1146
LETTER
Bromine in Methanol: An Efficient Reagent for the Deprotection of the tert-
Butyldiphenylsilyl Group
M. Teresa Barros,a Christopher D. Maycock,b Christine Thomassignya
a Departamento de Quimica, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, P-2825-114 Caparica, Portugal
b Instituto de Tecnologia Quimica e Biologia, Universidade Nova de Lisboa, Rua da Quinta Grande 6, Apartado 127, P-2780-156 Oeiras,
Portugal
Fax +351 295 4461; E-mail: mtbarros@dq.fct.unl.pt
Received 23 April 2001
Recently we have studied the use of selective silylation/
Abstract: A selective reagent for the deprotection of a tert-butyl-
desilylation11 and we required a selective method for the
deprotection of a TBDPS group in the presence of ben-
diphenylsilyl (TBDPS) ether in the presence of other protecting
groups, using a solution of bromine in methanol under reflux is pre-
sented. By extension, this reagent has been introduced for the
zoates, without benzoyl migration. As the recent method
deprotection of TBDPS amines and esters and has also shown good of Vaino and Szarek12 (using iodine in methanol at reflux
selectivity in the removal of a TBDMS ether in the presence of a
TBDPS one.
for the deprotection of a TBDMS group) was not applica-
ble to the bulkier TBDPS ether, we have managed to
Key words: tert-butyldiphenylsilyl (deprotection of), TBDPS, silyl
ether, silylamine, silyl ester
deprotect the silyl ether by treatment with a solution of the
smaller halogen, bromine in methanol.
The reaction procedure consists simply of the treatment of
the silyl ether with a solution of X% bromine in methanol
(see Table for the number of equivalents of bromine and
the dilution m/v of the solution) under reflux. When TLC
showed no more initial compound, the remaining bromine
was reduced by a solution 5% of Na2S2O3. The standard
treatment was then to extract the product with dichlo-
romethane, to dry the organic layers and to concentrate. A
purification by silica-gel chromatography or by distilla-
tion gave the pure product. In the case of very polar prod-
ucts (entries 1, 3 and 9), after neutralisation the overall
was concentrated and a part of the resulting crystals was
redissolved in an apropriate solvent. Filtration and evapo-
ration of the solvent furnished an oil which was purified
by chromatography. By varying the reaction time, the
number of equivalents of bromine and the concentration
of bromine in methanol, we have managed to obtain from
good to excellent yields of deprotection. As an example,
only thirty minutes of reflux are necessary for the obten-
tion of the 1,2-ethanediol (entry 1) with 3.0 equivalents of
bromine (1.0% solution in methanol) in 99%-yield. Three
hours were needed to obtain the same yield with only 0.5
equivalents of bromine (solution 1.0% in methanol). In
the presence of other protective groups, it was advanta-
geous to decrease the percentage of bromine in the solu-
tion (entries 2, 4). Other groups such as methyl ester
(entry 3), methyl ether (entries 8, 9), benzyl (entry 4), to-
sylate (entry 2), benzoate (entries 5, 8) or tri-O-methyl
gallate (entry 6) are stable under the conditions of depro-
tection. In particular, we noted the absence of migration of
the benzoate (entries 5, 8) or tri-O-methyl gallate (entry 6)
groups13 and the conservation of stereochemistry at other
hydroxyl groups (entry 3). Furthermore, the short reaction
times and the mild conditions allowed us to work with dis-
accharides such as a protected sucrose (entries 4-7) with-
out notable degradation of the glycosidic link. Entry 9
provides another example of the selective cleavage of a
Since its introduction by Hanessian1 in 1975, the tert-bu-
tyldiphenylsilyl (TBDPS) group has become a standard in
the protection of the alcoholic hydroxyl function.2-4 Its
great bulkiness induces a good selectivity in the protection
of one hydroxyl group in the presence of more hindered
ones, but also a good resistence to nucleophilic attack or
other chemical reactions. Furthermore, the use of TBDPS
has been extended3,5,6 to the protection of phenols,
amines, carboxylic acids, amides and other functional
groups. The different possibilities for the cleavage of the
TBDPS group in multiply functionalized substrates are
primordial in synthetic chemistry. Generally, the cleavage
of TBDPS derivatives can be achieved by the same meth-
ods as for the very similar TBDMS group and TBDPS
groups can be easily cleaved without affecting other non-
silylated groups. As a general rule, most of the methods
for the deprotection of silyl ethers are based on the affinity
of silicon for fluorine, or of a strongly acidic or basic hy-
drolysis. For the first method, the most common source of
fluoride ions is lipophilic tetrabutylammonium fluoride
(TBAF), which cleaves silyl groups rapidly at room tem-
perature without affecting most other protecting groups.
Unfortunately, the high basicity of fluoride, particularly
under anhydrous conditions, can affect base-sensitive
molecules adversely and has been responsible of acyl mi-
grations in numerous exemples. The deprotection of TB-
DPS ethers by acidic hydrolysis, as opposed to acidic
fluorolysis, is normally carried out with 1-5% alcoholic
hydrochloric acid.1,7-9 Another method with trifluoroace-
tic acid requires higher temperatures and longer reaction
times.10 In general, the methods used for the desilylation
of TBDPS ethers, as described in the literature, often re-
quired long reaction times and/or forcing conditions (par-
ticularly during acidic hydrolysis), and are most of the
time accompanied by acyl migration where possible.
Synlett 2001, No. 7, 1146–1148 ISSN 0936-5214 © Thieme Stuttgart · New York