Palladium- and Copper-Catalyzed Synthesis of Medium- and Large-Sized Ring-Fused Dihydroazaphenanthrenes and 1,4-Benzodiazepine-2,5-diones. Control of Reaction Pathway by Metal-Switching

Methods for the synthesis of dihydroazaphenanthrene fused to macrocycles I [X = CH2, O, Y = (CH2)m, m = 1,2,4,6, n = 1,2] and medium-ring heterocycles II (R1 = H, Me, CH2Ph, etc., R2 = Me, n-Bu, CH2Ph, etc.) as well as 1,4-benzodiazepine-2,5-diones, e.g. III, are developed. A distinctly different catalytic property of palladium and copper catalysts was uncovered that leads to the development of a divergent synthesis of two different heterocyclic scaffolds from the same starting materials, simply by metal-switching. Thus, starting from linear amide IV, palladium acetate triggers a domino intramol. N-arylation/C-H activation/aryl-aryl bond-forming process to provide II, while copper iodide promotes only the intramol. N-arylation reaction leading to the 1,4-benzodiazepine-2,5-diones. In combination with the Ugi multicomponent reaction (Ugi-4CR) for the prepn. of the linear amides, a two-step synthesis of either the 5,6-dihydro-8H-5,7a-diazacyclohepta[jk]phenanthrene-4,7-dione (4) or 1,4-benzodiazepine-2,5-diones (5), by appropriate choice of metal catalyst, is subsequently developed from very simple starting materials. [on SciFinder (R)]