Organic Chemistry Seminar: Professor Mike Hilinski, University of Virginia

Organic Chemistry Seminar: Professor Mike Hilinski, University of Virginia (Host: Paul Wender)

About the Seminar

"New Frontiers in Catalytic Heteroatom Transfer: Applications to Late-Stage Oxidation and Small Molecule Synthesis"

Heteroatom transfer reactions – frequently used by Nature for both the biosynthesis of natural products and the metabolism of xenobiotics – are fundamentally useful for the synthesis of pharmaceuticals and other bioactive compounds. As an example of one application, the site-selective oxidation of carbon-hydrogen bonds can be a powerful tool, especially when applied to late-stage functionalization. Transition metal catalysis of site-selective C–H oxidation has rapidly advanced in recent years, but there are nevertheless substantial challenges that remain with regards to achieving catalyst-controlled selectivity. Research in the Hilinski lab has focused on advancing organocatalysis as an alternative approach to transition metal catalysis of C–H functionalization, in order to exploit its potential advantages and complementarity. In this presentation, multiple approaches to organocatalytic C–H oxidation that have resulted in methods for C–H hydroxylation and the first organocatalytic method for C–H amination will be presented, with a focus on catalyst design, selectivity in complex settings, and mechanism. More recently, the lab’s focus on applications of catalytic heteroatom transfer has broadened to include other late-stage oxidations relevant to drug discovery (e.g. metabolic N-oxidation) and the discovery of novel cycloaddition reactions initiated by heteroatom transfer. Recent results in these areas will therefore also be presented, with a focus on applications relevant to bioactive small molecule synthesis.

About the Speaker

Michael Hilinski earned his B.S. degree in Chemistry at Tufts University in 2000. During this time, he performed research under the direction of Prof. Marc d’Alarcao, exploring the synthesis of insulin-mimetic carbohydrates. After a brief period of employment at AMRI in Albany, NY, he continued his studies as a graduate student in the laboratory of Professor Paul Wender at Stanford University. While at Stanford, he completed total syntheses of several structurally simplified analogs of bryostatin and laulimalide that retain the biological activity of the parent natural products. After receiving his Ph.D. in 2007, he worked as a medicinal chemist in several early-stage pharmaceutical companies before moving to the University of Virginia School of Medicine as a DOD Breast Cancer Research Program Postdoctoral Fellow in the laboratory of Professor Deborah Lannigan. There he applied his synthetic and medicinal chemistry expertise toward the development of inhibitors of the protein kinase RSK and used them to validate inhibition of RSK as a viable strategy for the treatment of breast cancer.  Since 2013, he has been a tenure-track assistant professor in the Department of Chemistry at the University of Virginia. His current research is focused in three main areas: (i) catalysis of selective C–H functionalization; (ii) synthetic methods broadly applicable to pharmaceutical and natural product synthesis; and (iii) anticancer drug discovery. In his independent career, he has received several awards including an NSF CAREER award (2019), a Thieme Chemistry Journals award (2019), and selection by UVa as a Mead Honored Faculty (2018) in recognition of teaching accomplishements.