 or using clay-
supported ammonium nitrate under microwave irradia-
tion.13 Many of these procedures suffer from one or more
drawbacks: use of a heavy metal which not ideal from
an environment point of view, lack of selectivity, unsat-
isfactory yield,14 cost of the reagent, or necessity of
anhydrous conditions. In this context there is still the
need to devise a method with environmental conscious-
ness using inexpensive reagents, and this has led us to
investigate a new methodology, which is able to carry out
the selective deprotection of PMB ether with good-to-
excellent yields.
Over recent years, lanthanide salt mediated Lewis acid
reactions has attracted tremendous interest throughout
scientific communities.15 Their low toxicity, ease of hand-
ing, and low cost make lanthanide derivative species
attractive alternatives to their classical competitors such
as TiCl4. For this, in the course of our studies on the use
of cerium(III) chloride in organic reactions,16 we have
developed new methods for deprotection of organic func-
tional groups.17 Thus, we have considered the possibility
of using cerium(III) chloride heptahydrate to promote the
cleavage of PMB ethers. In the same way that other
Lewis acids promote this reaction of deprotection, CeCl3
should also lead to activated PMB ethers for being
resolved to parent hydroxy compound. Now we describe
here that the cleavage of the p-methoxybenzyl protecting
group of alcohols and phenols in the presence of benzyl
Anna Cappa, Enrico Marcantoni,* and
Elisabetta Torregiani
Dipartimento di Scienze Chimiche, via S. Agostino 1,
I-62032 Camerino (MC), Italy
Giuseppe Bartoli,* Maria Cristina Bellucci,
Marcella Bosco, and Letizia Sambri
Dipartimento di Chimica Organica “A. Mangini”,
v.le Risorgimento 4, I-40136 Bologna, Italy
Received J anuary 4, 1999
In tr od u ction
Chemoselective transformation of polyfunctional com-
pounds is a challenging problem in organic synthesis,
especially in the cases where sensitive structural features
limit reagent choice. Although much recent work has
dealt with the development of methods and procedures
general and efficient enough to be employed across a wide
range of substrate molecules, hitherto the chemistry of
protective groups continues to be an active area of
research. There are hundreds of protective groups that
can be introduced and removed by a variety of methods,
but new and milder methods continue to be developed
for both the introduction and cleavage of many of the
existing protective groups.1 For this reason, protection
and deprotection of hydroxyl groups have been given
considerable attention in recent years, not only because
of their fundamental importance, but also as to their role
for multistep synthesis of complex natural products such
as polyketide-derived macrolide and polyether antibiotics.
The synthesis of polyhydroxylated compounds2,3 often
requires orthogonal protecting strategies to distinguish
between hydroxyl groups. In the realm of hydroxyl
protecting groups, benzyl ethers, both substituted and
unsubstituted, are among the most common because of
their stability toward acid, alkali, and a number of other
reagents. To be able to remove selectively a substituted
benzyl ether in the presence of an unsubstituted benzyl
ether under mild conditions is of great benefit. The
p-methoxybenzyl (PMB) group is one of the most useful
groups for alcohol protection because it can be selectively
cleaved in the presence of unsubstituted benzyl ethers.
There are various methods for selectively removing the
PMB group which include Lewis acid-catalyzed cleavege
with MeBBr,4 BF3‚OEt2-NaCNBH3,5 AlCl3-EtSH,6 and
a combination of TMSCl-SnCl2-anisole.7 The oxidation,
(8) Schmidt, W.; Steckhan, E. Angew. Chem., Int. Ed. Engl. 1979,
18, 801.
(9) Horita, K.; Yoshioka, T.; Tanaka, T.; Oikawa, Y. Yonemitsu, O.
Tetrahedron 1986, 42, 3021.
(10) Chandrasckar, S.; Sumitra, G.; Yadav, J . S. Tetrahedron Lett.
1996, 37, 1645.
(11) J ohansson, R.; Saumelsson, B. J . Chem. Soc., Perkin Trans. 1
1984, 2371.
(12) Yan, L.; Kahne, D. Synlett 1995, 523.
(13) Yadav, J . S.; Mashram, H. M.; Sudershan, G.; Sumitra, G.
Tetrahedron Lett. 1998, 39, 3043.
(14) The oxidative removal of the PMB group requires the combina-
tion of aqueous solvent organic and DDQ, and under these aqueous
conditions the 2,3-dichloro-5,6-dicyano-1,4-benzoquinone is reduced to
the corresponding 1,4-diphenol derivative, which may result in acidic
conditions.
(15) Marshman, R. Aldrichimica Acta 1995, 28, 77; and references
therein.
(16) (a) Bartoli, G.; Marcantoni, E.; Petrini, M. Angew. Chem., Int.
Ed. Engl. 1993, 32, 1061. (b) Bartoli, G.; Cimarelli, C.; Marcantoni,
E.; Palmieri, G.; Petrini, M. J . Chem. Soc., Chem. Commun. 1994, 715.
(c) Bartoli, G.; Marcantoni, E.; Sambri, L.; Tamburini, M. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2046. (d) Bartoli, G.; Marcantoni, E.;
Petrini, M.; Sambri, L. Chem. Eur. J . 1996, 2, 973. (e) Bartoli, G.;
Bosco, M.; Van Beek, J .; Marcantoni, E.; Sambri, L. Tetrahedron Lett.
1996, 37, 2293. (f) Bartoli, G.; Bosco, M.; Dalpozzo, R.; Marcantoni,
E.; Sambri, L. Chem. Eur. J . 1997, 3, 1941. (g) Bartoli, G.; Bosco, M.;
Cingolani, S.; Marcantoni, E.; Sambri, L. J . Org. Chem. 1998, 63, 3624.
(h) Bartoli, G.; Bosco, M.; Dalpozzo, R.; De Nino, A.; Marcantoni, E.;
Sambri, L. J . Org. Chem. 1998, 63, 3745.
(1) For general methods see: (a) Green, T. W. Protective Group in
Organic Synthesis; Wiley: New York, 1991. (b) Kocienski, P. J .
Protecting Groups; Thieme: New York, 1994.
(2) Lemieux, R. U. Chem. Soc. Rev. 1978, 7, 423.
(3) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155.
(4) He´bert, N.; Beck, A.; Lennox, R. B.; J ust, G. J . Org. Chem. 1992,
57, 1777.
(5) Srikrishna, A.; Viswajanani, R.; Sattigeri, J . A.; Vijaykumar, D.
J . Org. Chem. 1995, 60, 5961.
(6) Bouzide, A.; Sauve´, G. Synlett 1997, 1153.
(17) (a) Bartoli, G.; Bosco, M.; Marcantoni, E.; Nobili, F.; Sambri,
L. J . Org. Chem. 1997, 62, 4183. (b) Bartoli, G.; Bosco, M.; Marcantoni,
E.; Sambri, L.; Torregiani, E. Synlett 1998, 209.
(7) Akiyama, T.; Shima, H.; Ozaki, S. Synlett 1992, 415.
10.1021/jo990014r CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/24/1999