Ketals as protective groups

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. 

Enol ethers of saturated 3-ketones are not usually obtained directly from the ketone and therefore are of little importance as protective groups. However, enol ether (52) has been used instead of the bulkier 3-dimethyl ketal to protect the 3-ketone during angular methylation to (53). ... 

Ethylene glycol in the presence of an acid catalyst readily reacts with aldehydes and ketones to form cyclic acetals and ketals (60). 1,3-Dioxolane [646-06-0] is the product of condensing formaldehyde and ethylene glycol. Applications for 1,3-dioxolane are as a solvent replacement for methylene chloride, 1,2-dichloroethane, 1,1,1-trichloroethane, and methyl ethyl ketone as a solvent for polymers as an inhibitor in 1,1,1-trichloroethane as a polymer or matrix interaction product for metal working and electroplating in lithium batteries and in the electronics industry (61). 1,3-Dioxolane can also be used in the formation of polyacetals, both for homopolymerization and as a comonomer with formaldehyde. Cyclic acetals and ketals are used as protecting groups for reaction-sensitive aldehydes and ketones in natural product synthesis and pharmaceuticals (62). 

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). 

Although lV,lV-dimethylhydrazones are used as protective groups their use is not nearly as ubiquitous as the acetal and ketal. This is likely a result of the fact that these can still be deprotonated with strong base and are susceptible to nucleophilic reagents. 

Acetals and ketals have attracted a great deal of attention recently as protecting groups of PHOST due to their lower activation energies of deprotection than fBOC and terf-butyl esters. While the majority of chemical amplification resists require PEB to accelerate acid-catalyzed reactions, deprotection of ac-... 

TABLE 9.1. Dioxolans and Dialkyl Acetals and Ketals Representative Examples of Preparation, and Use as Protective Groups... 

Ketal (Section 19.10) An alternative name for an acetal derived from a ketone rather than an aldehyde and consisting of two -OR groups bonded to the same carbon, R2C(OR )2- Ke s are often used as protecting groups for ketones. 

As chemists proceeded to synthesize more complicated stmctures, they developed more satisfactory protective groups and more effective methods for the formation and cleavage of protected compounds. At first a tetrahydropyranyl acetal was prepared, by an acid-catalyzed reaction with dihydropyran, to protect a hydroxyl group. The acetal is readily cleaved by mild acid hydrolysis, but formation of this acetal introduces a new stereogenic center. Formation of the 4-methoxytetrahy-dropyranyl ketal eliminates this problem. 

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