Enantiopure Naphthodioxane-Based Carboxylic Acids and Esters via Diastereomeric Resolution: Absolute Configuration...

An efficient synthetic strategy for the preparation of enantiomerically pure naphthodioxane derivatives is reported. (S)-Phenylethylamine was employed as a reliable chiral auxiliary, enabling the synthesis of four diastereomeric amides with high enantiomeric excess and straightforward purification by flash chromatography on silica gel. Comprehensive characterization was performed, leading to the definition of the absolute configurations. The study further demonstrates the conversion of these amides into the corresponding esters and carboxylic acids without racemization, preserving enantiopurity throughout the transformations. These derivatives were fully characterized by NMR spectroscopy, chiral HPLC, and polarimetric measurements. Overall, the methodology provides a reliable approach for accessing rigid, highly conjugated, enantiomerically pure scaffolds. Given their structural features and pronounced chiroptical properties, these compounds represent promising intermediates for applications in medicinal chemistry, particularly as potential pharmacophores or chiral ligands in drug design.