Radical Polar Crossover -Application to Triplett-State Chemistry

• Applicant: Anton Möllerke
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 555126024

Photochemical reactions differ from thermal reactions in that photosensitizers and light can catalyze the formation of triplet diradical intermediates under mild conditions. The portfolio of transformations accessible by photochemistry includes cycloadditions, rearrangements, cyclizations, and many more. While the direct excitation of organic molecules is possible, it is often more feasible to employ visible-light-mediated photocatalysis to access the excited triplet-state. This can occur via a triplet energy transfer (TET) or a single electron transfer (SET) process. In this project, I seek to explore new reactions in this field. An interesting area is the photochemical radical-polar crossover (RPC) in the triplet state. Radical-polar crossover being the primary mode of action in photo redox catalysis and thermal radical chemistry of alkenes. Nonetheless, to the best of my knowledge, there are no reports of triplet-state alkene radical-polar crossover reactions. While the recent literature on triplet-state alkene photochemistry focuses on cycloaddition and isomerization, this project aims to facilitate an intersection with radical and polar crossover reactions. For this propose I will use an internal redox shuttle. Alkenes substituted by halogens liberate radicals by an addition-elimination mechanism. These released radicals may function as redox shuttles, as they can induce a single electron transfer, which generates a cation and the corresponding halide. These polar intermediates can then function as a platform for functionalization via two-electron chemistry, which allows for the rapid construction of complex scaffolds. This new mode of action will enable new reactivities and a different access to complex molecules. I will apply this technique for the construction of complex natural products, like Hasubanan or Lycorine. The stereocontrol of new reactions will maximize their usability in drug development and natural product synthesis. The Smith group has shown, that triplet-state alkenes can undergo enantioselective photocyclizations. In order to further develop the triplet-state RPC, I plan to utilize chiral Lewis acids. Another approach is the use of chiral auxiliars, for which I plan to utilize chiral sulfoxides generated by the Kagan oxidation. Another objective is to develop procedures for the interaction of triplet-state chemistry and transition metal chemistry for the difunctionalization of alkenes. For this, I will exploit the fact, that Ni-catalyzed reactions can capture radicals. Cross-coupling reactions are an important reaction class in organic chemistry, the interlink with photoredox catalysis is therefore important. I want to realize the addition of an aryl Ni(II) halide to a triplet-state diradical, upon radiation the so formed Ni species can release a halide radical, which can induce a SET to generate an ionic species. This approach might be expanded by the use of Ir-catalysts.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Professor Martin D. Smith, Ph.D.