Silver-Free Palladium-Catalyzed C(sp³)–H Arylation of Saturated Bicyclic Amine Scaffolds

Herein, we report a silver-free Pd­(II)-catalyzed C­(sp3)–H arylation of saturated bicyclic and tricyclic amine scaffolds. The reaction provides good yields using a range of aryl iodides and aryl bromides including functionalized examples bearing aldehydes, ketones, esters, free phenols, and heterocycles. The methodology has been applied to medicinally relevant scaffolds. Two of the intermediate palladium complexes in the catalytic cycle have been prepared and characterized, and a mechanism is proposed. Removal of the directing group proceeded with good yield under relatively mild conditions.本文中，我们报道了一种无银、钯(II)催化的饱和双环及三环胺骨架的C(sp³)-H芳基化反应。该反应可使用多种芳基碘化物与芳基溴化物（包括带有醛基、酮基、酯基、游离酚基及杂环的官能化底物）获得良好收率。该合成方法已应用于药物相关的骨架结构。我们已制备并表征了催化循环中的两种钯中间体配合物，并提出了相应的反应机理。导向基团的脱除反应在相对温和的条件下即可获得良好收率。