Dearomatized species intermediates

Transition metals continue to be enticing reagents for the dearomatization of aromatic molecules [1]. Not only do they allow transformations to be performed on the dearomatized species at (sub)ambient temperatures, but they also serve to stabilize the reaction intermediates. This latter facet allows a much broader range of manipulations than those accessible through the typical electrophilic/nucleophilic aromatic substitution pathways. 

As mentioned in the introduction, one of the major advantages of using transition metals for dearomatization is that they allow the isolation of reaction intermediates and, consequently, broaden the range of accessible manipulations. For example, when the naphthalene complex of [Os] (3) is treated with dimethoxymethane in the presence of HOTf, the resulting 3-lH-naphthalenium species 23 can be isolated in 88 % yield and stored for days at room temperature (Table 5). The electrophile adds anti to the face involved in metal coordination and pushes the proton at Cl toward the metal, which prevents spontaneous rear-omatization. As shown in Table 5, 23 reacts with MMTP, the conjugate base of dimethyl malonate, 2-trimethylsiloxypropene, tetrabutylammonium cyanoborohydride (TBAC), dime-... 

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. 

All the latter reactions lack practical utility. This is definitely not the case with the wealth of cyclization reactions that have emerged in the past decade. These enable the controlled dearomatization of benzenes and naphthalenes, which up to now have been the domain of Birch reductions. The new objective is to generate, mostly by metalation of an allylic or benzylic site, an organometallic species that is connected to an arene part by a carboxamide or sulfonamide type tether. Intramolecular attack on the arene ring followed by quenching of the enolate-like intermediate (e.g., 187 and 188) provides an annulated heterocycle for ftirther elaboration (Scheme 1-133). 

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