Cyclohexa-2,5-dienones

Generally, oxepins have a tendency to contract to a six-membered carbocycle when treated with acid. The driving force is the aromaticity of the phenol formed. However, when the less stable cyclohexa-2,5-diene-1,4-diol with an appropriate substitution pattern is treated with acid, the oxepin system is obtained. The treatment of cyclohexadienediols that are substituted with tert-butyl groups in the 2- and 6-positions and aryl at Cl and C4 with trifluoroacetic acid produces oxepins 1 with elimination of water.186 187 This reaction, however, is restricted to certain aryl substituents with at least some electron-donating effect. Generally, cyclohexa-2,4-dienone derivatives 2 are formed.187,188... 

The competition of Claisen rearrangement and [l,5]-acetyl shift upon thermal treatment of allyl aryl ether 356 resulted in a mixture of the expected Claisen product 357 and its isomer 358 (equation 129)184. It was assumed that the usual Claisen rearrangement (Section IV.E.l) resulted in an equilibrium with the intermediates of successive [3,3]-sigmatropic shifts. The cyclohexa-2,4-dienones 359 and 360 formed leave this equilibrium cycle due to enolization to form the Claisen product 357 or because of [l,5]-shift followed by enolization give the unexpected product 358 (equation 130). 

The alkenylation of phenols also proceeds smoothly in the presence of TMG (Scheme 6). The major products are not aryl alkenyl ethers but a-alkenylated cyclohexa-2,4-dienones. That is, C-alkenylation occurs exclusively at the ortho position of phenols. When 2-naphthol reacts with two equivalents of the alkenylbismuthonium salt, a,a-dialkenyl ketone is obtained in good yield as the sole alkenylated product. 

This includes two new pathways in cyclohexa-2,4-dienone 4,5-epoxides, the first involving the photorearrangement of the 6,6-dimethyl derivative (115) to the enol lactone (116) via the cyclopropane(117), and the second providing the first example of a-cleavage in systems of this type. Carbon-oxygen bond homolysis is almost certainly implicated in the photorearrangement of cyclopentadienone epoxide.98... 

The normally sluggish Diels-Alder cycloaddition between cyclohexa-1,3-diene and various enones and enals can be activated by precoordination of the diene to a jt-basic molybdenum complex TpMo(NO)MeIm(//-cyclohexadiene)].134 The 4-1-2-cycloaddition of cyclohexa-2,4-dienones with electron-deficient 2n -dienophiles produced bridged bicyclo[2.2.2]octenones. Triplet-sensitized irradiation of these bridged bicyclooctenones produced bicyclo[3.3.0]octanoids, whereas direct irradiation yielded bicyclo[4.2.0]octanes.135... 

Potent antileukemic agent, asatone (11), which was isolated from Asarum taitonense Hayata, was synthesized via dimerization of cyclohexa-2,4-dienone (138) generated by PIDA oxidation of o-methoxyphenol (137) [94] (Scheme 11). 

In 1974 Johnson and Mander (180) reported the synthesis of the tricyclic ketones 378 and 380 containing the 3.2.1 and 2.2.2-bicyclooctane ring systems incorporating a cyclohexa-2,4-dienone moiety. The Australian chemists prepared the diazoketones 377 and 379 by the earlier standardized method. 

Masked o-benzoquinones, as the most accessible type of cyclohexa-2,4-dienones, are of immense synthetic potential [187-193]. At both room temperature and reflux, the dienones 263 generated in situ from commercially available 2-methoxyphenols 262 by adding (diacetoxyiodo)benzene (DAIB, 1 equiv.) at 0 °C in MeOH underwent unusual Michael addition to indoles (2, 19, 264) followed by aromatization of the adducts to give highly functionalized 2-arylindoles 265a-c in excellent yields (Scheme 57) [193]. 

Electrooxidative activation is just one of the tools with which synthetic organic chemists can effect the dearomatization of arenois and their ethers to give cyclohexa-2,4-dienone derivatives. Other methods are based on the utilization of oxidizing reagents that mediate the oxidative nucleophilic substitution of 2-substituted arenois in the presence of appropriate nucleophilic species. These reagents are for the most part all based on metals (Section 15.2.2) or halogens (Section 15.2.3). 

Liao and Wei took advantage of the possibility of photochemically rearranging cyclohexa-2,4-dienones into bicyclo[3.1.0]hexenones in their approach to synthetically useful cyclo-pentenones such as 135 [6, 160-162]. This approach was based on the acid-catalyzed cyclopropane ring-opening of bicyclo[3.1.0]hexenones such as 134, as generated photochemically from non-dimerizing ortfio-quinone monoketals such as 133 (Figure 33) [165]. 

Recent density functional theory (DFT) calculations have suggested that cyclohexa-2,4-dienones and cyclohexa-2,5-dienones have essentially the same heat of formation, see D. Santoro, R. Louw, /. Chem. Soc., Perkin Trans. 2 2001, 645-649. D. J. Hart, P. A. Cain, D. A. Evans, /. 

When this reaction is carried out on a p,p disubstituted a,p-unsaturated complex, cyclohexa-2,4-dienones are obtained, evidently because tautomerization to a phenol is... 

Enols are generally more acidic (pA a ca 11-12) than their corresponding carbonyl tautomer (pATa ca 17-25). Exceptions to this arise when the carbonyl derivative is either destabilized relative to the enol component, or when the enol is exceptionally stable, as in the case of phenol [pATa (H20) = 9.95] vs. cyclohexa-2,4-dienone [pATa (H20) = —3 1]. Enol acidity can be controlled by O-H bond strength. In certain cases, the relative proportion of enol content can be determined by the relative strengths of the C=0 and C—H bonds in the carbonyl tautomer versus the C=C and O—H bonds in the enol. ... 

The total synthesis of the tricyclic sesquiterpene (+)-P-copaene was accomplished by E. Wenkert and co-workers. The required bicyclic starting material was prepared in three steps from carvacrol. In the first step, carvacrol was subjected to typical Reimer-Tiemann conditions. The abnormal Reimer-Tiemann product, 6-dichloromethyl-3-isopropyl-6-methyl-cyclohexa-2,4-dienone, was obtained, and upon treatment with sodium carbonate in DMSO, cyclization occurred to afford a bicyclic halo ketone. The double bonds were then hydrogenated in the presence of Pd(C) catalyst. 

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