Enaminoketones oxidation

Enaminoketones undergo a clean oxidative cleavage to a-diketones, presumably through a dioxetane intermediate.180... 

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. 

Intramolecular coupling also takes place in the anodic oxidation of N-benzyl- and N-P-phenethyl-enaminoketones. The oxidation was carried out in 0.3 M NaC104/ CH3OH at 10 °C using an undivided cell and graphite electrodes 15). 

Enaminoketones are readily oxidized in aqueous solution by Ag(I) or Ce(IV) salts79. The major product obtained is a dimer which incorporated an oxygen atom (Scheme 57). The mechanism proposed involves a radical-cation intermediate. 

The photosensitized oxidation of an enaminoketone (133b) and its conversion to Cis-alpinine (154g) via 158 and 159 was carried out by Orito, Manske, and Rodrigo (729) (Scheme 53). 

A soln. of the startg. isoxazole in methanol or ethanol hydrogenated with Raney-Ni at ca. 50 p.s.i.g. until 1 equivalent of Hg has been absorbed enaminoketone (Y 88%) refluxed 0.5 hr. in toluene with sulfur as oxidant, PgSg and sand with efficient stirring > 3-(2,6-didilorophenyl)-5-methylisothiazole (Y 51%). - By this method isothiazoles previously difficult to obtain can be readily prepared. F. e., also with diloranil as oxidant, s. D. N. McGregor et al.. Tetrahedron 25, 389 (1969). 

An interesting approach to the canthin-4-one alkaloid family has recently been reported by Tremmer and Bracher and involves a 1,3-dipolar cycloaddition of the readily available 1-ethynyl-p-carboline 301 with various nitrile oxides (Scheme 54) (2015T4640). The initially formed isoxazoles 302 were then cleaved reductively, and this was followed by heating the resulting enaminoketones 303 in DMF at 150 °C to give 6-substituted canthin-4-ones 304 in high yields. 

Compound 4 was subsequently converted to rhoeadine bases. The key step in this sequence was the photosensitized oxidation of the enaminoketone 5 to form the ketonic y-lactone 6. Analogs of this y-lactone had previously been converted into rhoeadines by the Brossi-Klotzer-Teitel team, so that a similar sequence was followed in the present case to obtain c/5-alpinine and m-alpinigenine ... 

The next stage of the synthesis called for conversion of the terminal olefin to an aldehyde. This was accomplished using a Johnson-Lemieux oxidation. The resulting ketoaldehyde was then converted to fr-ketal 15. Basic hydrolysis of the formamide provided 16 and hydrolysis of the acetals afforded a mixture of diastereometic enaminoketones 17. An acid-promoted intramolecular Mannich reaction gave 2. Presumably epimerization of the ketone allowed both diastereomers of 17 to follow the path to 2. Reduction of ketone 2 with sodium borohydride provided an alcohol, which underwent formal dehydration upon treatment with thionyl chloride and pyridine, to give porantherine (1) as a racemic mixture. 

As in the Corey synthesis, an intramolecular Mannich reaction converted 29 to 31. Mercuric acetate oxidation of 31 to the corresponding iminium ion, followed by basification, gave enaminoketone 32. This intermediate does not have the proper stereochemistry for an intramolecular Mannich reaction, but under acidic conditions, epimerization is followed by cyclization to provide 2. The synthesis of porantherine (1) was completed using a Bamford-Stevens reaction to introduce the olefin. ... 

This reaction is not usually a major factor with alkenes bearing only alkyl groups but is important for vinyl ethers and other alkenes with donor substituents. Enaminoketones undergo a clean oxidation to a-diketones, presumably through a dioxetane intermediate " ... 

The synthesis of alpinine illustrates a different approach to rhoeadine alkaloids, and is based on the photosensitized oxidation of the enaminoketone (A) and rearrangement of the resuiting dioxetan to a spiro keto lactone (B). The rest of the synthesis closely follows the pathway laid down earlier at Hoffman-La Roche for the synthesis of rhoeadine. ... 

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