ORGANIC
LETTERS
2009
Vol. 11, No. 13
2752-2755
Chemoselective Chemical and
Electrochemical Deprotections of
Aromatic Esters
Kevin Lam and Istva´n E. Marko´*
De´partement de Chimie, Baˆtiment LaVoisier, UniVersite´ Catholique de LouVain,
Place Louis Pasteur, 1 B-1348 LouVain-la-NeuVe, Belgium
istVan.marko@uclouVain.be
Received April 23, 2009
ABSTRACT
Alcohols can be easily and chemoselectively deprotected from the corresponding aromatic esters by using either SmI2/HMPA or by electrolysis
in the presence of a proton source.
To be effective, protecting groups must fulfill several
requirements such as easy availability of the reagents,
efficient preparation of the protected function and a high
yielding (ideally quantitative) deprotection step under mild
and orthogonal conditions.1 Aromatic esters such as ben-
zoates fulfill the first requirement since they can be easily
generated by an improved procedure.2 Unfortunately, they
are difficult to hydrolyze due to their enhanced stability.3
Apart from the classical acidic and basic methods of ester
deprotection, single electron transfer appears to be an
attractive alternative since aromatic esters have a lower
reduction potential than aliphatic esters.4 While such reduc-
tions have been reported previously in the literature using
dissolving metals,5 they proceed with negligible chemose-
lectivity. Organic electrosynthesis offers an obvious solution
to this problem since the reducing power of an electrode
can be easily controlled during electrolysis. During their
pioneering work in this field, Horner and Neumann showed
that benzoate esters could be converted to benzyl alcohols
by electrolysis.6 However, the electrolyses were carried out
only on primary aromatic esters, and they required the use
of a mercury cathode. Moreover, a tetramethylammonium
salt had to be added to produce the highly reactive Hg(Me4N)
amalgam, which is the true reactant.7 The occurrence of this
organomercurial derivative prevented any control over the
reduction potential.
Recently, we have developed a chemical8 and an electro-
chemical method for the reduction9 of toluate esters 1, which
generates initially the radical anion 2. Subsequent fragmenta-
tion of 2 leads to the production of the radical 3 and toluate
anion 4. While attempting to optimize this process, we have
serendipitously discovered that the addition of a protic
source to the reduction medium completely altered the fate
of the reaction. Instead of the deoxygenated product, the
alcohol 5, generated by selective cleavage of the toluoyl
fragment, was obtained in high yield. In this article, we
disclose a new and efficient way to deprotect toluate esters
chemoselectively in the presence of other sensitive functional
(1) (a) Kocienski, P. J. Protecting Groups, 3rd ed.; Georg Thieme
Verlag: New-York, 2005. (b) Green, T. W.; Wuts, P. G. M. ProtectiVe
Groups in Organic Synthesis, 4th ed.; Wiley-Interscience: New York, 2007.
(2) Sano, T.; Ohashi, K.; Oriyama, T. Synthesis 1999, 7, 1141.
(3) Yoshimoto, K.; Kawabata, H.; Nakamichi, N.; Hayashi, M. Chem.
Lett. 2001, 9, 934.
(6) Horner, L.; Neumann, H. Chem. Ber 1965, 98, 3462.
(7) Southworth, B. C.; Osteryoung, R.; Fleischer, K. D.; Nachod, F. C.
Anal. Chem. 1961, 33, 208.
(4) Cankar, P.; Dubas, D.; Banfield, S. C.; Chahma, M.; Hudlicky, T.
Tetrahedron Lett. 2005, 46, 6851.
(5) (a) Pinnick, H.; Fernandez, E. J. Org. Chem. 1979, 15, 2810. (b)
Belhoul, C.; Guijarro, D.; Yus, M. Synthesis 2006, 2, 308.
(8) Lam, K.; Marko´, I. E. Org. Lett. 2008, 10, 2773.
(9) Lam, K.; Marko´, I. E. Chem. Commun. 2009, 95.
10.1021/ol900828x CCC: $40.75
Published on Web 06/03/2009
2009 American Chemical Society