Deprotections

Deprotections are chemical steps that remove protecting groups from molecules, restoring the underlying functional groups after a sequence of transformations. Protecting groups are used to mask reactive sites during multistep syntheses, enabling selective reactions and preventing side reactions. Deprotection conditions must be compatible with other functional groups in the molecule and must minimize unwanted changes such as racemization or rearrangement.

The choice of deprotection method depends on the protecting group and the rest of the molecule. Common strategies include hydrolysis under acidic or basic conditions, hydrogenolysis, and specific reagents that target a particular protecting group. Orthogonality, the ability to remove one protecting group without affecting others, is a key consideration in planning sequences of reactions.

Common protecting groups and typical deprotections include: silyl ethers (for alcohols) deprotect with fluoride sources such as TBAF or HF-pyridine; acetals and ketals deprotect under aqueous acid; Fmoc groups on amines are removed by base such as piperidine; Boc groups are removed by strong acid (e.g., HCl, TFA); Cbz groups are often removed by hydrogenolysis; benzyl ethers or carbamates can be removed by hydrogenolysis with Pd/C and hydrogen; tert-butyl esters or tert-butyl ethers are cleaved by acid. Other specialized groups may require metal-catalyzed deprotections or highly selective reagents.

Deprotection is a central aspect of many fields, including organic synthesis, medicinal chemistry, and peptide and carbohydrate chemistry. Successful deprotection balances efficiency, selectivity, and compatibility with the other functionalities present in the molecule.