Efficient and chemoselective cleavage of TBS ethers by a sub-stoichiometric amount of decaborane

Article abstract of DOI:10.1039/b201794f

TBS ethers od aliphatic alcohols in THF-MeOH (or methanol) were deprotected chemoselectively to the corresponding alcohols using a sub-stoichiometric amount of decaborane at rt under nitrogen in high yields.

Full text of DOI:10.1039/b201794f

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Efficient and chemoselective cleavage of TBS ethers by
a sub-stoichiometric amount of decaborane
Yeon Joo Jeong, Ji Hee Lee, Eun Soo Park and Cheol Min Yoon*
1
Graduate School of Biotechnology, Korea University, 1,5-ga, Anam-dong, Sungbuk-gu,
Seoul 136-701, Korea
Received (in Cambridge, UK) 19th February 2002, Accepted 2nd April 2002
First published as an Advance Article on the web 18th April 2002
TBS ethers of aliphatic alcohols in THF–MeOH (or
methanol) were deprotected chemoselectively to the
corresponding alcohols using a sub-stoichiometric amount
of decaborane at rt under nitrogen in high yields.
the solution was increased, the reaction rate was increased. The
reaction of piperonyl alcohol TBS ether was complete within
25 min in methanol, whereas the reaction took 50 min for the
completion in a solution of THF and methanol (1 : 1) (entry
1). The TBS ethers of primary aliphatic alcohols under the
reaction conditions were deprotected to give the corresponding
alcohols in high yields in the two systems (Table 1). While
deprotection of electron sufficient TBS ethers proceeded
quickly, the electron deficient substrates were deprotected
slowly. For example, the TBS ethers of acetyl protected glucose
(entry 7) and benzyl alcohols with nitro groups (entries 5 and 6)
were deprotected slowly compared to the TBS ethers of benzyl
protected glucose (entry 8) and other primary alcohols (entries
1, 3 and 4) respectively. The reaction is mild enough not to
affect the carbon–carbon double bond in conjugated systems
(entry 2) and acetals (entries 7–8).
Under the conditions, TBS ethers of secondary alcohols were
deprotected slowly and not completely even at extended
reaction times (entries 1–4, Table 2). The exact reason is not
clear and is under investigation. The TBS ether of phenethyl
alcohol in a solution of THF and methanol (1 : 1) (or in meth-
anol) gave deprotected alcohol and recovered starting material
in 80% (89%) and 13% (8%) respectively (entry 1). The depro-
tection rate also depends on the electronic effect of the sub-
stituent. The TBS ether of a lactone (entry 4) was deprotected
very slowly to give an alcohol in 10% (method A) and 26% yield
(method B), respectively, and starting material was recovered in
85% (method A) and 72% (method B) yield, respectively. We
believe that the mechanism of this selective hydrolysis involves
the coordination of decaborane and/or its decomposed deriv-
atives to the oxygen of the TBS ether to form an oxonium ion
followed by nucleophilic attack of methanol (Scheme 1). The
oxonium intermediate was surmised on the basis of experi-
mental results that deprotection of electron deficient TBS
ethers (with electron withdrawing substituents) and sterically
more hindered TBS ethers (secondary alcohol TBS ethers) was
relatively slow compared with that of electron sufficient TBS
ethers and sterically less hindered THP ethers (primary alcohol
TBS ethers). The phenolic TBS ethers were not deprotected at
all after 25 h stirring at rt in the two solvent systems (entries 5
and 6). Therefore, our conditions could be used for the selective
deprotection of alkyl TBS ethers in the presence of aryl ethers.6
Extension of the method was investigated using piperonyl
alcohol as a model to compare the relative stability of the TBS
group with other protecting groups such as TBDPS, TIPS, Tr
and TPS using 2 mol% of decaborane in a solution of THF and
methanol (1 : 1),12 and the results are shown in Table 3. The
TBS ether was found to be more labile than TIPS, Tr and
TBDPS ethers and more stable than TPS ethers under the
conditions. This trend is the same as that of silyl cleavage using
BF3ؒEt2O in methylene chloride at rt.13 The TIPS ether was
deprotected to give an alcohol in only 7% yield even in the case
of extended reaction time (24 h) and other bulky protecting
groups such as trityl and TBDPS remained intact even after
24 h stirring at rt.
Protection and deprotection of alcohols play a key role in the
organic synthesis of polyfunctional organic molecules and a lot
of protecting groups have been developed for this purpose.
Among silyl ethers, tert-butyldimethylsilyl (TBS) ether is the
most popular protecting group for alcohols because of its easy
preparation1,2 and stability in a variety of reaction conditions.
Although tetra-n-butylammonium fluoride3 is the most com-
mon reagent for the cleavage of TBS ethers, the strong basicity
of the fluoride anion makes it inappropriate for base-sensitive
substrates.4 In addition, the phase transfer properties of
tetrabutylammonium cations often cause difficulties in the
work-up and purification of products. A variety of reagents for
the removal of TBS ethers have been developed to solve these
problems.1,2,5–6 However, most of these procedures require
complicated procedures, drastic reaction conditions, moisture
sensitive reagents and cumbersome work-up. As synthetic
targets become increasingly complex, selective methods to
deprotect in the presence of another are very demanding. Here
we report a mild, selective, simple and efficient deprotection of
TBS ethers of alcohols using a sub-stoichiometric amount of
decaborane (Scheme 1).
Scheme 1
Decaborane (B10H14)7,8 is a commercially available white
solid that decomposes only slowly in air. Decaborane has been
reported as a reducing reagent in organic synthesis, but it is
inefficient from a synthetic point of view due to its low reducing
power in polar solvents.9 By changing the solvent to protic
solvents and/or adding additives, decaborane was found to be a
mild reducing agent in reactions such as reductive amination,10a
reductive etherification,10b and reduction of carbonyls.10c
Decaborane is also a good Lewis acid that can form adducts
with Lewis bases (SH, OH, NH etc.).11 As a continuous study
on decaborane, decaborane was used for the deprotection of
TBS ethers as a Lewis acid catalyst. The TBS ethers used in this
experiment were prepared from the corresponding alcohols
using well-known procedures3 and the TBS ethers were
subjected to deprotection using a sub-stoichiometric amount of
decaborane in a solution of methanol and THF (or methanol
as a sole solvent) at room temperature. The deprotection results
for TBS ethers of primary, secondary alcohols and phenolic
TBS ethers are collected in Tables 1 and 2. Although the
reaction proceeds well with 1 mol% of decaborane, 2 mol% of
decaborane was used to reduce the reaction time, especially
with the less reactive TBS ethers. If the amount of methanol in
In conclusion, TBS ethers of primary aliphatic alcohols in
THF–MeOH (or MeOH) were converted to the corresponding
DOI: 10.1039/b201794f
J. Chem. Soc., Perkin Trans. 1, 2002, 1223–1225
This journal is © The Royal Society of Chemistry 2002
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Table 1 Deprotection of TBS ethers of primary alcohols
Entry
1
Substratee
Product
Reaction time
Yielda
50 minb (25 min)c
97%b (98%)d
2
3
1 h (30 min)
98% (97%)
96% (96%)
50 min (30 min)
4
5
1.5 h (1 h)
9 h (5 h)
97% (97%)
90% (93%)
6
7
9 h (5 h)
9 h (7 h)
92% (94%)
97% (95%)
8
9
6 h (2.5 h)
6 h (5 h)
90% (99%)
96% (93%)
a Isolated yields. b Yields obtained in THF and methanol (1 : 1). c Parenthesis times show reaction time in methanol. d Parenthesis yields were
obtained in methanol. e TBS: tert-butyldimethylsilyl, Ac: acetyl, Bn: benzyl, Cbz: benzyloxycarbonyl.
Table 2 Deprotection of TBS ethers of secondary alcohols and phenols
Entry
1
Substrate
Product
Reaction timed
12 h
Yielda
A: 80% (13%)b
B: 89% (8%)
2
9 h
A: 1: 75% 2: 19%
B: 1: 36% 2: 59%
3
4
12 h
12 h
A: 70% (28%)
B: 92% (7%)
A: 10% (85%)
B: 26% (72%)
5
6
12 h
12 h
N.R.
N.R.
7
1.5 h
A: 93%
B: 94%
a Isolated yields. N.R. = no reaction. b The yields in parentheses are those of recovered substrates. c A: method A, B: method B. d The reactions were
quenched and worked up after the same reaction time in both methods.
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Table 3 The relative stability of other protecting groups
Method B
Yield (%)a
N.R.
The procedure is the same as that of method A except for the
solvent used. 3 ml of methanol was used instead of 3 ml of a
solution of THF and methanol used in method A.
Entry
1
Substrate
Time
24 h
Acknowledgements
2
3
4
5
24 h
N.R.
This work was supported by Korea Research Foundation Grant
(KRF-2001-015-DP0302).
24 h
7 % (91 %)b
97 %
Notes and references
6 min
50 min
1 (a) T. W. Greene and P. G. M. Wuts, Protective groups in organic
synthesis. 3rd edn. John Wiley & Sons, New York, 1991; (b) P. J.
Kocienski, Protecting groups, Georg Thiemen Verlag, New York,
1994.
97 %
2 For a recent review on silyl ethers and their selective deprotections,
see: T. D. Nelson and R. D. Crouch, Synthesis, 1996, 1031.
3 E. J. Corey and A. Venkateswarlu, J. Am. Chem. Soc., 1972, 94,
6190.
4 (a) β-elimination: T. Toshima, K. Tatsuta and M. Kinoshita, Bull.
Chem. Soc. Jpn., 1988, 61, 2369; (b) transacylation: F. Franke and
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6 (a) B. H. Lipshutz and J. Keith, Tetrahedron Lett., 1998, 39, 2495; (b)
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Boron Hydride Chemistry, Academic Press, New York, 1975.
8 Decaborane was purchased from Katchem Ltd. E. Krasnohorske 6
110 00 PRAHA 1 and used without any further purification.
9 T. Tanaka, T. Matsuda, K. Kimijima and Y. Iwasaki, Bull. Chem.
Soc. Jpn., 1978, 51, 1259.
a Isolated yields. b Yield of the recovered substrate in parentheses.
c Relative stability based on the reaction: TBDPS = Tr > TIPS ӷ TBS >
TPS. TBDPS: tert-butyldiphenylsilyl, TPS: triphenylsilyl, TIPS:
triisopropylsilyl, Tr: triphenylmethyl or trityl.
alcohols using a sub-stoichiometric amount of decaborane
(2 mol%) at rt under nitrogen in excellent yields. The depro-
tection of TBS ethers of secondary alcohols is slow and
incomplete, but gave the corresponding alcohols in high yields
and recovered substrate in low yield. The reaction conditions
are mild enough not to affect the double bond of allyl alcohols,
acetals and TBS ethers of phenolic alcohols. In addition, TBS
ether showed selectivity against TBDPS, Tr and TIPS ethers
under our conditions.
Experimental
Typical experimental procedure:
Method A
To a solution of TBS ether of piperonyl alcohol (100 mg, 0.38
mmol) in 3 ml of a solution of THF and methanol (1 : 1) was
added decaborane (0.9 mg, 2 mol%) and the resulting solution
was stirred at rt. Reaction was monitored by TLC using a
solution of ethyl acetate and hexane (1 : 4). After 50 min, the
reaction was concentrated and chromatographed on silica gel
using a solution of ethyl acetate and hexane (1 : 4). The con-
centration gave the alcohol as a light yellow solid in 97% yield
(55.4 mg).
10 (a) J. W. Bae, Y. J. Cho, S. H. Lee, C. O. Maing Yoon and C. M.
Yoon, Chem. Commun., 2000, 1857; (b) S. H. Lee, Y. J. Park and
C. M. Yoon, Tetrahedron Lett., 1999, 40, 6049; (c) J. W. Bae,
S. H. Lee, Y. J. Jung, C. O. Maing Yoon and C. M. Yoon,
Tetrahedron Lett., 2001, 42, 2137.
11 R. M. Grimes, Carboranes, Academic Press, New York, 1970.
12 Due to the limited solubility of substrates, mixed solvent system
(1 : 1 = THF–methanol) instead of methanol was used.
13 S. Mabic and J.-P. Lepoittevin, Synlett, 1994, 851.
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