Cobalt-catalyzed hydroarylation of alkynes and olefins via chelation-assisted C-H bond activation

Abstract

Over the past two decades, extensive investigations into transition metal-catalyzed C–H activation processes have greatly improved our understanding on how to activate inert C–H bonds, and subsequently how to use them for various functional group transformations. However, as the field matures and more refinements are being made to currently available techniques, new challenges emerge. As it stands now, an overwhelming majority of C–H functionalization reactions rely on precious metals such as rhodium, palladium, and ruthenium as catalysts. This raises the question—is it possible to use earth abundant first row transition metals in lieu of the less readily available 2nd and 3rd row transition metals as catalysts for C–H activation? This thesis describes part of our group ongoing studies on developing cobalt based catalytic framework for C–H functionalization. The hydroarylation of alkynes and alkenes represents one of the most straightforward and atom-economical method for generating new C–C bonds. It is also one the most well developed and well-understood C–H functionalization, hence we initiated our investigations on cobalt catalysis by examining this class of reaction. Chapter 2 details our successful development of an imine-mediated cobalt-catalyzed syn-addition of aromatic ketimines to internal alkynes. The reaction took place even at room temperature, which is unusual for C–H functionalizations, and we observed an unprecedented secondary directing ability effect by meta-halogen and cyano substituents on the C–H cleavage processs. In Chapter 3, we describe the imine-directed branched-selective hydroarylation of styrene derivatives. This reaction demonstrated the unusual regioselectivity of the cobalt catalytic system because analogous reactions catalyzed by Ru or Rh would generate the linear-adduct. In Chapter 4, we describe our development of an asymmetric intermolecular styrene hydroarylation. Although the arene substrate scope was ultimately limited to indole derivatives, it was nevertheless a rare example of a transition metal mediated, intermolecular asymmetric hydroarylation of alkenes via a C–H activation, migratory insertion sequence.