Enaminate anions

Among the compounds capable of forming enolates, the alkylation of ketones has been most widely studied and applied synthetically. Similar reactions of esters, amides, and nitriles have also been developed. Alkylation of aldehyde enolates is not very common. One reason is that aldehydes are rapidly converted to aldol addition products by base. (See Chapter 2 for a discussion of this reaction.) Only when the enolate can be rapidly and quantitatively formed is aldol formation avoided. Success has been reported using potassium amide in liquid ammonia67 and potassium hydride in tetrahydrofuran.68 Alkylation via enamines or enamine anions provides a more general method for alkylation of aldehydes. These reactions are discussed in Section 1.3. 

Other reactions involving the formation of the pyrrole ring include reactions of enamine anions with 1,2-dichloroethane or epichlorohydrin... 

The reaction of azirines with Grignard reagents is an anomalous reaction of imines. Normally an a-hydrogen is abstracted to give the enamine anion which is unreactive toward further attack of the Grignard reagent.64 The enamine derived from a 1-azirine is a 2-azirine (146) it is an unknown and probably unstable compound (Section I,A). 

The use of quinone monoketals in the reaction with an exocyclic enaminoester is a new variation150. It is not a typical Nenitzescu reaction since an enamine anion is used. Tricyclic intermediates are obtained, which nevertheless formally give typical Nenitzescu products in high yield and regioselectively (equation 58). In this way annelated indoles of mitomycin type become accessible. 

The special properties associated with pyridine a- and y-positions are evident again in the reactions of alkyl-pyridines protons on alkyl groups at those positions are particularly acidified because the enaminate anions formed by side-chain deprotonation are delocalised. The ability to form side-chain anions provides a useful means for the manipulation of a- and y-side-chains. 

Resonance stabilisation of enaminate anions formed by deprotonating the methyl groups... 

The enaminate anions produced by deprotonating a- and y-alkyl-pyridines can participate in a wide range of reactions, being closely analogous to enolate anions some examples are given below. Note that dimethyl-pyridines are often referred to as lutidines - thus the example below is 2,4-lutidine (2,4-dimethylpyridine). 

The nucleophilic reactivity of 17 can be increased by N-deprotonation and the best results were obtained with the in situ generated lithium salts. The latter react with acrylates by Michael addition and ring closure to give a single product. The problem of regioselectivity arises because the enamine anion 47 is delocalized and can react both at the nitrogen anion and/or at the enamine carbon. Both cases are known in the literature with similar substrates (ref. 49). These two pathways should lead to the isomeric dihydro a- or y-pyridones (Scheme 53). 

Deprotonation to the enamine anion, selective coupling with the allylic terminus of dibromide 114, followed by an intramolecular enamine alkylation, afforded reduced isoquinoline 119. A rather elegant conversion to aminoaldehyde 122 ensued. Immonium ion formation in 119 via protonation with perchloric acid at first yielded the kinetic trans isomer, which underwent equilibration upon reflux in methanol to give the corresponding crystalline cis product 120. Diazomethane treatment led to aziridinium salt 121, which upon exposure to DMSO, ring opened with concomitant oxidation in a Komblum fashion to the aldehyde 122.63 Treatment with Lewis acid effected B-ring closure, thus... 

Essentially the same reaction was then used to combine the east and west halves of corrin chromophores regioselectively. Donor (enamine anion) and acceptor (imidic ester) were both located on the western half. The eastern half carried an imidic ester as acceptor. Upon deprotonation of the western half, it was deactivated toward self-dimerization, because two anions would not react with each other. It rather reacted with the eastern half s imidic ester to form an open-chain tetrapyrroline. Complexation with nickel (template effect) and treatment with base (removal of an allylic proton) then led to the desired nickel corrinate in 80% yield (Scheme 7.3.19) (Eschenmoser, 1974 Pfaltz et al. 1997). 

Pyrrolidino-3-penten-2-one treated at - 60° with an equimolar amount of n-butyl-lithium followed by methyl iodide 4-p3 rolidino-3-hexen-2-one. Y 76%. F. e. s. M. Yoshimoto, N.Ishida, and T.Hiraoka, Tetrah. Let. 7975,39 phenyl-stabilized enamine anions s. H. W. lliompson and B. S. Huegi, Chem. Commun. 1973, 636. 

Alkylation via enamines or enamine anions provides a more general method for alkylation of aldehydes. These reactions will be discussed in Section 1.9. 

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