Direct Access to CF3-Containing 4H-1,3-Oxazines and 2-Aminopyrimidines Via a [4 + 2] Annulation Using In Situ Generated Carbodiimide Anions

Abstract

The carbodiimide anions which were generated in situ from N-cyano-N-aryl-p-toluenesulfonamides (NCTS) in the presence of the base participated in annulations that remain less reported to date. Herein, we have developed for the first time an efficient and environmentally friendly [4 + 2] annulation reaction of CF₃-substituted hetero-1,3-dienes with NCTS for the efficient synthesis of CF₃-substituted 4H-1,3-oxazines and 2-aminopyrimidines under transition-metal-free conditions. The methodology demonstrates the advantages of readily available substrates, simple operation, good functional group tolerance, and broad substrate scope, providing a promising route to the synthesis of structurally diverse CF₃-substituted scaffolds. The products followed by simple transformations provide a facile route to TAS2R14 agonist analogues.