Enamino-diketones

The IR, Raman and XH-NMR spectra and the X-ray crystallographic study of 2,2-diacetylethenamines (63) and 2-aminomethylene-5,5-dimethylcyclohexane-l,3-diones (64) show that these substances exist exclusively in the chelated enamino-diketone form, and that the conjugated system contained in them is essentially planar. The open-chain enamino-diketones 63, exist either in the solid state or in solution in the (E,Z,E) conformation (65). A similar conjugated core, having the fixed (Z,Z, ) conformation (66),... 

Dehydrogenation of heterocyclic enamino diketones of the azasteroid series was also effected by means of oxygen28 (Scheme 14). 

A new ring transformation reaction of 4,5-dibenzoyl-l,2,3-triazoline (395) has been reported, which appears to involve nitrogen expulsion followed by a C—NH proton shift. This sequence opens a novel route to enamino diketones (396) and tetraacylpyrrolidines (and traces of aziridine 398) <76jhci 153). 

Ionic hydrogenation of azasteroids containing an enamino diketone function is selective The reaction was carried out by treating a 1 40 8 mixture of the substrate, CFjCOOH/EtaSiH with 3% BF3 OEtj in 1% aq. UCIO4 in CF3COOH. 

Enamino diesters Enamino diketones Enamino esters Enamino ketones... 

New syntheses of enamino-ketones by the ring-opening of isoxazoles with samarium di-iodide and with pentacarbonyliron, by the reaction of 2-alkyl-thiomethyl-3-alkylthioacrylophenones with amines, and by the intramolecular photoarylation of A -[2-(haloaryl)ethyl]-(3-enaminones, of enamino-diketones by the reaction of (3-chlorosulphonic acid chlorides with amines and by amino-methylenation of cyclic (3-dicarbonyl compounds, and of enamino-esters by aminomethylenation of esters and lactones and by the reaction of nitriles with magnesium enolates have been reported. 

The alternative way to 5-aryl substituted y-pyrone 2a,b is based on the readily available aminoenones 5a,b. Reaction of 5a,b with ethyl trifluoroacetate in the presence of f-BuOK afforded enamino diketones 6a,b cyclized to pyrones 2a,b [6]. Compounds 6b and 2b are starting materials for the preparation of 4-pyridones exhibited potent antimalarial activity [5] (Scheme 3). 

Rosa FA, Machado P, Fiss GF, Vaigas PS, Fernandes TS, Bonacorso HG, Zanatta N, Meutins MAP (2008) Synthesis of ethyl pyrimidine-4-carboxylates from unsymmetrical enamino diketones and their application in the first synthesis of pyrimido[4,5-d] pyridazin-8(7H)-ones. Synthesis 22 3639-3648... 

Even 5,5-dimethyl-3-cyclohexylaminocyclohex-2-en-l-one (52), the mono-Schiff s base derived from the 1,3-diketone which is stable in the enamino ketone form (7) and theoretically could alkylate on nitrogen, gave the O-alkylated product (53) (23). 

There is some spectral evidence that acylation of enamines of cyclic ketones with acid chlorides having an a-hydrogen in the presence of triethylamine proceeds via the ketene and subsequent cycloaddition (84). The intermediate cyclobutanone is then opened to give the enamino ketone which is hydrolyzed to the 2-acyl cyclohexanone. In the case of enamines of larger cyclic ketones the alternate mode of the cyclobutanone opening predominates, with the formation of ring-expanded 1,3-diketones upon... 

This is the most common method for the preparation of enamines and usually takes place when an aldehyde or ketone containing an a hydrogen is treated with a secondary amine. The water is usually removed azeotropically or with a drying agent, but molecular sieves can also be used. Stable primary enamines have also been prepared.Enamino-ketones have been prepared from diketones and secondary amines using microwave irradiation on silica gel. ° Secondary amine perchlorates react with aldehydes and ketones to give iminium salts (2, p. 1178). Tertiary amines can only give salts (12). 

A somewhat related approach was followed by Molteni and coworkers, who have described the three-component, one-pot synthesis of fused pyrazoles by reacting cyclic 1,3-diketones with DMFDMA and a suitable bidentate nucleophile, such as a hydrazine derivative (Scheme 6.195) [357]. Again, the reaction proceeds by initial formation of an enamino ketone as the key intermediate from the 1,3-diketone and DMFDMA precursors, followed by a tandem addition-elimination/cydodehydration step. The details of this reaction, carried out in superheated water as solvent, have been described in Section 4.3.3.1. 

Irradiation of mixtures of 1,3-diketones and aliphatic or aromatic primary or secondary amines absorbed over montmorillonite clay or silica in a microwave oven affords enamino ketones, e.g. equation 99311. 

Enamino ketones undergo a clean oxidative cleavage to a-diketones, presumably through a... 

Other pyridine-forming reactions of this class bear some resemblance to the Friedlander synthesis and its near relations. The enamino ketones (328) condense with 1,3-diketones... 

The second major class of enamines contains the enamino ketones, made from ammonia or an amine and a 1,3-diketone. By this route the same 1,3-diketone can provide both halves of the resulting pyridine such an example is provided by the synthesis of 5-benzoyl-2-phenylpyridine (444) (54YZ259). As in the case of the crotonates, the first examples of the condensation of an enamino ketone with an a,/ -unsaturated ketone were provided by Knoevenagel and Ruschhaupt (1898CB1025), who prepared the range of 3-acetyldihy-dropyridines (445) to (447). Similarly, Mumm and Bohme obtained the 3-acetyl- and 3-benzoyl-2,6-dimethylpyridines (448) and (449) from ethyl acetylpyruvate (21CB726). 

Two closely related reports of pyrazole generation by condensation of substituted hydrazines with enamino carbonyl compounds have appeared. In situ formation of an enaminoketone, by treatment of a diketone with dimethylformamide dimethyl acetal, was followed by tandem Michael addition-elimination/cyclodehydration under aqueous conditions in sealed microwave vessels (Scheme 3.12)17. Isoxazoles and pyrimidines were also prepared by replacing the substituted hydrazine with hydroxylamine or amidines, respectively (see Chapter 5, Section 5.3.2). The overall process may be regarded as another example of a multi-component coupling. In a similar fashion, enamino propenoates were condensed with substituted hydrazines to afford substituted pyrazoles (see Chapter 5, Section 5.3.2) (Scheme 3.12)18. 

Tris(organoamino)boranes have been utilized to prepare, in reasonable yields,4,5 mono- and dihalo(organoamino)boranes which are often difficult to obtain by direct amination of the boron trihalides. Carboxylic acids, 1,3-diketones, ketones, and /3-ketoesters have been converted into carboxamides, enamino-ketones, enamines, and j -enamino-amides, respectively, by reaction with an appropriate tris(organoamino)borane under very mild conditions.6 Sulfenamides (R2NSC6H5) have also been prepared in high yield from selected tris(organoamino)boranes and sulfenic esters under relatively mild conditions.7... 

A slightly modified version of the same reaction allowed the synthesis of poly-functionalized a-diketones from linear enamino ketones23 (Scheme 8). 

Enamino ketones. MejSiOTf is a catalyst for the condensation of 1,3-diketones with secondary amines. 

The reaction of enamines with iminium ions provides access to substituted j3 amino aldehydes and ketones (Scheme 61). In a similar manner the Mannich reaction gives access to oc,) -unsaturated aldehydes or -amino ketones (Scheme 62). Enamines undergo the Vilsmeier reaction to give a-formyl ketones Solvolysis of the Vilsmeier salt with aqueous or alcoholic sodium hydrogen sulphide produces an enamino thioaldehyde. The use of A-dichloromethylene-A,A -dimethylammonium chloride gives tertiary /5-ketoamides (Scheme 63). Iminoalkylation of enamines with nitrilium salts provides access to enamino ketones and j3-diketones (Scheme 64). 

An interesting application to the synthesis of a-diketones, a-ketoesters and a-ketoa-mides, starting from ketones, esters and amides, was achieved by Wasserman and Ives . The method involves conversion of the starting carbonyl compound to the corresponding enamino carbonyl compound, followed by oxidative cleavage of the enamine double bond by singlet oxygen (Scheme 7). 

N-Heterocyclic jS-enamino esters which are unsubstituted in the 1-position are well suited for a double condensation reaction when treated with 1,3-dicarbonyl compounds to give annelation of a [1,2-a] pyrimidine ring. Thus, the condensation of 2-aminopyrroline affords pyrrolo[l,2-a]-pyrimidines.82,114 Shvedov et al. treated 2-amino-3-pyrrolecarbonitrile 187 with / -diketones or ethyl acetoacetate74115 to give 188. No ring closure... 

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