Asymmetric Pudovik Reaction as a Tool for Functionalizing 3-Formyl Chromones

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-formyl chromones demonstrated the viability of this methodology. The absolute configuration of the final products was established through NMR analysis of diastereomeric derivatives with (S) Naproxen, complemented by computational calculations, including a study of the correlation between dipole moment and molecular polarity.