Modular, Metal-Catalyzed Cycloisomerization Approach to Angularly Fused Polycyclic Aromatic Hydrocarbons and Their Oxidized Derivatives

Palladium-catalyzed cross-coupling reactions of 2-bromobenzaldehyde and 6-bromo-2,3-dimethoxybenzaldehyde with 4-methyl-1-naphthaleneboronic acid and acenaphthene-5-boronic acid gave corresponding <i>o</i>-naphthyl benzaldehydes. Corey–Fuchs olefination followed by reaction with <i>n</i>-BuLi led to various 1-(2-ethynylphenyl)­naphthalenes. Cycloisomerization of individual 1-(2-ethynylphenyl)­naphthalenes to various benzo­[<i>c</i>]­phenanthrene (B<i>c</i>Ph) analogues was accomplished smoothly with catalytic PtCl₂ in PhMe. In the case of 4,5-dihydrobenzo­[<i>l</i>]­acephenanthrylene, oxidation with DDQ gave benzo­[<i>l</i>]­acephenanthrylene. The dimethoxy-substituted benzo­[<i>c</i>]­phenanthrenes were demethylated with BBr₃ and oxidized to the <i>o</i>-quinones with PDC. Reduction of these quinones with NaBH₄ in THF/EtOH in an oxygen atmosphere gave the respective dihydrodiols. Exposure of the dihydrodiols to <i>N</i>-bromoacetamide in THF-H₂O led to bromohydrins that were cyclized with Amberlite IRA 400 HO^– to yield the series 1 diol epoxides. Epoxidation of the dihydrodiols with <i>m</i>CPBA gave the isomeric series 2 diol epoxides. All of the hydrocarbons as well as the methoxy-substituted ones were crystallized and analyzed by X-ray crystallography, and these data are compared to other previously studied B<i>c</i>Ph derivatives. The methodology described is highly modular and can be utilized for the synthesis of a wide variety of angularly fused polycyclic aromatic hydrocarbons and their putative metabolites and/or other derivatives.