Dynamic Equilibria in the Products of Intramolecular Buchner Additions of Diazoketones to Aryl Rings Bearing Methoxy Substituents

Abstract

Rhodium carboxylate catalyzed aromatic addition reactions of a range of diazoketones bearing methoxy-substituted aryl rings have been explored. While the existence of norcaradiene-cycloheptatriene equilibria in related compounds is well established, the aromatic addition products in this study display more complex dynamic equilibria due to conjugation with the methoxy group; the experimental evidence for this is discussed in detail. In the azulenone products 21-26 derived from p-methoxy-substituted diazoketones 14-16, the diastereomers interconvert via a spiro intermediate 39. A related mechanistic process in the azulenones 43-46 derived from the o-methoxy-substituted diazoketones 17, 18 interconverts regioisomers, explaining the conflicting reports for the regioselectivity of the cyclization of diazoketone 1. With the m-methoxy-substituted diazoketone 19, involvement of the methoxy group through a different pathway results in fragmentation of the azulenone to form the tetralone 47. With the azulenones 21-26 exclusive trapping of the norcaradiene associated with the less thermodynamically stable diastereomers in a cycloadduct with N-phenylmaleimide is observed. Due to the presence of the activating methoxy substituent on the aromatic ring, the aromatic addition reactions of the diazoketones studied were not very sensitive to the nature of the rhodium catalyst.

Efficient construction of novel carbocyclic frameworks via intramolecular aromatic addition of diazoketones followed by Diels-Alder cycloaddition

“…The syntheses of the methoxy-substituted diazoketones 8 -10 and azulenones 14-16 were described previously by our group. 6 Formation of the trans isomer only was observed by 1 H NMR in the rhodium(II) acetate catalysed cyclisation of the 4-methyl-substituted diazoketone 7 (i.e. diastereoselectivity was typically >98:2 trans:cis) which was in agreement with our previously published results on the diastereoselectivity of related aromatic addition reactions to unsubstituted phenyl rings.…”

“…The 2'-methoxy-substituted aryl diazoketones 33 and 34 were prepared and cyclised using rhodium acetate or perfluorobutyrate to give a mixture of azulenones bearing the methoxy substituent at the 4 and 8 positions respectively with the kinetic product being the 4-substituted azulenones 35 and 36. 6 Following the mechanistic rationale developed earlier, the isopropyl-substituted azulenone 36 was formed stereoselectively with only the trans isomer of the 4-methoxy azulenone and accordingly only the cis isomer of the 8-methoxy azulenone detected. Diels-Alder cycloadditions of azulenone 35 unsubstituted at the 3-position proceeded efficiently, resulting in a single cycloadduct in each case derived from reaction of the NCD of the 4-methoxy azulenone (Table 2).…”

“…However, it quickly became apparent that the presence of the 6-methoxy substituent leads to more complex dynamic behaviour in the azulenones 14-16 with interconversion between the cis and trans diastereomers of the azulenones 15 and 16 observed (Scheme 5). 6 Indeed, the cycloadduct formation discussed below proved key to understanding the dynamic properties of these complex azulenones.…”

“…6 Thus in addition to the NCD-CHT interconversion the presence of the 6-methoxy substituent enables interconversion of the trans and cis diastereomers through a spiro intermediate. Though this particular equilibrium process was novel there is a precedent for the involvement of a methoxy substituent in the cleavage of norcaradiene in reactions described by Mander.…”

“…We have reported the details of this X-ray crystal structure previously. 6,9 (b) One pot preparation of adduct 29 from N-phenylmaleimide and 2-diazo-5-(4'-methoxyphenyl)hexan-3-one 9. This was prepared following the procedure described for 18, from 2-diazo-5-(4'-methoxyphenyl)hexan-3-one 9 (150 mg, 6.47 x 10 -4 mol) in dichloromethane (100 mL) and rhodium acetate (0.5 mg) in dichloromethane (100 mL) to give the crude azulenone 15.…”