Can Biomimetic Zinc Compounds Assist a (3 + 2) Cycloaddition Reaction? A Theoretical Perspective

Compounds bearing tetrazole rings are valuable facets in numerous branches of chemistry including metabolic imaging and the production of drugs and high-energy materials. Synthesis of tetrazoles with the help of organocatalysts has intensively been explored, while enzyme-directed click chemistry has attracted less attention and was only used in inhibitor design so far. Herein, we have investigated the possibility of a biomimetic catalyst based on a Lewis acid approach by exploring the anionic cycloaddition of azide and acetonitrile catalyzed by ZnBr₂ in comparison with different biomimetic Zn(II) models. Density functional based calculations in the gas phase and with implicit solvation indicate that a variety of bioinspired zinc complexes should be able to catalyze tetrazole formation with catalytic enhancements comparable to zinc bromide salts. Such bioinspired routes could provide new possibilities for the stereo- and regioselectively controlled synthesis of tetrazoles.