A facile chemoselective deprotection of the p-methoxybenzyl group

Article abstract of DOI:10.1016/S0040-4039(00)00574-8

The p-methoxybenzyl (PMB) group can be chemoselectively cleaved at low temperature in the presence of SnCl₄ and thiophenol. This method is especially useful in the cases where oxidative reagents such as DDQ and CAN need to be avoided. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00574-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 4015–4017
A facile chemoselective deprotection of the p-methoxybenzyl
group
Wensheng Yu, Mei Su, Xiaobang Gao, Zhiqiang Yang and Zhendong Jin ∗
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, IA 52242,
USA
Received 30 January 2000; revised 3 April 2000; accepted 4 April 2000
Abstract
The p-methoxybenzyl (PMB) group can be chemoselectively cleaved at low temperature in the presence of SnCl4
and thiophenol. This method is especially useful in the cases where oxidative reagents such as DDQ and CAN need
to be avoided. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: p-methoxybenzyl group; thioglycosides; orthoganol deprotection.
The p-methoxybenzyl (PMB) group is a very useful protecting group and has been employed widely
in the synthesis of complex natural products and carbohydrate chemistry.1 Its utility lies in the fact that
it is more readily cleaved oxidatively than unsubstituted benzyl ethers. The oxidants that are used most
frequently are 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)2 and ceric ammonium nitrate (CAN).3
One problem associated with these oxidative conditions is that other moieties, such as thio groups can
also be easily oxidized in the presence of DDQ or CAN. To solve this problem, many other deprotection
methods have been developed.1 One attractive strategy employs the combination of a Lewis acid and
a soft nucleophile to remove the PMB group chemo-selectively.4 However, these methods often suffer
from slow reaction rates and low yields.
It has been reported that SnCl4 is an efficient reagent for the selective deprotection of the PMB group
in carbohydrates.5 However, thioglycosides failed to react with SnCl4 under the reported conditions.5 We
have discovered that the combination of SnCl4/PhSH was able to cleave the PMB group in carbohydrates
including thioglycosides in a highly chemo- and regioselective manner at low temperature. The reaction
was quite clean and fast and the yields were uniformally superb. Furthermore, a variety of functionalities
and protecting groups were found to be compatible with these mild reaction conditions.
∗
Corresponding author. E-mail: zhendong-jin@uiowa.edu (Z. Jin)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00574-8
tetl 16853

4016
The results of cleavage of the PMB group in various substrates under our conditions are summarized
in Table 1. Three PMB groups of compound 1 were removed under our conditions at −78°C in 5 minutes
(entry 1) and the yield was excellent. Two PMB groups were sucessfully chemoselectively cleaved in
the presence of a benzyl group (entry 2). Many other protecting groups including allyl, acetonide, t-
butyldiphenylsilyl (TBDPS), esters, and acetal remained intact under the reaction conditions (entries
3–6). Chemoselective deprotection of the PMB group in the presence of 1,3-dithiolane was also possible
(entry 7).
Table 1
Selective cleavage of p-methoxybenzyl (PMB) ethers

4017
A typical procedure used in the above deprotection reactions follows: To a solution of p-
methoxybenzyl ether (1.0 equiv.) and thiophenol (1.2 equiv.) in anhydrous CH2Cl2 at −78°C was
added SnCl4 (1.05 equiv.) under nitrogen. The resulting mixture was stirred at −78°C, and the reaction
was monitored by TLC. In some cases (entries 3, 5, and 6) prolonged reaction times and higher
temperatures were required. After the reaction was complete, aqueous NaHCO3 was added, and the
reaction mixture was extracted with CH2Cl2 three times. The combined organic phase was washed with
brine, dried over anhydrous Na2SO4, and concentrated by rotary evaporation. The product was purified
by flash column chromatography.
In conclusion, we have developed a highly efficient and chemoselective reaction for the deprotection of
the PMB group. Our method is particularly useful in the cases where oxidative reagents such as DDQ and
CAN need to be avoided. Compared to SnCl4 conditions,5 the combination of SnCl4/PhSH has shown
the same substituent tolerance, but has demonstrated its distinctive advantage in thioglycosides. This
method should provide a new orthogonal deprotection approach for the removal of the PMB group in
carbohydrates and other complex molecules.
Acknowledgements
This work was supported by a Research Project Grant RPG-00-030-01-CDD from the American
Cancer Society and the Central Investment Fund for Research Enhancement (CIFRE) at The University
of Iowa. Special thanks are due to the Center for Biocatalysis and Bioprocessing at The University of
Iowa for providing a fellowship to W. Yu.
References
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Y.; Yonemitsu, O. Tetrahedron 1986, 42, 3021.
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B. J. Chem. Soc., Perkin Trans. 1 1984, 2371; (c) Onoda, T.; Shirai, R.; Iwasaki, S. Tetrahedron Lett. 1997, 38, 1443; (d)
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