Computational Studies of Reactions of 1,2,4,5-Tetrazines with Enamines in MeOH and HFIP.
J Am Chem Soc
; 146(27): 18706-18713, 2024 Jul 10.
Article
in En
| MEDLINE
| ID: mdl-38941192
ABSTRACT
The reaction between 1,2,4,5-tetrazines and alkenes in polar solvents proceeds through a Diels-Alder cycloaddition along the C-C axis (C3/C6 cycloaddition) of the tetrazine, followed by dinitrogen loss. By contrast, the reactions of 1,2,4,5-tetrazines with enamines in hexafluoroisopropanol (HFIP) give 1,2,4-triazine products stemming from a formal Diels-Alder addition across the N-N axis (N1/N4 cycloaddition). We explored the mechanism of this interesting solvent effect through DFT calculations in detail and revealed a novel reaction pathway characterized by C-N bond formation, deprotonation, and a 3,3-sigmatropic rearrangement. The participation of an HFIP molecule was found to be crucial to the N1/N4 selectivity over C3/C6 due to the more favored initial C-N bond formation than C-C bond formation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
J Am Chem Soc
Year:
2024
Type:
Article
Affiliation country:
China