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

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 (PS 1.5k -Nb) and polyethylene glycols with either tetrazine or aryl azido functionalities (PEG 3k/5k -Tz, PEG 3k/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 PS 1.5k -Nb with PEG 3k/5k -Az requires 1 H-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 PS 1.5k -Nb with PEG 3k/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.