Diastereoselective Synthesis of Dialkylated Bis(phosphino)ferrocenes: Their Use in Promoting Silver-Mediated Nucleophilic Fluorination of Chloroquinolines
Résumé
The diastereoselective synthesis of dialkylated ferrocenyl bis(phosphane)s bearing aryl, alkyl, and hetero- or polycyclic substituents on the phosphino groups is reported, together with their characterization in the solid state by X-ray structure analysis and in solution by multinuclear NMR spectroscopy. Introduction of various alkyl groups on the ferrocene backbone, namely, tert-butyl, isopropyl, and trimethylsilyl, has a significant influence on the stereoselectivity of the ensuing lithiation/phosphination reactions. Only the introduction of the tert-butyl groups ensures both a high yield and perfect diastereoselectivity, which leads to the exclusive formation of the rac planar chiral tert-butylated diphosphanes. The introduction of electron-rich and -poor phosphorus-based functional groups, namely, furyl-, isopropyl-, cyclohexyl-, phenyl-, mesityl-phosphino, and benzophosphindole, is achieved and gives new alkylated ferrocenyl diphosphanes in moderate to high yields. Investigations are conducted to apply these robust alkylated diphosphanes as auxiliaries in the very challenging palladium-catalyzed nucleophilic fluorination of chloroquinolines at the C-Cl bond. Unexpectedly, a significant favorable effect from the ferrocenyl phosphanes is evidenced by using the commercial AgF reagent for this fluorination that renders any palladium addition useless. This innovative nucleophilic fluorination thus avoids harsh conditions (strictly anhydrous) and highly specialized reagents.