Silyl Ethers - Thieme Chemistry

Scheme 16 Cleavage of Triethylsilyl Ethers with Tetrabutylammonium Fluoride [45]
O
O
OTBDPS
O
MsO
PMBO OTES
32
TBAF, THF, 0 o C, 45 min
94%
O
O
OTBDPS
O
MsO
PMBO OH
(7R)-5-O-(tert-Butyldiphenylsilyl)-7-{(2S)-4-[(2R)-2-hydroxy-4-(4-methoxybenzyloxy)butyl]-2-
(methylsulfonyloxy)pent-4-enyl}-1,2-O-isopropylidene-3,7-anhydro-4,6-dideoxy-d-riboheptitol
(33): [45]
To a soln of 32 (167 mg, 180 ìmol) in THF (8 mL) at 08C was added a soln of 1.0 M TBAF in
THF (270 ìL, 270 ìmol). The soln was stirred at 0 8C for 45 min then diluted with EtOAc
(60 mL), washed with H 2O (10 mL) and brine (10 mL), and the combined aqueous phases
were extracted with EtOAc (10 mL). The combined organic phases were dried (MgSO 4), filtered
and concentrated by rotary evaporation. Flash chromatography (hexanes/EtOAc 2:1)
afforded 33 as a colorless oil; yield: 137 mg (94%).
4.4.17.3 tert-Butyldimethylsilyl Ethers
The tert-butyldimethylsilyl (TBDMS) group [46] has become extremely popular among synthetic
chemists as a protecting device for alcohols, and is now the most widely used silyl
ether for this purpose. Both tert-butyldimethylsilyl chloride and tert-butyldimethylsilyl
trifluoromethanesulfonate are effective silylating agents for primary alcohols and many
secondary alcohols; tertiary alcohols are often resistant to silylation with these reagents.
A wide variety of conditions has been developed for the preparation of tert-butyldimethylsilyl
ethers, some of which permit selective silylation of seemingly similar hydroxy
functions.
tert-Butyldimethylsilyl ethers are much more stable toward basic reagents than are
trimethylsilyl and triethylsilyl ethers. They are readily cleaved with tetrabutylammonium
fluoride or hydrogen fluoride±pyridine complex, however, and are sometimes removed
in the course of reduction with hydride reagents such as lithium aluminum
hydride and diisobutylaluminum hydride. tert-Butyldimethylsilyl ethers, although less
sensitive toward acidic reagents than their trimethylsilyl counterparts, are nevertheless
quite readily cleaved in the presence of acetic acid or trifluoroacetic acid. This mode of
cleavage of tert-butyldimethylsilyl ethers can have the advantage of avoiding the strongly
basic reaction medium associated with tetrabutylammonium fluoride.
Formation
FOR PERSONAL USE ONLY
4.4.17 Silyl Ethers 383
4.4.17.3.1 Method 1:
Silylation ofAlcohols with tert-Butyldimethylsilyl Chloride
A widely employed method for the preparation of tert-butyldimethylsilyl ethers utilizes
tert-butyldimethylsilyl chloride (TBDMSCl) together with imidazole in dimethylformamide
at temperatures ranging from ambient to 808C. [46] Primary alcohols are readily silylated
under these conditions, as exemplified in the conversion of the triol 34 into the
tris(tert-butyldimethylsilyl ether) 35 (Scheme 17). [47]
33
for references see p 410
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG