Silyl Ethers - Thieme Chemistry

ly common with tert-butyldimethylsilyl ethers, [9] but less so with triisopropylsilyl and tertbutyldiphenylsilyl
ethers. Silyl migration of this type is most frequently seen where oxygens
bear a 1,2-relationship [10] or a 1,3-relationship, [11] although more distant migrations
are known. This aspect of silyl ether chemistry has sometimes presented problems in
complex syntheses where a specific hydroxy protection is desired. It can pose severe difficulties
for researchers in the fields of carbohydrate [12] and ribooligonucleotide [13] synthesis
where unwanted silyl migrations often occur quite readily.
Silyl migration between carbon and oxygen has long been recognized as an important
feature of silicon chemistry; in fact, the rearrangement can be used as a preparative
method for silyl ethers. [14] The transfer of a silyl group from carbon to oxygen was first described
in the context of a [1,2]shift by Brook, [15] for whom the rearrangement is named. It
was subsequently found that migration can occur between nonadjacent atoms, leading to
[1,n]-Brook rearrangements where n £5. [16] It has been shown that silicon retains its configuration
in the course of a Brook rearrangement. [17] The rearrangement requires the
presence of a strong base and is synthetically most useful when the carbanion resulting
from silyl migration is stabilized. [18]
The reverse migration of silyl groups from oxygen to carbon (retro-Brook rearrangement)
was discovered by West, initially as a [1,3]shift [19] and later as a [1,2]migration. [20]
Longer range retro-Brook rearrangements have also been noted. [21] These reactions take
place when silyl ethers are exposed to a strong base, such as an alkyllithium, which may
be used to effect halogen±metal or metal±metal exchange. Silyl migration to the resultant
carbanion is driven by the formation of a more stable alkoxide species.
4.4.17.1 Trimethylsilyl Ethers
As the least stable of the family of silyl ethers, trimethylsilyl (TMS) ethers have found only
limited utility as protecting groups in complex synthesis. Their sensitivity toward mild
acids (e.g., acetic acid) and bases (potassium carbonate in methanol) makes their survival
through multistep operations in a synthetic sequence problematic. Even chromatography
on silica gel can suffice to cleave a trimethylsilyl ether. The most frequent use made of
trimethylsilyl ethers is to mask polar functional groups, primarily hydroxy and carboxy
groups, for the purpose of increasing the volatility of an otherwise nonvolatile compound.
Since trimethylsilyl ethers are thermally quite stable, the resultant (poly)silyl
ether can be subjected to gas chromatography and mass spectrometry without fear of decomposition.
This technique has been widely applied in the carbohydrate area where exhaustive
silylation, for example with N-(trimethylsilyl)acetamide, leads to a persilylated
sugar. [22]
Formation
FOR PERSONAL USE ONLY
372 Science of Synthesis 4.4 Silicon Compounds
4.4.17.1.1 Method 1:
Silylation ofAlcohols with Chlorotrimethylsilane
A variety of silylating agents is available for the preparation of trimethylsilyl ethers, but
chlorotrimethylsilane (TMSCl) is perhaps the most frequently employed. It is used in the
presence of a base, typically imidazole or triethylamine, which removes hydrogen chloride
formed during the silylation. There is very little difference in the rate of silylation
of primary, secondary, and tertiary alcohols with this reagent, and selectivity in protection
of alcohols is not usually possible. A typical silylation with chlorotrimethylsilane is
that of alcohol 1 to give silyl ether 2 (Scheme 1); it is noteworthy that the terminal alkyne
of 1 does not undergo silylation under these conditions. [23]
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG