Silylering

Silylering, or silylation, is the introduction of a silyl group into a molecule, most commonly to convert alcohols and phenols into silyl ethers. This protection strategy is widely used in organic synthesis to mask reactive hydroxyl groups during multi-step sequences, preserving functionality for later manipulation. Silylation also serves in some contexts to modulate chemical reactivity or solubility, and to enable selectivity by masking competing sites.

Reagents and groups: The most common reagents are silyl chlorides (R3SiCl) and silyl triflates (R3SiOTf). A base such as imidazole, DIPEA, or pyridine facilitates formation of the Si–O bond from an alcohol, typically in dry organic solvent at ambient temperature. Popular silyl groups include trimethylsilyl (TMS), tert-butyldimethylsilyl (TBDMS or TBS), triisopropylsilyl (TIPS), and tert-butyldiphenylsilyl (TBDPS). The resulting silyl ethers are usually stable to bases and many nucleophiles but differ in acid sensitivity and fluoride lability. Deprotection is commonly achieved with fluoride sources (TBAF, CsF) or, for acid-labile groups, with mild acid, depending on the protecting group.

Applications and considerations: Silylering is central to protecting-group strategies in carbohydrate chemistry, natural product synthesis, and pharmaceutical development. The choice of silyl group balances protection stability, steric demand, and ease of deprotection; bulky groups can sterically hinder subsequent transformations, while very labile groups may be removed prematurely. Moisture sensitivity and the use of moisture- and air-sensitive reagents require dry conditions and compatible workups.