for the bromination of TBDMS-protected cinnamyl alcohol
(6) for an ongoing project, we discovered that TBDMS ether
was removed quantitatively within 10 min. This result was
not surprising since the other halogen (I2),7 I2/MeOH,3a
interhalogen compounds I-Cl and I-Br,3g and BiBr3/
MeCN3m have been used for the deprotection of TBDMS
ethers. It is believed that the haloacids generated in situ from
the above reagents might be the species responsible for the
hydrolysis of TBDMS ethers. It has been shown that
benzyltrimethylammonium tribromide generates HBr and
MeOBr in methanol.8 In the present case the hydrolysis may
be catalyzed by HBr that is generated in situ from the reaction
of TBATB with MeOH as shown in Scheme 1. In a control
Table 1. Solvent-Dependent Cleavage of C10-TBDMS Ether
solvent(s)
MeOH
time/h
yield/%a
0.40
1.80
1.80
10.0
3.00
24.0
24.0
99
99
93
98
95
nil
nil
MeOH:H2O (9:1)
EtOH
i-PrOH
CH3CN
toluene
CH2Cl2
a GC determined.
Scheme 1. Proposed Mechanism of Deprotection of TBDMS
Group
The reaction times are as shown for each substrate in Table
2. It is important to note that a lower quantity of TBATB
(i.e., 0.01 mol %) also gave satisfactory results at longer
reaction times. For instance, substrate 1 containing a primary
TBDMS group was deprotected at room temperature in a
quantitative yield within 2.5 h, but a TBDMS-protected
secondary alcohol (4) could be deprotected in up to 93%
yield in 4 days at room temperature. However, refluxing the
reaction mixture can accelerate the reaction rate (90%, 6 h).
For the present investigation, 0.1 mol % of the reagent has
been used for each substrate.
A wide spectrum of structurally varied TBDMS ethers was
subjected to deprotection by this procedure, and the result
is summarized in Table 2. Aliphatic TBDMS-protected
primary alcohols 1, 2, and 3 were deprotected quantitatively
in nearly 1 h. TBDMS-protected secondary alcohols 4 and
5 produced the corresponding alcohols in excellent yields,
but the reaction rates were relatively slow. The slow rate of
deprotection of TBDMS-protected cholesterol (5) could be
in part due to the different solvent (MeOH:CH2Cl2, 1:1)
system used for this substrate.
The compatibility of the reagent is further illustrated by
selective deprotection of TBDMS-protected alcohols contain-
ing ethylenic (6) and acetylenic (7) systems. Importantly,
no other side product viz. bromination was observed,
although this reagent is an efficient brominating agent for
ethylenic and acetylenic substrates.5
The selectivity of this methodology is further tested with
other substrates containing tert-butyldiphenylsilyl (TBDPS)
ethers (8), phenolic TBDMS ethers (9), primary THP ether
(10), secondary THP ether (11), and DMT ethers (12 and
13), and the results are shown in Table 2. Facile deprotection
of acid-sensitive DMT ethers (12 and 13) further supports
the formation of HBr, proposed in Scheme 1.
We also examined the intramolecular chemoselective
deprotection of TBDMS ethers in the presence of isopropy-
lidene (14), Bn (15), Ac (16), Bz (17), THP (18), and TBDPS
(19), and the result is very encouraging as shown in Table
2. Intermolecular chemoselectivity9 for aliphatic TBDMS
ether (1) in the presence of phenolic TBDMS ether (9),
secondary TBDMS ether (8), and primary DMT ether (12)
experiment, treatment of silyl ether (1) with 0.01 equiv of
48% HBr in MeOH at room temperature in < 5 min leads
to a deprotected alcohol in a quantitative yield. When the
TBDMS ether of 2-propanol was treated with TBATB in
2-propanol, no deprotection was observed even after 48 h.
This is because the deprotected 2-propanol reacts with tert-
butyldimethylsilyl bromide to yield the starting TBDMS
ether, rendering its effective concentration practically unal-
tered. However, addition of methanol shifted the equilibrium
to the right, leading to a 90% deprotection after 5 h in support
of the mechanism proposed in Scheme 1. We therefore
explored the possibility of utilizing tetrabutylammonium
tribromide (TBATB) as an effective reagent for the cleavage
of TBDMS ethers.
The results of solvent dependent cleavage of primary
TBDMS ether (1) with TBATB (0.1 mol %) as shown in
Table 1 suggests that polar organic solvents are relatively
more suitable for deprotection and methanol turns out to be
the best protic medium for desilylation.
In a typical reaction, to a solution of TBDMS ether (1
mmol) in methanol (5 mL) is added TBATB (0.1 mmol).
(5) Chaudhuri, M. K.; Khan, A. T.; Patel, B. K.; Dey, D.; Kharmawoph-
lang, W.; Lakshmiprabha, T. R.; Mandal, G. C. Tetrahedron Lett. 1998,
39, 8163.
(6) Paquette, L. A., Ed. Encyclopedia of Reagents for Organic Synthesis;
John Wiley & Sons: New York: 1995; Vol. 7, pp 4738.
(7) Vaino, A. R.; Szarek, W. A. Chem. Commun. 1996, 2351.
(8) Kajigaeshi, S.; Kakinami, T.; Hirakawa, T. Chem. Lett. 1987, 627.
4178
Org. Lett., Vol. 2, No. 26, 2000