Use as protecting groups

Several methoxy-substituted benzyl ethers have been prepared and used as protective groups. Their utility lies in the fact that they are more readily cleaved oxidatively than the unsubStituted benzyl ethers. The table below gives the relative rates of cleavage with dichlorodicyanoquinone (DDQ). ... 

Cyclic carbonates and cyclic boronates have also found considerable use as protective groups. In contrast to most acetals and ketals the carbonates are cleaved with strong base and sterically unencumbered boronates are readily cleaved by water. 

The carbonyl group forms a number of other very stable derivatives. They are less used as protective groups because of the greater difficulty involved in their removal. Such derivatives include cyanohydrins, hydrazones, imines, oximes, and semicarbazones. Enol ethers are used to protect one carbonyl group in a 1,2- or 1,3-dicarbonyl compound. 

Derivatives of carbonyl compounds that have been used as protective groups in synthetic schemes are described in this chapter some of the more important protective groups are listed in Reactivity Chart 5. ... 

S-Benzyl and substituted S-benzyl derivatives, readily cleaved with sodium/ammonia, are the most frequently used thioethers. n-Alkyl thioethers are difficult to cleave and have not been used as protective groups. Alkoxymethyl or alkylthio-... 

Carbamates can be used as protective groups for ammo acids to minimize race-mization in peptide synthesis. Raccmi/ation occurs during the base-catalyzed coupling reaction of an W-protected, catboxyl-uc ivated amino acid, and takes place in the intermediate oxazolone that foro S readily from an N-acyl protected amino... 

Many carbamates have been used as protective groups. They are arranged in this chapter in order of increasing complexity of stmcture. The most useful compounds do not necessarily have the simplest stmctures, but are /-butyl (BOC), readily cleaved by acidic hydrolysis benzyl (Cbz or Z), cleaved by catalytic hy-drogenolysis 2,4-dichlorobenzyl, stable to the acid-catalyzed hydrolysis of benzyl and /-butyl carbamates 2-(biphenylyl)isopropyl, cleaved more easily than /-butyl carbamate by dilute acetic acid 9-fluorenylmethyl, cleaved by /3-elimination with base isonicotinyl, cleaved by reduction with zinc in acetic acid 1-adamantyl, readily cleaved by trifluoroacetic acid and ally], readily cleaved by Pd-catalyzed isomerisation. 

Enol acetates are not very stable compounds and this limits their use as protecting groups. They are readily hydrolyzed to the parent ketones by acids and bases. 

Semicarbazones are used as protecting groups as a consequence of their stability to reducing agents such as potassium borohydride, sodium boro-hydride and lithium borohydride. Semicarbazones are cleaved by strong acids and by heating in acetic anhydride-pyridine. " ... 

The formation of vinylogous amides from primary amines and -dicarbonyl compounds gives rise to hydrolyzable amine derivatives with greatly decreased nucleophilicity of the nitrogen function. Thus these derivatives have found some use as protecting groups in peptide syntheses 617-619). 

Two derivatives have been prepared that may prove useful as protective groups for 2-hydroxybenzenethiols. 

Polymer-supported esters are widely used in solid-phase peptide synthesis, and extensive information on this specialized protection is reported annually. Some activated esters that have been used as macrolide precursors and some that have been used in peptide synthesis are also described in this chapter the many activated esters that are used in peptide synthesis are discussed elsewhere. A useful list, with references, of many protected amino acids (e.g., -NH2, COOH, and side-chain-protected compounds) has been compiled/ Some general methods for the preparation of esters are provided at the beginning of this chapter conditions that are unique to a protective group are described with that group/ Some esters that have been used as protective groups are included in Reactivity Chart 6. 

Acetal (Section 19.10) A functional group consisting of two -OR groups bonded to the same carbon, R2C(OR )2-Acetals are often used as protecting groups for ketones and aldehydes. 

Although many examples of this type of ring system are known in the literature, the vast majority of these are cyclic acetals, which have been used as protecting groups for diols. These have not been included in this chapter. Otherwise, the majority of the compounds which fall into this category are either natural products or derivatives of, or precursors to, the natural products. 

Oximes have been used as protecting groups for carbonyl compounds owing to their hydrolytic stability. Consequently, the development of newer deoximation reagents... 

While C-C bond formation via metallation and alkyl or aryl halides is well known (COMC (1982) 5.4.2.7.5), the C-C bond formation with TBAF and aldehyde, enones, or enals is new (Figure 9).318 Carboranyl groups can actually be used as protecting groups for aldehydes and ketones due to the facile cleavage of the cage C-C(OH) bond with... 

These desiratives have been useful for gas chromatographic and mass spectral analyses, but since they are very sensitive to hydrolysis, their use as protecting group in multistep organic synthesis become limited. But since trimethylsilyl ethyl derivatives are more stable towards hydrolysis and can be easily removed under very mild conditions, they are more useful for protection of amines and carboxylic acids. 

The protection of alcohols by conversion into light-sensitive ethers is most attractive. Initially, the preparation of 2-nitrobenzyl (nBn) ethers presented a problem, although their potential usefulness as protecting groups, stable under a variety of reaction conditions, that nevertheless are readily photolyzed at >320 nm (see Scheme 2) was recognized immediately. 

Acylals (geminal diacetates) are frequently used as protecting groups for aldehydes because of their stability to neutral and basic conditions [8]. In addition, the acylal functionality can be converted into other useful functional groups [9]. For example a novel synthesis of chiral allylic esters has been developed using palladium-catalyzed asymmetric allylic alkylation of gem-diesters [10]. The allylation of... 

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