Silyl Ethers - Thieme Chemistry

in vacuo and purified by column chromatography (silica gel, 25±50% EtOAc/hexanes, then
10±30% MeOH/hexanes) to provide hydroxy acid 98 as a white foam; yield: 0.123 g (68%).
4.4.17.5.5 Method 5:
Cleavage of tert-Butyldiphenylsilyl Ethers with
Tetrabutylammonium Fluoride in Acetic Acid
Acetic acid may be used as a buffer in the cleavage of tert-butyldiphenylsilyl ethers with
tetrabutylammonium fluoride in tetrahydrofuran. [95] This valuable technique moderates
the basicity that accompanies this source of fluoride ion and which can sometimes lead to
destruction of base-sensitive substrates. An application of this method is seen in the final
step of a synthesis of (+)-acutiphycin (100), where a tert-butyldiphenylsilyl ether is
smoothly removed from 99 (Scheme 49). [96] An attempt to unmask this ether with unbuffered
tetrabutylammonium fluoride led to decomposition.
Scheme 49 Cleavage of a tert-Butyldiphenylsilyl Ether with Tetrabutylammonium
Fluoride in the Presence of Acetic Acid [96]
OTBDPS
O
OH H
O O
O
99
FOR PERSONAL USE ONLY
406 Science of Synthesis 4.4 Silicon Compounds
OH
TBAF, AcOH
THF, rt, 42 h
95%
OH
O
OH H
O O
O
(+)-Acutiphycin (100): [96]
A stock soln was prepared by addition of AcOH (0.15 mL) to a soln of 1.0 M TBAF in THF
(2.5 mL). Silyl ether (+)-99 (6.0 mg, 8.7 ìmol) was dissolved in THF (3.3 mL) and treated
with a portion of the stock soln (1.5 mL). After 42 h at rt, the mixture was diluted with
EtOAc (25 mL), washed with sat. aq NaHCO 3 (2 ” 15 mL) and brine (15 mL), dried (MgSO 4),
filtered, and concentrated. Flash chromatography (hexane/EtOAc 2:1) afforded (+)-100 as a
colorless, amorphous solid; yield: 3.8 mg (95%).
4.4.17.5.6 Method 6:
Cleavage of tert-Butyldiphenylsilyl Ethers with
Tris(dimethylamino)sulfur (Trimethylsilyl)difluoride
The mild fluoride source tris(dimethylamino)sulfur (trimethylsilyl)difluoride (TASF) [59]
can be employed to cleave a tert-butyldiphenylsilyl ether in the presence of certain other
silyl ethers, including a tert-butyldimethylsilyl ether. This valuable selectivity arises from
the increased propensity of a silicon atom to suffer nucleophilic attack when it carries
aryl substituents as compared to alkyl groups. A demonstration of the unique selectivity
of tris(dimethylamino)sulfur (trimethylsilyl)difluoride has been provided in the conversion
of the bis(silyl ether) 101 into alcohol 102 (Scheme 50). [97]
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG
100
OH