Palladium(II)-Catalyzed Tandem γ-C(sp²)–H Arylation and Cyclization for the Construction of Natural Product-Like Polycyclic Fused ortho-Quinone Scaffolds

Abstract

Here, we report a novel strategy for the direct construction of polycyclic fused ortho-quinone scaffolds through palladium(II)-catalyzed tandem γ-C(sp 2 )−H arylation and cyclization of arylglyoxals with aryl iodides. This transformation features unique tandem transient directing of γ-C(sp 2 )−H arylation and cyclization reaction mode, broad substrate scope, especially for the aromatic substrates containing oxygen and sulfur atoms, and avoiding the common issue of aromatization due to the construction of the hexatomic ring. ortho-Quinone scaffolds, such as 1,2-naphthoquinones and 9,10-phenanthrenequinones (PQs), are commonly found as the core structure in a variety of drugs and biologically active natural products. These scaffolds exhibit a wide range of pharmacological activities, including anticancer, antibacterial, anti-inflammatory, and antituberculosis effects (Figure 1). 1