TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 965–967
Benzylsulfonyl: a valuable protecting and deactivating group in
phenol chemistry
Anne Briot,a Corinne Baehr,b Raymond Brouillard,a Alain Wagnerb,* and Charles Mioskowskib,*
aLaboratoire de Chimie des Polyphe´nols, UMR 7509 du CNRS, Institut Le Bel, Universite´ Louis Pasteur, Faculte´ de Pharmacie,
74, route du Rhin, 67400 Illkirch, France
bLaboratoire de Synthe`se Bioorganique, UMR 7514 du CNRS, Universite´ Louis Pasteur, Faculte´ de Pharmacie,
74, route du Rhin, 67400 Illkirch, France
Received 15 November 2002; revised 26 November 2002; accepted 30 November 2002
Abstract—We introduce benzylsulfonyl (Bns) as a valuable protecting group in phenol chemistry. Bns proved to be stable under
drastic reaction conditions and towards many common reagents. The deprotection proceeds quantitatively using catalytic
hydrogenolysis. Additionally the Bns deactivating properties make this protecting group useful for tuning the reactivity of
phenolic substrates. © 2003 Elsevier Science Ltd. All rights reserved.
Protecting groups not only temporarily block reactive
sites but they also modify the intrinsic reactivity of the
substrates.1 Usually this side effect is considered by the
chemist as a negative aspect of protecting group strate-
gies. However, sometimes, the reactivity alteration
induced by the protecting group becomes synthetically
useful. As an example, Trost reported a lithiation of a
trioxygenated benzene by inhibiting the ortho directing
effect of an oxygen substituent when introducing a
t-butyldimethylsilyl protection.2 Also, we have recently
shown that the regioselectivity of aromatic electrophilic
substitution can be inverted by converting a phenol
group into its methanesulfonate derivative. Indeed, the
strong electron withdrawing effect of sulfonyl residue
neutralizes the phenol ortho/para directing effect.3 The
use of ‘Not-so-innocent bystanders’ protecting groups,
as stated by Kocienski,4 to affect and influence the
quently encountered protecting groups in polyphenol
chemistry.
Therefore, we searched for a phenol protecting group
that would combine both deactivating properties and
mild hydrogenolysis cleavage feature. An interesting
candidate appeared to be the benzylsulfonyl (Bns)
group. Although Bns has only been rarely reported in
the literature6 it is readily introduced, using inexpensive
commercially available benzylsulfonyl chloride in the
presence of triethylamine or pyridine. Surprisingly, no
mild deprotection method has been described.
Herein we describe the reactivity chart of Bns esters.
We show that while stable under acidic and basic
conditions, Bns can be readily cleaved under an hydro-
gen atmosphere using catalytic Raney Nickel (Scheme
1). Moreover, Bns exhibits the same deactivating prop-
erties as its methanesulfonic parent.
outcome of
opportunities.
a reaction, provides novel synthetic
The ‘deactivating’ properties of sulfonic esters would be
very useful in polyphenol chemistry since it would
enhance the stability of the various intermediates. How-
ever, we and others5 have observed that conditions for
deprotection of aromatic methanesulfonic esters are not
compatible with polyphenol skeletons.
To evaluate the scope and the limitations of the Bns as
a phenol protecting group and to define a reactivity
chart, a model compound (ArOH=4-ethylphenol) was
Until now, because of the mildness of hydrogenolytic
cleavage, benzyl-type ethers are among the most fre-
Scheme 1. General scheme for catalytic hydrogenolysis of
benzylsulfonyl protecting groups (Bns).
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02745-4