Azomethine-enolate condensations

In contrast to the extensive studies that have been directed at the elucidation of the stereochemical control elements of the aldol process, parallel investigations on the condensations of metal enolates with imines (eq. [63]) have been far less extensive. A review of the 

An analogous set of four transition states for the (Z)-imine geometry could also be constructed. The transition state descriptors, such as B(Z,E) and C(Z,E), may be employed to denote boat (B) or chair (C) transition states respectively, possessing (Z)-enolate and ( )-imine geometries. The interrelationships between the stereochemical features of reactants, transition states, and products are summarized in Table 28. Unfortunately, the kinetic diastereoselection in such condensations as a function of either enolate or imine geometry has not been systematically studied. In all the early work in this field 

Enolate Geometry Imine Geometry Transition State Product Stereochemistry 

The influence of temperature on aldol diastereoselection has been noted in several instances. The condensation of zinc enolates 85a to 

More recently, a study pertaining to the condensation of lithium ester enolates with substituted imines has appeared (eq. [66]) (79). Although monosubstituted enolates (Rj = H R2 = Ph, N=C(OLi)Ph] afforded moderate yields (35-45%) of trans-lactam 87, disubstituted enolates (Rj = OLi, CH3 R2 = Ph, CH3) afforded good yields (66-91%) of lactam products. The authors concluded from their study that the condensation step was probably reversible. 

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N-Metalated azomethine ylides generated from a-(alkylideneamino) esters can exist as tautomeric forms of the chelated ester enolate (Scheme 11.8). On the basis of the reliable stereochemical and regiochemical selectivities described below, it is clear that the N-metalated tautomeric contributor of these azomethine ylides is important. Simple extension of the above irreversible lithiation method to a-(alkylideneamino) esters is not very effective, and cycloadditions of the resulting lithiated ylides to a,(3-unsaturated carbonyl compounds are not always clean reactions. When the a-(alkylideneamino) esters bear a less bulky methyl ester moiety, or when a,(3-unsaturated carbonyl compounds are sterically less hindered, these species suffer from nucleophihc attack by the organometalhcs, or the metalated cycloadducts undergo further condensation reactions (81-85). 

The photostimulated arylation of ketone enolate ions has been shown to be of fairly wide scope, although the reaction fails with the enolate ions of acetophenone and several -dicarbonyl compounds and is impeded by steric crowding. Coupled with new, mild methods for the regeneration of the carbonyl group (see Section 4), the chemistry of azomethine ketone derivatives has taken on new dimensions. The alkylation of such derivatives has been of particular interest recently. For example, two groups of workers have shown that only yn-dianions are formed on metalation of oximes. Furthermore, the dianions are configurationally stable, allowing alkylation and aldol condensation to be effected stereo-specifically (Scheme 22). - . 

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