Cross-conjugated dienone

Metal-ammonia solutions reduce conjugated enones to saturated ketones and reductively cleave a-acetoxy ketones i.e. ketol acetates) to the unsubstituted ketones. In both cases the actual reduction product is the enolate salt of a saturated ketone this salt resists further reduction. If an alcohol is present in the reaction mixture, the enolate salt protonates and the resulting ketone is reduced further to a saturated alcohol. Linearly or cross-conjugated dienones are reduced to enones in the absence of a proton donor other than ammonia. The Birch reduction of unsaturated ketones to saturated alcohols was first reported by Wilds and Nelson using lithium as the reducing agent. This metal has been used almost exclusively by subsequent workers for the reduction of both unsaturated and saturated ketones. Calcium has been preferred for the reductive cleavage of ketol acetates. 

Cross-conjugated dienones are quite inert to nucleophilic reactions at C-3, and the susceptibility of these systems to dienone-phenol rearrangement precludes the use of strong acid conditions. In spite of previous statements, A " -3-ketones do not form ketals, thioketals or enamines, and therefore no convenient protecting groups are available for this chromophore. Enol ethers are not formed by the orthoformate procedure, but preparation of A -trienol ethers from A -3-ketones has been claimed. Another route to A -trien-3-ol ethers involves conjugate addition of alcohol, enol etherification and then alcohol removal from la-alkoxy compounds. 

The investigation of the photochemistry of steroidal cross-conjugated dienones was initiated by both Barton and Jeger and was pursued most extensively by the latter group. Despite the frequently complex product patterns which result from prolonged dienone irradiations, some prepara-tively convenient and useful methods for the synthesis of novel systems have been worked out in this field. 

Dehydrotestosterone acetate (174) in nonprotic solvents (dioxane, benzene) undergoes a rearrangement to the isomer (175). This product is photolabile and isomerizes readily to new cross-conjugated dienones. Thus, ultraviolet irradiation of (174), its 1-, 2- and 4-methyl homologs, and its lOa-stereoisomer (188) in dioxane solution causes, in each case, a series of rearrangements as summarized on page 331 for (174) and (188). ... 

In the latter compounds, the cross-conjugated dienone is replaced by a fu-ran ring conjugated to an E double bond. Biosynthetically, it is not known if these compounds arise from 1,4-dione precursors such as 138 by a Paal-Knorr type cyclization (Scheme 2) or from the a-angelica lactones 134 by reduction of the lactone carbonyl followed by loss of water. 

In contrast with all the other species of Crematogaster studied till now, the venom of C. sp. 2 from Papua New Guinea did not contain mixtures of homologous compounds. Two derivatives, 136 and 137, characterized by the presence of a conjugated triene on one end of the chain, and by a 1,3-hydroxyketone at the other end, were isolated from this species (Fig. 23). These structures could constitute biosynthetic intermediates en route to the cross-conjugated dienone system. The venom of C. sp. 3 contained 4-oxo-2,5-dienyl acetates similar to... 

The Nazarov reaction [196] is a conrotatory electrocyclization involving four electrons over a five-carbon span. Usually, a more highly substituted cyclopentenone is obtained. However, contrathermodynamic products may be generated by placing a silyl group at the p-position of a bare vinyl moiety in the cross-conjugated dienone [197]. The acceptor facilitates and controls the regiochemistry of the cyclization process. 

Dlsubstituted 2-cycbpentenones. Cross-conjugated dienones, or the corresponding ethylene kelals, are cyclized almost entirely to 2,3-disubstituted 2-cyclo-pentenones by H3P04-HCOOH (1 1) or HBr-CHjCOOH (1 3). 3,4-Disubstiluted 2-cyclopentenones are formed, if at all, in low yield. 

It is in this area of dienone photochemistry that the effect of structure on reactivities of excited states seems to be especially complex. For example, Kropp has shown that the presence of the 4-methyl group in santonin is responsible for preferential formation of the fused 5,7 ring system in photosantonic lactone.403 An analogous cross-conjugated dienone with a 2-methyl substituent yields only a spiro compound in acidic media,404 while a dienone with neither 2- nor 4-substituents yields mixtures of the two types of products.409... 

Among the very early reports (1911) of photochemical rearrangements of cross-conjugated dienones is the report that the diphenylketene-quinone adduct (Formula 70) on irradiation in benzene solution gives... 

The solvent effects observed in the photochemical rearrangements of cross-conjugated dienones suggest that the availability of a proton to an excited state of the ketone may be an important controlling factor. It is interesting to consider the possibility that protonation of an excited state may lie behind the apparent polar reactions. Triplet states are likely to be more polarizable and to be stronger bases than the corresponding... 

The demonstration that both double bonds of the cross-conjugated dienone system are not necessary for photoisomerization considerably extends the potential utility of these rearrangements because of the greater availability of a,/3-unsaturated ketones. It is safe to predict that photochemical rearrangements of a,/3-unsaturated ketones will be subject to intense investigation in the immediate future. 

The synthetically most useful reaction of this type is the Nazarov cyclization, in which a cross-conjugated dienone like 4.89 forms a cyclopentenone 4.92 when treated with acid, in this case a Lewis acid. 

In the monocyclic series, the 2,4-cyclohexadienones rearrange to photoproducts of potential synthetic value. However, for efficient 1,2-acyl migration, only a relatively small number of substrates are suitable. These must be highly substituted, for example (48). Whereas on direct excitation in methanol, cleavage to the isomeric ketenes (49) (4> 2 0.42) predominates, the remarkably stereoselective 1,2-acyl shift to the bicyclohexenone (50) is found either in trifluoroethanol or when the dienone is adsorbed on silica gel. The conversion to (50) is followed by a reversible phototransformation to the cross-conjugated dienone (51) and accompanied by aromatization to (52) to a minor extent. Such reactivity has also been verified for tetra- and penta-methylated 2,4-cyclohexadienones. The only photoreaction of the hexamethylated homolog, on the other hand, is ketene formation. ° ... 

Both linear and cross-conjugated dienones are reduced by solutions of metals in liquid ammonia. For example, steroidal 4,6-dien-3-ones (Scheme 12) and related compounds are reduced initially to 3,5-dienolates while addition of ammonium chloride to the latter leads to formation of the noncon-... 

Cross-conjugated Dienones.- The photochemical rearrangement of a series of cyclohexadienones (244 - 247) has been studied by Schultz and his coworkers. The reactions encountered are typical of such compounds and involve rearrangement to a bicyclic species. In the first example, the irradiation of (244), the bicyclic species could not be isolated or detected since rapid ring opening was presumed to take place affording... 

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