A DISCOURSE BETWEEN THE PAST AND PRESENT OF METAL-MEDIATED C-H BOND ACTIVATION: DIRECTIONS FOR THE FUTURE OF HALOGENATION CATALYSIS

Abstract

C-H bond activation has been around for decades, as the capability to replace the ubiquitous hydrogen atom in organic molecules with a medicinally relevant functional group is highly desirable. There are enzymes that functionalize these bonds very well, such as hydroxylases and halogenases. Naturally, the focus of the field has been to develop further catalysts, beyond just these enzymes, that are effective in C-H functionalization. Yet, there is sparse attention being paid to the underlying biochemistry in order to understand what factors are contributing to making these catalysts more efficient and selective. By applying the mechanistic perspective provided by the Groves group to new advances in the field of C-H functionalization catalysis, this critical review offers an improved mechanistic understanding of what is truly going on underneath the surface of catalyst optimization. This work could be advantageous for the field by potentially creating a roadmap for rational catalyst design, rather than relying on catalyst development based on yield and substrate scope studies. This review will connect past mechanistic studies to present developments of new catalysts for halogenation reactions, thereby suggesting critical next steps forward for the future of this field.