Silicon-Based Protecting Groups

Silicon-based protecting groups are used extensively in organic synthesis. They are formed by reaction of an halosilane with an alkoxide, their removal can easily be affected by displacement with either fluoride or oxygen nucleophiles. The bulkier the silicon-protecting group is the more difficult is it to remove it. The simplest protecting group is the trimethylsilyl (TMS) unit. Trimethylsilylation can be carried out using TMS-Cl and base or other related reagents in which silicon is activated towards nucleophilic attack. As it is the least sterically hindered silyl ether it is relatively easily cleaved with aqueous acid or base. You should be familiar with all silicon protecting groups listed below and their acronyms.

In general, the bulkier the alkyl substituents on the silicon the harsher the conditions required for removal of the protecting group. The bulkier the group, the more difficult the formation of the silylether is. Imidazole is added to increase the reaction rate (nucleophilic catalysis, Tutorial Link: Physical Organic Chemistry). The TBDMS group is easily introduced by treating the alcohol with TBDMSCl in DMF in conjunction with imidazole. With bulkier groups, such as TBDMS, it is possible to distinguish between primary and secondary alcohols. This is an example of regiocontrol.

The most common deprotection procedure of sterically demanding Si-protecting groups involves flouride cleavage with TBAF (tetrabutylammonium fluoride) as reagent.