Assessment of Directing Groups in Reductive Coupling Reactions

• Jacob Letnaunchyn, Chemistry, University of Delaware

• Don Watson, Department of Chemistry and Biochemistry, University of Delaware

Axially chiral biaryl structures are major backbones to many naturally occurring products, pharmaceuticals, and chiral ligands. Axial Chirality occurs between when there is a nonplanar arrangement of tetra ortho-substituted biaryl structures causing restricted rotation around the aryl-aryl bond. Recent discussions surrounding the synthesis of axially chiral biarenes through nickel-catalyzed reductive cross-coupling reactions are at the forefront of our research. It has been shown that the homocoupling of aryl structures is possible, however, cross-coupling is more difficult due to the cross-selectivity of the directing groups. We aim to expand the scope of directing groups in reductive cross-coupling reactions through High Throughput Experimentation (HTE). To do so, a selection of aryl bromides with varying directing groups have been cross-coupled on HTE scale and quantified by LCMS and GCMS analysis. Through this substrate scope, we report a wide range of cross-coupling products with which we have started to scale up and characterize.