Tetrazine-norbornene versus azide-norbornene ligation: evaluating the toolbox for polymer-polymer coupling

Abstract

The selective ligation chemistry of the stable norbornene (Nb) with an asymmetric tetrazine (Tz), accessible in a one-pot reaction is adapted to the ligation of polymer segments yielding block copolymers. The Tz/Nb inverse electron-demand Diels-Alder reaction (IEDDA) is compared with the more classical azide (Az)-norbornene Huisgen 1,3-cycloaddition (CA) to ligate end-functionalized polymers. An endo/exo-norbornene end-functionalized polystyrene (PS1.5k-Nb) and polyethylene glycols with either tetrazine or aryl azido functionalities (PEG3k/5k-Tz, PEG3k/5k-Az) are synthesized. While the Tz/Nb IEDDA proceeds cleanly and leads to full conversion in stochiometric mixtures, the Az/Nb CA requires less effort but suffers from slower coupling kinetics and some side reactions. The coupling of PS1.5k-Nb with PEG3k/5k-Az requires 1H-NMR analysis to follow the kinetics and the products suffer from incomplete conversion as well as slight decomposition of the Az-moieties. In contrast, the ligation of PS1.5k-Nb with PEG3k/5k-Tz is robust. The reaction, which is conveniently monitored by UV/Vis spectroscopy, yields the desired PS-block-PEG in high yields and may offer potential for easy scale-up.