Silyl Ethers - Thieme Chemistry

4.4.17.4 Triisopropylsilyl Ethers
Triisopropylsilyl (TIPS) ethers are used as protection for primary and certain secondary
alcohols, [74] the large steric bulk of the silyl group ensuring good selectivity in most instances.
[75] Secondary alcohols can only be converted into their triisopropylsilyl ethers under
more forcing conditions, and tertiary alcohols in general cannot be converted into triisopropylsilyl
ethers. A principal advantage of triisopropylsilyl ethers is their stability
toward basic conditions which cause cleavage of other functional groupings, including
silyl ethers such as tert-butyldimethylsilyl. [76] Thus, esters can be saponified without destruction
of a triisopropylsilyl ether, and strong bases such as tert-butyllithium, which
can deprotonate the methyl group of a tert-butyldimethylsilyl ether, are without effect
on a triisopropylsilyl ether. The triisopropylsilyl ether is among the weakest of the silyl
ethers in terms of coordination to metal cations. [77] It is advisable not to use an excess of
silylating agent, since it is sometimes contaminated with the more reactive, isomeric diisopropyl(propyl)silyl
reagent. [78]
Formation
4.4.17.4.1 Method 1:
Silylation ofAlcohols with Triisopropylsilyl
Trifluoromethanesulfonate and 2,6-Lutidine
The large steric demand imposed by the triisopropylsilyl group makes triisopropylsilyl
trifluoromethanesulfonate (TIPSOTf) the most useful reagent for silylations in this class.
In the presence of 2,6-lutidine and with dichloromethane as solvent, it is generally feasible
to convert a primary alcohol into its triisopropylsilyl ether without affecting a secondary
alcohol. [51] The conversion of diol 70 containing a primary and secondary hydroxy substituent
into its mono(silyl ether) 71 reflects the selectivity that can be attained with this
reagent (Scheme 35). [79]
Scheme 35 Selective Silylation of a Primary Alcohol with
Triisopropylsilyl Trifluoromethanesulfonate [79]
H
O O
70
OH
FOR PERSONAL USE ONLY
396 Science of Synthesis 4.4 Silicon Compounds
HO TIPSO
TIPSOTf, 2,6-lut
CH2Cl2, −8 oC 91%
H
O O
(4aR,5R,6RS,8aR)-6-Hydroxy-5,8a-dimethyl-5-[2-(triisopropylsiloxy)ethyl]octahydronaphthalen-1(2H)-one
Ethylene Ketal (71): [79]
To a soln of the diol 70 (5.28 g, 18 mmol) and 2,6-lutidine (3.15 mL, 27 mmol) in CH 2Cl 2
(25 mL) was added a soln of TIPSOTf (4.85 mL, 18 mmol) in CH 2Cl 2 (5 mL) over 1 h at ±88C.
After the mixture had been stirred for 4 h, the reaction was quenched by the addition of
aq NaHCO 3. After separation of the organic layer, the aqueous layer was extracted with
EtOAc (2 ”). The combined extracts were washed with brine and evaporated to dryness.
The residue was purified by column chromatography (silica gel, hexane/EtOAc 5:1) to
give alcohol 71; yield: 7.47 g (91%).
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG
71
OH