Seok Ju Hong, Dong Hyeon Kim, Yujin Lim, Yongseok Kwon, Sangkyu Lee, Han Yong Bae

Advanced Functional Materials

DOI: 10.1002/adfm.76220

Abstract

Sulfur fluoride exchange (SuFEx) has emerged as a powerful click platform for the construction of functional molecules and advanced materials. However, the lack of water‐compatible, structurally versatile SuFEx‐active linchpins has limited their broader implementation in modular molecular engineering and in DNA‐based bioconjugates. Here, we introduce a diazonium linchpin platform that enables rapid molecular diversification and direct DNA functionalization under mild and scalable conditions. The linchpins are prepared through a chromatography‐free, decagram‐scale synthesis to afford aryldiazonium tetrafluoroborates that exhibit exceptional stability toward oxygen and aqueous environments. These multifunctional building blocks undergo rapid Pd(II)‐catalyzed cross‐coupling in aqueous media, delivering structurally diverse aryl sulfonyl fluorides in 10 min with good functional‐group tolerance. This platform further extends to halo‐ and azido‐functionalized SuFEx hubs, providing streamlined access to triazenes, sulfonates, sulfonamides, and sulfonyl azides as versatile connectors for functional molecular assembly. More importantly, the intrinsic water compatibility of this system enables highly efficient, catalyst‐free on‐DNA SuFEx ligation with amino‐ and phenol‐modified double‐stranded DNA headpieces, directly integrating small‐molecule diversification with biomolecular conjugation. By unifying rapid, scalable aqueous diversification with bioorthogonal functionalization, this work tentatively establishes a versatile, small‐molecule materials‐oriented strategy for constructing SuFEx‐active molecular libraries and DNA‐conjugated architectures, including DNA‐encoded libraries.