A mild and selective cleavage of tert-butyldimethylsilyl ethers by indium(III) chloride

Article abstract of DOI:10.1039/b004937i

Alkyl tert-butyldimethylsilyl ethers are selectively deprotected to the corresponding alcohols in high yields for the first time by indium(III) chloride in refiuxing aqueous acetonitrile. Several functional groups like OBn, Boc, CBz, OBz, O-allyl, OTBDPS, OAc, OMe, ethers, esters and olefins present in the substrate are unaffected.

Full text of DOI:10.1039/b004937i

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A mild and selective cleavage of tert-butyldimethylsilyl ethers by
indium(III) chloride¤
Jhillu S. Yadav,* Basi V. Subba Reddy and Chinnala Madan
Organic Chemistry Division I, Indian Institute of Chemical T echnology, Hyderabad, 500 007,
India
L e t t e r
Received (in Montpellier, France) 19th June 2000, Accepted 27th July 2000
First published as an Advance Article on the web 6th October 2000
Alkyl tert-butyldimethylsilyl ethers are selectively deprotected
to the corresponding alcohols in high yields for the Ðrst time by
indium(III) chloride in reÑuxing aqueous acetonitrile. Several
functional groups like OBn, Boc, CBz, OBz, O-allyl,
OTBDPS, OAc, OMe, ethers, esters and oleÐns present in the
substrate are una†ected.
selectivity among alkyl and aryl TBS ethers. TBDPS ethers
did not cleave under the present reaction conditions even by
increasing reaction time or amount of catalyst. Furthermore, a
catalytic amount of indium(III) chloride (10% w/w of ether) in
reÑuxing acetonitrileÈwater (1 : 1) smoothly deprotected
primary alkyl TBS ethers, leaving secondary alkyl TBS ethers
intact (Table 1, entry i). Such selectivity can be applied in syn-
thetic sequences in which two protected hydroxy groups must
be unmasked at di†erent stages of the synthesis. The alkyl
TBS ethers are deprotected in high yields (75È93%) within
0.5È3 h reaction time. The cleavage required relatively longer
reaction times with hydrated indium(III) chloride to a†ord
yields comparable to those obtained with anhydrous
indium(III) chloride. The reaction conditions are compatible
with various functional groups like Boc, Cbz, O-allyl, OBz,
OTBDPS, OAc, OBn, ethers and oleÐns present in the mol-
ecule.
In conclusion, this letter describes a mild and efficient pro-
cedure using indium(III) chloride for the selective removal of
alkyl TBS ethers over TBDPS and aryl TBS ethers. The
method o†ers several advantages like mild reaction condi-
tions, greater selectivity, compatibility with other acid-
sensitive functional groups and high yields of the desilylated
products, which makes it a useful addition to the existing
methods.
The strategy of protecting a hydroxy group and subsequently
deprotecting it is frequently used in the multi-step synthesis of
complex natural products.1 Among various hydroxy protec-
tive groups, tert-butyldimethylsilyl (TBS) ethers are the most
versatile2 due to their ease of installation/removal and also to
their stability under basic or mildly acidic conditions. A
variety of reagents3h10 are employed for their cleavage under
various reaction conditions. Furthermore, a few methods11
are reported for the selective cleavage of alkyl TBS ethers over
aryl TBS ethers. Many of these methods involve acidic, basic,
reducing or oxidizing conditions that limit their efficiency.
However, in spite of their potential utility, these methods often
encounter some disadvantages like unsatisfactory yields,
incompatibility with other functional groups, long reaction
times and the use of large quantities of polar solvents such as
DMSO, DMF and HMPA, which require tedious aqueous
work-up. Consequently, the development of new reagents that
are more efficient and lead to convenient procedures and
better yields is desirable. In recent years indium(III) chloride
mediated transformations12 have received considerable atten-
tion due to its stability and recoverability from water.
Experimental
In continuation of our interest in the applications of indium
for various transformations,13 herein we report a new, efficient
and practical method for the selective cleavage of TBS ethers
using indium(III) chloride in aqueous acetonitrile. The cleavage
General procedure for the cleavage of alkyl TBS ethers
A mixture of alkyl TBS ether (10 mmol) and indium(III) chlo-
ride (1 mmol) and in acetonitrileÈwater (1 : 1, 20 ml) was
stirred under reÑux for the appropriate time (Table 1). After
complete conversion as indicated by TLC, the reaction mass
was diluted with water (10 ml) and extracted twice with ether
was e†ected by a catalytic amount of InCl in reÑuxing
3
aqueous acetonitrile with high chemoselectivity. The pro-
cedure is highly selective to cleave alkyl TBS ethers over
TBDPS (the diphenylsilyl) and aryl TBS ethers (Scheme 1).
Such selectivity is a highly desirable feature in the cleavage of
silyl ethers, o†ering various beneÐcial prospects in organic
synthesis. It is of interest to note that longer reaction times
(
2 ] 25 ml). The combined organic layers were washed with
brine, dried over anhydrous Na SO and concentrated in
vacuo followed by puriÐcation on silica gel (Merck, 100È200
mesh, ethyl acetateÈhexane, 2 : 8) to give pure alcohol.
2
4
(
6È10 h) and the use of a large quantity of catalyst (50%)
cleaves aryl TBS ethers in fairly good yields whereas TBDPS
ethers are una†ected under similar conditions. It indicates the
Entry d. Silyl ether: liquid. 1H NMR (CDCl ): d 0.05 (s,
3
6
4
1
H), 0.85 (s, 9H), 1.05 (s, 9H), 1.25È1.35 (m, 2H), 1.45È1.55 (m,
H), 3.55È3.65 (m, 4H), 7.45È7.65 (m, 10H, Ar-H). Alcohol:
.05 (s, 9H), 1.25È1.35 (m, 2H), 1.45È1.55 (m, 4H), 2.5 (br s,
OH), 3.55È3.65 (m, 4H), 7.45È7.65 (m, 10H, Ar-H).
Entry m. Silyl ether: 1H NMR (CDCl ): d 0.05 (s, 6H), 0.15
3
(
s, 6H), 0.85 (s, 9H), 0.95 (s, 9H), 4.55 (s, 2H), 6.7 (d, 2H,
J \ 7.8 Hz), 7.15 (d, 2H, J \ 7.8 Hz). Alcohol: 0.05 (s, 6H),
.80 (s, 9H), 1.5 (br s, OH), 4.35 (s, 2H), 6.55 (d, 2H, J \ 7.8
Hz), 7.0 (d, 2H, J \ 7.8 Hz).
Scheme 1
0
¤
IICT Communication No. 4515.
DOI: 10.1039/b004937i
New J. Chem., 2000, 24, 853È854
853
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2000

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Table 1 Indium(III) chloride catalyzed selective cleavage of TBS ethers
Reaction
time/h
Yield
(%)b
Entry
a
Silyl ether
Producta
2.0
3.0
90
87
b
c
0.5
0.5
91
89
d
e
3.0
93
f
1.0
1.5
0.5
88
84
81
g
h
i
0.5
75c
j
1.5
1.0
90
85
k
l
2.0
0.5
91
78
m
n
o
p
0.5
1.5
2.5
82
90
85
q
3.0
87
a All products were characterized by 1H NMR and IR spectra. b Isolated yields after puriÐcation. c Secondary alkyl TBS ether was deprotected
after 6 h reaction time.
7
8
9
G. Bartori, M. Bosco, E. Marcantoni, L. Sambri and E. Torre-
giani, Synlett, 1998, 209.
Acknowledgement
B.V.S. thanks CSIR, New Delhi for the award of a fellowship.
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1
985.
(a) E. J. Corey and G. B. Jones, J. Org. Chem., 1992, 57, 1028; (b)
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