826
LETTER
Montmorillonite Clay: A Novel Reagent for the Chemoselective Hydrolysis
of t-Butyl Esters
M
ontmori
.
llonite Clay:
S
The Chemose
.
lective Hydr
Y
olysis of
t
-Butyl
E
a
sters dav,* B. V. Subba Reddy, K. Sanjeeva Rao, K. Harikishan
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax +91(40)7160512; E-mail: yadav@iict.ap.nic.in
Received 7 February 2002
In this report, we wish to describe a simple and efficient
Abstract: A mild and highly selective hydrolysis of t-butyl esters
has been achieved in high yields using montmorillonite KSF in re-
fluxing acetonitrile. The method is compatible with a variety of pro-
tecting and functional groups such as BOC, Cbz, propargyl, allyl,
method for the chemoselective hydrolysis of t-butyl esters
in the presence of a wide range of functional groups using
an inexpensive and reusable catalyst solid acid KSF clay.
benzyl, t-butyl ethers, allyl, methyl and benzyl esters present in the The t-butyl esters were smoothly deprotected to the parent
molecule.
carboxylic acids in the presence of montmorillonite KSF
clay under mild reaction conditions (Scheme).
Key words: solid acids, tert-butyl esters -amino acids
Protection of acids with appropriate protecting groups
plays an important role in organic synthesis, especially in
the synthesis of natural products.1 Carboxylic acids can be
protected as anhydrides, amides or esters.2 However, the
final stage of chemical process frequently requires their
cleavage so as to regenerate the parent carboxylic acid.
Among various acid protective groups, t-butyl esters are
widely used in the synthesis of peptides, alkaloids and
other natural products, because of their ease of formation
and/or removal under specific conditions.3 Removal of t-
butyl esters often involves the use of strong protic acids1,2
such as TFA and HCl as well as Lewis acids4 including
ZnBr2, silyl triflates and CeCl3 7H2O–NaI.5–7 However,
many of these procedures are of limited synthetic scope
due to the lack of selectivity, the use of stoichiometric
amount of reagents, corrosive and/or hazardous reagents,
the requirement of high temperature or long reaction time
and the necessity for anhydrous conditions. Moreover, no
attempt has been made to recycle the catalyst thereby
making the process economic and environmentally
friendly. Thus, the development of new reagents that are
more efficient and lead to convenient procedures and im-
proved yields with good functional group compatibility is
still of interest.
Scheme
The cleavage was affected by montmorillonite clay in re-
fluxing acetonitrile. The deprotection proceeds efficiently
in high yield with high chemoselectivity. This method se-
lectively cleaves t-butyl esters leaving benzyl, methyl and
allyl esters intact. Such selectivity can be applied in syn-
thetic sequences in which two ester moieties must be un-
masked at different stages of the synthesis. It should be
noted that the t-butyl esters bearing -stereogenic centers
gave the parent acids with complete retention of the orig-
inal configuration.8 This method is highly chemoselective
for deprotecting tert-butyl esters without affecting the
other functional groups. However, in the absence of cata-
lyst, the reaction did not yield any product even after a
long period in refluxing acetonitrile. The reactions are
clean, and complete within 1.5–3.5 hours. Due to the short
reaction time required for this cleavage, a number of func-
tional groups, which are capable of reacting in the pres-
ence of clay, remain intact. The major advantage of this
cleavage is in the selective removal of t-butyl esters in the
presence of other acid sensitive protecting groups such as
carbamates, esters and ethers, a selectivity is lacking in
the reported procedures. t-Butyl esters were more rapidly
deprotected than allyl ether and acetates by these condi-
tions. Furthermore, the compatibility of this procedure is
illustrated by the selective removal of a t-butyl group
without affecting olefins, carbamates, ethers and halides.
There are many advantages in the use of montmorillonite
clay for this cleavage, which avoids the use of either
strongly acidic or basic conditions. This method does not
require the use of anhydrous conditions or solvents and no
precautions need to be taken to exclude moisture from the
reaction medium. Thus, the present method is mild and
tolerates a wide range of functional groups. As evident
In recent years, the use of solid acid catalysts such as clays
and zeolites has received considerable attention in differ-
ent areas of organic synthesis due to their environmental
compatibility, recyclability, greater selectivity, non-cor-
rosiveness, simplicity in operation, low cost and ease of
isolation. In particular, clay catalysts render reaction pro-
cesses convenient, more economic, environmentally be-
nign and can act as Bronsted as well as Lewis acids in
their natural or ion-exchanged forms, enabling them to
function as efficient catalysts for various transformations.
Synlett 2002, No. 5, 03 05 2002. Article Identifier:
1437-2096,E;2002,0,05,0826,0828,ftx,en;D02502ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214