72116-54-2Relevant academic research and scientific papers
Nucleophilic Attack on Nitrogen in Tetrazines by Silyl-Enol Ethers
Schnell, Simon D.,Schilling, Mauro,Sklyaruk, Jan,Linden, Anthony,Luber, Sandra,Gademann, Karl
supporting information, p. 2426 - 2430 (2021/04/05)
The nucleophilic addition of silyl-enol ethers to nitrogen in 3-monosubstituted s-tetrazines mediated by BF3 is reported. The preference for this azaphilic addition over the usually observed inverse electron demand Diels-Alder reactions was evaluated theoretically and corroborated by experiments. The substrate dependency of this unusual reaction was rationalized by determination of the activation barriers and on the basis of the activation strain model by employing density functional theory.
Divergent Synthesis of Monosubstituted and Unsymmetrical 3,6-Disubstituted Tetrazines from Carboxylic Ester Precursors
Fang, Yinzhi,Fox, Joseph M.,Huang, Zhen,Tallon, Amanda M.,Xie, Yixin,am Ende, Christopher W.
supporting information, p. 16967 - 16973 (2020/08/10)
Since tetrazines are important tools to the field of bioorthogonal chemistry, there is a need for new approaches to synthesize unsymmetrical and 3-monosubstituted tetrazines. Described here is a general, one-pot method for converting (3-methyloxetan-3-yl)methyl carboxylic esters into 3-thiomethyltetrazines. These versatile intermediates were applied to the synthesis of unsymmetrical tetrazines through Pd-catalyzed cross-coupling and in the first catalytic thioether reduction to access monosubstituted tetrazines. This method enables the development of new tetrazine compounds possessing a favorable combination of kinetics, small size, and hydrophilicity. It was applied to a broad range of aliphatic and aromatic ester precursors and to the synthesis of heterocycles including BODIPY fluorophores and biotin. In addition, a series of tetrazine probes for monoacylglycerol lipase (MAGL) were synthesized and the most reactive one was applied to the labeling of endogenous MAGL in live cells.
