Hydrazone Anions

Abstract

Carbanions derived from hydrazones are primarily used as equivalents of carbanions derived from ketones and aldehydes. Reactions that ultimately lead to electrophilically substituted carbonyl derivatives through hydrazone anions proceed through four separate steps. First, the hydrazone has to be prepared from the starting carbonyl compound. In most cases, this requires a simple, facile condensation reaction between a hydrazine derivative and a ketone or aldehyde. Second, the neutral hydrazone has to be converted into a nucleophile; typically this involves deprotonation with a strong base. Both regiochemical and stereochemical considerations affect this step. Third, the nucleophilic anion so formed undergoes electrophilic substitution. Various electrophiles can be used; the most common are sp3-hybridized carbon electrophiles (e.g. alkyl halides) and sp2-hybridized carbon electrophiles (e.g. carbonyl compounds). This chapter will concentrate on the latter reactions, introducing alkylations only when appropriate for discussions of regiochemistry and stereochemistry in anion generation. Finally, the product hydrazones produced in these electrophilic substitution reactions have to be converted back into carbonyl compounds, as hydrazones are rarely if ever the desired final product. In a few instances, one or both nitrogens of the hydrazone can be used for heterocycle formation. In such instances, the last step then becomes a more efficient convergent step in an overall synthetic strategy.