Tetrahedron Letters
Cesium carbonate mediated aryl triflate esters’ deprotection
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Alice E. Green, Vangelis Agouridas , Eric Deniau
Université Lille Nord de France, ENSCL, E.A. 4478 Chimie Moléculaire et Formulation, Cité Scientifique, 59652 Villeneuve d’Ascq Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
A variety of diversely substituted aryl triflate esters were efficiently deprotected to the parent phenols by
exposure to cesium carbonate in toluene. This procedure proved highly compatible with existing func-
tional groups.
Received 19 September 2013
Revised 15 October 2013
Accepted 18 October 2013
Available online 25 October 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Phenol
Aryl triflates
Trifluoromethanesulfonate
Cesium carbonate
Deprotection
Praised for their oxidoreductive and acidobasic properties, phe-
nols and their derivatives have found use in numerous and multi-
farious industrial applications, namely dyes, food antioxidants,
pharmaceuticals, or polymers. However, synthetic chemistry of
phenolic-based compounds usually requires to temporarily shut
down their reactivity and to derivatize the hydroxyl moiety with
a protecting group. Among the plethora of existing methods,1a al-
kyl/silyl ethers (–OMe, –OMOM, and –OTBDMS) are by far the most
represented. Their removal is generally carried out in the presence
of a Brönstedt or Lewis acid whereas also commonly used alkyl/
aryl esters (–OAc and –OBz) get cleaved in basic media. More sel-
dom, sulfonate esters, and particularly trifluoromethanesulfonates,
have been exploited as efficient alternatives to conventional pro-
tecting groups for phenols.1b Owing to their high stability under
a wide range of experimental conditions, they provide ample space
for ‘extended’ chemistry but are not devoid of several drawbacks.
Only a few procedures, typically involving strong reductive condi-
tions or the use of hard nucleophiles to effect the S–O bond cleav-
age, are available in the literature and not always compatible with
the presence of other sensitive functional groups.
Metal catalyst,
Base
O
O
N
H
Toluene, Δ
N
H
O
OEt
O
OEt
OTf
OH
1a
2a
100% conversion
Scheme 1. Quantitative cleavage of triflate ester 1a.
onates was possible with primary amines.4 More recently, a mild
and highly efficient method related to hydrolysis was proposed
by Nishiyama and co-workers upon treatment with Et4NOH in
wet dioxane.5
In the course of our investigations aimed at synthesizing highly
functionalized isoindolinones, a variety of enamides as exemplified
with 1a were submitted to a set of different metal catalyzed cou-
pling reactions under anhydrous conditions (freshly distilled and
degassed solvents, dried reagents). Due to their sluggish reactivity,
we were able to notice that whenever cesium carbonate was used
as a base, triflates were quantitatively converted to the parent phe-
nol within a few hours (Scheme 1).
This result prompted us to study the details, scope, and limita-
tions of the reaction with the aim of proposing a new procedure for
the mild deprotection of aryl triflate esters.
For example, Katzenellenbogen and co-workers took advantage
of the inertness of the estrogen core to cleave an aryl triflate ester
under harsh conditions using either a large excess of LiAlH4 or
NaOH.2 It was also mentioned that partial deprotection could occur
in acceptable yields upon exposure to a fluoride anion source as
nBu4NF.3 Upon their study of aromatic nucleophilic substitution
reactions between aryl triflates and secondary amines, Schio
et al. evidenced that aminolysis of aromatic trifluoromethanesulf-
Salicylaldehyde was initially selected as a model substrate for a
short screening of experimental conditions (Table 1). The study
confirmed that 3 equiv of Cs2CO3 with heating to 80 °C was re-
quired for complete conversion of the starting material in a decent
period of time (Table 1). A decrease to a single equivalent (entry 3)
resulted in partial reaction within a similar timeframe. Trapping
water traces with molecular sieves 4 Å (entry 4) was of no conse-
quence for the conversion. The nature of the base seemed to be
⇑
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