The Role of Protective Groups in Organic Synthesis

HFIP in Organic Synthesis

“…Protection and deprotection reactions remain important tools in multistep synthesis despite the fact that their use generally introduces two additional steps to a synthetic sequence. , The utility of fluorinated alcohols in transesterification reactions has led to their deployment in various deprotection reactions. For example, mild deprotection of N -triphenylmethyl, ( N -trityl or N -Tr), N - p -biphenylylisopropoxycarbonyl ( N -Bpoc), 2-chlorotrityl chloride resin, and N - tert -butoxycarbonyl ( N -Boc) compounds have been carried out under various conditions using HFIP or TFE.…”

“…The relatively hindered tert -butyl ester offers exceptional stability toward a wide range of reaction conditions and is therefore one of the most widely used protecting groups for carboxylic acids. , tert -Butyl esters are typically deprotected via acidic hydrolysis using Brønsted or Lewis acids. Jaime-Figueroa and co-workers exploited the unusual properties of HFIP and TFE to cleave the acid-labile tert -butyl esters and tert -butyl carbonates under thermolytic conditions in the absence of any acid catalysts (Scheme ).…”

Solvent-free N-Boc deprotection by ex situ generation of hydrogen chloride gas

“…We started with several simple primary, secondary and benzylic protected amines, which could be fully deprotected within 1 hour (1-5). Noteworthy are the liquid substrates that were converted to the solid hydrochloride products in quantitative yields under Please do not adjust margins Please do not adjust margins solvent-free conditions (2,3,26). Some other solid substrates went through a viscous liquid state during the transformation to also end up as the solid hydrochloride product.…”

“…1,2 To prevent the formation of undesired bonds and side reactions, synthetic chemists make strategic use of their ability to mask and, at a later stage in the synthesis, liberate functional groups to unlock their desired reactivity. 3 The tert-butyloxycarbonyl protecting group (Boc group) is one of the most important amino protecting groups and has contributed substantially to the achievements in present organic synthesis. 4 Its applicability comes from the ability to be introduced into the molecule under mild conditions in a selective and high-yielding manner.…”