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" 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 allow them to be easily removed afterwards ("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 carbanions to give trimethylsilyl derivatives.^[3] Lithium acetylides react to give trimethylsilylalkynes 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.^[4] 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.

Dehydrations

Dehydration of metal chlorides with trimethylsilyl chloride in THF gives the solvate as illustrated by the case of chromium trichloride:^[5]

$${\displaystyle {\ce {CrCl3 * 6 H2O + 12 Me3SiCl -> CrCl3(THF)3 + 6 (Me3Si)2O + 12 HCl}}}$$

Other reactions

Trimethylsilyl chloride is used to prepare other trimethylsilyl halides and pseudohalides, including trimethylsilyl fluoride, trimethylsilyl bromide, trimethylsilyl iodide, trimethylsilyl cyanide, trimethylsilyl azide,^[6] and trimethylsilyl trifluoromethanesulfonate (TMSOTf). These compounds are produced by a salt metathesis reaction between trimethylsilyl chloride and a salt of the (pseudo)halide (MX):

$${\displaystyle {\ce {MX + Me3Si-Cl -> MCl + Me3Si-X}}}$$

TMSCl, lithium, and nitrogen molecule react to give tris(trimethylsilyl)amine, under catalysis by nichrome wire or chromium trichloride:

$${\displaystyle {\ce {3 Me3SiCl + 3 Li}}+{\tfrac {1}{2}}\,{\ce {N2 -> (Me3Si)3N + 3 LiCl}}}$$

Using this approach, atmospheric nitrogen can be introduced into organic substrate. For example, tris(trimethylsilyl)amine reacts with α,δ,ω-triketones to give tricyclic pyrroles.^[7]

Reduction of trimethylsilyl chloride give hexamethyldisilane:

$${\displaystyle {\ce {2 Me3SiCl + 2 Na -> 2 NaCl + Me3Si-SiMe3}}}$$