Coated and Immobilized Polysaccharides‐Based Stationary Phases for Planar Metallocenes Enantioseparation in Liquid Chromatography

ABSTRACT

Interest in unsymmetrically disubstituted metallocene derivatives, originally developed for asymmetric synthesis, emerged later in medicinal chemistry. In this study, 21 novel compounds were investigated, including (i) 1,2‐, 1,3‐, and 1, n ′‐disubstituted ruthenocenes and ferrocenes; (ii) ruthenocenes and ferrocenes with central chirality; and (iii) a ruthenocene possessing both central and planar chirality, for which four stereoisomers are expected. The compounds were analyzed by normal‐phase mode liquid chromatography under arbitrarily selected conditions of 20°C and a flow rate of 1 mL/min, with UV detection at 260 nm. Eight polysaccharide‐based chiral stationary phases were evaluated, using n ‐heptane combined with either 20% ethanol or 2‐propanol as the mobile phase. In addition to coated silica gel stationary phases, including cellulose tris (3‐chloro‐4‐methylphenylcarbamate), immobilized silica gel stationary phases, such as cellulose tris (3,5‐dichlorophenylcarbamate), and amylose and cellulose tris (3,5‐dimethylphenylcarbamate), were investigated for these derivatives. Significant differences in enantioseparation were observed depending on the molecular structure of the derivative, the nature of the stationary phase, and the type and percentage of alcohol used in the mobile phase. Notably, none of the columns tested was able to separate all isomers, regardless of whether identical or varied alcohol types and concentrations were employed.