P-Quinone monoketals

From the viewpoint of organic synthesis, nature provides us with a number of target molecules, which have novel structures and a variety of biological activities. As already shown in Section II.A, electrochemical oxidation of phenols has been applied successfully to natural products synthesis. Hypervalent (diacyloxyiodo)benzenes have also been proved to be effective for natural products synthesis. Generally, oxidation of o- and p-methoxyphenols in MeOH provides the corresponding o- and p-quinone monoketals, respectively. They are utilized as promising synthons for natural products and related bioactive compounds, as demonstrated by Swenton . Recently, these quinone monoketals have been utilized for syntheses of terpenoids, neolignans, anthraquinones, alkaloids and related compounds. 

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... 

Quinone imine ketals have also been recognized to be quite useful for heterocycle synthesis. In a series of quinone mono- and bis-ketal chemistry, Swenton and coworkers carried out anodic oxidation of trifluoroacetamido-substituted p-methoxyphenols . For example, the readily available p-methoxyphenol derivative 88 underwent constant current electrolysis (60 mA) in 2% LiC104 in methanol, followed by hydrolysis with 5% aqueous KOH to afford quinone imine ketal 89 in 82% overall yield, through quinone monoketal 90 (Scheme 17). Furthermore, acid treatment of 89 with TsOH provided 5-methoxyindole (91). 

Treatment of a 2,5-disubstituted 1,4-dimethoxybenzene 877 with CAN provided a 97% yield of p-benzoquinone 878 °. The fully substituted 1,4-dimethoxybenzene derivative 879 was treated with CAN to afford in 64% yield the quinone monoketal 880. This was submitted to catalytic hydrogenation to give the precursor of a-tocopherol 881 (Scheme 178). A variety of substituted 1,4-dimethoxybenzenes were also oxidized with CAN to give high yields of p-benzoquinones. 

A similar oxidation of p-alkoxyphenols or 4-methoxynaphthols with (diacetoxyiodo)benzene in the presence of alcohols affords the respective quinone monoketals (Scheme 3.94) [277, 295, 296],... 

Likewise, the oxidative dearomatization ofpara-methoxy substituted N-protected anilines 288 using (diace-toxyiodo)benzene in the presence of methanol gives p-quinone monoimide ketals 289 (Scheme 3.120) [358]. If the oxidation of aniline derivatives is performed in the presence of water, the final isolated products are the respective / -benzoquinones or p-benzoquinone monoketals resulting from the hydrolysis of initially formed monoimide ketals 289 [358,359]. 

As described earlier, quinone monoketals (e.g., 139) are not only good substrates for the DPM reaction, but they also participate in acid-catalyzed [5+2]cycloaddition reactions with styrene derivatives (e.g., p-methylstyrene) to givebicyclo[3.2.1]octenediones (e.g., 140) that can themselves participate in ODPM processes to give multiftinctional, donor-acceptor cyclopropanes (e.g., 141). The last type of conpound can participate in fiirther reactions generating several additional and novel scaffolds that may be useful in drug discovery settings. Meanwhile, iminium ethers that are readily derived from [5+2] cycloadducts of type 140 participate in ADPM rearrangements. 

In 2012, Fukuyama s group reported a novel synthesis route to the spiro-p-lactonic sesquiterpene (-)-anisatin, and they also relied on the construction of a bicyclo[2.2.2]octane system via a DIB-mediated methoxylative phenol dearomatization followed by an intramolecular Diels-Alder reaction [127]. The homochiral phenolic dihydrobenzofuran propargyl ether 231 thus afforded, via the ort/io-quinone monoketal 232 and treatment of its intramolecular [4+2] epimeric cycloadducts with camphorsulfonic acid in MeOH, the bicyclo[2.2.2] octanedienone 234 as a single diastereomer (Fig. 56). Further transformation of 234 gave the vinyl 235, whose trisubstituted double btmd bridge was oxidatively cleaved by mild ozonolysis to furnish the ketoaldehyde 236, en route to (-)-anisatin [127]. 

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). 

Churcher, I., Hallett, D. and Magnus, P. (1998) Synthesis of the antitumor agent aglycon ( )-calicheamicinone using an o-quinone monoketal strategy. Journal of the American Chemical Society, 120(40), 10350-10358. 

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