Executive Summary : | Heterobiaryl compounds, which consist of π-electron-rich heterocycles, are a versatile class with significant applications in materials, medicine, and synthetic methods. The current CDC methodologies for accessing electron-rich heterobiaryls often use precious metals, particularly Pd, in combination with an external chemical oxidant or strong stoichiometric oxidants, which are not sustainable. This study proposes a mechanistic approach inspired by metallozymes like multicopper oxidase and laccase, which catalyze the oxidation of electron-rich aromatic rings in nature. The range of oxidation potentials of substrates of these enzymes overlaps with the range of oxidation potentials of electron-rich heterocycles, such as pyrrole, indole, (benzo)furan, and imidazole. The proposed CDC methodologies would fulfill the criteria of sustainable chemistry from the standpoint of synthetic methods, as well as catalysts and reagents. The biggest challenge is ensuring chemoselectivity in oxidation, as both heterocycles could be potential substrates for oxidation. Key to success lies in identifying oxidative conditions that are strong enough to oxidize at least one heterocycle but mild enough to oxidize just one. The project aims to develop CDC of multiple pairs of electron-rich heterocycles through judicious substrate combinations, providing a general, expedient, and sustainable access to a larger repertoire of electron-rich heterobiaryls. This could potentially fuel more applicative research in organic materials and beyond. |