Iridium catalyzed regiodivergent functionalization of all three C-H bonds of arenes by a single ligand.

Abstract

Functionalization of all three distinct C-H bonds (para, meta, and ortho) within a particular arene has remained a long-standing challenge in chemical synthesis. However, overcoming this challenge would significantly benefit medicinal chemistry and drug discovery research. It would also streamline lengthy synthetic pathways, making them more efficient for total synthesis and industrial applications. The present study aims to address the challenge of functionalizing all three distinct C-H bonds (para, meta & ortho) within diverse classes of arenes. Here, we report, a general concept demonstrating the ability of a single ligand framework to selectively activate all three electronically distinct C-H bonds (para, meta & ortho) of a given arene just by varying the additives under iridium catalysis. The proposed mechanistic aspects are validated by experimental results and DFT computations. In addition, the developed method enables the selective installation of a deuterium atom or other functional groups at any desired C-H bond of arenes using boron as the linchpin. Finally, the application of the developed method using a single ligand scaffold is demonstrated in the short synthesis of an indole-derived combretastatin molecule.