Observations relevant to the differential intercalation of enantiomers between the strands of brush-type chiral stationary phases

Abstract

Differential penetration of the enantiomers of certain analytes between the strands of “brush-type” liquid chromatographic chiral stationary phases (CSPs) has been invoked in several instances to explain the progressive change in separation factors as one proceeds, chromatographically, through a homologous series of these analytes. These “intercalative effects” are presumed to arise as a consequence of the semi-ordered, side-by-side bonding of selector strands in conventional brush-type CSPs. Thus, they are not expected to occur in the absence of the stationary phase. A recently developed proline-derived CSP affords large separation factors for the enantiomers of some esters, thioesters, and amides of N-acylated α-amino acids, the separation factor being dependent upon the length of the C-terminal substituent of the analyte. For example, the separation factors increase with the length of the linear thioalkyl substituent when N-(3,5-dinitrobenzoyl)leucine thioesters are chromatographed on the proline-derived CSP. However, the length of this substituent does not affect the enantiomeric purity attained when the enantiomers of these thioesters are stereochemically equilibrated in solution in the presence of the proline-derived selector employed in the CSP. These observations further support the concept of differential intercalation of enantiomers between the strands of brush-type CSPs and may have implications for asymmetric syntheses conducted with immobilized catalysts or reagents.