Aldehyde N,N-dialkylhydrazones as neutral acyl anion equivalents:: Umpolung of the imine reactivity

The isoelectronic replacement of the alpha-carbon of enamines by nitrogen leads to the corresponding hydrazones, and thus, they can be termed "aza-enamines". Hence, aldehyde N,N-dialkylhydrazones enable analogous electrophilic substitutions at the imine carbon that corresponds to the beta-carbon of enamines. In addition, after hydrolysis of the product hydrazones to the parent ketones or aldehydes, these reactions constitute an umpolung of the classical carbonyl reactivity and overall a nucleophilic acylation or formylation. This review covers the aza-enamine chemistry from its very beginning in the late 1960s up to this year. In the first part, reactions of aromatic, aliphatic, and heterocyclic aldehyde N,N-dialkylhydrazones with highly reactive substrates such as the Vilsmeier and Mannich reagents, sulfonyl isocyanates, per-fluoroacetic anhydride, and inorganic electrophiles such as halogens and phosphorus tribromide are described. The hydrazones of alpha,beta-unsaturated aldehydes react as vinylogous aza-enamines at the terminal carbon providing unsaturated aldehydes. As electron-rich dienes and dienophiles, they also form Diels-Alder adducts and thus interesting N-heterocycles. The second part covers carbon-carbon bond formations of the sterically less-demanding formaldehyde N,N-dialkylhydrazones with synthetically very useful electrophiles such as various Michael acceptors and carbonyl compounds. Formaldehyde SAMP-hydrazone and related derivatives generally give excellent asymmetric inductions. Finally, first organocatalytic versions of the aza-enamine chemistry are presented. In summary, the rich chemistry of aldehyde N,N-dialkylhydrazones as neutral acyl anion, formyl anion, and cyanide equivalents is demonstrated. (c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007).