Preparation of Unsymmetrical 1,2,4,5-Tetrazines via a Mild Suzuki Cross-Coupling Reaction

Article abstract of DOI:10.1021/acs.orglett.7b02868

N-Alkyl substituted chlorotetrazines were coupled with various boronic acids under Suzuki conditions in high yield at room temperature, giving a mild and straightforward synthetic route toward diverse unsymmetrical 1,2,4,5-tetrazines, a rare heteroarene. This chemistry not only expands the known substrate scope of tetrazine cross-coupling reactions but also allows for the synthesis of novel, tetrazine-containing biologically active molecules with improved DMPK properties.