tertbutyldimethylsilyl

The tert-butyldimethylsilyl group, commonly abbreviated TBDMS (also written as TBDMS or TBS), is a widely used protecting group for alcohols in organic synthesis. It forms tert-butyldimethylsilyl ethers (TBDMS ethers), enabling chemists to mask alcohol functionality during multi-step sequences while allowing selective manipulation of other sites.

Chemistry and structure: The TBDMS group consists of a silicon atom bonded to the oxygen of the alcohol, a tert-butyl substituent, and two methyl groups. The overall fragment attached to oxygen is Si( t-Bu )(Me)2, giving an O–Si bond that protects the hydroxyl group. This bulky group increases resistance to many reaction conditions compared with smaller silyl ethers such as trimethylsilyl (TMS).

Installation and removal: TBDMS ethers are typically installed by treating the alcohol with tert-butyldimethylsilyl chloride (TBDMSCl) or related reagents in the presence of a base such as imidazole or 2,6-lutidine. Deprotection is commonly achieved with fluoride sources, including tetrabutylammonium fluoride (TBAF) in THF or other solvents, or with HF-pyridine. Strong acids can also cleave TBDMS ethers, though conditions are generally less common for routine deprotection.

Applications and properties: The TBDMS group offers a balance of stability and lability suitable for many synthetic sequences, being more robust than TMS ethers but less so than larger silyl groups like TBDPS. Its use is particularly prevalent in carbohydrate chemistry and complex organic syntheses where selective protection and deprotection are required. The group can be employed in orthogonal protection strategies alongside other silyl or non-silyl protecting groups.