Silyl Ethers - Thieme Chemistry

Scheme 40 Selective Cleavage of a Triisopropylsilyl Ether under Acidic Conditions [84]
TBDMSO
TIPSO
81
OMe
OMe O
NH
OMe
TsOH, MeOH, rt, 30 min
90%
TBDMSO
HO
82
OMe
OMe O
(5R,6E,8E,10E,13S,14S,15S,16Z)-15-(tert-Butyldimethylsiloxy)-13-hydroxy-5,22,24-trimethoxy-14,16-dimethyl-2-azabicyclo[18.3.1]tetracosa-1(24),6,8,10,16,20,22-heptaen-3-one
(82): [84]
A soln of triene 81 (50 mg, 0.066 mmol) in MeOH (6.0 mL) was treated with catalytic TsOH
(3.0 mg, 0.017 mmol, 0.25 equiv). The mixture was stirred at rt for 30 min and subsequently
diluted with NaHCO 3 and H 2O (20 mL). The mixture was extracted with EtOAc
(3 ” 25 mL), dried (MgSO 4), and concentrated in vacuo. Purification on silica gel (20 to
30% EtOAc/petroleum ether) afforded alcohol 82 as a colorless oil; yield: 36 mg (90%).
4.4.17.5 tert-Butyldiphenylsilyl Ethers
The tert-butyldiphenylsilyl (TBDPS) ether as a masking device for alcohols was introduced
by Hanessian in order to provide a protecting group more stable toward acidic reagents
than other silyl ethers. [85] tert-Butyldiphenylsilyl ethers are inert under acidic conditions
which can cleave tert-butyldimethylsilyl ethers, and they typically survive those acidic reagents
used to cleave alkyl ethers such as trityl and tetrahydropyranyl. The diminished
reactivity of tert-butyldiphenylsilyl ethers toward electrophiles is thought to be due to
the electron-withdrawing effect of the phenyl substituents attached to silicon. However,
the tert-butyldiphenylsilyl group is more easily cleaved than the tert-butyldimethylsilyl
group with sodium hydroxide. [86]
Formation
FOR PERSONAL USE ONLY
4.4.17 Silyl Ethers 401
4.4.17.5.1 Method 1:
Silylation ofAlcohols with tert-Butyldiphenylsilyl Chloride
Both primary and secondary alcohols can be converted into their tert-butyldiphenylsilyl
ethers, the usual reagent for this being the chlorosilane (tert-butyldiphenylsilyl chloride,
TBDPSCl). Secondary alcohols, if sterically hindered, may require elevated reaction temperatures
for efficient silylation with this reagent, as seen in the protection of ethyl (2S)-2hydroxy-3-methylbutanoate
(83) as its tert-butyldiphenylsilyl ether 84 (Scheme 41). [85]
NH
OMe
for references see p 410
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG