Novel C-C Coupling Reactions under Nickelaphotoredox Catalysis

• Applicant: Dr. Dominik Kölmel
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2016 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 315258406

Catalysis is a powerful strategy in organic chemistry that allows for efficient and economic syntheses of many substances. Over the past few years photoredox catalysis has been established as a new research field, which has gained widespread attention due to its ability to access non-traditional sites of reactivity under mild conditions. Specifically, photoredox catalysis can convert suitable organic substrates into reactive radicals in the presence of a photocatalyst by harnessing the energy of visible light.Within this research project the strength of photoredox catalysis should be merged with nickel-catalyzed cross-coupling reactions (nickelaphotoredox catalysis) to enable the construction of challenging C-C bonds. By combing those two modes of catalysis, previously unknown or inaccessible mechanistic pathways should be utilized for the rapid assembly of complex molecules. The first part of the project investigates the development of a decarboxylative cross-coupling of alkyl oxalates with aryl halides. The oxalate should function as a stable radical precursor, which can undergo a stepwise loss of two molecules of CO2 in the presence of a photocatalyst to generate a carbon-centered radical. Those radicals can subsequently be coupled with aryl halides to form C-C bonds in a nickel-catalyzed reaction. This methodology would be of widespread utility, since the required oxalates could be easily obtained from readily available alcohols.The second part of the project examines a similar decarboxylative coupling to enable a CO2-extrusion-recombination of aryl esters. During this reaction, the nickel catalyst should insert into the phenolic C-O single bond between the arene and the ester. This is followed by CO2-extrusion, which should be facilitated by the photocatalyst. Finally, the nickel catalyst can undergo reductive elimination, which recombines the two organic fragments via a newly formed C-C bond. The proposed reaction would be of general interest, since esters are very prevalent in common organic molecules and can be easily synthesized from alcohols and carboxylic acids.Within the last part of the research project, an asymmetric version of the two described nickelaphotoredox reactions should be developed. Being able to control the stereochemistry of the coupling products would significantly increase the value of those reactions, since having access to enatiopure compounds is crucial for biological and medicinal applications. In order to achieve this, the reaction conditions should be modified by introducing a chiral ligand on the nickel catalyst. This ligand would generate a chiral environment so that the reductive elimination of the intermediate diorganylnickel species could occur in an enantioselective manner. Since the oxalate cross coupling and the CO2-extrusion-recombination coupling both proceed through similar diorganylnickel complexes, this strategy should be universally applicable.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor David W. C. MacMillan, Ph.D.