Title "Oxidopyrylium-Based (5+2) Cycloadditions: Old Roads, New Borders, and Unexpected Pathways"

Dr. Andy Mitchell, Professor, Organic Chemistry

Illinois State University, Dept of Chemistry

Hosted By: Dr. Brett VanVeller 

We train next generation scientists by guiding them through important research questions in the realm of oxidopyrylium-based (5+2) cycloadditions. Initial efforts probed the mechanism of formation and cycloaddition of oxidopyrylium intermediates, which led to a (5+2) cycloaddition conjugate addition cascade (C³) sequence in which 3 new rings, 4 new bonds, and 6 new stereocenters were constructed with high diastereoselectivity. In collaboration with the Tantillo group, several experimental observations were corroborated via theoretical calculations including evidence for the RDS of deprotonation and Kinetic Isotope Effects that matched our ²H-labeling experiments. More recently, our research groups have explored silyloxypyrone-based (5+2) cycloadditions that are extremely dependent on the nature of the dipolarophile. Neutral alkenes were the least reactive, whereas both electron-deficient and electron-rich dipolarophiles were more reactive, thus providing evidence for ambident oxidopyrylium intermediates. Qualitative rate studies, Hammett linear free energy relationships, and theoretical calculations combined to provide evidence for a spectrum of reactivity that passes through the borderlands of concerted and stepwise. We have also investigated applications such as efforts toward the total synthesis of toxicodenane A and net intermolecular silyloxypyrone-based (5+2) cycloadditions. Within this framework, scientists in training are invited to formulate and test hypothesis-based research questions in the context of these fascinating cycloadditions.

Bio:

Andy Mitchell earned his B.S. at Grove City College (PA) and his Ph.D. at Texas A&M University in 2008 with Prof. Daniel Romo. He was a postdoctoral associate at the University of Pennsylvania with Prof. Jeffrey Bode before joining the Illinois State University Department of Chemistry as an Assistant Professor in August 2010. He was promoted to Associate Professor with tenure in August 2016 and then Professor in August 2021. His research group focuses on natural products inspired organic synthesis in the context of training next-generation scientists. Outside of organic chemistry, Andy enjoys spending time with his wonderful family, reading, and attempting to play sports without injuring himself.