Unsymmetrical Dipolar Regulation of Tetrazine Cycloaddition to C ₆₀ : Modulating the Reactivity and Switching Site Selectivity on the 1,4-C ₆₀ Adducts

Herein, we report that 1,4-unsymmetric modification of the fullerene core can tune the site selectivity and reactivity of C₆₀. An unconventional hydrated 4,5-dihydropyridazine ring structure was formed due to the site-selective 1,2,4,5-tetrazine cycloaddition of 1,4-unsymmetrical C₆₀ adducts. Indole substituents on C₆₀ have been found to create a shielding effect on the nearby [6,6] double bond, influencing its reactivity toward 1,2,4,5-tetrazine cycloaddition. Furthermore, we found that by varying the 1,4-unsymmetrical bifunctionalization, bifunctional sheltering-activation tuning could be reversed, allowing site selectivity to be modulated across different hemispheres of the fullerene. 1,4-Unsymmetric C₆₀ adducts have been demonstrated as a significant platform for the discovery and site-selective preparation of multiadducts that are rare and challenging to synthesize.