Acylation enamine

The formation of an enamine from an a,a-disubstituted cyclopentanone and its reaction with methyl acrylate was used in a synthesis of clovene (JOS). In a synthetic route to aspidospermine, a cyclic enamine reacted with methyl acrylate to form an imonium salt, which regenerated a new cyclic enamine and allowed a subsequent internal enamine acylation reaction (309,310). The required cyclic enamine could not be obtained in this instance by base isomerization of the allylic amine precursor, but was obtained by mercuric acetate oxidation of its reduction product. Condensation of a dihydronaphthalene carboxylic ester with an enamine has also been reported (311). 

Enamine acylations have been extended to include the Vilsmeier reaction (409) and thus provide a method for the generation of formyl ketones without the use of strong base. By this method an unsaturated potential trialdehyde could be formed as an intermediate in a pyridine-3-carboxaldehyde synthesis (410). 

The intermediacy of ketenes in some enamine acylation reactions using acid chlorides was described above (386,387). Direct addition of ketene to enamines was studied simultaneously by several groups (414-420). The initially formed aminocyclobutanone products could be isolated in some instances, depending on the substitution of the initial enamine. Opening to give either the acylated enamine or the alternative vinylogous amide was found to occur spontaneously or on heating, particularly in adducts derived from enamines with an olefinic proton. 

One of the extensively investigated applications of enamines to heterocyclic syntheses is based on the bifunctional character of enamine acylation products. Thus the vinylogous ureas and thiorueas obtained from enamines and phenylisocyanate and phenylisothiocyanate (-433) have been converted to aminopyrazoles and thiouracils with hydrazine (566) and phenylisocyanate (567). 

The formation of five- (362) and six- (581) membered vinylogous lactams and pyrroles by intramolecular enamine acylations has been accomplished in some examples by formation of the cyclization precursor through an initial enamine exchange (362). 

Enamines acylate lactim sulfonates, among them 91, to yield lactimen-amines, exemplified by 92.121 The latter compound provided a route to m-aminocarboxylic acids via co-aminoketo acids. For example, beginning with 91, one can prepare m-aminododecanoic acid.121a... 

Dimethyl 2,4 dioxopentanedioate (as a monoenol) can be obtained by normal enamine -acylation of 2-aminopropenoic acid derivatives after hydrolysis of the resulting enaminone (equation 232),... 

The equilibrium between imine (7) and enamine (8) forms of harmaline has been demonstrated by exchange at the C-1 methyl group in methanolic solution and the enamine reactivity of tautomer (8) by alkylation, as in the reaction with methyl acrylate under mild conditions. Intramolecular enamine acylation occurs after initial alkylation at in reactions at higher temperature (Scheme 2). 

Further details have appeared of the ways in which trifluoromethylfluoroketen has been sought by American and Russian chemists, as yet without success. It may be trapped as a cycloadduct with acetone or with cyclopentadiene, and it reacts in situ with DMF to give (163). Like bis(triiluoromethyl)keten, it equilibrates readily over metallic fluorides with its isomer, perfluoroacryloyl fluoride the latter also reacts with DMF, but gives an enamine-acyl fluoride (164) and COFa (see Scheme 45). 

Enamine acylation reaction product recognition element... 

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