title: Computational study on the reactivity of tetrazines toward organometallic reagents.
abstract: The possible reaction pathways between methyllithium and disubstituted 1,2,4,5-tetrazines (bearing methyl, methylthio, phenyl, and 3,5-dimethylpyrazolyl groups) were investigated by means of the density functional theory B3LYP/6-31G* method. Solvation was modeled using the supermolecule approach, adding one tetrahydrofuran molecule to the complexes. Comparison of the calculated energies and structures for the alternate azaphilic and nucleophilic addition pathways showed that the azaphilic addition is kinetically favored over nucleophilic addition, while thermodynamically the nucleophilic addition is usually preferred. The coordination of the tetrazine molecule with methyllithium was found to play a crucial role in the process. These findings provide the first rationale for the experimentally observed unique reactivity of tetrazines toward polar organometallic reagents, suggesting the presence of a kinetically controlled process.
authors.affiliation: Institute of Chemistry, Eötvös Loránd University, 1/A Pázmány Péter Stny., H-1117 Budapest, Hungary.
authors.forename: Krisztián
authors.initials: K
authors.lastname: Lorincz
authors.forename: András
authors.initials: A
authors.lastname: Kotschy
authors.forename: Jaana
authors.initials: J
authors.lastname: Tammiku-Taul
authors.forename: Lauri
authors.initials: L
authors.lastname: Sikk
authors.forename: Peeter
authors.initials: P
authors.lastname: Burk
mesh_terms: D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013777:Tetrazoles / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D009942:Organometallic Compounds; D013777:Tetrazoles