California Institute of Technology
Chemically and Electrochemically Orchestrating Transition Metal Catalysts for Selective Organic Synthesis
Transition metal catalysis is an indispensable tool for building up molecular complexity from simple organic building blocks. The development of new strategies to control catalyst reactivity and selectivity enables widespread applications in a variety of sub-disciplines, such as the synthesis of bioactive compounds, agrochemicals, and materials. Thus, novel approaches toward catalyst control from both chemical and electrochemical perspectives is highly desirable. In the first part of this seminar, I will present on nickel-catalyzed difunctionalization of unactivated alkenes using a directing group strategy. Specifically, I will describe the 1,2-arylalkylation of non-conjugated alkenes enabled by an 8-aminoquinoline (AQ) directing group via three-component cross-coupling using aryl halides and organozinc reagents. Building on this, evolution from a removable bidentate directing group to native carbonyl-containing functional groups will be discussed. Key to the success of this advance is the identification of a suitable ligand, dimethyl fumarate, to accelerate the key reductive elimination step. A combination of experimental and computational mechanistic studies sheds light on the reaction mechanism, leading to the expansion of native directing groups beyond simple amides. Next, I will present on the development of electrocatalytic proton-coupled electron transfer (ePCET) using a cobaltocene-derived mediator toward the hydrogenation and hydrofunctionalization of organic substrates. Under controlled-potential electrolysis (CPE), net H-atoms can be selectively delivered directly to model substrates, such as aryl ketones and electron-deficient alkenes, offering a unique mode of chemoselectivity in organic electrosynthesis. To conclude, I will describe ongoing efforts to engage ePCET mediators with transition metal co-catalysts to generate metal hydrides, repurposing traditional hydrogen evolution electrocatalysts toward new substrates.