Photocatalytic Giese-Type Reactions: Expanding the Scope using C–C and C–N Bond Formation

Abstract

The Giese reaction, a radical-based carbon–carbon bond-forming strategy, has long served as a valuable method for constructing complex molecular architectures from simple precursors. However, traditional Giese protocols often require harsh conditions such as high temperatures and toxic radical initiators which limit their applicability in the synthesis of complex and functionalized molecules. To address these limitations, visible-light- induced photocatalysis has recently emerged as an efficient and environmentally benign alternative for generating carbon-centered radicals under mild conditions. Utilizing transition metal complexes or organic dyes as photocatalysts, this approach offers enhanced chemo- and regioselectivity, along with significantly expanded substrate scope. In this study, we highlight the synthetic potential of radical-based photocatalytic strategies, focusing on recent advances in C–C and C–N bond-forming transformations mediated by carbon- and nitrogen- centered radicals. Through this research, we aim to provide insights into the growing utility and versatility of visible-light photocatalysis in modern organic synthesis. Flavanones are important bioactive compounds with diverse therapeutic applications. We report a mild, photocatalyst-free Giese-type radical addition of 1,3-dioxolane to chromones, enabled by Brønsted acid coordination. Benzoic acid lowers activation barriers and enhances visible-light absorption, promoting efficient radical formation and addition under mild conditions. The method tolerates various functional groups and heterocycles, delivering flavanone derivatives in good yields (up to 94% yield). Mechanistic studies support a radical pathway and highlight the role of substrate activation by the acid catalyst. In chapter 2, we provide a simple and efficient approach for photochemical radical functionalization in flavanone synthesis, and highlights the potential of chromone to act as an intrinsic photocatalyst. β-Homoproline derivatives are valuable scaffolds in biologically active molecules and pharmaceuticals. However, efficient methods for synthesizing α-substituted β-homoproline derivatives remain underdeveloped. In chapter 3, we report a photoredox-catalyzed intramolecular aminocarboxylation of alkenes using atmospheric CO₂ under mild conditions. This transformation provides a broad range of α-substituted β-homoprolines in good to excellent yields (up to 93%) and high diastereoselectivity (up to 12:1). The synthetic utility of the products was demonstrated through various downstream transformations.