Closer Look at Inverse Electron Demand Diels-Alder and Nucleophilic Addition Reactions on s-Tetrazines Using Enhanced Sampling Methods.

ABSTRACT: Inverse electron demand [4+2] Diels-Alder (iEDDA) reactions as well as unprecedented nucleophilic (azaphilic) additions of R-substituted silyl-enol ethers (where R is Phenyl, Methyl, and Hydrogen) to 1,2,4,5-tetrazine (s-tetrazine) catalyzed by BF3 have recently been discovered (Simon et al. in Org Lett 23(7):2426-2430, 2021), where static calculations were employed for calculation of activation energies. In order to have a more realistic dynamic description of these reactions in explicit solution at ambient conditions, in this work we use a semiempirical tight-binding method combined with enhanced sampling techniques to calculate free energy surfaces (FESs) of the iEDDA and azaphilic addition reactions. Relevant products of not only s-tetrazine but also its derivatives such

SUBMITTER: Ketkaew R 

PROVIDER: S-EPMC8816378 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature