Synthesis of Recyclable Fluorous Chiral Ligands and Evaluation of Their Catalytic Activity toward Asymmetric Addition of Dimethylzinc to Aldehydes

The asymmetric addition of Me2Zn to aldehydes is very slow and mostly gives low ee values. Previously, we reported the synthesis of a fluorous chiral ligand, (4R,5S,alpha'R)-2,2-dimethyl-alpha,alpha,alpha'-tris(perfluorooctyl)-2,3-dioxolane-4,5-dimethanol (1a), derived from tartarate as a chiral pool. Ligand 1a showed high activity toward the addition of Me2Zn to aldehydes with high enantiomeric excess. However, the very high content of fluorine makes I a difficult to dissolve in common solvents; hence, much solvent is required, which limits its use. This report describes the modification of 1a by replacing either the perfluorooctyl groups with shorter perfluoroalkyl ones or the acetone ketal part with cyclohexanone ketal. The perfluorobutyl analogue 1c is much more soluble than 1a and shows comparable asymmetric induction toward the addition of Me2Zn to aldehydes. Furthermore, 1c has a much lower molecular weight than 1a. This means that 1c is used in smaller amounts (weight) than 1a. The cyclohexanone ketal analogue Id is more soluble than 1a and more easily synthesized owing to its high solubility and ease of crystallization. Ligand Id showed much higher asymmetric induction toward cyclohexanecarbaldehyde, a branched aldehyde, than 1a. Thus, 1a was modified into ligands with higher performance.