Solvent-assisted one-pot green and diastereoselective synthesis of 1,4-oxazines and 1,4-thioxazines under metal-free conditions

A novel and efficient three-component, one-pot green and diastereoselective synthesis of 1,4-oxazines and 1,4-thioxazines using formyl-chromone-based enamines under mild reaction conditions is presented. The desired products are afforded in <i>anti</i>-conformation and high yields (up to 95%). This method offers a significant improvement over traditional approaches, which often require harsh conditions, multiple steps, and expensive reagents. The broad substrate scope and high functional group tolerance make this protocol a powerful tool for highly diastereoselective synthesis of diverse classes of 1,4-oxazine and 1,4-thioxazine compounds, known for their wide range of biological activities. The synthetic route is environmentally friendly, aligning with the principles of green chemistry, as it avoids the use of toxic solvents and heavy metal catalysts.