Cross-Coupling Reactions Through Room Temperature Catalytic C-F Bond Activation

Angew. Chem. Int. Ed.: A group of scientists led by RESOLV member Prof. Lukas J. Gooßen has made a significant advancement in catalytic C–F bond activation.

This breakthrough, published in Angewandte Chemie International Edition, is a significant departure from conventional methods that often require harsh conditions or highly reactive nucleophiles. The team employed a methyl naphthyl (MeNAP) palladium trifluoroacetate/tBuBrettPhos catalyst in combination with lithium bis(trimethylsilyl)amide (LiHMDS) as the base.

The unique combination facilitates the insertion of palladium into the C-F bond, allowing for α-arylations of enolates with non-activated aryl fluorides under exceptionally mild conditions. Density Functional Theory (DFT) calculations revealed that the coordination of lithium salts to the fluorine atom plays a crucial role in this process.

This discovery not only expands the scope of possible cross-coupling reactions but also paves the way for more sustainable and efficient synthetic methodologies. This breakthrough extends to a wide range of enolates, including those derived from ketones, esters, nitriles, and even amides, opening new avenues for synthetic chemistry. This breakthrough extends to a wide range of enolates, including those derived from ketones, esters, nitriles, and even amides, opening new avenues for synthetic chemistry.