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.