Asymmetric diethyl- and diphenylzinc additions to aldehydes by using a fluorine-containing chiral amino alcohol: A striking temperature effect on the enantioselectivity, a minimal amino alcohol loading, and an efficient recycling of the amino alcohol

Abstract

A chiral pyrrolidinylmethanol derivative containing perfluoro-ponytails (5) was prepared from (S)-proline. The use of this perfluoro-substituted amino alcohol in catalytic asymmetric additions of organozinc reagents to aldehydes affords products with high enantioselectivities in both pure hexane and a mixture of hexane and FC-72 (perfluorohexane). Enantiomeric excesses up to 94 and 88 % ee have been achieved in Et2Zn and Ph2Zn additions, respectively. For the reactions in the biphasic solvent system, a striking temperature effect was observed. Thus, when the temperature was raised from 0 to 40 degreesC the ee value of the product increased from 81 to 92 %. Furthermore, the catalyst loading could be remarkably low, and with only 0.1 mol % of amino alcohol 5 a product with 90 % ee was obtained in the Et2Zn addition to benzaldehyde in hexane. The perfluoro-ligand was easily recovered by simple phase separation, and until the ninth repetition its reuse proceeded without significant loss of enantioselectivity and reactivity.