Dearomatization, mechanisms

Fernandez, I. Forcen-Acebal, A. Garcia-Granda, S. Lopez-Ortiz, F. Synthesis of functionalized 1,4-cyclohexadienes through intramolecular anionic dearomatization of N-alkyl-N-benzyldiphenylphosphinamides. Insight into the reaction mechanism. /. Org. Chem. 2003, 68, 4472-4485. 

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. 

Dearomatization of r -benzylpalladium complexes represents an electronically reversed variation on the reactions described earlier. Initial examples utilized allyl and allenyl stan-nanes as nucleophilic components in combination with benzyl halides and invoked mechanisms involving aryl-alkyl Pd(II) intermediates [84]. Subsequently, direct addition of stabilized nucleophiles (e.g., malonate anions) to q -naphthylpalladium complexes has been achieved [85]. 

The mechanism of the dearomatization was studied by NMR and by computational methods. An adduct between the diaUylcalcium moiety and pyridine initially forms, followed by aUyl migration from calcium to the ortho position of two of the coordinated pyridines to afford the product of double 1,2-insertion. Next, the final double 1,4-insertion product is formed by a rate-determining cope rearrangement step. 

The postulated mechanism for the hydrogenation of CO2 using the iiidium-trihydride complex 32 is shown in Fig. 14. Upon reaction with CO2, complex 32 generates the intermediate formate complex 33, which reacts with hydroxide to give the dearomatized amidoiridium dihydride complex 34. Reaction of 34 with H2 regenerates complex 32, closing the catalytic cycle. The dearomatized complex 34 was prepared by the reaction of 32 with CSOH.H2O, which upon reaction with H2 led to the formation of the iridium-trihydride complex 32, supporting the proposed catalytic cycle. 

Aromatic amides like 1 (both benzamides and naphthamides) can be dearomatized to yield bi- and polycyclic amides 2 in a stereoselective cyclization reaction triggered by a benzylic lithiation a to the amide nitrogen to form organolithium intermediate 3. The proposed mechanism of the reaction consists of the intramolecular conjugate addition of the benzylic anionic center in 3 into the electron-deficient ortho position of the aromatic ring (Scheme 28.1). In most cases, the addition of l,3-dimethyltetrahydro-2(l//)-pyrimidinone (DMPU) to the reaction medium is required to promote the cyclization step. Considering the proposed mechanism, the high stereoselectivity observed in the cyclization is truly remarkable. 

The mechanism of the dearomatization-cyclization of aromatic amides takes place by initial lithiation at the ortho position of the aromatic ring. This species is in equilibrium with the more stable a-amide lithiated compound, which forms the final product by means of a 6n electrocyclic ring closure. 

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