Methods of deprotection

Substituents that serve as protectors are of value because they are removable. The critical feature of each protector is, therefore, how it is removed. Therefore, instead of discussing protectors on the basis of their constitution, the subject of protection is presented on the basis of the methods of deprotection, using the more common protectors as examples. 

Example 22 removal of allyl group attached to a phosphorus centre with Pd, Pt and Rh complexes is a well established procedure [51] but is inconvenient for synthesis of therapeutic compounds on a large scale. During the deprotection step the palladium catalyst is susceptible to poisoning especially with P-S compounds resulting in loss of catalytic efficiency. Furthermore traces of organometallic compounds remain in the product after deprotection. In the paper of Manoharan et al. other methods of deprotection of allyl... 

One astute way to obtain macrocyclic systems with TTF is the stepwise method of deprotection/alkylation of cyanoethyl-protected TTF-thiolates. With this method molecular units can be built but with the precaution of preserving one cyanoethyl group in order to be able to iteratively proceed with the oligomerization. Combining such units, larger units can be produced. An example of a TTF dendrimer containing 21 TTFs is shown in Fig. 2.15 (Christensen et al, 1998). Here only the main philosophy of the synthesis is discussed. 

Tetrahydropyranyl ethers are readily prepared from the alcohol and 2,3-tetrahydropyran in the presence of acid, and the reaction is widely used as a method of protection of hydroxyl groups. Preparative procedures and the methods of deprotection are given in Section 5.4.6, p. 551). 

Deprotection may be effected by vigorous acidic or alkaline hydrolysis (p. 918). Alternative methods of deprotection are sodium hydride in refluxing dimethoxyethane,227 or by heating with 85 per cent hydrazine hydrate (hydra-zinolysis).228... 

Scheme 4.351665 illustrates the most common method for synthesising carbonates — reaction of the hydroxyl group with a chloroformate in the presence of base - and a particularly mild method of deprotection, hydrogenolysis, giving toluene and a carbonic acid monoester that decarboxylates to liberate the free hydroxyl.666 Alkoxycarbonyl groups can be easily installed on carbohydrates by reaction with the appropriate chloroformate in the presence of TMEDA at low... 

There are many different types of peptide coupling reagents (e.g., carbodiimides, aminium/uranium salts, and phosphonium salts). The choice of meth-od(s) and reagent(s) depend on a variety of factors, including the specific sequence of peptide to be synthesized, the preferred method of deprotection, the preferred solvents, and the type of active intermediate desired. 

Carboxylic esters react with bis(tributyltin) oxide under mild conditions to give the corresponding tin carboxylates and tin alkoxides, providing a method of deprotecting esters in aprotic solvents under neutral conditions, tolerant of other functional groups,43 16 for example ... 

Photolysis of o-Nitrobenzyl Derivatives - The cleavage of o-nitrobenzyl derivatives is one of the relatively few classes of photofragmentations in which the two fragments can both bear complex functionality. The protection of alcohols as o-nitrobenzyl ethers is well known, and provides a photochemical method of deprotection, but other applications include the design of photoclea-vable polymers and photochemically active links for molecules synthesized on polymer beads. 

Extensive searching of microorganisms led to the identification of p-nitro-benzyl esterase (p-NB esterase) from B. snbtz7zs, which resulted in high yields of product in the deprotection step [62]. Nevertheless, the rate of the reaction was too slow, among other factors, to compete effectively with the traditional chemical method of deprotection. 

The enantiomeric purity of our synthetic (S)-141, however, was only 59% ee. Acid treatments (H I and 1 141) in the course of the synthesis caused partial racemization due to retro-aldol/aldol and/or retro-Michael/Michael reactions. Unfortunately, milder methods of deprotection such as hot dilute acetic acid or trifluoroacetic acid in dichloromethane were not effective enough to give 141 in appreciable yield. In enantioselective syntheses, retro-aldol/aldol and/or retro-Michael/Michael processes are most dangerous reactions to cause partial racemization. 

The isomerization of ally ethers with a transition metal catalyst, though normally used as a method of deprotection of the allyl group,can be considered as a convenient method of enol ether synthesis. The conversion of (22) to the propenyl ether (23) serves as an example. ... 

Sequential catalytic hydrogenation of the imine bond followed by hydrogenoly-sis of the resultant yV-diphenylmethylamine is an alternative method of deprotection which was used in a solid-phase synthesis of O-glycosyl cyclic Enkephalin analogues [Scheme 8.236]. Note the comprehensive deprotection of 4 benzyl ethers, a diphenylmethyl ester, and an N-diphenylmethyleneamine in a single operation. iV-Diphenylmethyleneamine derivatives of serine have also been applied to the synthesis of Sphingosines. ... 

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