Executive Summary : | Cross-electrophile coupling has emerged as an alternate tool for C-C bond formation. Such reaction protocols frequently use readily available and stable organic (pseudo)halides. C(sp3)-C(sp2) cross-electrophile coupling reactions with nickel catalysis provide a broad platform to synthetic organic chemists. Mechanistic studies on specific nickel-catalyzed reactions have demonstrated that cross-selectivity with C(sp2) and C(sp3) electrophiles is caused by separate, hybridization-dependent activation mechanisms. Methods for selective coupling of two C(sp3) electrophiles, on the other hand, remain underdeveloped due to the fine changes in reactivity between the two coupling partners. Moreover, the aryl ring is the most common compound in commercially available pharmaceuticals, indicating its long history of use in pharmaceutical research as a pharmacophore or framework that reflects druggable components. This point of view highlights the creation and deployment of bioisosteric analogues for a phenyl ring, which may open up new avenue for practical solutions to challenges faced in lead optimization initiatives. The aim of this work is to employ photoredox-nickel dual catalysis to generate effective, safe, and active pharmaceutical ingredients by designing and synthesizing aromatic bioisosters and various heterocyclic and carbocyclic rings via halogen atom transfer reaction. We will synthesize bioisosters of meta- and para-substituted aromatic scaffolds as prime targets using this dual catalysis chemistry. A bicyclo[2.2.1]heptane (BCH) scaffold is a preferred molecular structure embedded in bioactive natural compounds. In particular, we are interested to explore the alternate synthetic routes toward Fenchone and Bornaprine derivatives using our protocol. The BCH scaffold acts as the basis for asymmetric synthesis and catalysis in many cases. Enantioselective methods to functionalize BCH are crucial for target- and diversity-oriented syntheses of related physiologically significant compounds, and hence highly desirable for relevant drug discovery. |