Dearomatization, oxidative

1 Oxidative Dearomatization with Formation of Carbon-Heteroatom Bonds 

Intramolecular [4+2] cycloaddition can also be initiated via incorporation of a dienophile into the nucleophilic participant in an oxidative dearomatization sequence (e.g., an ally lie alcohol) [45]. Additionally, dienophilic alcohol moieties can be tethered to phenol substrates 

SCHEME 15.18 Tandem oxidative dearomadzation-intramolecijlar 4+2 cycloaddition. 

SCHEME 15.19 Desymmetrization of a p-quinol obtained from oxidative dearomatization. 

SCHEME 15.20 Substrate-controlled diastereoselective oxidative dearomatization. 

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Mejorado, L. H. Pettus, T. R. R. Total synthesis of (+ )-rishirilide B development and application of general processes for enantioselective oxidative dearomatization of resorcinol derivatives. J. Am. Chem. Soc. 2006, 128, 15625-15631. 

En route to the total synthesis oftashironin (7-114a) and the debenzoylated compound 7-114b, which shows an interesting promotion of neurite growth, Danishefsky and coworkers have developed a domino oxidative dearomatization/trans-annular Diels-Alder reaction [54]. In this line, treatment of 7-115 with phenyl-iodine(III) diacetate (PIDA) led to an intermediate 7-116, which immediately underwent a transannular Diels-Alder reaction to furnish the complex cycloadducts 7-117 in good yields (Scheme 7.31). 

Scheme 7.31. Domino oxidative dearomatization/transannular-Diels-Alder reaction.

The copper-mediated stoichiometric enantioselective oxidative dearomatization of pyronoquinone (Eq. 18) was achieved with a Cu species and (-)-sparteine as the chiral auxiliary ligand [235]. 

Oxidation of a phenol to an acetoxy enone The key step in a recent synthesis of anthracyclinones is the oxidative dearomatization of the A ring of 1 to the enone 2 in 50-55% yield. The product was converted in several steps into the aglycone SM-173B (3). 

Efficient routes to epoxysorbicillinol (26) and bisorbicillinol (27) were developed by Pettus and co-workers [ 103]. The key step is the hypervalent iodine(III)-induced oxidative dearomatization to produce a stable and highly malleable p-quinol intermediate (146) (Scheme 17). 

Scyphostatin (20) was isolated in 1997 as a potent inhibitor of neutral sphingomyerinase (N-SMase) [41, 42]. Synthetic studies on this therapeutically important molecule are currently in progress (Section 15.3.3) [43, 44]. Its structure features an epoxycyclohexenone moiety, which could conceivably be made through an oxidative dearomatization approach (Figure 7). 

The humulones 23a-d have been known for many years, but they can still be considered as a topical family of natural products (Figure 8). Found in hop resins and brewing hops, these natural ortho-quinols aroused early interest because of their antibiotic and tuberculostatic properties. Oxidative dearomatizing hydroxylation of their phenolic parents 24a-d was used in their synthesis [1]. 

New data on the chemistry of 4,5-dihydroisoxazole 2-oxides were reported. Oxidative dearomatization of phenol 51 with bis(trifluoroacetoxyiodo)benzene (PIFA) afforded spironitronate 52 in 74% yield. Lastly, spiroisoxazoline 53 was obtained in quantitative yield by reduction of 52 with refluxing trimethylphosphite <07OL3229>. 

An intramolecular Michael reaction (catalyzed by 2C) following the oxidative dearomatization of 4-substituted phenols provides valuable octalones. A method involving two consecutive Michael reactions to form optically active polysubstituted cyclopentanes should be highly rated. 

Oxidative dearomatization. The modification of a naphthol by oxidative lactonization is critical toward a synthesis of lactonamycin. Lead(IV) acetate fulfills this need. ... 

In principle, cyclohexadienones can be accessed through tautomerization of the corresponding phenol. However, the loss of aromatic stabilization makes this impractical in all but the most specialized of cases. In order to access an isolable cyclohexadienone, the aromaticity of the phenol must be destroyed. One way to do this is through C-alkylation, but this is mostly limited to intramolecular electrophiles. Oxidative dearomatization of the phenol is by far the most conunon method used to prepare both 2,4- and 2,5-cyclohexadienones. A variety of oxidants can be used for this transforma-tiOTi, but iodine(III)- and iodine(V)-based oxidants" have emerged as the reagents of choice in many cases. An attractive feature of these oxidants, especially those based on iodine(III), is that they can be used with a variety of different nucleophiles, thereby providing access to cyclohexadienones with different substitutents. 

What follows is a description of the trials and tribulations we experienced during our development of a short synthetic route to sorbicillactone a target that Porco has described as a deceptively simple molecule. To be clear, this work led to the synthesis of racemic material. Our group does have a strong interest in developing aryl iodide catalysts for asymmetric oxidative dearomatization reactions, and we have made some progress in this area. However, this has proved to be a very challenging area of research and still requires a fair amount of development. ... 

There were hints in the literature that certain silylated phenols were more efficient substrates than free phenols in hypervalent iodine-mediated oxidative dearomatization reactions." The mechanistic underpinnings for this observation are still murky. Nevertheless, when phenol 40 was first converted into the corresponding trimethylsilyl ether and then treated with PhI(OAc)2 in acetonitrile-water, the desired quinol (42) was formed with improved yields (77-95%) and on larger scale (>1 g) (Scheme 16B). The conditions used to... 

The Realization of an Oxidative Dearomatization-Intramolecular Diels-Alder Route to Vinigrol... 

We thus postulated that the Adler-Becker oxidation could be used for this purpose (Figure 2). This approach would also benefit from the use of common intermediates previously synthesized during our Wessely oxidation campaign. Our new retrosynthetic route is outlined in Scheme 6 and apart from the key oxidative dearomatization step, it is identical to the previous one (Scheme 2). We envisioned that the more substituted site of the resulting epoxide could be selectively reduced after cycloaddition to reveal the desired C4-secondary alcohol found in vinigrol with correct stereochemistry. We were surprised to learn from the Adler-Becker oxidation literature that there were only a handful of examples employing secondary benzylic alcohols, and none of them were part of systematic studies in fact, the vast majority of published examples used only methylene alcohol derivatives as substrates. 

Oxidative Dearomatization-intramolecular Diels-Alder Chapter [ 11 347... 

With the exciting validation of our expedient strategy to form the tetracyclic cage structure using the oxidative dearomatization/Diels-Alder approach followed by consecutive cyclizations, we were now in position to modify each component to best serve the needs to realize a successful total synthesis of vinigrol. 

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