Ni-Catalyzed Indenone Synthesis: Studies on the Mechanism, Regioselectivity, and Subsequent Derivatization

Bio: Dr. Dale Wilger grew up in Western New York. He obtained his BS degree in chemistry from Fredonia State University (SUNY Fredonia) before moving to the University of North Carolina at Chapel Hill to pursue his PhD and postdoctoral studies. As an undergraduate, Dale performed research with Professor Philip Kumler and learned to love this method for applied experiential learning. For his PhD, Dale studied peptide chemistry and energy transfer mechanisms with Professor Marcey Waters. He later joined the lab of Professor David Nicewicz and developed new synthetic methods using photoredox catalysis. Dale joined the faculty at Samford University in 2015, where he now teaches several different organic chemistry courses and directs a productive undergraduate research lab. He is deeply interested in developing new and useful chemical reactions that are catalyzed by the first-row transition metals. The first-row transition elements provide promising new reactivity, while remaining less toxic, less expensive, and more environmentally sustainable compared to heavier metals. When Dr. Wilger is not at Samford, he enjoys spending time with his wife, Colleen, and their three children, Benjamin (8), Ruth (5), and Caleb (3).

Abstract: Transition-metal-catalyzed methods to synthesize indenones have expanded rapidly in previous decades due to a broad interest in this class of molecule. Indenones are frequently found to be biologically active, displaying antibiotic, anticancer, anti-inflammatory, and pain-relieving properties, while remaining structurally manageable from a synthetic perspective. Transition-metal-catalyzed strategies for indenone synthesis often focus on cross-coupling reactions with alkynes, but many examples are low yielding and/or poorly selective with alkyl- and silyl-substituted reactants. Our group has developed a Ni-catalyzed cross-coupling reaction that produces alkyl- and silyl-substituted indenones in high yields from commercially available starting materials. Reactions with silyl-substituted alkynes are often highly regioselective. The broad scope of this reaction and ease of mechanistic analysis led to the discovery of a previously unknown electronic effect on alkyne migratory insertion selectivity. Some of our more recent findings have elucidated these electronic effects on regiocontrol. These mechanistic findings will be presented along with current efforts to develop new Ni-catalyzed reactions and methods for indenone synthesis.