Switchable SuFEx Linker Chemistry for Sequential Assembly of Heterocycles and Phenols Enabled by Intramolecular Non-covalent Interactions

Abstract

Sequence control is essential for the construction of both biomacromolecules and synthetic drugs or materials. We proposed switchable linker chemistry for the sequential assembly of readily accessible precursors. In this study, ethene sulfonyl fluoride (ESF) was selected as a switchable linker, which contains an alkene group capable of undergoing efficient Michael addition with aromatic nitrogen-containing heterocycles and a less reactive alkyl sulfonyl fluoride group. Upon reacted with heterocycles, the sulfonyl fluoride group was “switched on” through intramolecular non-covalent interactions between the SVI-F/O and the heterocycles. This interaction activates the otherwise less reactive sulfonyl fluoride group, making it more prone to undergo SuFEx reactions with phenols. The existence of this interaction was confirmed by single crystal structures of five representative substrates. The SuFEx linker has been successfully applied to achieve both effective coupling of nitrogen-containing heterocycles and phenols, as well as the synthesis of sequential-defined polymers.