Phenols dearomatization

A trispirobisdienone has been obtained by double intramolecular C-alkylation with phenol-dearomatization . 

In 2(X)9 Quideau et al. [183] reported a hydroxylative phenol dearomatization through in situ generation of iodanes from chiral iodoarenes as organocatalysts and w-CPBA as a co-oxidant (Scheme 12.35). The enantioselectivities were low and 1.0 to 2.0 equiv. of the chiral iodoarene were needed to obtain 122 in good yield. Using an excess of m-CPBA, the authors obtained 123 through a regio- and diastereose-lective epoxidation. 

Phenol Dearomatization A Powerful Strategy in Organic Synthesis... 

This review is devoted to an overview of phenol dearomatization and its application in natural product synthesis through the use of a special class of phenolophile reagents that has attracted much attention in recent years, the hypervalent iodine reagents. These polyvalent iodine compounds, also called iodanes, are oxidizing electrophiles that can mediate a wide number of diverse chemical transformations not only of (hetero)aromatic compounds, but also of inter alia alkenes, alkynes, alcohols, sulfides, amines and amides, (enolizable) carbonyl... 

Phenol Dearomatization with Hypervalent Iodine Reagents... 

Fig. 2 Examples of possible mechanistic options for phenol dearomatization using organo-X -iodane reagents...

Fig. 13 DIB-mediated methoxylative phenol dearomatization/Diels-Alder cyclodimeiization cascade reaction of 5-fluoro-2-methoxyphenol, followed by substitution of the vinylic fluorine atom by conjugate addition/elimination reactions with amines...

Fig. 17) [57]. The use of this outstanding DIB-mediated phenol dearomatization/ Pd-catalyzed domino reaction sequence was then also further extended to build polycyclic benzofurans [57]. Fan had also earlier described a related method using the same initial DIB-mediated phenol dearomatization tactic in the presence of indole nucleophiles and an Ag(I) catalyst to prepare 4-indolylbenzofurans from 4-aUcyl-2-aIk ynylphenols [58]. 

Fig. 23 Birman s and Quideau s as5Tnmetric hydroxylative phenol dearomatization/Diels-Alder cyclodimerization cascade reaction...

Another interesting case of carbo-spirocyclization of phenolic substrates is that reported by Chabaud and GuUlou on the conversion of para-hydroxy acetanilides of type 133 into 1,2-aza/carbo-dispirodienones 134, using BTI in TFE at 0°C (Fig. 34) [92]. This is the first example of a synthesis of 1,2-dispirodienones via a X -iodane-mediated phenol dearomatization. 

Organoiodane-Mediated Phenol Dearomatization in Natural Product Synthesis... 

Another recent and outstanding achievement of Canesi s group is their version of a synthesis of rac-isostrychnine in only nine steps starting from the readily available phenol 166, which was first converted into the phenohc amide 167 (Fig. 42) [106]. This compound was subjected to a DIB-mediated methoxylative phenol dearomatization to afford the para-quinol ether 168, the amide function of which was then engaged in an intramolecular aza-Michael addition (Mito its cyclohexa-2,5-dienone moiety to forge the fused bicyclic system 169 en route to isostrychnine, which was obtained after six additional steps (Fig. 42) [106]. Canesi s group also reported several elegant applications of the phenol dearomatization-induced processes of their own invention in natural product synthesis, such as in... 

In 2014, two first enantioselective syntheses of (-)-maoecrystal V were reported by Zakarian and by Thomson, and were published back-to-back in the Journal of the American Chemical Society [124, 125]. Both syntheses include a key step involving an organoiodane-mediated phenol dearomatization. Zakarian adapted his intramolecular Diels-Alder (IMDA) method for the construction of the... 

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]. 

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