Catching up with tetrazines: coordination of Re(i) to 1,2,4-triazine facilitates an inverse electron demand Diels-Alder reaction with strained alkynes to a greater extent than in corresponding 1,2,4,5-tetrazines

Inverse electron demand Diels Alder (IEDDA) reactions of 1,2,4-triazines are of interest to biorthogonal chemistry but suffer from slow kinetics. It is shown here that coordination of Re(i) to a 1,2,4-triazine ring speeds up the IEDDA reaction with bicyclooctyne (BCN) by a factor of 55. Comparative analysis with corresponding 1,2,4,5-tetrazine analogues reveals that the origin of the increased reactivity is markedly different and more profound than in tetrazine analogues. DFT calculations and subsequent analysis indicated the greater increase for the triazine than the tetrazines on coordination could be attributed to the triazine's lower distortion energy and more favourable interaction energy for the triazine, the latter attributable to lower Pauli repulsion than the tetrazines rather than to favourable frontier orbital energies.

Automated summary

It has been discovered in this study that the coordination of Re(i) to a 1,2,4-triazine ring can significantly accelerate the reaction rate with bicyclooctyne (BCN) by a factor of 55. Comparative analysis with corresponding 1,2,4,5-tetrazine analogues showed that the increased reactivity of triazine is more profound and different than tetrazines, which can be attributed to its lower distortion energy, more favorable interaction energy, and lower Pauli repulsion.