Wessely reaction

Scheme 28. Lead(IV)-mediated oxidation (Wessely reaction) of a simple gallic acid derivative without biaryl formation.

Scheme 3)10. Indeed, independent photolysis of 2,4-cyclohexadien-l-ones 12 and 13 afforded the macrolides 15. These reactions likely proceed via a common intermediate, in this case dienylketene 14, which is trapped intramolecularly by the pendant hydroxyl group. Adjustment of the oxidation level and functional group interconversion then led efficiently to the desired macrolide 17. The sulfonyl group was used for two reasons first, to easily transform lactones 15 into dienyl lactones 16 needed for 17, and secondly, to control the regiochemistry of the Wessely oxidation of phenolic precursor needed to produce the photolysis substrates 12 and 13. 

The reaction of NCA s with amines was reported by Fuchs (10) in 1922 and by Wessely (11) in 1925. From the resulting mixture they isolated amides formed by the interaction such as... 

The early work of Wessely suggested the occurrence of some side reactions which led to the formation of diketopiperazines (77) or hydan-toins (27). These reactions may put an upper limit to the degree of polymerisation which may be obtained in poly-additions of NCA s but it is more probable that these products arise from an unsuccessful initiation (see p. 40) rather than from a termination. Their participation in the process decreases the yield of C02 evolved in the polymerisation. 

Oxidative nucleophilic substitution is, however, a more versatile technique and a much better choice for target-oriented synthesis (Sections 15.1.1 and 15.1.2.2). In 1950, Wessely and co-workers examined the use of lead tetraacetate (LTA) in acetic acid to determine the structure of phenols and, in doing so, they developed their oxidative acetoxylation reaction, referred to herein as Wessely oxidation (Figure 13) [68-76]. If both an ortho- and a para-position are available to accommodate the entry of the acetoxy nucleophile, ortho products often predominate even when the ortho position is already occupied by a resident alkyl (e.g. 40 —> 41a/b) or allcoxy group (Figure 13) [69, 74]. 

The convenient generation of bicyclo[2.2.2]octenones through the use of ortho-quinol derivatives in Diels-Alder reactions recently inspired Wood and co-workers in their studies toward the total synthesis of CP-263,114 (110) [148]. They relied on the Wessely-Yates tandem oxidative acetoxylation/intramolecular Diels-Alder sequence to build bicyclo[2.2.2]octenones such as 114 en route to advanced isotwistane intermediates such as 111b, which could eventually be fragmented to furnish the carbocyclic core of 110 (i.e. 111a —> 110, Figure 29) [149-153],... 

The last example of this section serves to demonstrate that the oxidative conversion of arenols into ortho-quinol derivatives is not only a useful tactic to activate the aromatic nucleus toward further structural elaboration, but that it can also constitute the key reaction enabling the formation of strategic bonds. Cox and Danishefsky provided us with a glowing illustration of such synthetic applications in their recent report on the synthesis of lactona-mycin (161) [179]. A tetracyclic model 164 of this natural antibiotic was constructed by a Wessely oxidation applied in an intramolecular fashion to the phenolic acid 162 (Figure 41). 

The rearrangements of phenols which are accompanied by hydroxy group transpositions are called the Wessely-Moser reaction (equations 50 and 51). In essence, these rearrangements are recyclizations of flavonoides 114 via the ring-opened form 115 to give the novel structures 116. Compounds that can participate in these rearrangements are flavones (114, R = H, R = Aryl), flavonoles (114, R = OH, R = Aryl), isoflavones (114, R = Aryl, R = H), chromones (114, R = H, R = Alkyl), chromonoles (114, R = OH, R = Alkyl), xanthones (114, R R = benzo) as well as benzopyrylium salts (e.g. see Reference 95). 

When the reactions of phenols with aryllead triacetates were performed in the presence of pyridine, only the C-arylated dienones were formed in a nearly quantitative yield (90% ratio ortho para = 4 1). Under the classical conditions (phenol organolead triacetate base in a ratio 1 1 3), the reaction of methylated phenols only proceeds in high yield when both ortho positions are substituted. There is a preference for attack ipso to a methoxyl group compared to a methyl group. As in the Wessely acetoxylation, there is a marked preference for orr/io-arylation. 

The reaction is general for ortAo-substituted phenols and for a, -unsaturatcd acids, but yields are somewhat low (ca. 207 ) in the case of cresol. One useful result of this route is that the bicyclo[2.2.2]octenones are regioisomers of the adducts formed by intermolecular Diels-Alder reactions of the 2,4-dienones obtained by usual Wessely oxidation. ... 

Our initial approach centered on the use of a strategic Wessely oxidation reaction to transform an appropriately decorated resorcinol precursor into a tricyclic cage architecture formed by an in situ intramolecular Diels-Alder cycloaddition reaction (Scheme 1). From there we envisioned a 6-exo-type cyclization to form the tetracyclic core, which in the best case scenario would also set the C9-methyl stereocenter. Manipulation of the functional groups on the tetracyclic core would then be followed by a late-stage C—C bond fragmentation reaction to access the vinigrol core. Conversion of the exocyclic methyl ketone group was expected to afford the desired isopropyl moiety. 

Our first specific Wessely oxidation approach is outlined in Scheme 2. Following an aldol-type reaction between an appropriately protected resorcinol fragment and an aldehyde, we expected the Wessely oxidation to selectively dearomatize at the ortho position of both phenols. The intramolecular Diels-Alder cycloaddition reaction was then expected to form the tricyclic core, which could then be converted to the critical tetracyclic cage via a samarium diiodide(II)-type 6-exo-trig ketyl radical cyclization reaction. 

Wessely-Moser rearrangement refers to the rearrangement of benzopyran-4-ones possessing a 5-hydroxyl group, such as the demethylation product of 5,7,8-methoxyflavone 1, to yield scutellarein 2, its isomeric product. Acidic conditions are most commonly used for such transformation however, several examples of base-catalyzed reactions have also been reported. The reversibility of the rearrangement largely depends on the substituent pattern of the benzopyranone. 

Fritz Wessely and Georg H. Moser published their work on the synthesis and stmctural elucidation of scutellarein 2 in 1930 one of the key steps was the titled reaction featuring the unprecedented rearrangement from 1 to 2. This unique isomerization method soon found application in the structural elucidation of flavanoids and fruther by extension to chromones, xanthones, and their derivatives. In addition, Wessely-Moser rearrangement has been used as a surrogate of direct synthesis toward 5,6,7-substituted flavones." ... 

Fig. 1.15 Tandem Wessely oxidative dearomatization/DVIDA reaction (Reprinted with the...

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