SuFEx‐Based Polysulfonate Formation from Ethenesulfonyl Fluoride–Amine Adducts

Abstract

In this work, we describe the SuFEx-based polycondensation between bisalkylsulfonyl fluorides (AA monomers) and bisphenol bis(t-butyldimethylsilyl) ethers (BB monomers) using [Ph3P=N-PPh3]+[HF2]− as the catalyst. The AA monomers were prepared via the highly reliable Michael addition of ethenesulfonyl fluoride and amines/anilines while the BB monomers were obtained from silylation of bisphenols by t-butyldimethylsilyl chloride. With these reactions, we were able to achieve a remarkable diversity of monomeric building blocks by exploiting readily available amines, anilines, and bisphenols as starting materials. The SuFEx-based polysulfonate formation reaction exhibited excellent efficiency and functional group tolerance, producing polysulfonates with a variety of side chain functionalities in >99% conversion within 10 min to 1 h. When bearing an orthogonal group on the side chain, the polysulfonates can be further functionalized via click-chemistry based post-polymerization modification.

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.…”

“…The facilitating agents are "H + " or "R 3 Si + ." The process especially favors a 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU)-type amine catalyst (13,40,41), and is also thought to involve bifluoride counterion species (16,17,42).…”

Installation of sulfonyl fluorides onto primary amides

“…Sulfur(VI) fluoride exchange (SuFEx), is a new class of click chemistry developed by Professor K. B. Sharpless and coworkers in 2014, for creating molecular connections based on the unique stability-reactivity pattern of S VI -F bond with absolute reliability and unprecedented efficiency, which has been widely applied in organic synthesis, chemical biology and drug discovery [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Among all the developed S(VI)-F species, sulfonyl fluoride (RSO2F) was specifically recognized as unique scaffold for covalent protein inhibitors and biological probes with the affinity-driven activation for forming covalent linkages with the amino acid residues of protein binding sites (Figure 1) [20].…”

SuFEx Chemistry of Thionyl Tetrafluoride (SOF4) with Organolithium Nucleophiles: Synthesis of Sulfonimidoyl Fluorides, Sulfoximines, Sulfonimidamides, and Sulfonimidates

“…[3] Sulfur fluoride derivatives are uniquely suited for click chemistry owing to their inherent thermodynamic and redox stability, [4] yet, given the right conditions have alacrity for certain transformations through a cooperative engagement of catalyst, reagent and solvent. [1] The power of SuFEx click chemistry has been demonstrated in applications, including the development of synthetic methods, [5] the preparation of polymers, [6] and in medicinal chemistry programs. [7] Most intriguingly, there is growing evidence to suggest that S–F handles (e.g.…”