Enaminoketones synthesis

Isoxazoles are susceptible to attack by nucleophiles, the reactions involving displacement of a substituent, addition to the ring, or proton abstraction with subsequent ring-opening. Isoxazolium salts are even more susceptible to attack by a variety of nucleophiles, providing useful applications of the isoxazole nucleus in organic synthesis. Especially useful is the reductive cleavage of isoxazoles, which may be considered as masked 1,3-dicarbonyl compounds or enaminoketones. 

Synthesis of 1,2,3-dithiazoles is the most extensively studied. The widely used and very long-known Herz reaction of arylamines with S2CI2 to give benzo-l,2,3-dithiazolium salts (Section 4.11.8.5) has been extended to hetarylamines (Scheme 17). More importantly, a new impetus for its investigation and development was provided when benzo-l,2,3-dithiazolyl radicals were shown by Mayer and co-workers to be intermediates. The reaction in a modified form was transformed by the above authors to an effective method for synthesis of this new class of stable radicals. When applied to acyclic enaminoketones the thiosulfinylamine precursor of the free radical could be isolated (Scheme 18). It was also extended to cyclic and acyclic oximes to afford fused and monocyclic... 

Reaction of the nitrile oxide (498) with the enone (499) gave after chromatography the expected isoxazoline (500) plus some of its dehydro derivative (76TL3983). Hydrogenation of (500) using 30% Pd/SrC03 as catalyst yielded an enaminoketone (501) which was further hydrolyzed to the diketone (502 Scheme 110). This compound is a gem-dimethyl isomer of dehydrocycloheximide, a key intermediate in a previously reported synthesis of the glutarimide antibiotic cycloheximide. 

A different type of indole ring synthesis was accomplished via an intramolecular cyclization of enaminoketones that proceeds through intermediate arylpalladium complexes (90H911). /3-Hydrocarbolines (33) were obtained as the final products. Similar results were obtained in the photo-cyclization of enaminoesters (91TL6129) and enaminolactones (95H1939). Results obtained in the cyclization of A-arylenamines to indoles with... 

Condensation reactions of enaminoesters, enaminoketones, and enam-inonitriles with benzo- and chloronaphthoquinones have been described (94JIC281). Utilization of diamines (38) as novel synthons in the Nenitzescu reaction has resulted in a new synthesis of 2-(3-benzofuryl)indoles (40) [95KFZ(9)47,95MC69].The pathway in the scheme leading to 40 has... 

The microwave-mediated condensation of hydroxylamine with enaminoketones to generate isoxazoles has been mentioned earlier (refer to Scheme 3.12)17. In a procedure analogous to the Paal-Knorr thiophene synthesis, 2-aminoacyl carbonyl compounds... 

Synthesis of annelated diazepines based on unsaturated aromatic diazepines may involve the preliminary transformation of ketones into the corresponding l,3-diaryl-2,3-dibromopropane-3-ones (chalcone dibromides). The interaction between o-PDA or some of its substituted analogues with chalcone dibromides leads to the formation of aziridine derivatives [64] (see Chap. 1). However, in the case of 4-nitro-o-PDA, either azirenoquinoxalynes 53 or benzodiazepine derivatives 54 may be obtained depending on the reaction conditions [65] (Scheme 4.15). Diazepine derivatives 56 are obtained by the condensation of chalcone dibromides 51 with 5,6-diamino-1,3-dimethyluracil 55 [66], but aziridine derivatives are not isolated in this reaction. It should be noted that compounds 54 and 56 are formed owing to cyclization of the intermediate (3-enaminoketones [65, 66, 67] and are easily isolated from the reaction mixture. 

Regioselective synthesis of substituted 3-cyano-2(lT/)-pyridinethiones and -selenones from unsymmetrical p-enaminoketones 90MI5. 

A very recent study presented by Dujardin et al. describes the complementary use of chiral enol ethers as dienophiles in oxa Diels-Alder reactions. This approach has yielded promising results with regard to the synthesis of enantio-merically pure carbohydrates [481]. Further noteworthy studies directed to the preparation of biologically active amino sugars from enaminoketones have been carried out in our group [110]. 

In an example illustrating a modification of the Knorr synthesis, the Weinreb amide derivative 171 is converted to the -enaminoketone 172 and annulated to the target pyrrole 173 (Scheme 97). Numerous pyrrole derivatives can be prepared using variations of this approach <1999T6555>. 

Early work on isoxazoles revealed that they were readily cleaved under reducing conditions by the time of the earlier review many examples were known, but the potential of these reactions in synthesis was only beginning to be realized.1 Since then the isoxazole ring has become a major tool as a masked 1,3-dicarbonyl compound or enaminoketone, particularly for the synthesis of homo- and heterocycles.213... 

As early as 1891 Claisen noted that isoxazoles, when treated with sodium and either pentyl alcohol or moist diethyl ether, undergo reductive ring opening to give 1,3-enaminoketones. These products may then be hydrolyzed to 1,3-dicarbonyl compounds. In more recent times the use of readily available isoxazoles as masked 1,3-dicarbonyl compounds has found wide application in synthesis, although dissolving... 

The reaction sequence of Scheme 3 might well be classified as an imidazole synthesis from other heterocycles, but it seems more logical to treat this as a cyclization involving formation of the 1,5-bond. The enaminoketone condensation products (12) of 3-amino-l,2,4-oxadiazoles and 1,3-dicarbonyl compounds are cyclized by base to imidazoles (13) in 60-80% yields." Such a reaction makes use of the well-established general attack of a nucleophilic center in the side chain on N-2 of the oxadiazole ring. Benzamidine combines with 2-amino-3-phenacyl-l,3,4-oxadiazolium bromides to produce 1-acyl-amino-2-benzimidoylamino-4-arylimidazoles. ... 

Kadkin ON, Kim EH, Kim SY et al (2009) Synthesis and liquid crystal properties of copper(ll) and palladium(II) chelates with new ferrocene-containing enaminoketones. Polyhedron... 

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