Development of an Enantioselective Allylic Alkylation of Acyclic α‐Fluoro‐β‐ketoesters for Asymmetric Synthesis of 3‐Fluoropiperidines

The first useful enantioselective Pd‐catalyzed asymmetric allylic alkylation of α‐fluoro‐β‐ketoesters has been achieved using the Trost family of chiral ligands yielding products in up to 92 % ee. This work provides new insights regarding the typically modest selectivities associated with acyclic α‐fluoroenolates and shows experimental evidence that the typically poor levels of enantiocontrol associated with these systems are not necessarily due to the presence of E/Z enolate mixtures. Finally, this methodology allows the easy preparation of useful 3‐fluoropiperidine intermediates, and it is demonstrated that these systems are applicable to a range of functionalization reactions leading to new building blocks for the discovery of bioactive products.