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-萘硼酸以及邻菲罗林硼酸进行交叉偶联反应，得到相应的邻萘基苯甲醛。通过Corey-Fuchs烯丙基化反应，随后与n-丁基锂反应，制备出多种1-(2-乙炔基苯基)萘化合物。在苯甲基苯中，利用催化量的氯化铂，将单个1-(2-乙炔基苯基)萘化合物环异构化为多种苯并[c]菲喃（BcPh）类似物。对于4,5-二氢苯并[l]醋基菲喃，通过DDQ氧化得到苯并[l]醋基菲喃。在BBr3的作用下，二甲氧基取代的苯并[c]菲喃进行脱甲基化，随后用PDC氧化生成邻醌。这些醌在四氢呋喃/乙醇溶液中通入氧气，经NaBH4还原得到相应的二醇二氢化合物。将二醇二氢化合物暴露于四氢呋喃-水溶液中的N-溴乙酰胺，得到溴醇，随后通过Amberlite IRA 400 HO-进行环化，得到系列1的二醇环氧化合物。使用mCPBA对二醇二氢化合物进行环氧化，得到系列2的二醇环氧化合物。所有烃类以及甲氧基取代的烃类均通过X射线晶体学进行结晶和分析，并将这些数据与之前研究过的BcPh衍生物进行比较。所描述的方法具有高度的模块化，可用于合成多种角状融合的多环芳烃及其潜在代谢物和/或其他衍生物。