Diastereoselective Synthesis of Substituted Chromenopyrrolidinones from Amino Acid Derived Nitriles

Novel substituted chromenopyrrolidinones were synthesized from natural amino acid derivatives through an unprecedented route involving a Knoevenagel/transesterification sequence and an allylative palladium-catalyzed cyclization reaction. The products were nature-inspired heterocycles derived from natural amino acids. The targets were synthesized with varying degrees of stereoselectivity: racemization is a known issue with amino acids, and this provided a formidable challenge to our method development. In total, six derivatives were synthesized in moderate to good yields.