Development of novel asymmetric allylation reactions by dual photoredox-/transition metal catalysis

• Applicant: Professor Dr. Bernhard Breit
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 508111715

Allylation reactions are among the most important transformations in organic chemistry. Allylic compounds are synthetically versatile in use and ubiquitous substructures in various natural products. The standard allylation methods like allylic substitution, allylic oxidation, hydrofunctionalization of allenes, alkynes and 1,3-dienes and addition reactions of allyl-metal species to carbonyls/imines often suffer from limitations in terms of applicability. Especially the introduction of formally “hard” nucleophiles is often difficult. Together with the establishment of photoredox catalysis a mechanistic change in C,C-bond formation chemistry from common two-electron to one-electron processes happened. This simplified the access to some previously challenging molecular patterns significantly. The combination of photoredox catalysis and transition metal catalysis (dual catalysis) was a major driving force in this context. Apart from few literature examples, stereodivergent dual photoredox-/transition metal catalyses are hardly known. Completely unknown are stereodivergent synergistic transition metal catalyses where one of the metal catalysts is additionally taking the role of a photocatalyst. Within the framework of a PhD project this approach should be elaborated towards an asymmetric synthesis for amino acids. In concrete, the light-induced, dual palladium-/copper-catalyzed Allylation of glycine esters is planned. A removable metal- directing group shall facilitate substrate binding to a photocatalytically active copper catalyst and subsequent radical formation. In parallel, the palladium catalyst should activate an allylic electrophile and together with the copper catalyst enable the C,C-bond formation. The main focus of this project lies in the establishment of stereodivergent catalytic conditions.In a second project, “hard” nucleophiles should be applied in allylation reactions by combination of photocatalysis and rhodium catalysis. Therefore, the allylation of photocatalytically generated acyl radicals with rhodium-allyl complexes is planned. Next to the direct formation of acyl radicals, their indirect formation after CO incorporation should be investigated. Allenes and Alkynes should serve as allylic precursors in this reaction. The use of 1,1-disubstituted allenes should enable the construction of chiral quaternary carbon atoms. Finally, the value of the methodology for the fabrication of important synthetic building blocks should be demonstrated.Both projects include mechanistic studies for a better understanding of the reaction process. Apart from that, the synthetic viability of the developed methods should be demonstrated by elaboration of a comprehensive substrate-scope.

• DFG Programme: Research Grants