Trimethylsilyl Chloride - Reactions and Uses - Silylation in Organic Synthesis

Silylation in Organic Synthesis

By the process of silylation, polar functional groups such as alcohols and amines readily undergo reaction with trimethylsilyl chloride, giving trimethylsilyl ethers and trimethylsilyl amines. These new groups "protect"s the original functional group by removing the labile protons and decreasing the basicity of the heteroatom. The lability of the Me₃Si-O and Me₃Si-N groups can later be removed ("deprotected"). Trimethylsilylation can also be used to increase the volatility of a compound, enabling gas chromatography of normally nonvolatile substances such as glucose. Trimethylsilyl chloride also reacts with metal acetylides to give trimethylsilyl alkynes such as bis(trimethylsilyl)acetylene. Such derivatives are useful protected forms of alkynes.

In the presence of triethylamine and lithium diisopropylamide, enolisable aldehydes, ketones and esters are converted to trimethylsilyl enol ethers. Despite their hydrolytic instability, these compounds have found wide application in organic chemistry; oxidation of the double bond by epoxidation or dihydroxylation can be used to return the original carbonyl group with an alcohol group at the alpha carbon. The trimethylsilyl enol ethers can also be used as masked enolate equivalents in the Mukaiyama aldol addition.