Development of an Enantioselective Allylic Alkylation of Acyclic <i>α</i>‐Fluoro‐<i>β</i>‐ketoesters for Asymmetric Synthesis of 3‐Fluoropiperidines
Jiaxin Han, Larry Hoteite, Joseph P. A. Harrity
Abstract
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.