Organic Chemistry Seminar

Over the past 4 decades, transition-metal-catalyzed cross-coupling and olefin functionalization reactions have transformed the discovery and manufacture of pharmaceuticals, agrochemicals, and materials. Despite the economic and environmental impetus to pursue reaction development with more terrestrially abundant elements, first-row (3d) transition metals are not typically suitable as direct substitutes for their precious metal congeners. Nonetheless, there is growing interest in exploring the unique reactivity of earth-abundant and relatively inexpensive 3d metals such to generate novel products and/or take advantage of substrate combinations that remain difficult to access with their precious metal congeners. In particular, nickel is prized for its ability to engage minimally activated polar functional groups and to traverse formal oxidation states ranging from Ni(0) to Ni(IV) through both 1 and 2 electron pathways. However, compared with the detailed understanding of the fundamental reactivity of precious metals informed by decades of mechanistic elucidation, the identity, speciation, and controlling features of nickel catalysts remain poorly defined in many cases, thus limiting their development. In this seminar, I will introduce my team's progress using well-defined nickel precatalysts and organometallic intermediates to tease apart the structural features and mechanistic steps necessary for achieving high activity and chemoselectivity in a variety of transformations. Our work relies on a synergy between mechanistic study of and precatalyst design for homogeneous catalysis, taking advantage of cooperative design principles informed by heterogeneous and biological catalysis. These insights are translated into the design of novel catalyst structures and synthetic transformations with enhanced efficiency. In Part I, I will describe cross-coupling reactions using weakly activated carboxylic-acid derivatives, where a series of mechanistic studies enabled the development of carbonyl "deletion" protocols and cyclometallated NHC nickel precatalysts amenable to parallel ligand diversification. In Part II, I will describe the describe the development of pyridonate-containing ligands for metal-ligand-cooperative substrate activation. I will extend this design principle in Part III to discuss development of a family of dimeric iminopyridonate nickel complexes that enable cooperative halogen-atom-transfer (XAT) and single-electron-transfer (SET) activation of aliphatic electrophiles and application to C(sp2)–C(sp3) cross-coupling.