Optimization of a Novel Photoredox Catalyzed Lactonization

Authors: Liam Sullivan, Jennifer Hirschi

Field of Study: Chemistry

Program Affiliation: Summer Scholars and Artists Program (SSAP)

Faculty Mentors: Jennifer Hirschi

Easel: 88

Timeslot: Morning

Abstract: Widely present in natural products, γ-lactones exhibit a variety of biological activities including anti-cancer and anti-heart disease effects. The investigation of γ-lactone-forming reactions therefore represents a step towards the development of many promising active pharmaceutical ingredients (APIs). In April 2025, the Glorius group published a novel γ-lactonization facilitated by a phenothiazine sulfoxide photocatalyst. To probe the rate-determining step of reactions, the Hirschi Lab employs kinetic isotope effect (KIE) studies. To obtain a conversion that facilitated KIEs of this lactonization, an optimization of the model reaction was undergone through modification of reagent equivalents, catalytic loading, and photoreactor conditions. Product formation was measured via 1H NMR analysis using a methyl octanoate internal standard. Optimization under these selected conditions afforded conversions reaching 44%, suggesting the need for further modification before proceeding towards a mechanistic study.