Use of hydrazones

The use of hydrazone or enamine derivatives of ketones or aldehydes offers the advantage of stcreocontrol via chelated azaenolates. Extremely useful synthetic methodology, with consistently high anti selectivity, has been developed using azaenolates based on (S)- or (R)-l-amino-2-(methoxymethyl)pyrrolidine (SAMP or RAMP)51 58 (Enders method, see Section 1.5.2.4.2.2.3.). An example which illustrates the efficiency of this type of Michael addition is the addition of the lithium azaenolate of (5 )-l-amino-2-(methoxymethyl)pyrrolidine (SAMP) hydrazone of propanal (R = II) to methyl (E )-2-butenoate to give the nub-isomer (an 1 adduct) in 80% yield with a diastereomeric ratio > 98 2,... 

The use of hydrazones is particularly important to form die enolate equivalents of aldehydes. Aldehydes are quite reactive as electrophiles, so as soon as some enolate has been formed, it reacts witii die unreacted aldehyde present in solution. Conversion of die aldehyde to its /V, /V-dimetliy 1 hydrazone (=NNMe2) lowers the electrophilicity so that a-proton removal can take place and then the electrophile of choice can be added. Hydrolysis gives back the aldehyde. In this case the geometry of die hydrazone is unimportant since aldehydes have only one a position from which protons can be removed by base. 

The synthetic uses of hydrazones and oximes for carbon-bond formation differ little from those of imines as their anions represent enolate equivalents except for certain methods that have been developed for asymmetric induction. Conversely, the formal replacement of the carbon substituent of imines by a heteroatom (nitrogen for hydrazones and oxygen for imines) opens reaction pathways such as the Beckmann rearrangement of oximes and the Wolff-Kishner and Shapiro reductions of hydrazones that have no analogy in the chemistry of imines. 

Allan, V., Bienayme, H., El Kaim, L., Majee, A. The use of hydrazones for efficient Mannich type coupling with aldehydes and secondary amines. Chem. Common. 2000,1585-1586. 

Since hydrazone anion chemistry is complementary to more conventional deprotonation-electrophilic substitutions effected with carbonyl derivatives such as ketones and aldehydes, and since hydrazone chemistry involves two additional synthetic operations, the use of hydrazones has to have some additional advantages. Compensating for the additional synthetic effort required to prepare and hydrolyze the... 

Another important use of hydrazones is the Wolff—Kishner reduction, first mentioned in Section 15.9B, and whose mechanism we shall present below now that we have discussed hydrazones. 

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