Metal‐Free Synthetic Approach to 3‐Monosubstituted Unsymmetrical 1, 2, 4, 5‐Tetrazines Useful for Bioorthogonal Reactions. Issue 37 (13th August 2018)

• Record Type: Journal Article
• Authors: Qu, Yangyang; Sauvage, François‐Xavier; Clavier, Gilles; Miomandre, Fabien; Audebert, Pierre
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 37(2018)
• Page Start: 12057
• Page End: 12061
• Publication Date: 2018-08-13
• Subjects: bioorthogonal reactions -- click chemistry -- cycloadditions -- metal-free synthesis -- tetrazines; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201804878
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A facile, efficient and metal‐free synthetic approach to 3‐monosubstituted unsymmetrical 1, 2, 4, 5‐tetrazines is presented. Dichloromethane (DCM) is for the first time recognized as a novel reagent in the synthetic chemistry of tetrazines. Using this novel approach 11 3‐aryl/alkyl 1, 2, 4, 5‐tetrazines were prepared in excellent yields (up to 75 %). The mechanism of this new reaction, including the role of DCM in the tetrazine ring formation, has been investigated by 13 C labeling of DCM, and is also presented and discussed as well as the photophysical and electrochemical properties. Abstract : Cycloadditions : A facile, efficient and metal‐free synthetic approach to 3‐monosubstituted unsymmetrical 1, 2, 4, 5‐tetrazines is presented. Dichloromethane (DCM) is for the first time recognized as a reagent in tetrazine synthesis. Using this approach 11 tetrazine compounds have been prepared in excellent yield (up to 75 %). The role of DCM in the tetrazine ring formation was studied with 13 C labeled DCM (MW=microwave).