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.

钯催化下，2-溴苯甲醛与6-溴-2,3-二甲氧基苯甲醛与4-甲基-1-萘硼酸及蒽-5-硼酸发生交叉偶联反应，生成相应的邻萘基苯甲醛。随后，Corey-Fuchs 烯化反应，并经与n-丁基锂反应，得到多种1-(2-乙炔基苯基)萘化合物。在催化PtCl2和PhMe的条件下，单独的1-(2-乙炔基苯基)萘化合物通过环异构化顺利转化为多种苯并[c]菲（BcPh）类似物。对于4,5-二氢苯并[l]乙撑菲，经DDQ氧化后得到苯并[l]乙撑菲。二甲氧基取代的苯并[c]菲通过BBr3脱甲基，并经PDC氧化至邻醌。这些醌在THF/EtOH和氧气氛围中用NaBH4还原，得到相应的二羟基化合物。将二羟基化合物暴露于THF-H2O中的N-溴乙酰胺，得到溴醇，经Amberlite IRA 400 HO-环化，得到系列1二醇环氧化合物。二羟基化合物用mCPBA环氧化为异构系列2二醇环氧化合物。所有烃类，包括甲氧基取代的烃类，均通过X射线晶体学结晶并分析，并将这些数据与先前研究过的BcPh衍生物进行比较。所述方法高度模块化，可用于合成多种角状融合的多环芳烃及其假定的代谢物和/或其他衍生物。