Protection trimethylsilyl ethers, chlorotrimethylsilane

Cyanohydrin trimethylsilyl ethers are generally useful as precursors of carbonyl anion equivalents and as protected forms of aldehydes. Direct conversion of p-anisaldehyde into O-TRIMETHYLSILYL-4-METHOXYMANDELO-NITRILE employs a convenient in situ generation of trimethylsilyl cyanide from chlorotrimethylsilane. A general synthesis of altenic esters is a variant of the Wittig reaction. Ethyl (triphenylphosphoranylidene)acetate converts pro-pionyl chloride into ETHYL 2,3-PENTADIENOATE. 

Protection of an enone as the dithiane derivative without destruction of an accompanying dioxane was accomplished during a synthesis of Aphidicolin [Scheme 2.90]181 by using the hw-trimethylsilyl ether of propane- 1,3-dithiol in the presence of zinc iodide as the catalyst.182 In the same vein, a synthesis of a fully functionalised B-ring system of Taxol [Scheme 2.91] included the selective thio ace tali sat ion of an aldehyde in the presence of a ketone using silver(I)-cata-lysed thioacetalisation with EtS-TMS and chlorotrimethylsilane.183... 

The trimethylsilyl group was the first to be developed and is widely used for the protection of serine and threonine (Table 6). Chlorotrimethylsilane, l,14 3,3,3-hexamethyldisilazane, and A(0-bis(trimethylsilyl)acetamide are commercially available reagents used for the conversion of alcohols into the corresponding trimethylsilyl derivatives.Furthermore, trimethylsilyl cyanide has been used to protect the side chains of serine, threonine, and ty-rosine.f This silyl protection allows the formation of A -carboxyanhydrides from H-Ser(TMS)-OH and H-Thr(TMS)-OH, and their application in peptide synthesis in the aqueous phase.f l The TMS group can be removed under various conditions, depending on the kind of functional group to which it is bound the TMS ethers are more stable than related amino or carboxy derivatives.These differences in stability allow the direct application of completely silylated hydroxy amino acids in peptide synthesis.b ... 

One of the most common methods of alcohol protection is reaction with chlorotrimethylsilane to yield a trimethylsilyl (TMS) ether. The reaction is carried out in the presence of a base (usually triethylamine) to help form the alkoxide anion from the alcohol and to remove the HCl by-product from the reaction. 

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