Synthesis of 2‐Trifluoromethyl Pyridines through Multicomponent Kröhnke Reaction

Abstract

A multicomponent Kröhnke reaction route toward 2‐trifluoromethyl pyridines from reaction of chalcones with easily available and stable 1‐(3,3,3‐trifluoro‐2‐oxopropyl)pyridin‐1‐ium bromide and ammonium acetate is reported. The reaction is found to be general with a range of substituted chalcones, and the applicability of the methodology in gram scale is demonstrated. Preliminary results suggest that this transformation is initiated by 1,4‐Michael addition, followed by inter‐ and intramolecular nucleophilic addition, and elimination.