Methyl itaconate–anthracene adducts (MIAs) facilitate the enantiomeric separation of 1,1′-bi-2-naphthols via thin-layer chromatography (TLC) with trends predicted by molecular dynamics simulations

Abstract

1,1′-bi-2-naphthols (BINOLs) and their derivatives have been extensively studied over the years. Enantiopure BINOLs are crucial in asymmetric synthesis, circularly polarized luminescent dyes, and charge transfer host systems. Several methods, including asymmetric oxidative coupling, enzymatic resolution, and chemical resolution, have been explored to prepare enantiopure BINOLs. Chemical resolution by chromatography offers the advantage of obtaining both enantiomers with high purity. Herein, we employed methyl itaconate–anthracene adducts (MIAs) as chiral resolving agents (CRAs) for the resolution of racemic BINOLs. Diastereomers were obtained via esterification in yields ranging from 37% to 62%. ¹H NMR revealed distinct H_y proton behaviors, correlating with the orientation of the second naphthol ring as predicted by DFT calculations. In the diastereomers without 3,3′-dibromo-substituted BINOLs, the H_y protons were shielded from the anisotropic effect, whereas 3,3′-dibromo-substituted BINOLs diastereomers exhibited the opposite effect. MIAs effectively resolved racemic BINOLs on TLC, showing significant differences in retardation factor (R_f). Molecular dynamics simulations predicted TLC resolution trends by examining the number of hydrogen bonds between diastereomers and silica gel. For diastereomers without 3,3′-dibromo-substituted BINOLs, the (S,S)-diastereomers formed more hydrogen bonds than the (S,R)-diastereomers, resulting in lower R_f values. Conversely, for diastereomers of 3,3′-dibromo-substituted BINOLs, the (S,R)-diastereomers exhibited stronger hydrogen bonding.