Small molecule drugs have received much recognition in the pharmaceutical industries due to their distinct therapeutic advantages. However, current synthetic methodologies such as cross-coupling chemistry for synthesizing small molecules face some challenges. Mainly, Suzuki−Miyaura, carbon-sulfur, and direct heteroarylation cross-coupling techniques are air- and moisture sensitive, as well as the catalysts, are expensive regarding the ligand design and synthetic procedures. Considering these setbacks, the alpha diimine based group 10 catalytic system offers unique advantages regarding air- and moisture-stabilities and easy synthesis procedures. In these possibilities, both iminopyridine- and acenaphthene-based ligand settings were incorporated for synthesizing nickel(II) and palladium(II) complexes. Accordingly, various ligand steric effects, including bite angles, were evaluated and correlated with the reaction outcomes in the Suzuki−Miyaura, carbon-sulfur, and direct heteroarylation cross-coupling techniques. Notably, a wide variety of pharmaceutically active aryl, heteroaryl, and alkyl moieties were incorporated for synthesizing the small molecules. Specifically, higher steric bulk and ligand bite angle directly promoted catalytic performance. Consequently, the findings suggest that Nickel-based systems with alpha diimine ligands could replace palladium counterparts regarding the sustainable alternatives in those cross-coupling methods.

Highly efficient alpha diimine based group 10 catalytic systems for synthesizing pharmaceutically relevant small molecules

ACS Spring Meeting 2021

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