Carbon as protecting group

Carbonates are less reactive than esters towards basic hydrolysis owing to the reduced electrophilicity of the carbonyl afforded by the resonance deactivation by two oxygens. However, hydrolytic methods confer little advantage to carbonates as protecting groups and in general, the conditions that would attack esters may also attack carbonates... 

The utility of thiol esters and carbonates as protecting groups is limited by their vulnerability to hydrolysis, The poor overlap between the non-bonded electrons on the sulfur atom (3p) and the n-system of the carbonyl (2p) precludes or diminishes resonance stabilisation of the type enjoyed by normal esters thereby raising their ground state energy, The carbonyl group of the thioester is more electrophilic than a normal ester and hence more reactive. Thiocarbonate derivatives are marginally more stable. The 5-benzoyl derivative of cysteine is 95% hydrolysed in 30 minutes with 2 M ammonia whereas the 5-benzyloxycarbonyl derivative is only 20% hydrolysed in 30 minutes under the same conditions.54... 

The usefulness of cyclic carbonates as protecting groups depends largely on their comparative stability towards acithc reagents. Thus the cyclic carbonate group withstood the relatively drastic conditions of acidic hydrolysis required to remove the isopropylidene group in the preparation of (104)... 

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. 

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. 

Benzyl and Allyl Carbon Atoms Hydrogenolysis of a carbon-heteroatom bond is extremely fast if the heteroatom is connected to allylic or benzylic carbon atoms. The benzylic compounds are used very frequently in organic chemistry as protecting groups. Because of its great importance the benzylic compounds are discussed separately in the next section. 

The grouping C—O—C—O—C is characteristic of an acetal or a ketal (see Section 15-4E), but it also can be regarded as an ether with two ether links to one carbon. Compared to other ethers (except for the oxacyclopropanes), substances with the C—O—C—O—C group are very active toward acidic reagents, as pointed out in connection with their formation from alcohols (Section 15-4E) and their use as protecting groups for the OH function (Section 15-9C). 

Allyl carbonates can function as protecting groups for alcohols, with removal of the protecting group being effected by R3SnH and Pd° (equation 101).299... 

Reductions resulting in cleavage of a carbon-halogen bond have been discussed in Chapter 8. Here are mentioned only some cases in which halogens have been used as protecting groups. 

The preparation and properties of tran.s-eyclic carbonates have been studied by using acetal groups as protecting groups.159,160 Further examples may be found in studies of epoxy substituents,181 xantha-tion,162-164 and halogen substitution.165... 

Until about 30 years ago, hydrazones derived from carbonyl compounds were not used in organic synthesis. They were used only for analytical purposes , and as protecting groups of aldehydes and ketones ". Corey investigated dimethylhydrazones of ketones and aldehydes with a-hydrogens, and found that they undergo deprotonation with LDA or BuLi in THF at the a-carbons to the hydrazonic moiety in 90-100% yield. The formed lithium compounds, used as enolate anion equivalents, create new carbon-carbon bonds in their reaction with different electrophiles such as alkyl halides or oxiranes, ketones and aldehydes (equation 21). 

Benzyl carbonates and carbamates also have reactive benzylic C-O bonds, and consequently can be hydrogenolyzed easily. They are frequently used as protecting groups (O- or Af-benzyloxycarbonyl groups) [39]. The extent of hydrogenoly-sis can be followed by measuring the amount of carbon dioxide produced (Scheme 3). 

Vert de lilas is useful as an additive in soaps since acetals, unlike aldehydes and ketones, are stable to the alkali in soaps. The main use tor acetals in synthesis is as protecting groups for aldehydes and ketones (see Chapter 9). Cyclic acetals (e.g, 4) are usually used for ketones (Chapter 7) the disconnection is the same once the carbonyl carbon has been discovered. 

Esters, Ethers, and Related Derivatives of Alcohols.— The mode of transmission of the effect of remote substituents upon reaction rates and equilibria has been discussed previously under three headings, viz. inductive effects, electrostatic field effects, and conformational transmission.A new survey,quoting over 50 references, covers most of the main studies in this field, and suggests direct interactions as a fourth class. Rates of acetylation of 3j3-hydroxy-A"-steroids variously substituted at C-17 show only small variations, which did not permit of any mechanistic interpretation. The formation of 17a,20- and 20,21-cyclic carbonates and their use as protecting groups for diols have been investigated. ... 

Derivatives of carbonic acid, which are commonly used in organic synthesis as protective groups or reaction intermediates, might be good ctmdidates for photoinduced reduction of... 

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