Reactivity and Selectivity Controls in Radical Reactions Enabled By Proton-Coupled Electron Transfer

Abstract

Free radicals are often considered high-energy and fleeting intermediates. Controlling their reactivity remains a great challenge in organic synthesis. My graduate work centers on using proton-coupled electron transfer (PCET) as a general strategy for developing radical transformations with high selectivities and unprecedented reactivities. In these reactions, stepwise or concerted transfer of electron and proton serves as a key process to activate organic molecules and achieve selective catalysis.In Chapter 1, I describe developing a catalytic strategy for the light-driven deracemization of cyclic urea. Deracemization is a process where a racemic mixture is converted into a single enantiomer of the same molecule. Despite its synthetic benefits for late-stage stereo-correction, catalytic protocols for deracemization remain extremely rare. To this end, we developed a ternary catalyst system that enables photocatalytic deracemization. Excellent enantioselectivity is achieved for the homolysis and reformation of a stereogenic C–H bond through orchestrated movements of an excited-state electron, proton, and hydrogen atom. In Chapter 2, I report a novel strategy for the homolysis-enabled electronic activation of aryl electrophiles. While heteroatom-centered radicals are known to be highly electrophilic, their ability to serve as transient electron-withdrawing groups and facilitate polar reactions at distal sites has not been extensively studied. In this work, we describe a strategy for the electronic activation of halophenols, wherein homolysis of the aryl O–H bond enables direct nucleophilic aromatic substitution of otherwise inert aryl halides with carboxylate nucleophiles under mild conditions.