Where HAS you been? A manganese-mediated annulation of 2-isocyanobiaryls with organoboronic acids is developed for the synthesis of a broad range of phenanthridine derivatives. Mechanistic studies indicate that the reaction proceeds by the intramolecular homolytic aromatic substitution (HAS) of an imidoyl radical intermediate.

We have developed a method for the synthesis of 2-borylindoles via the copper(I)-catalyzed borylative cyclization of 2-alkenylphenyl isocyanides using diboronate. The reaction proceeds at room temperature under neutral conditions and exhibits high tolerance to functional groups, such as Br, CO(2)R, COR, CONMe(2), and CN. The 2-borylindoles synthesized in the present study can be elaborated into an array of indole-based derivatives, for example, through the Suzuki-Miyaura reaction. The utility of this method is demonstrated in the rapid synthesis of a kinase inhibitor, paullone. The reaction can be extended to the synthesis of 2-hydride indole and 2-silylindole by using hydroboronate (or hydrosilane) and silylboronate, respectively. Under these copper-catalyzed conditions, a quinoxaline ring system can also be constructed by using 1,2-isocyanobenzene as a substrate.

Homolytic aromatic substitution (HAS) by an aryl radical and related processes [1,2] have recently attracted considerable attention as alternatives to transition-metal-catalyzed CÀH bond arylation [3] for the construction of biaryl motifs. These HAS reactions have several advantages over the conventional methodology, including unique chemo-and regioselectivity as well as avoiding the requirement for precious-metal catalysts and ligands. Mechanistically, it has been proposed that the HAS reaction proceeds by the addition of an aryl radical to an arene, followed by the oxidative re-aromatization of the resulting cyclohexadienyl-type radical. [1,2] Although there has been only limited application of the intermolecular HAS to the synthesis of biaryl systems because of issues associated with low levels of efficiency and selectivity, the application in intramolecular settings largely alleviates these issues and allows for straightforward access to biaryl moieties embedded in polycyclic system (Scheme 1 a). It was envisioned that the utility of this intramolecular HAS could be considerably expanded if a radical generated by the intermolecular addition of an external radical could undergo a HAS type cyclization (Scheme 1 b). Herein, we report the development of a reaction guided by this hypothesis for the synthesis of phenanthridine framework. [4]

No abstract