Quinols quinones, synthesis

It has been reported that vitamin Kj and several of the vitamin K2 homologues are capable of restoring electron transport in solvent-extracted or irradiated bacterial and mitochondrial preparations. Other reports suggest that vitamin K is concerned with the phosphorylation reactions accompanying oxidative phosphorylation The capacity of these compounds to exist m several forms, e.g., quinone, quinol. chromanol, etc., appears to strengthen the proposal that links them to oxidative phosphorylation. Information has suggested that vitamin K acts to induce prothrombin synthesis. Since prothrombin has been shown to be synthesized only by liver parenchymal cells m the dog, it would appear that the proposed role for vitamin K is not specific for only prothrombin synthesis, but applicable to other proteins. 

Under different reaction conditions, phenols can be oxidized to p-quinones (equations 272600-602 and 273603), but in the case of phenol itself, insufficient selectivity has prevented, as yet, the commercial application of this potentially important synthesis of p-benzoquinone and hydroquin-one. The selectivity of p-benzoquinone, or p-quinol formation can be increased at the expense of oxidative coupling products by using a large excess of the copper reagent [Cu4Cl402(MeCN)3 or CuCl + 02 in MeCN] with respect to the phenolic substrate.604 The suggested mechanism involves the oxidation of the phenoxide radical (189) by a copper(II)-hydroxo species to p-quinol (190) which can rearrange (for R2 = H) to hydroquinone (191 Scheme 14), which is readily oxidizable to p-quinone.6... 

Oxidative Conversion of Arenols into ortfio-Quinols and ortfio-Quinone Monoketals - A Useful Tactic in Organic Synthesis... 

The oxidative activation of arenes is a powerful and versatile synthetic tactic that enables dearomatization to give useful synthons. Central to this chemistry are hydroxylated arenes or arenols, the phenolic functions of which can be exploited to facilitate the dearomatizing process by two-electron oxidation. Suitably substituted arenols can hence be converted, with the help of oxygen- or carbon-based nucleophiles, into ortho-quinone monoketals and ortho-quinols. These 6-oxocyclohexa-2,4-dienones are ideally functionalized for the construction of many complex and polyoxygenated natural product architectures. Today, the inherent and multiple reactivity of arenol-derived ortho-quinone monoketals and ortho-quinols species is finding numerous and, in many cases, biomimetic applications in modern organic synthesis. 

The ability of the cydohexa-2,4-dienone unit of ortbo-quinone monoketals and other ortho-quinol derivatives to react as either a diene or a dienophile component in [An+2n cydoadditions is arguably their prindpal virtue in organic synthesis, and paradoxically it is also the prindpal reason why it is often difficult to exploit them in synthesis they often dimerize faster than they can combine with another -system partner. Adler, Andersson, and coworkers have extensively studied the behavior of ortbo-quinols in Diels-Alder cydoadditions,... 

Alkylation of quinones with organocadmium reagents allows the synthesis of quinol derivatives, without any formation of hydroquinones or bis-addition products (Equation (178)).315 The regiochemistry of the addition is strongly... 

Indium mediates the Reformatsky reaction of y>-quinones to give good yields of />-quinols under mild conditions. Naturally occurring quinol esters such as jacaranone are conveniently prepared in a one-pot synthesis (Scheme 90).326... 

Glycal-substituted quinols and quinol ketals, derived from the 1,2-addition of lithiated glycals to quinones or quinone monoketals, are versatile intermediates for the synthesis of aryl C-glycosides, providing access to all four substitution patterns found in the natural products. For example, reduction of a quinol provides a p-hydroxyaryl glycal (8 9,11 -> 12). On... 

Hydro-quinol may be synthesized by any of the general methods. Of special interest is its synthesis by the electrolytic oxidation of benzene. It crystallizes in colorless prisms, m.p. 170°. With ferric chloride it gives no color reaction, but is oxidized to quinone, the same oxidation occurring in the air in alkaline solutions. It reduces Fehling s solution and its important use is as a reducing agent in photography. 

The photochemical addition of ethene at 0°C in methylene chloride to the enedione (77) affords a high yield of the adduct (78). This was converted to the monochloro derivative (79) which also undergoes photoaddition of ethene to yield the Z> adduct (80). This on elimination of HCl yielded the quinol (81) which can be oxidised to the quinone (82). Cycloaddition of alkenes (cyclopentene, cyclohexene, and cycloheptene) has been carried out to the same enedione (77) to yield the adducts (83). lyoda et al. have also described a convenient synthesis of the bicyclo-octanediones(84) by a photochemical addition of alkenes to the enedione (77). The adducts (84) can be reduced by zinc in acetic acid to the desired products. Cycloaddition of ethyne to the same enedione followed by reduction affords the bicyclooctanes (85). The photoaddition of alkenes to the dibromo-enedione (86) is also effective and yields, after reduction, the adducts (87). 

Dihydrophenanthrene synthesis. Evans et al. have reported a new route to dihydrophenanthrene derivatives based on the condensation of p-quinone mono-ketals (1) or monosilyl cyanohydrin derivatives (5, 721-722) with the enolate of methyl 3-(3,4,5-trimethoxyphenyl)propionate (2) to give p-quinol ketals (3). These undergo acid-catalyzed cyclization to dihydrophenanthrene derivatives (4). A typical example is formulated in equation (I). The choice of the Lewis acid catalyst is sometimes critical for the cyclization. In the case of the cyclization shown above, use of SnCL, CF3COOH and BF3 etherate resulted in much lower... 

Isoprenylation of quinones. Evans and Hoffmann have developed a useful route to prenylated quinones, which are natural products involved in various biological processes. The process is illustrated in equation (I) for the synthesis of 2-isopentenylhydroquinone (3). Reaction of the protected quinone (1) with the allylic bromide in the presence of Rieke magnesium (5, 419) affords the epimeric quinols (2). On deprotection the initial product (a) undergoes a facile rearrangement, probably a Cope rearrangement, to (3) in high yield. 

The Lewis acid-catalysed orientation reversal in the reaction between substituted cyclohexa-1,3-dienes and 2,6-dimethyl-l,4-benzoquinone ° has been employed in an interesting synthesis of quassin (218). ° Thus, reaction at room temperature of the diene (215) with the above quinone in the presence of an equivalent quantity of Bp3,OEt2 gave the adduct (216) which was converted by several subsequent steps into (218). In the absence of the catalyst the alternative adduct (217) was obtained. Periodic acid oxidation of substituted o-cresols ° and of 2-methoxyphenols in methanol solution affords intermediate o-quinol methyl ethers or o-quinone dimethyl ketals which dimerize to give dienediones with structures related to those of (216) and (217). Another report concerns the formation of a Diels-Alder dimer upon hypochlorite oxidation of 2,2 -methylenebis(4-methyl-6-t-butyl)phenol. ... 

C deau S (2002) Oxidative ctmvCTsirai of arenols into ortAo-quinols and o/tAo-quinone mmioketals - ausefiil tactic in organic synthesis. In Astruc D (ed) Modem arene chemistry. Wiley-VCH, Weinheim, pp 539—573... 

Monoacyl hydroquinone derivatives are, however, deacylated when treated with oxidizing agents (Ce, Tl, N-bromo-succinimide and bromine) [133, 134]. Thus the quinone (79) is prepared in high yield from the monoacetyl derivative (78) with AT-bromosuccinimide [135]. This method of deacylation is useful in the synthesis of quinones and the corresponding quinols. 

The reaction mechanism of PQ synthesis equals that of aT synthesis. The synthesis also occurs exclusively at the inner chloroplast envelope membrane /8/ (Fig. 4), however, it can be assumed that either prenylquinone is formed by its own enzyme garniture. 2-Methyl-6-nonaprenyl-(solanosyl-)qulnol is formed from homogentlsate plus nonaprenyl-(solanosyl-)PP. The quinol formed is then methylated by SAM to yield PQH /6/ (Fig. 4). Even if the sequence in PQ synthesis is clarified Homogentlsate — 2-Methyl-6—nonaprenylqulnol —PQH. no data are available for the synthesis of hydroxylated quinones... 

Another approach to the synthesis of phenanthroid compounds that is of general applicability utilises the condensation of protected p-quinones such as the monoketal (373) with phenethyl carbanions, resulting in the p-quinol (374), which cyclizes to the phenanthrene (375). 

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