Quinone ketal

The cis-2,3-diaryl-2,3-dihydro-l,4-benzoxathiin is a very unique structural motif. Other than scattered reports in the literature on the formation of this scaffold, there was no effective asymmetric synthesis for it [6]. We explored two major synthetic approaches to realize the key chiral as-diaryl dihydrobenzoxathiin scaffold, as shown in Scheme 5.3. One was the quinone ketal route in which the quinone ketal 13 and the chiral mercaptol alcohol 14 were the key intermediates. The other approach was the stereo- and enantioselective reduction of the diaryl benzoxathiin 16. The key mercaptol alcohol 14 and the diaryl benzoxathiin 16 were both envisioned to be prepared from the key, common iodoketone intermediate 15. 

The mercaptol alcohol rac-14 undergoes facile Michael addition reaction with quinone ketal 13 which is commercially available or can be readily prepared. 

Oxidation of phenols.1 The reagent oxidizes 1,2- and 1,4-dihydroxyphenols to the quinones in almost quantitative yield at 25° in methanol. 4-Alkylphenols are oxidized to 4-alkyl-4-methoxycyclohexadienones (mixed quinone ketals) in >90% yield. Monohydric phenols can be oxidized to p-quinone diketals on oxidation with 2 equiv. of the reagent in CH,OH at 25°. 

Quinone dyes, 9 503 Quinone ketals, anodic oxidation of hydroquinone ethers to, 21 264 Quinone methides, 2 209-211 Quinone Michael addition chemistry, 21 248-249, 250, 252 Quinone monoacetals, 21 251 Quinone monoimine (QMI), 19 246 Quinone oximes, formation of,... 

Substituted quinone ketals, prepared in this manner, serve nicely in annelation strategies leading to natural products. Two are illustrated, one in Scheme 20 leading to (+)-4-demethoxydaunomycinone (87) and (+)-daunomycinone (88) [46-48], the other in Scheme 21 serving as a pathway to a-citromycinone (94). The first calls for a Michael addition of (84) to quinone ketal (83) followed by capture of the intermediate enolate, and leads to annelated... 

In a clever adaptation of the acid-catalyzed addition of />-quinone ketals to olefins Buchi and Chu condensed 586 with 1,2-dimethylcyclopentene in the presents of stannic chloride and inun ately reduce the two diastereomeric adducts with sodium borohydride The major alcohol 587 was separated, catalytically hydrogenated, and converted to the tetrahydropyranyl derivative 588 (Scheme XLVII). 

Deffieux D, Eabre 1, Courseille C, Quideau S (2002) ElectrochemicaUy induced spiro-lactonization of a-(methoxyphenoxy)alkonoic acids into quinone ketals. J Org Chem 67 4458-4465. 

It was also shown that this aromatic quinone ketal dissociates at room temperature as follows... 

The anodic oxidation of hydroquinone ethers to quinone ketals yields synthetically useful intermediates that can be hydrolyzed to quinones at the desired stage of a sequence. 

A more concise route to ( )-cherylline was also devised and commenced with the reductive animation of isovanillin with methylamine followed by reaction of the intermediate benzylamine with vinyl triphenylphosphonium bromide to provide the aminophosphonium salt 619. Sequential treatment of 619 with n-butyllithium and the quinone ketal 615 followed by reaction of the resulting crude allylic amine 620 with boron trifluoride etherate gave the phenolic amine 618 in good overall yield (225). 

Calculations performed at the HF/3-21G level indicated smaller energy gaps between the HOMOs of the aforementioned electron-rich dienophiles and the LUMOs of the quinone ketals, as can be expected for inverse electron-demand Diels-Alder reactions under FMO control [141]. Regiochemical controls observed with quinone ketals such as 76a were well corroborated by the relative magnitudes of the atomic coefficients of the frontier orbitals. The highest coefficients at C-5 of the quinone ketal LUMO and at C-2 of the electron-rich alkenes would indeed promote bond formation between these centers. The results of calculations on other quinone ketals were, however, rather vague [141]. 

The oxidative coupling of 2,6-disubstituted phenols to poly-(arylene oxides) is a polycondensation reaction, in which polymer molecules couple with other polymer molecules as well as with monomer. Unstable quinone ketals formed by coupling of a polymeric aryloxy radical at the para position of the phenolic ring of a second radical are believed to be intermediates or the reaction. The ketals may be converted to polymeric phenols either by a series of intramolecular rearrangements or by disproportionation to aryloxy radicals, leading to a mobile equilibrium between polymer molecules of varying degree of polymerization. Both processes have been shown to occur, with their relative importance determined by the reaction conditions. 

Quinone Ketal Redistribution. This mechanism suggests that in the coupling of two aryloxy radicals the oxygen atom of one attacks at the para position of the phenolic ring of the second to yield the unstable quinone ketal. This rapidly decomposes either to yield the aryloxy radicals from which it was formed or two different aryloxy radicals, as shown... 

The sequence accounts satisfactorily for the production of polymer from low oligomers and for the shape of the DP-conversion curve in the oxidation of 2,6-xylenol. Formation of quinone ketals similar to III is, furthermore, a known reaction of hindered aryloxy radicals (I, 14). The major objection to this proposal is the great number of steps required to produce a monomer radical from two polymeric radicals of a high degree of polymerization. 

Similar results were obtained by Cooper and by Mijs et ah (24) from a number of other substituted dimers. With lightly substituted dimers, however, Mijs observed that at low temperatures the initial products consist almost entirely of tetramers the tetramer, moreover, is that corresponding to the quinone ketal rearrangement, rather than to head-to-tail coupling (Reaction 20). 

The experiments cited above show that redistribution, presumably via a quinone ketal intermediate, occurs during the oxidative polymerization of 2,6-xylenol and must be responsible at least partially for the polycondensation characteristics of the reaction. Although the conditions under which Mijs and White demonstrated rearrangement are different from those usually employed for oxidative polymerization of xylenol, it appears certain that this process also contributes to the coupling of polymer molecules. Redistribution and rearrangement are complementary reactions. Dissociation into aryloxy radicals can occur at any point... 

Addition of p-quinone ketals to olefins. The ketal 1 reacts with 1,2-dimethyl-cyclopentene in the presence of stannic chloride to afford, after reduction with sodium borohydride, 2 and its diastereomer 3. The major alcohol (2) was used by Biichi and Chu in a total synthesis of the sesquiterpene gymnomitrol (4). Several other syntheses of this substance have recently been reported. ... 

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