Silyl Ethers - Thieme Chemistry

4.4.17.6 Other Silyl Ethers
FOR PERSONAL USE ONLY
4.4.17 Silyl Ethers 409
The need for selectivity in the protection of alcohols has brought forth a suite of silylating
agents bearing a variety of substituents at the silicon atom that extend beyond the structural
types described in Sections 4.4.17.1±4.4.17.5. Silyl ethers prepared with these reagents
possess reactivity toward cleavage which varies widely and which can be ªtunedº
to particular applications. The combination of steric and electronic effects of substituents
at silicon in these silyl ethers leads to properties that are often difficult to predict, and
most of the information about silyl ethers in this group has been obtained from empirical
observation.
Although ethers in this group have been less extensively exploited in synthesis than
the silyl ethers described in the foregoing sections, specific examples suggest that they
can play a valuable role in the differential protection of alcohols during a complex synthesis,
and may find more general application as their reactivity becomes better understood.
All of the silyl ethers in this group can be prepared by one or more of the methods described
for silyl ethers in Sections 4.4.17.1±4.4.17.5, the most frequently used method being
reaction of an alcohol with either the silyl chloride, bromide or triflate. The subtle but
real variation in the behavior of these silyl ethers towards cleavage reagents forms the basis
for their utility as specific protection devices for alcohols.
Thus, diethylisopropylsilyl ethers are more stable than triethylsilyl ethers, but are
more easily cleaved than tert-butyldimethylsilyl ethers. Conditions have been described
that result in retention of a secondary tert-butyldimethylsilyl ether while removing a diethylisopropylsilyl
ether. [101] As an operational principle, a diethylisopropylsilyl ether is
considered to be approximately 90 times more stable than a trimethylsilyl ether towards
acidic hydrolysis and 600 times more resistant than a trimethylsilyl ether towards cleavage
with fluoride ion.
An isopropyldimethylsilyl ether [102] is even more labile towards acidic hydrolysis
than a diethylisopropylsilyl ether, and is cleaved rapidly in aqueous acetic acid at room
temperature. [103] Other hydroxy protecting groups, such as a tetrahydropyranyl ether,
will survive conditions that typically cleave an isopropyldimethylsilyl ether.
Triphenylsilyl ethers are usually prepared from the corresponding silyl chloride, [104]
and are quite labile towards basic hydrolysis. They are approximately 400 times less reactive
towards acidic cleavage than trimethylsilyl ethers.
Methyldiphenylsilyl ethers [105] are intermediate in stability between trimethylsilyl
and triethylsilyl ethers. Unlike most trimethylsilyl ethers, they will survive chromatography
on silica gel, but a serious limitation is that they do not withstand many of the common
reagents used in synthesis, including acids, bases, reducing agents, and oxidants.
tert-Butylmethoxyphenylsilyl ethers provide protection for alcohols where selectivity
is desired in the presence of other silyl ethers, especially tert-butyldimethylsilyl or tertbutyldiphenylsilyl
ethers. [106] The tert-butylmethoxyphenylsilyl ether is appreciably more
stable towards acidic hydrolysis than a tert-butyldimethylsilyl ether. On the other hand, a
tert-butylmethoxyphenylsilyl ether is cleaved more readily with fluoride than either a
tert-butyldimethylsilyl or a tert-butyldiphenylsilyl ether, allowing for removal of the former
in the presence of the latter two classes of ethers. [107] Primary, secondary, and tertiary
alcohols can be converted quite readily into their tert-butylmethoxyphenylsilyl ethers,
but the fact that the silicon atom in this class of ethers is stereogenic will result in diastereomers
if the parent alcohol is chiral.
Tris(trimethylsilyl)silyl (sisyl) ethers are among the most stable of the silyl ethers. [108]
Readily prepared by reaction of an alcohol with tris(trimethylsilyl)silyl chloride in the
presence of 4-(dimethylamino)pyridine, these ethers withstand strongly acidic conditions
that will cleave most other silyl ethers. Tris(trimethylsilyl)silyl ethers are cleaved with tetrabutylammonium
fluoride, however, and they can be cleanly removed by photolysis in
methanol.
for references see p 410
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG