Asymmetric Pudovik Reaction as a Tool for Functionalizing 3-Formylchromones

Abstract We report a preliminary proof of concept for the first asymmetric synthesis of a novel series of chromone-derived compounds via the Pudovik reaction, employing the chiral organocatalyst (DHQ)2Phal. Although only moderate enantiomeric excess values were obtained, the scope of the reaction using different electron-withdrawing and electron-donating groups on substituted 3-formylchromones demonstrated the viability of this methodology. The absolute configuration of the final products was established through NMR analysis of diastereoisomeric derivatives with (S)-naproxen, complemented by computational calculations, including a study of the correlation between dipole moment and molecular polarity.