Construction of axial chirality through addressing the meta constraint in Catellani reaction

Abstract

Axially chiral biaryls represent an important class of atropisomers that are prevalent in organic ligands, bioactive molecules, and materials. Despite recent advances in the synthesis of atropisomers via the Catellani reaction, the construction of axial chirality at the meta position of aryl iodides remains unexplored due to the low reactivity of aryl iodides with bulky meta substituents, known as the meta constraint. Herein, we report that introducing a directing group at the meta position of aryl iodides enables the formation of the aryl-norbornyl-palladacycle (ANP) intermediate, thereby successfully addressing the meta constraint. Computational studies show that the designed directing group favors a palladium–potassium heterodimer low barrier transition state, enabling palladium to cleave ortho-C−H bonds so as to form the ANP intermediate in an enantioselective manner. A variety of indoloquinolone atropisomers were synthesized with good yields and excellent enantioselectivity using a chiral norbornene (59 examples, up to 80% yield and 99% ee). The practicality of this method is further demonstrated by successful scale-up synthesis and diverse transformations, including the preparation of a chiral [7]helicene and a chiral phosphine ligand. The polycyclic ring systems of the products and their helically chiral derivative are crucial for potential applications in organic optoelectronic materials.