Lithiated dimethylhydrazone

This is known as the directed aldol reaction. Similar reactions have been performed with oc-lithiated dimethylhydrazones of aldehydes or ketones and with a-lithiated... 

Metalation of dimethylhydrazone derivatives of aldehydes and ketones occurs cleanly. Unsymmetrical ketones suffer proton abstraction from the lesser-alkylated a-carbon atom specifically, and the a-lithiated dimethylhydrazones react more vigorously than the corresponding enolates with halides (Scheme 23), oxirans, and carbonyl compounds (Scheme 23). Cuprate derivatives can be obtained from the lithiated species in the usual manner and the cuprates undergo Michael addition to ajS-unsaturated ketones. 

The azaallyl oidates, Le. enolates derived from ketone imines or hydrazones are synthetic equivalents of the ketone endates and thus two examples of azaallyl enolates are included in th section. Lithiated cyclrdiexanonephenylimine (151) crystallizes out of hydrocarbon solution as the dimeric diisopropylamine solvate (152). Significant disorder between the cyclohexyl and the phoiyl moieties is obse ed in this crystal structure however, it is clear that there are no V-az yl carbm contacts in this structure. This lithiated imine structure can be compared with the lithittted dimethylhydrazone of cyclohexanone... 

The sodium salt of the stabilized enolate derived from the heteroaryl-substituted 2-oxoglutaric acid ester (186) is reported to have the alkene geometry as shown in formula (187). Hnally, Collum et al. have reported the structure of the lithiated anion derived from the A, A -dimethylhydrazone of 2-methoxy-carbonylcyclohexanone (188). This enolate crystallizes as the dimeric, bis-THF-solvated aggregate (189). 

Because previous investigations showed that there is no syn-anti isomerization in oxime dianions , in contrast to dimethylhydrazone anion where a syn-anti mixture gives after lithiation only one (jy/i) monoanion, Ensley and Lohr checked the ability of the oxime ether to undergo isomerization of this type. An E and Z mixture of the 2-heptanone tetrahydropyranyl oxime gave, after lithiation and reaction with acetone, a substitution product only on the methyl group (equation 41). 

Corey, Enders and Bock were among the first to describe the utility of lithium dimethylhydrazone anions for crossed aldol reactions. In the reaction shown in equation (14), an azaallyllithium reagent derived from an aldehyde dimethylhydrazone was first silylated with trimethylsilyl chloride to yield a silyl aldehyde dimethylhydrazone. Subsequent lithiation using lithium diethylamide at -20 C for 1 h generated the silylated azaallyllithium reagent (29). Subsequent addition of one equivalent of an aldehyde or ketone at -78 C and warming to -20 C then yielded the product a,p-unsaturated aldehyde dimethylhydrazone in yields of 85-95%. Hydrolysis produced the unsaturated aldehyde in 75% overall yield. 

Figure 3 Molecular structure of the asymmetric unit of lithiated cyclohexanone dimethylhydrazone polymer (hydrogen positions have been left off for clarity) ...

The alternative approach involves generation of an enolate equivalent, and lithiated dialkylhydrazones (16) show considerable promise from this point of view. Unsymmetrical dimethylhydrazones (DMH s) are lithiated with notable regioselectivity and the products are readily converted into ketones by oxidative hydrolysis with NaI04. Furthermore, use of optically active hydrazones (17) allows a very respectable level of asymmetric induction at the new chiral centre. DMH s... 

The solid state structures (as well as those in solution) have been determined for the dimeric species (i) lithiated 2-Me02 Cyclohexanone dimethylhydrazone... 

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