Photoredox-Catalyzed Modification and Synthesis of Carbo- and Heterocycles

• Applicant: Professor Dr. Frank Glorius
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 543968423

Photoredox catalysis utilizing visible light has undoubtedly shaped organic synthesis of the early 21st century, enabling single electron transfer (SET) events throughout a wide range of oxidation and reduction potentials under mild conditions. Enabling redox-neutral reaction pathways, the successful combination with a variety of catalysis platforms added to its wide-spread application. As ring systems are key structural components throughout chemistry, their synthesis and derivatization are pivotal. While many fields relied on de novo synthesis and peripheral adjustment of heterocycles in the past, recent years have seen an advent of one or two atom insertion strategies, leading to rapid diversification of accessible (hetero-)arenes. Seeking for both core and peripheral adjustment in a single step, insertion of “functionalized atoms” in a wide variety would be highly desirable. Towards exploration of 3D space to “escape from flatland”, insertion of small carbocyclic structures in (partially) unsaturated (hetero-)cycles could be highly revolutionary, enabling the synthesis of pharmaceutically relevant polycyclic motifs. Difunctionalization procedures are an appealing gateway towards delivering densely functionalized ring systems. Regarding photochemistry, the cyclobutane motif has been traditionally targeted by [2pi+2pi]-cycloadditions, while stereocontrol remains challenging despite recent advances. With the re-emergence of strain-releasing elements like BCBs, stereoselective difunctionalization of cyclobutane cores has come into perspective. However, seminal reports suffer from limited scope and tedious reaction setup, requesting for simple, atom-efficient alternatives. This work aims to combine the toolbox of photoredox catalysis and the unique features of strained ring systems or intermediates in open-shell systems. Along these lines, targeted transformations include insertion of functionalized carbon-atoms and of small carbocycles into (hetero-)arenes, while the reactive intermediates may differ in radical or distonic radical species (separated radical and ionic localization), respectively. Utilizing the latter for open-chain substrates, the two-component, highly regio- and diastereoselective difunctionalization of strained ring systems is discussed. Future developments include targeting carbocycle and (hetero-)arene core editing - comprising insertions, formal cycloadditions and exchange strategies– accompanied by the development of computationally guided design strategies.

• DFG Programme: Research Grants