unmasking5 with 20 mol % of DDQ-Mn(OAc)3. In
continuation of our studies on the masking/unmasking
of the hydroxyl groups,9 herein we report an efficient
ZrCl4-catalyzed10 protocol for the deprotection of PMB
ethers and esters in short reaction times and good to high
yields (eq 1).
Zir con iu m (IV) Ch lor id e Ca ta lyzed New a n d
Efficien t P r otocol for th e Selective
Clea va ge of p-Meth oxyben zyl Eth er s†
Gangavaram V. Madhava Sharma,*
Ch Govardhan Reddy, and Palakodety Radha Krishna
D-211, Discovery Laboratory, Organic Chemistry
Division III, Indian Institute of Chemical Technology,
Hyderabad 500 007, India
esmvee@iict.ap.nic.in
Thus, PMB ether 1 on treatment with ZrCl4 (20 mol
%) in CH3CN at room temperature underwent a facile
deprotection of PMB group in 30 min and gave 1a in 86%
yield (Table 1). Having observed efficient unmasking of
1, to study the generality of the protocol, PMB ethers
were prepared from a variety of substrates having
different protecting groups and submitted to the new
protocol using ZrCl4 as Lewis acid. Accordingly, PMB
ethers 3 and 4, having acid-sensitive THP and MEM
ethers, respectively, underwent smooth demasking of the
PMB group in 40 min to give the products 3a (85%) and
4a (79%), respectively. PMB ethers 5 and 6, having base-
sensitive groups such as Ac and Bz, also underwent
efficient PMB removal in 45 min to give 5a (92%) and
6a (88%). In a further study on ethers 7 and 8 with
O-allyl and O-prenyl ethers, respectively, the ZrCl4 (20
mol %)-catalyzed cleavage was effected in 45 min to give
the alcohols 7a (88%) and 8a (90%), respectively.
Similarly, compound 9, containing an acid-sensitive
isopropylidene group as well as a glycosidic bond, when
treated with ZrCl4, gave the alcohol 9a (82%) in 45 min,
while carbohydrate derivative 10 having a glycosidic bond
and a benzyl group furnished 10a (89%) in 45 min very
efficiently. Further, ZrCl4-catalyzed PMB deprotection of
terpenoidal ethers viz. 11 with a primary OH group and
12 with a secondary OH group was smooth in furnishing
the corresponding alcohols 11a (76%) and 12a (78%) in
60 min.
Received December 23, 2002
Abstr a ct: A highly selective and efficient method for the
unmasking of p-methoxybenzyl (PMB) ethers and esters has
been developed by use of 20 mol % of zirconium(IV) chloride
as Lewis acid in acetonitrile. The present method is very
fast, and the conditions are tolerable to a variety of acid/
base-sensitive protecting groups and substrates such as
carbohydrates, terpenes, and amino acids. The products are
obtained in good to high yields.
Selective and efficient masking and unmasking1,2 of
hydroxyl groups play a crucial role in organic synthesis,
with a special reference to polyhydroxylated compounds.
Of the several benzyl ether type protecting groups
reported, p-methoxybenzyl (PMB)3 ether enjoys a unique
position due to the ease of its introduction and removal.
PMB group demasking, in general, is mediated either by
oxidizing agents (i.e., DDQ,3 CAN,4 and DDQ-Mn-
5
(OAc)3 ) or by Lewis acids6 and other methods.7 Lewis
acid mediated removal of PMB groups suffers from the
use of (a) reagents in stoichiometric quantities (BF3‚OEt2,
CeCl3‚7H2O, Me2BBr), (b) added reagents (ex. NaI, EtSH,
anisole, etc.), and (c) sometimes longer reaction times.
In spite of the availability of a variety of methods for
PMB deprotection, development of milder and new
methods is warranted to overcome the above drawbacks.
We have previously reported efficient protocols for the
PMB protection8 of alcohols using catalytic Yb(OTf)3 and
In a further study, aminol 13 having a NHBoc group
underwent smooth deprotection to give 13a in 82% yield,
while 14 with trityl group gave diol 14a by a simulta-
neous deprotection of both the trityl and PMB groups.
Further, esters 15-17 were deprotected with ZrCl4 (20
mol %) to give the corresponding acids 15a -17a , amply
indicating that PMB esters also can be cleaved with equal
ease as PMB ethers.
† IICT Communication No. 021112.
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Wiley: New York, 1991. (b) Kocienski, P. J . Protecting Groups;
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(3) Horita, K.; Yoshioka, T.; Tanaka, T.; Oikawa, Y.; Yonemitsu, O.
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A comparative study on the PMB deprotection was
conducted with different Lewis acids such as AlCl3, BiCl3,
TiCl4, and FeCl3, the results of which is indicated in Table
2. For example, when 1 was treated with TiCl4 and FeCl3
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10.1021/jo026897v CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/02/2003
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