Quantitative and Orthogonal Formation and Reactivity of SuFEx Platforms

Abstract

The constraints of minute reactant amounts and the impossibility to remove any undesired surface‐bound products during monolayer functionalization of a surface necessitate the selection of efficient, modular and orthogonal reactions that lead to quantitative conversions. Herein, we explore the character of sulfur–fluoride exchange (SuFEx) reactions on a surface, and explore the applicability for quantitative and orthogonal surface functionalization. To this end, we demonstrate the use of ethenesulfonyl fluoride (ESF) as an efficient SuFEx linker for creating “SuFEx‐able” monolayer surfaces, enabling three distinct approaches to utilize SuFEx chemistry on a surface. The first approach relies on a di‐SuFEx loading allowing dual functionalization with a nucleophile, while the two latter approaches focus on dual (CuAAC–SuFEx/SPOCQ–SuFEx) click platforms. The resultant strategies allow facile attachment of two different substrates sequentially on the same platform. Along the way we also demonstrate the Michael addition of ethenesulfonyl fluoride to be a quantitative surface‐bound reaction, indicating significant promise in materials science for this reaction.

Complementary Base Lowers the Barrier in SuFEx Click Chemistry for Primary Amine Nucleophiles

“…[10,23] Overall it is observed that strong bases and H2Fcan act as catalysts for the reaction. [10,19,24] We challenge and extend this understanding in the present study. Very recently, the mechanism of the Si-Free SuFEx reaction with phenolate anions was investigated with the help of density functional theory (DFT) and an addition-elimination mechanism with very low barriers and early transition states was found while an SN2-type reaction could not be excluded under experimental conditions.…”

SuFEx-enabled, agnostic discovery of covalent inhibitors of human neutrophil elastase

“…Considering the monocovalent attachment mode of 1, with the second -SO 2 F intact, it was envisaged that 1 of the 2 sulfonyl fluoride groups could be substituted so as to perhaps improve the capture rate, and/or selective binding (Table 1). A set of benzenesulfonyl fluoride cores carrying ortho-substituents (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) was therefore examined. Compounds 8-18 (90) were synthesized by the efficient aqueous potassium bifluoride exchange procedure from commercially available sulfonyl chlorides but showed poorer reactivity/binding with hNE.…”

“…click chemistry | SuFEx | agnostic | covalent inhibitor | elastase S ulfur fluoride exchange (SuFEx)-the new-generation click chemistry, since first introduced in 2014 (1), has quickly found diverse applications across an array of fields (DOI: 10.1039/C8CS00960K), including chemical synthesis (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), material science (13)(14)(15)(16)(17)(18)(19), chemical biology (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32), and drug discovery (33,34). SuFEx creates robust intermolecular links between modules.…”

Complementary Base Lowers the Barrier in SuFEx Click Chemistry for Primary Amine Nucleophiles

“… 17 , 18 In this context, single-step reaction procedures like SuFEx are strongly preferred due to the synthetic constraints added by the surface. 19 Furthermore, optimization of reaction conditions in UHV chemistry is limited since variation of, e.g., solvent or pH values are not possible. Thus, a “click”-type reaction is sought for.…”

“…Suitability of SuFEx for surface functionalization and the “click”-character under typical reaction conditions has been shown recently in several studies. 19 − 21 It has also been noted that for surface functionalization, amine-based nucleophiles ( Scheme 1 ) are preferred over the standard SuFEx route since no prior installation of silyl ethers on the surface is necessary. 19 We thus set out to understand the reaction mechanism of SuFEx in vacuum as well as wet chemical conditions to test its feasibility for the scenarios of surface functionalization mentioned above.…”