Synthesis of novel pyridinium 1,5-zwitterions and their reactivity with isatin-based α-(trifluoromethyl)imines: a sulfur-controlled domino reaction

Abstract

A new stable pyridinium 1,5-zwitterion, generated from azadiene and 4-dimethylaminopyridine, was isolated for the first time. According to DFT calculations, the stability of this species was attributed to be the polarization effect on the exocyclic double bond. The reaction of pyridinium 1,5-zwitterion with isatin-derived α-(trifluoromethyl)imine was regulated by experimental temperature. The umpolung [4 + 3] annulation with isatin-derived α-(trifluoromethyl)imine was reported for the first time at 20 °C in CH₃CN. In contrast, the formal Michael addition occurred when performing the reaction at reflux. Compared to the oxygen and methylene analogues, a sulfur atom changed the reaction mode from the umpolung [4 + 3] to the classical [3 + 2] annulation.