Formation of Cyclohexadienones

Fig. 2.34. Formation of cyclohexadienones from 2,2-disubstituted vinylcarbene complexes.

The oxidation of phenols has many different aspects. In this account, oxidative coupling, the formation of cyclohexadienones, conversion to quinones and other carbonylic and transformation products (other than those obtained by electrophilic substitution or rearrangement of phenyl esters) are considered. Particular attention has been paid to work carried out in the last decade. An early review has described initial work (ref.1) and that carried out later is available in the same source (ref.1, Ch.2). To a certain extent this present chapter inevitably impinges on the chemistry of alkylphenols (Ch.6), although oxidation has been excluded in that section except in the case of hindered phenols which are only briefly referred to in the following examples. 

Under more drastic conditions than for formation of cyclohexadienones,... 

Formation of cyclohexadienones occurs in 42 ps and can be followed by the appearance of characteristic carbonyl stretching bands at 1697 and 1765 cm" from the enone and acetyl groups, respectively. Using appropriate kinetic models, the recombination quantum yield is estimated as 0.74, and hence, the corresponding value for the escape process is 0.26. Recombination includes recovery of and formation of cyclohexadienones (quantum yields of 0.54 and 0.20, respectively). Final tautomerization to the final PFR products is not detected in the maximum time scale (2.5 ns), confirming that carbon to oxygen H transfer is a very slow process [37]. 

Polymerization Mechanism. The mechanism that accounts for the experimental observations of oxidative coupling of 2,6-disubstituted phenols involves an initial formation of aryloxy radicals from oxidation of the phenol with the oxidized form of the copper—amine complex or other catalytic agent. The aryloxy radicals couple to form cyclohexadienones, which undergo enolization and redistribution steps (32). The initial steps of the polymerization scheme for 2,6-dimethylphenol are as in equation 6. 

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 ... 

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... 

Formation of the ethano-dimer of a-tocopherol (12) by reduction of spiro dimer (9) proceeds readily almost independently of the reductant used. This reduction step can also be performed by tocopheroxyl radicals as occurring upon treatment of tocopherol with high concentrations of radical initiators (see Fig. 6.10). The ready reduction can be explained by the energy gain upon rearomatization of the cyclohexadienone system. Since the reverse process, oxidation from 12 to 9 by various oxidants, proceeds also quantitatively, spiro dimer 9 and ethano-dimer 12 can be regarded as a reversible redox system (Fig. 6.22). 

In aqueous acid cross-conjugated cyclohexadienones are principally photoconverted to one or more hydroxy ketones. In the case of a-santonin (1), isophotosantonic lactone (5) is formed in about 50% yield. A series of papers by Kropp and co-workers has aided in understanding this reaction/32-39-411 They have shown that the presence of a 4-methyl group (steroid numbering) results in the preferential formation of the 5-7 fused ring system (isophoto-... 

Linearly conjugated cyclohexadienones usually photorearrange with ring fusion to a czs-diene-ketene. The reaction is reversible, so that in the absence of a nucleophile little change is observed. A good example of this type of transformation is the formation of photosantonic acid ... 

The perhalogenated carbenes lg and lh are of unusual reactivity towards molecular hydrogen and hydrocarbons.62 Annealing of H2- or CH4-doped argon matrices containing the carbenes lg or lh at 30-45 K rapidly results in the formation of insertion products (Scheme 10). With H2 2,5-cyclohexadienone (14) is formed and with CH4 the 4-methyl-2,5-cyclohexadienone (16). The... 

An unusual one-pot intramolecular sulfoxide alkylation-elimination reaction was found by Gibson et al. <2001SL712>. These authors found that treatment of 459 with potassium bis-trimethylsilylamide resulted in a ring closure to 460 in acceptable yield. Furthermore, Batori and Messmer found an effective method for preparation of [l,2,3]triazolo[l,5- ]pyrimidinium salts <1994JHC1041> oxidative cyclization of hydrazones 461 by 2,4,4,6-tetrabromo-2,5-cyclohexadienone gave rise to the quaternary salts 462. Under certain reaction conditions, the formation of 6-bromo-salts 462 (R6 = Br) was also experienced. As neither the starting compound nor the quaternary triazolopyridinium salt underwent bromination in this position, the authors assumed that this bromination process occurred on one of the intermediates in the course of the above-mentioned cyclization reaction. 

In a novel total synthesis of the tricyclic sesquiterpene (—)-longifolene, an intramolecular diazoalkane cycloaddition to a cyclohexadienone ring followed by thermal ring contraction of the resulting pyrazoline gave the tricychc vinylcyclo-propane 261 and this constitutes the key steps in this synthesis (314) (Scheme 8.63). The interesting features of this sequence are the separation of dipole and dipolarophile by five atoms and the formation of a seven-membered ring in the cycloaddition step. 

Cyclohexadienones. The perturbation of the electronic absorption spectra by adsorption on silica gel can have a significant effect on subsequent photochemical reactions. For example, Hart has shown that 2,4-cyclo-hexadienones photochemically degrade cleanly in nonpolar solvents to a ketene (1) but in highly polar solvents or adsorbed on silica gel bicyclic ketone (2) is the predominant product.33 The absorption spectra indicate that in nonpolar solvents the lowest singlet state is the n,n state, from which the formation of the ketene proceeds. This n -n band is obscured by the band in polar media, inversion of the energy levels of the n,n, and the first... 

When the second component is an a,/i-unsaturated aldehyde, somewhat different results are reported. Thus crotonaldehyde reacts with ethyl aceto-acetate to give 4/f-pyran 65,86 whereas 3-substituted crotonaldehydes with 1,3-cyclohexadiones afford 67 to 80% of the corresponding 2//-pyrans 66. ° The reaction with 1,3-pentanedione proceeded also in the second way,110 but the former cyclization with ethyl benzoylacetate gave no pyran.8 If asymmetrically substituted 1,3-cyclohexadienone components are used, the formation of mixtures of isomeric 2//-pyrans may be expected, as shown in Eq. (2)."°... 

The effectiveness of the UV absorbers may not be completely explained in terms of tautomerism. Among other mechanisms that have been proposed are energy transfer, involving an excited triplet state of the polymer (B-79MI11506), and peroxy radical scavenging, involving the formation of stable cyclohexadienones (78MI11502). 

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. 

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