Reactions of N-amino isoquinaldinium and N-alkylpicolinium salts with s-tetrazines

Abstract

A dearomative/rearomative reaction between 3,6-diaryl-s-tetrazines and quaternary N-amino isoquinaldinium salt was discovered afford pyrazolo[5,1-a]isoquinolines. Its mechanism was elucidated on the basis of isolated intermediates, stabilized by specific carbon-to-nitrogen atom replacements in the tetrazine counterpart. The reaction pathway includes sequential enamine/tetrazine cycloaddition, bridged [1,2,4,5]-tetrazepine ring closure, spontaneous hydrazone dehydrogenation, and diazo-intermediate fragmentation steps. In turn, with cyanodiazines, N-amino isoquinaldinium salt reacts with an unusual loss of the C1-methyl group to form triazolo[5,1-a]isoquinolines. Additionally, a related reaction of unsymmetrically substituted tetrazines with N-methyl 2-picolinium or quinaldinium salts to give heterostilbenes with high regio- and stereoselectivity was demonstrated. A mechanistic explanation was suggested, and facile photochemical cis→trans isomerization was shown. The findings, outlined in this study could be helpful for researchers involved in tetrazine chemistry, or those, pursuing dyes and photoswitches.