Hydrazones carbonyl group protection

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. 

Reactivity Chart 6, 433-436 Hydrazones, substituted, to protect carbonyl groups, 212-214... 

For decades oximes and hydrazones have been used for the derivatization of carbonyl compounds and are mainly applied for carbonyl group characterization in analytical procedures. However, they can also be applied as viable protecting groups in complex reaction schemes. For instance in the synthesis of ery-thronolide A a carbonyl group had to be converted to an oxime to allow the selective removal of the remaining isopropylidene protecting group without side reactions. The reconversion of the oxime to the carbonyl compound proceeds by A -nitrosation (Scheme 92). The previously attempted removal of the... 

Organometallic addition to the /V-methoxy-A -methylamide (15) also affords an exceptionally stable tetrahedral intermediate (16) and carbonyl-protecting group, first used in the synthesis of X-206. Deprotonation of the hydrazone in intermediate (16) was subsequently carried out with lithium diisopropylamide. The resulting dianion initiated a novel attack upon epoxide (17) and in the ensuing transformation was followed by tetrahydrofuran ring formation as depicted, in 71% yield, all in one pot (Scheme 4). 

The semicarbiizoiic " " and para-loluenesulfonylhydrazonc " of diethyl l-formylmeth-ylphosphonate can be metallated with NaH in THF or DME for reaction with carbonyl compounds at room temperature, whereas the oxazine and dimethylhydra/inc -derivatives require metallation with n-BuLi in THF at low temperature. The oxazine protecting group is removed by sequential treatment with NaBH4 and aqueous oxalic acid at reflux. The pora-toluenesulfonyl-hydrazone participates in cyclization reactions with the release of sodium para-toluenesulfinate to produce pyrazoles (Scheme... 

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). 

The various derivatives of carbonyl compounds that involve formation of carbon-nitrogen double bonds at the carbonyl center (see Section 8.1) are not very generally useful as protecting groups. This includes oximes, semicarbazones, and hydrazones. The compounds are usually formed easily enough, but mild conditions for removal are not available. An exception involves the removal of the oxime group by conversion to the acetate ester, followed by chromous ion reduction ... 

Palladium-catalyzed Deprotection Processes. Several palladium-catalyzed and mild methods for the deprotection of various functional groups have been developed. For example, a system for the conversion of hydrazones into the corresponding carbonyl compounds that is catalytic in both Pd(OAc)2 and SnCl2 has been reported, as has a procedure for the Pd(OAc)2-catalyzed cleavage of allyloxycarbonyl (Alloc) protected alcohols. ... 

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