2.4- Cyclohexadienones, spirocyclic

The thermal isomerization of a spirocyclic enol ether to the ketone [202] (Eq. 176) is probably a homolytic process. However, it is noted that part of the driving force for the reaction must be the bonding of the ethereal oxygen to a designated donor atom of the cross-conjugated cyclohexadienone moiety. 

The conformation and dimensions of the substituted spirocyclic chromans (160) have been ascertained. The heterocyclic ring adopts a C-2, C-3 half-chair form, whilst the spiro-annelated cyclohexadienone ring is a C-T envelope (80TL4973, 8lAX(B)1620, 82AX(B)1001>. 

The occurrence of a similar reaction has recently been indicated by studies carried out in this laboratory (7). If p-hydroxybenzyl alcohol (XXXVI) was oxidized with sodium bismuthate, the spirocyclic epoxy-cyclohexadienone (XXXVII) was obtained. The epoxide ring of this compound was hydrolyzed almost instantaneously by 2N aqueous hydrochloric acid and in a few hours by 10% aqueous acetic acid. However, the expected glycol (XXXVIII) could not be isolated since it decomposed immediately into equimolar amounts of hydroquinone and formaldehyde. (Attempts are now being made to prepare compounds analogous to XXXVIII but containing, in addition to the HOCH2 group, a carbon sub-... 

In the l960s, Kropp showed that fused bicyclic dienones structurally related to santonin could potentially serve as synthetically useful precursors to either spirocyclic skeletons or hydroazulenones. One of these cases, 91, was successfully used by Marshall and Johnson as the starting point in an elegant synthesis of the spirocyclic sesquiterpene )6-vetivone (Scheme 23). More recently, a variety of bicyclic cyclohexadienones have been studied by Caine and coworkers. For example, bicyclic dienone 92 could be photochemically rearranged to the oxygenated bicyclo[4.3.0]nonenone system 93, along with other rearrangement products, via acetic acid solvolysis of the cyclopropyl ketone intermediate. ... 

Interestingly, the same cychzation with a 4-hydroxyphenyl substituent as in 89 proceeds to an entirely different product 90. In this case, the authors employed Selectfluor 91 as oxidant for paUadium(IV) generation. Nucleophihc attack of the arene at the palladium(IV) center leads to reductive C-C bond formation, providing spirocyclic cyclohexadienones. The latter product was considered as a potential precursor to the synthesis of the platenmysin core. 

Arene oxidation leading to direct C—C bond formation allows rapid assembly of complex and ste-reochemically rich carbocyclic ring systems. Crucial to the success of this approach is the identification of carbon nucleophiles that are stable in the presence of oxidation agents typically used to effect arene dearomatization. Enolates and enol ethers are problematic as these species undergo rapid oxidation under mild conditions [62]. Stabilized enolates (such as those derived from activated methylenes) exhibit greater compatibility with oxidation conditions and have been used as nucleophilic participants in intramolecular oxidative dearomatizations initiated by [Fe(CN)g] and PIDA to afford spirocyclic cyclohexadienones [63, 64]. Detailed mechanisms for these reactions have not been defined so it is unclear whether bond formation occurs through ionic or radical intermediates. 

A more recent report includes the biomimetic total syntheses of potent antiviral spirooliganones A and B utilizing the phenol oxidative dearomatization/ spirocyclization to buUd the spiro-fused cyclohexadienone/tetrahydrofuran moiety... 

The last example that deserves to be highlighted in this section on spirocyclization is the DIB-induced domino reaction described by Fujioka, Kita, and co-workers [99] (Fig. 38), who utilized phenolic cyclobutanols of type 151 in aqueous HFIP with the aim of producing spiroketonic cyclohexadienones of type 153 through a 1,2-cycloalkyl shift analogous to the DIB-mediated Wagner-... 

Spiro compounds s. a. Di-(spiroazonia)compounds, Metalcarbonyl-phosphorus complex compounds, spiro-cyclic Trispirobis-2,5-cyclohexadienones fcfra-jHcf-Spirocyclics s. Tetrathiospirocyclics 4,5 -Spiro-d diisoxazolines, ring opening, preferential 21, 981... 

Finally, the method was applied to the cycloisomerization of an 1,6-enyne with a cyclohexadienone scaffold which is shown in Fig. 10.25, which produced the corresponding spirocyclic structure in excellent enantiomeric excess. This strategy ensured a suitable enantioselective access to the polycyclic moiety of... 

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