Flow-enabled strategies for the synthesis of fluorinated and sulfur-containing organic molecules

This thesis develops flow-enabled, photocatalytic strategies for the synthesis of fluorinated and sulfur-containing organic molecules, addressing longstanding challenges in accessing pharmacophores that remain difficult to install through conventional batch chemistry.
Chapter 1 introduces the principles of continuous-flow chemistry and photocatalysis, including hydrogen atom transfer, energy transfer, and single-electron transfer, as a foundation for the work that follows.
Chapter 2 reports a photocatalytic C(sp3)-H sulfinylation of light alkanes, from gaseous alkanes, using decatungstate-mediated hydrogen atom transfer and sulfur dioxide trapping in flow, overcoming the gas-liquid mass transfer limitations that hinder these transformations in batch.
Chapter 3 describes a packed-bed reactor platform using caesium fluoride to generate α,α-difluoromethylene amine (NCF2R) anions from imidoyl chlorides on demand, enabling a modular, three-point diversification strategy applied to complex bioactive scaffolds.
Chapter 4 extends this anion-generation approach to the late-stage arylation of NCF3 and SCF3 groups, coupling flow-generated heteroatom-CF3 anions with aryl thianthrenium salts under copper-mediated photocatalysis to functionalize drug-like molecules including flurbiprofen and pyriproxyfen derivatives.
Chapter 5 builds on this platform with a three-component radical-polar crossover reaction, merging the NCF3 anion, styrenes, and diverse radical precursors under photoredox conditions to construct molecular complexity in a single step.
Together, these chapters demonstrate that combining on-demand generation of reactive fluorinated and sulfur-containing intermediates with the enhanced mass transfer and mild conditions of flow chemistry provides a practical, scalable platform for late-stage functionalization, expanding the synthetic toolkit available for medicinal and agrochemical discovery.