Silyl Ethers - Thieme Chemistry

4.4.17.3.6 Method 6:
Cleavage of tert-Butyldimethylsilyl Ethers under Acidic Conditions
A wide variety of acidic reagents has been used for the cleavage of tert-butyldimethylsilyl
ethers. Several of these reagents exhibit good selectivity for the removal of a particular
tert-butyldimethylsilyl ether while leaving other silyl ethers, even a trimethylsilyl ether,
intact. For example, exposure of the bis(silyl ether) 56 to hydrofluoric acid in acetonitrile
cleaves the primary tert-butyldimethylsilyl ether but does not alter the angular trimethylsilyl
ether (Scheme 28). [34] The resulting alcohol 57 would have been difficult to obtain
from 56 by other silyl ether cleavage methods; the selectivity observed probably reflects
more facile protonation of the primary ether oxygen.
Scheme 28 Selective Cleavage of a tert-Butyldimethylsilyl Ether with Hydrofluoric Acid [34]
H
O
O OTMS
Ac
56
O
FOR PERSONAL USE ONLY
4.4.17 Silyl Ethers 391
O
O
49% aq HF
H
O
MeCN, 0
O
o H C, 6 min
H
90%
OTBDMS
O OTMS
(3aR,3bS,5S,6aR,8S,9aS,9bR,10R,11aS)-11a-Acetyl-5,9b-epoxy-5-(hydroxymethyl)-8,10-dimethyl-6a-(trimethylsiloxy)dodecahydroazuleno[5,4-e]-1,3-benzodioxole-2,7(3aH)-dione
(57): [34]
49% Aq HF (4.0 mL) was added dropwise to a soln of the silyl ether 56 (1.30 g, 2.23 mmol) in
MeCN (30 mL) at 08C. After being stirred for 6 min, the mixture was quenched with sat. aq
NaHCO 3 (CAUTION: careful addition was required until the evolution of CO 2 was no longer observed),
diluted with H 2O (150 mL), and extracted with EtOAc (3 ” 100 mL). The combined
organic extracts were dried (MgSO 4), filtered, and concentrated in vacuo. Purification by
flash chromatography (EtOAc/hexanes 1:1) gave the alcohol 57; yield: 0.934 g (90%).
4.4.17.3.6.1 Variation 1:
With Hydrogen Fluoride±Pyridine Complex
Hydrogen fluoride±pyridine complex, a reagent which is often used in a mixed solvent
system comprising pyridine and tetrahydrofuran, is highly effective for the cleavage of
tert-butyldimethylsilyl ethers. [62] In general, primary tert-butyldimethylsilyl ethers are
cleaved much more rapidly than their secondary or tertiary ether counterparts with hydrogen
fluoride±pyridine complex, and selective cleavage is usually possible with this reagent.
Reaction temperature is the critical factor in achieving selective cleavage in these
cases. A representative silyl ether cleavage with hydrogen fluoride±pyridine complex is
the conversion of the chlorothricolide intermediate 58 into the primary alcohol 59
(Scheme 29). [63] None of the other functional or protecting groups of thioester 58 (which
was a mixture of two diastereomers resulting from the convergence of racemic subunits)
are affected by this reagent.
57
Ac
O
OH
O
for references see p 410
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG