Synthesis And Application Of Fluorous Bis(Oxazolines) Ligand

Chiral bis(oxazolines) ligands could be used to form bis(oxazolines) ligand-metal complexes with various metal salts such as Cu, Ni, Pd, Co, Ru, Yb, Zn, Mg, Ir, Ca, Ti. The bis(oxazolines) ligand-metal complexes have been proved to be efficient catalysts in numerous asymmetric reactions including Diels-Alder reactions,1,3-dipolar cycloaddition, cyclopropanation reactions, Mukaiyama-Aldol reactions, Mukaiyama-Michael addition reactions, Henry reactions, Friedel-Crafts reactions, allylic substitution reactions. The synthesis of bis(oxazolines) ligands have attracted considerable "attention because of their ready accessibility, structural diversity and a wide range of application in metal catalyzed asymmetric reactions.However, most of the bis(oxazolines) ligands are difficult to be recovered and reused. Fluorous technology provides the possibility to design recyclable and subsequently reusable ligands. In this paper, a novel fluorous bis(oxazolines) ligand was synthesized with 70% overall yield in 5 steps starting from 5-aminoisophthalic acid.The fluorous bis(oxazolines) ligand was applied in the one-pot synthesis of a-aminophosphonates via copper-catalyzed Kabachnik-Fields reaction. In order to probe the influence of the ligand, six different bis(oxazolines) ligands were then examined in the reaction. It was found that the yields were obviously increased by the addition of bis(oxazolines) ligands and the fluorous bis(oxazolines) ligand showed the best result. To demonstrate the generality of this method, we investigated the scope of this reaction. The reactions of various aldehydes, amines and diethyl phosphate under the optimized conditions giving the corresponding a-aminophosphonates in moderate to excellent yields (68-95%).The recyclability of the fluorous bis(oxazolines) ligand was studied by choosing the reaction of benzaldehyde, aniline and diethyl phosphate as a model. After the reaction was finished, the ligand was recovered by FluoroFlash silica gel. The recovered ligand could be used directly for the next run. The results showed that recovery ratio was more than 90% and the fluorous bis(oxazolines) ligand could be reused for four times without significant loss of activity.