Oxime from enone

Finally, a rather early (but from a mechanistic viewpoint a very interesting) sequence of radical reactions has been described by Pattenden and coworkers, in which an acetylenic oxime ether 3-312 was converted into the bicyclic oxime 3-319 in 70% yield (Scheme 3.78) [126]. Hydrolysis of 3-319 led to the bicyclic enone 3-320, which in fact can also more easily be synthesized by a Robinson annulation. 

In a similar approach, Shishido et al. (241) used oxime 215 [derived from the monoterpene (+)-citronellal (214)] for the synthesis of (—)-mintlactone (218) and (+)-isomintlactone (219), sweet compounds isolated from some Mentha species (Scheme 6.89). Bicyclic isoxazoline 216 was obtained in good yield from the cycloaddition. As expected, the product possessing tra i-l,4-substimtion prevailed. Reductive hydrolysis of the major isomer of 216 using hydrogen-Raney Ni-trimethyl borate provided p-hydroxyketone 217. This compound was dehydrated to give an enone and this was followed by carbonyl reduction-lactonization to complete the synthesis of both lactones 218 and 219 (241). 

Kozikowski and Li (268) also made use of this protocol for the construction of the hexahydronaphthalene portion of the hypocholesteremic agent compactin (256) (see Section 6.4.2.2). The oxime derived by from alcohol 253 (via y-lactone 252) was heated with aqueous sodium hypochlorite in the presence of triethylamine to give the tricyclic isoxazoline adduct 254 (Scheme 6.96). Reductive hydrolysis and dehydration afforded enone 255, which in several further steps led to compactin (256) (268). 

A variation of this route was applied to the preparation of a-methylenecyclo-pentane 179, an intermediate that was employed for the synthesis of prostaglandin PGF2o, (180) (Scheme 6.82). The acetonide-protected oxime-diol 175 [derived from propanal (174)] was treated with sodium hypochlorite without the addition of base. This led to the tricyclic adduct 176 with high stereoselectivity. One of the side chains was subsequently elaborated and the fully protected cyclopentano-isoxazo-line (177), when exposed to Raney Ni/boron trichloride, gave the 2-hydroxymethyl-cyclopentanone (178). This compound was dehydrated using mesyl chloride/ pyridine to furnish enone (179) (324). In another related synthesis of PGF2q, the p-side-chain (3-hydroxyoctenyl) was introduced prior to the cycloaddition (325). 

DMF is recommended as diluent in the Ullmann synthesis of diaryls from aryl halides and as solvent for the Beckmann rearrangement of steroidal enone oximes. The Willgerodt-Kindler reaction (a carbonyl compound with a secondary amine and sulfur to give a thioamide) can be carried out in good yield at 50-60 if DMF is... 

Nitrogen can be incorporated as an oxime into a different kind of ene reaction that has been explored by Grigg and his group. The ene component now bears no resemblance to a diene one pair of electrons comes from the lone pair on nitrogen and the other from the OH bond of the oxime 140. The enophile is a more conventional enone and the initial product is a nitrone 141. No nitrogen heterocycle is formed in this step, but, if the enophile contains a second alkene, a 1,3-dipolar cycloaddition gives a bicyclic structure. The simplest reagent for this job is the rather unstable divinyl ketone (penta-l,4-dien-3-one, 143). Fortunately this can be released from the dichloroketone 142 with base and distilled with the solvent THF into the reaction mixture.24... 

The enone 2.1b (0.9 g, 2.8 mmol), hydroxylamine hydrochloride (0.3 g, 4.2 mmol) and pyridine (0.3 g, 4.2 mmol) were heated at reflux in 100 mL of ethanol for 52 h. After cooling the mixture to room temperature, the solvent was removed under vacuum and the crude dissolved in ether, washed with 3 x 100 mL portions of 10% aqueous HCl and then with water. The organic layer was dried over magnesium sulfate. The desiccant was filtered off and the solvent was removed under reduced pressure. The crude product obtained was purified by flash chromatography (silica gel 60 230-400 mesh) using hexane/ethyl acetate (1 1) as eluant. The chromatography yielded 0.9 g (95%) of the oxime 2.1c as colorless crystals, mp 185 - 187 °C from ethanol. 

In any event, this discovery provided a solution for the problem of unmasking the enone. Thus, oximation of F3, followed by lithium aluminum hydride reduction, acetylation, and oxidation afforded the a-enone F4 as a single diastereomer. Clearly, reduction at the C-4 trigonal center had occurred stereo-selectively from the convex surface to give the desired axially oriented amino group in F4. 

Conjugate reductions and reductive alkylations of enones are listed in Section 74 (Alkyls from Alkenes). Ketones from oximes are listed here. 

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