Silyl Halide

Silylation is the introduction of one or more (usually) substituted silyl groups (R₃Si) to a molecule. Silylations are core methods for production of organosilicon chemistry. Silanization, while similar to silylation, usually refers to attachment of silyl groups to solids. Silyl groups are commonly used for: alcohol protection, enolate trapping, gas chromatography, electron-impact mass spectrometry (EI-MS), and coordinating with metal complexes.

Protection Chemistry

Protection

Silylation is often used to protect alcohols, as well as amines, carboxylic acids, and terminal alkynes. The products after silylation, namely silyl ethers and silyl amines, are resilient toward basic conditions. Protection is typically done by reacting the functional group with a silyl halide by an SN2 reaction mechanism, typically in the presence of base.

The protection mechanism begins with the base deprotonating the alcohol group. Next, the deprotonated alcohol group attacks the silyl atom of the silyl halide compound. The halide acts as a leaving group and ends up in solution. A workup step follows to remove any excess base within the solution. The overall reaction scheme is as follows:

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Other silylating agents include bis(trimethylsilyl)acetamide (BSA). The reaction of BSA with alcohols gives the corresponding trimethylsilyl ether, together with acetamide as a byproduct (Me = CH₃):
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Deprotection

Due to the strength of the Si-F bond, fluoride salts are commonly used as a deprotecting agent of silyl groups. The primary fluorous deprotecting agent is tetra-n-butylammonium fluoride (TBAF), as its aliphatic chains in help incorporate the fluoride ion into organic solvents.

Deprotection with a fluoride ion occurs by an S_N2 mechanism, followed by acidic workup to protonate the resulting alkoxide:

Deprotection of the alcohol can also be done using either Brønsted acids or Lewis acid conditions. Brønsted acids, like PyBr₃ (pyridinium tribromide), deprotect the alcohol by acting as a proton donor.

Modifying Silyl Reactivity

Sterically bulkier alkyl substituents tend to decrease the reactivity of the silyl group. Consequently, bulky substituents increase the silyl group's protective abilities. To add bulkier alkyl silyls, more strenuous conditions are required for alcohol protection. As bulkier groups require more strenuous conditions to add, they also require more strenuous conditions to remove. Additionally, bulkier silyl groups are more selective for the type of alcohols they react with, resulting in a preference for primary alcohols over secondary alcohols. Thus, silyl groups such as TBDMS and TIPS can be used to selectively protect primary alcohols over secondary alcohols.  

In acidic conditions, alkyl substituents acting as electron withdrawing groups decrease the reaction rate. As bulker silyl groups are more likely to be electron withdrawing, it is easier to differentiate between less and more bulky silyl groups. Therefore, acidic deprotection occurs fastest for less sterically bulky alkyl silyl groups. In basic conditions, alkyl substituents acting as electron donating groups decrease reaction rate.

Enolate Trapping

Silylation can also be used to trap reactive compounds for isolation or identification. A common example of this is by trapping reactive enolates into silyl enol ethers, which represent reactive tautomers of many carbonyl compounds. The original enolate can be reformed upon reaction with an organolithium, or other strong base.

Applications in Analysis

The introduction of a silyl group(s) gives derivatives of enhanced volatility, making the derivatives suitable for analysis by gas chromatography and electron-impact mass spectrometry (EI-MS). For EI-MS, the silyl derivatives give more favorable diagnostic fragmentation patterns of use in structure investigations, or characteristic ions of use in trace analyses employing selected ion monitoring and related techniques.

Of metals

Coordination complexes with silyl ligands are well known. An early example is CpFe(CO)₂Si(CH₃)₃, prepared by silylation of CpFe(CO)₂Na with trimethylsilyl chloride. Typical routes include oxidative addition of Si-H bonds to low-valent metals. Metal silyl complexes are intermediates in hydrosilation, a process used to make organosilicon compounds on both laboratory and commercial scales.

See also

* Silyl ether
* Hydrosilylation

References

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External links

Identification of Silylation Artifacts in Derivatization Reactions for Gas Chromatography

Desilylation methods

Chemical processes
Organosilicon compounds