Synthesis of perfluoroalkyl-substituted bis(oxazolines) as ligands for catalytic enantioselective reactions

Two chiral perfluoroalkyl-substituted bis(oxazolines) (F-box) have been prepared for the first time by a reaction sequence that involved formation of the properly functionalized box followed by introduction of two (ligand 9) or four (ligand 6) n-C8F17 residues. The fluorine content of these F-box was 49.2 and 55.5%, respectively. These ligands were employed in the ene reaction between a-methylstyrene and ethylglyoxalate carried out in the presence of [Cu(OTf)2] (up to 67% ee), and in the cyclopropanation of styrene in combination with CuOTf (up to 78% ee). In both cases the F-box with the lower fluorine content performed better than the more fluorinated one in terms of chemical yield and enantioselectivity. Ligand 9 was recovered by flash chromatography; ligand 6 by phase separation of the reaction solvents. Comparisons between the use of perfluoroalkyl groups and of soluble and insoluble polymers as solubility devices for the recovery and recycling of the bis(oxazoline) ligand are also reported.