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 o-naphthyl benzaldehydes. Corey–Fuchs olefination followed
by reaction with n-BuLi led to various 1-(2-ethynylphenyl)­naphthalenes.
Cycloisomerization of individual 1-(2-ethynylphenyl)­naphthalenes to
various benzo­[c]­phenanthrene (BcPh) analogues was accomplished smoothly with catalytic PtCl2 in PhMe. In the case of 4,5-dihydrobenzo­[l]­acephenanthrylene,
oxidation with DDQ gave benzo­[l]­acephenanthrylene.
The dimethoxy-substituted benzo­[c]­phenanthrenes were
demethylated with BBr3 and oxidized to the o-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 N-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 mCPBA
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 BcPh 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.