2.4- Cyclohexadienone derivatives

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

Quideau and coworkers have developed a hypervalent iodine-mediated regioselective protocol for the oxidative dearomatization of 2-alkoxyarenols in the presence of external carbon-based nucleophiles, such as allylsilanes or silyl enol ethers [342-345]. For example, the oxidation of 2-alkoxynaphthol 269 with [bis(trifluoroacetoxy)iodo]benzene in the presence of allylsilane affords 2,4-cyclohexadienone derivative 270 (Scheme 3.112) [342]. 

Reaction with the electrophilic peroxodisulfate occurs preferentially at the para position, leading to formation of a cyclohexadienone derivative 5, which loses a proton to give the aromatic compound 6. Subsequent hydrolysis of the sulfate 6 yields 1,4-dihydroxybenzene 3 ... 

Analogous olefin trapping chemistry employing 2,7-cyclooctadienone has been investigated51. With this substrate, the oxyallyl zwitterion 112 could be intercepted intermolecularly with simple alkenes in a (presumably stepwise) 3 + 2 manner (Scheme 27). Importantly, intermediate 112 differs from 2,5-cyclohexadienone-derived zwitterions in terms of its lack of a facile rearrangement pathway. An interesting side-issue... 

The voltammetric response of curcumin and carthamin must, in principle, be dominated by the oxidation of the phenol and/or methoxyphenol groups (see Scheme 2.2). The electrochemistry of methoxyphenols has claimed considerable attention because of their applications in organic synthesis [159-163]. As studied by Quideau et al., in aprotic media, 2-methoxyphenols are oxidized in two successive steps into cyclohexadienone derivatives [163], whereas a-(2)- and a-(4-methoxyphenoxy) alkanoic acids undergo electrochemically induced spirolac-tonization to develop synthetically useful orthoquinone bis- and monoketals. In the presence of methanol, the electrochemical pathway involves an initial one-electron loss, followed by proton loss, to form a monoketal radical. This undergoes a subsequent electron and proton loss coupled with the addition of alcohol to form an orthoquinone monoketal. The formal electrode potential for the second electron transfer... 

This cation cannot yield the product of electrophilic aromatic substitution by loss of a proton from the ring but can lose a proton from oxygen to give a cyclohexadienone derivative. 

The intramolecular [2 + 2] photocycloaddition of cyclohexadienone derivative 51, which is substituted with chiral piperidine ring in the solid state, proceeds enantioselectively and optically active products 52 and 53 were obtained [28], Two crystal modifications of 51, the a-form (mp 102-104°C) and (3-form (mp 127-128°C), gave optically active 52 and 53, respectively, upon irradiation in the solid state. 

Arenols 4 and their conjugate arenolate bases are both (a) oxygen- and (b) carbon-based nucleophiles, which react with a wide range of electrophilic reagents (Figure 3). Their reactions with soft electrophiles can lead directly to cyclohexadienone derivatives this is the case, for example, with electrophilic halogenation, which effectively occurs at the electron-rich carbon centers (4 —> 5b) [29, 30]. 

In spite of the encouraging results obtained in the TBCHD-sensitized photooxygenation of several unsaturated substrates, however, this procedure suffers a severe limitation fundamentally due to the thermally and/or photochemically low stability of the sensitizer. The photoreactions of different cyclohexadienone derivatives have been widely studied by Schuster and co-workers [191-192],... 

Since the arylated 1,3-cyclohexadienone derivatives are usually synthesized from smaller building blocks, their reactions will be found in Section 2.6. This is also true for the cyclohexanone derivatives. 

Cyclohexadienone derivatives that have two alkyl groups in the 4 position undergo, on acid treatment, 1,2 migration of one of these groups from 64 to give the phenol. Note that a photochemical version of this reaction has been... 

A walk rearrangement of hydroxybicyclohexenyl cation 69 is involved in the acid catalyzed isomerization of bicyclohexanone 68 to cyclohexadienone 70. The reversible nature of this walk rearrangement has been demonstrated by the equilibration 69-4-CD3s=t 69-5-CD3, which precedes the ring opening to the protonated cyclohexadienone derivative (Figure 12) (109). 

In contrast, Porco and coworkers had reported a system for preparing enan-tioenriched cyclohexadienone derivatives, but this required the use of stoichiometric amounts of a chiral copper source. The Porco system was also limited to the synthesis of orf/to-quinols. It was clear that a general catalytic enantioselective entry into this class of compounds was missing from the literature. 

Ogiso, a., M. Kurabayashi, H. Mishima, and M. C. Woods The Structure of Futoenone, a Novel Spiro-cyclohexadienone Derivative. Tetrahedron Letters 1968, 2003. 

An interesting one-step construction of the tricyclic seychellene skeleton developed at Tohoku University involves as the key step an intramolecular Diels-Alder addition of monocyclic cyclohexadienone derivative (B). The desired dienophile in (B) is generated by pyrolysis of the dimethylamino N-oxide (A). 

The monolithium salt of 4-hydroxy-4-(phenylethynyl)-2.5-cyclohexadienone (12), prepared in situ by the addition of lithium acetylide to /7-benzoquinone, was treated with methylmagnesium chloride in l HF-TMEDA or in THF —DMPU. The syn-, 4-addition adduct 13, derived from intramolecular delivery of the carbon nucleophile by the hydroxy oxygen, as well as the <7s-1,4-diol 14, obtained via intermolecular 1,2-addition, were obtained in varying amounts depending on the conditions. The selectivity on 1,4- to 1,2-addition increased by the addition of cation chelating agents such as DMPU, TMEDA, and 15-crown-5. Although the 1,4 to 1,2... 

The basic principle of all diazotizations of aromatic amines with a hydroxy- or a sulfonamido group in the 4-position relative to the amino group involves a deprotonation of the OH or NH group, respectively, after diazotization of the amino group. There is also a case of a deprotonation of a CH group in the 4-position of an aniline derivative, namely in the diazotization of 4-aminophenylmalononitrile (2.41) which, by the sequence of steps shown in Scheme 2-23, yields 3-diazo-6-dicyanomethylene-1,4-cyclohexadienone (2.42), as found by Hartzler (1964). This product can also be represented by a zwitterionic carbanion-diazonium mesomeric structure. 

A plausible pathway is that the aromatisation of the cyclohexadienone 92 by a proton shift is accelerated in the presence of Ac20 under formation of acetate 93. The simultaneously generated acetic acid then cleaves the acetate to form the free phenol 94 (Scheme 44). This effect was observed for the first time during studies towards the total synthesis of the lipid-alternating and anti-atherosclerotic furochromone khellin 99 [64].The furanyl carbene chromium complex 96 was supposed to react with alkoxyalkyne 95 in a benzannulation reaction to give the densely substituted benzofuran derivative 97 (Scheme 45). Upon warming the reaction mixture in tetrahydrofuran to 65 °C the reaction was completed in 4 h, but only a dimerisation product could be isolated. This... 

AIMcs to cyclohexadienone with thioether hgands 86-7 AlMes to linear aliphahc enones with binaphthalene-derived hgands 75-8... 

Direct interception of the initially formed bicyclic oxyallyl zwitterion derived from cyclohexadienones is difficult, due to its facile rearrangement to cyclopropyl ketone. One notable exception is the observation that 4-trichloromethyl-substituted dienone 94 gave solvent adduct 97 when irradiated in methanol, and both 97 and 98 upon irradiation in acidic methanol (Scheme 24)48. It was proposed that 97 arises either from a facile... 

BHT (2,6-di-tert-butyl-4-methylphenol), a phenolic antioxidant, on reaction with NO under neutral conditions, results in scavenging of the potentially harmful NO via radical reactions [143]. Sodium phenolate under basic conditions undergoes a Traube-type reaction at the ortho-position to produce a cupferron derivative [144]. When the ortho-positions are sterically blocked and the para-position does not bear a proton, cyclohexadienone diazeniumdiolates may be formed (Scheme 3.12) [145]. 

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