Iterative Synthesis of Stereo‐ and Sequence‐Defined Polymers via Acid‐Orthogonal Deprotection Chemistry

Abstract

AbstractAbsolute control over polymer stereo‐ and sequence structure is highly challenging in polymer chemistry. Here, an acid‐orthogonal deprotection strategy is proposed for the iterative synthesis of a family of unimolecular polymers starting with enantiopure serines, featuring precise sequence, stereoconfiguration and side‐chain functionalities that cannot be achieved using traditional polymerization techniques. Acid‐orthogonal deprotections proceed independently of one another by the selection of protecting groups that feature the respective acid‐lability. Under p‐toluenesulfonic acid, acidolysis of tert‐butyloxycarbonyl can proceed exclusively, while low‐dosage trifluoroacetic acid and low temperature only trigger the selective and quantitative cleavage of trityl. The pioneering use of this acid‐orthogonal deprotection chemistry increases the compatibility with otherwise sensitive groups and opens up pathways to facilely introduce structural and functional diversity into stereo‐ and sequence‐defined polymers, thus imparting their unique properties beyond natural biopolymers.