1,2,4,5-Tetrazines serve as versatile two-carbon synthons, essential for synthesizing a variety of (hetero)aromatic compounds. Their specific reactivity with certain dienophiles, without interfering with biochemical processes, makes them ideal for bioorthogonal ligation. Despite their broad utility, current synthetic methods are costly and raise safety concerns, particularly during scale-up. This study introduces safer and more cost-effective synthetic strategies utilizing zinc chloride or boron trifluoride diethyl etherate as catalysts. These alternatives significantly reduce costs and enhance safety, potentially expanding the applicability of tetrazine synthesis across broader research domains.
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1F1A1061297), the Core Research Institute Basic Science Research Program through the NRF funded by the Ministry of Education (No. 2021R1A6A1A10044950), and the H2KOREA funded by the Ministry of Education (2022Hydrogen fuel cell-002, Innovative Human Resources Development Project for Hydrogen Fuel Cells). This research was also supported by Global\u2013Learning & Academic research institution for Master's\u00B7PhD students, and Postdocs (G-LAMP) Program of the NRF grant funded by the Ministry of Education (No. RS-2023-00285390).This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1F1A1061297), the Core Research Institute Basic Science Research Program through the NRF funded by the Ministry of Education (No. 2021R1A6A1A10044950), and the H2KOREA funded by the Ministry of Education (2022Hydrogen fuel cell\u2010002, Innovative Human Resources Development Project for Hydrogen Fuel Cells). This research was also supported by Global\u2013Learning & Academic research institution for Master's\u00B7PhD students, and Postdocs (G\u2010LAMP) Program of the NRF grant funded by the Ministry of Education (No. RS\u20102023\u201000285390).
