Normal-phase HPLC enantioseparation of aldols on polysaccharide-based chiral stationary phases bearing chlorinated substituents

Aldol condensation of two carbonyl compounds is one of the most important methods for the construction of carbon-carbon bonds and the increase of molecular complexity through the introduction of one or two stereogenic centres starting from relatively simple and achiral compounds. The products of such reaction, the aldols, are important synthons in the preparation of polyhydroxylated compounds and aldol structural units are found in many important molecules, whether naturally occurring or synthetic [1-3]. Two families of aldols, obtained from the condensation of aromatic aldehydes with cyclohexanone or acetone (ten examples in each group), were analysed in normal phase elution mode on three polysaccharide-based chiral stationary phases of the Lux serie, namely Lux Cellulose-2, Lux Cellulose-4 and LuxAmylose-2, which share the common feature of chlorinated substituents in the chiral selectors. Following simple optimization steps, the enantioseparation of all aldols derived from cyclohexanone was achieved and the highest values of separation factor ? (1.38 <?<1.99) and resolution (Rs, 4.5 < Rs <11.90) were observed on Lux-Cellulose 2, with the only exception of the 4-nitro-substituted derivative that was better resolved on Lux-Cellulose-4. On the contrary, Lux-Amylose 2 was the best choice for aldols derived from acetone and only specific analytes in this group could be resolved on the cellulose-based CPSs and the enantiodiscrimination ability markedly increase using EtOH as alcohol modifier in the mobile phase.