Title: "Unlocking New Reactivity Through Catalytic Radical–Polar Crossover"

Zuxiao Zhang, Assistant Professor

University of Hawaiʻi at Mānoa

Host: Yuan Zhang

Abstract: Catalytic radical–polar crossover has emerged as a powerful strategy for accessing reactive intermediates beyond the limitations of conventional two-electron chemistry. However, the ability to selectively control the fate of these transient intermediates remains a fundamental challenge. Our research program seeks to develop catalytic platforms that merge radical and polar reactivity to enable selective bond construction and programmable molecular editing.

In this seminar, I will discuss our recent efforts in developing hybrid palladium catalysis and photocatalytic radical–polar crossover strategies. We first established approaches to repurpose industrial refrigerants as practical fluoroalkyl reagents for alkene functionalization through controlled radical generation and selective manipulation of alkylpalladium intermediates. Mechanistic understanding of these intermediates enabled stereoselective difunctionalization of cyclic dienes, rapid construction of complex molecular architectures, and selective functionalization of unactivated alkenes by controlling competing alkylpalladium pathways. We further expanded this concept to achieve deoxygenative aldehyde difunctionalization through synergistic ketyl radical and light/dark palladium catalysis.

Beyond palladium catalysis, we developed photocatalytic radical–polar crossover strategies for carbon skeletal editing, including formal alkene insertion into C–F bonds and divergent two-carbon homologation of alcohols, enabling programmable molecular remodeling.

Together, these studies demonstrate how controlling radical and polar reaction pathways can unlock new reactivity and provide new strategies for the synthesis and modification of complex molecules.

Bio: Zuxiao Zhang is an Assistant Professor of Chemistry at the University of Hawaiʻi at Mānoa. His research focuses on developing new synthetic methods for drug discovery, with particular interests in fluorine chemistry, radical chemistry, and asymmetric catalysis. The Zhang group develops catalytic strategies that combine radical and polar reactivity to selectively functionalize otherwise unreactive chemical bonds, enabling efficient access to biologically relevant molecules and the late-stage modification of complex drug molecules. [manoa.hawaii.edu], [wipos.org]

Zhang earned his M.S. in Organic Chemistry from the Shanghai Institute of Organic Chemistry under Guosheng Liu and his Ph.D. from the University of Florida under William R. Dolbier Jr.. He subsequently conducted postdoctoral research with David Nagib at The Ohio State University. After beginning his independent academic career at Zhejiang Normal University in 2021, Zhang joined the University of Hawaiʻi at Mānoa in 2023.