Deprotection

Deprotection is the removal of a protecting group from a molecule, typically as part of a multi-step synthesis in organic chemistry. Protecting groups mask reactive functionalities to prevent undesired reactions and to enable selective transformations elsewhere in the molecule. Deprotection is performed under conditions that cleave the protecting group without altering other sensitive features. The choice of protecting group depends on the planned sequence, its stability under future steps, orthogonality with other groups, and the ease and selectivity of its removal.

An effective protecting group is stable during earlier manipulations but can be removed under mild, selective conditions that do not affect the unmasked functionality or other protecting groups. In practice, chemists select groups that can be installed and removed with orthogonal chemistries, allowing sequential deprotections without disturbing remaining groups.

Common protecting groups and their typical removal strategies include: for amines, Boc (tert-butylocarbonyl) removed by acidic conditions; CBz (benzyloxycarbonyl) removed by hydrogenolysis or strong acids; Fmoc removed by base; for alcohols and phenols, silyl ethers (TBS, TMS, TES) removed by fluoride sources; benzyl ethers removed by hydrogenolysis; and acetate esters removed by hydrolysis. For carboxylic acids, ester protecting groups such as methyl or tert-butyl esters are removed by hydrolysis under basic or acidic conditions; for carbonyls, acetal and ketal protections are removed by acid-catalyzed hydrolysis. For thiols, protecting groups like trityl (Trt) or tert-butylthio can be removed under acidic or specific conditions depending on the group.

The protecting group strategy is a central aspect of planning complex syntheses, balancing protection and deprotection steps to maximize yield and efficiency.