Application of [4+2] Cycloaddition Reaction of Tetrazine with Cyclooctyne in the Construction of Pyridazine Structure with Axial Chirality

The application of [4+2] cycloaddition reaction of tetrazine with cyclooctyne in the construction of pyridazine structure with axial chirality was studied. The inverse electronic demand Diels-Alder reaction of tetrazine bearing bulky groups with macrocyclic tension's cyclooctyne could take place under catalyst-free conditions in dichloromethane. The reaction underwent a six-membered bridged transition state, gently release a molecule of nitrogen to get axial chiral pyridazine structure. The transformation of the reaction can be determined by the change of color. The reaction could get potential axial chiral pyridazine structure with high yiled (95%) under mild conditions.