Addition of a Cyclophosphine to Nitriles: An Inorganic Click Reaction Featuring Protio,Organo, and Main‐Group Catalysis

The addition of a cyclotriphosphine to a broad range of nitriles gives access to the first examples of free 1‐aza‐2,3,4‐triphospholenes in a rapid, ambient temperature, one‐pot, high‐yield protocol. The reaction produces electron‐rich heterocycles (four lone pairs) and features homoatomic σ‐bond heterolysis, thereby combining the key features of the 1,3‐dipolar cycloaddition chemistry of azides and cyclopropanes. Also reported is the first catalytic addition of P−P bonds to the C≡N bond. The coordination chemistry of the new heterocycles is explored.     

Biocompatible SuFEx Click Chemistry: Thionyl Tetrafluoride (SOF4)‐Derived Connective Hubs for Bioconjugation to DNA and Proteins

We report here the development of a suite of biocompatible SuFEx transformations from the SOF₄‐derived iminosulfur oxydifluoride hub in aqueous buffer conditions. These biocompatible SuFEx reactions of iminosulfur oxydifluorides (R‐N=SOF₂) with primary amines give sulfamides (8 examples, up to 98 %), while the reaction with secondary amines furnish sulfuramidimidoyl fluoride products (8 examples, up to 97 %). Likewise, under mild buffered conditions, phenols react with the iminosulfur oxydifluorides (Ar‐N=SOF₂) to produce sulfurofluoridoimidates (13 examples, up to 99 %), which can themselves be further modified by nucleophiles. These transformations open the potential for asymmetric and trisubstituted linkages projecting from the sulfur(VI) center, including versatile S?N and S?O connectivity (9 examples, up to 94 %). Finally, the SuFEx bioconjugation of iminosulfur oxydifluorides to amine‐tagged single‐stranded DNA and to BSA protein demonstrate the potential of SOF₄‐derived SuFEx click chemistry in biological applications.     

A New Portal to SuFEx Click Chemistry: A Stable Fluorosulfuryl Imidazolium Salt Emerging as an “F−SO2+” Donor of Unprecedented Reactivity,Selectivity, and Scope

Sulfuryl fluoride, SO₂F₂, has been found to derivatize phenols in all kinds of environments, even those in highly functional molecules. We now report that a solid fluorosulfuryl imidazolium triflate salt delivers the same “F−SO₂ + ” fragment to Nu−H acceptor groups in the substrates. However, this triflate salt is a far more reactive fluorosulfurylating agent than SO₂F₂ and displays selectivity preferences of its own. Moreover, the new azolium triflate reagent reacts once with primary amines and anilines before the reaction stops. On the other hand, with triethylamine and two equivalents of the “F−SO₂ + ” donor present, it proceeds on to the bis(fluorosulfuryl)imides in good yield—two important conversions that we have never seen with sulfuryl fluoride as the electrophile.     

Efficient Construction of Well‐Defined Multicompartment Porous Systems in a Modular and Chemically Orthogonal Fashion

A microfluidic assembly approach was developed for efficiently producing hydrogel spheres with reactive multidomains that can be employed as an advantageous platform to create spherical porous networks in a facile manner with well‐defined multicompartments and spatiotemporally controlled functions. This strategy allows for not only large scale fabrication of various robust hydrogel microspheres with controlled size and porosity, but also the domains embedded in hydrogel network could be introduced in a modular manner. Additionally, the number of different domains and their ratio could be widely variable on demand. More importantly, the reactive groups distributed in individual domains could be used as anchor sites to further incorporate functional units in an orthogonal fashion, leading to well‐defined multicompartment systems. The strategy provides a new and efficient route to construct well‐defined functional multicompartment systems with great flexibility and extendibility.     

Anisotropically Swelling Gels Attained through Axis‐Dependent Crosslinking of MOF Crystals

Anisotropically deforming objects have attracted considerable interest for use in molecular machines and artificial muscles. Herein, we focus on a new approach based on the crystal crosslinking of organic ligands in a pillared‐layer metal–organic framework (PLMOF). The approach involves the transformation from crosslinked PLMOF to polymer gels through hydrolysis of the coordination bonds between the organic ligands and metal ions, giving a network polymer that exhibits anisotropic swelling. The anisotropic monomer arrangement in the PLMOF underwent axis‐dependent crosslinking to yield anisotropically swelling gels. Therefore, the crystal crosslinking of MOFs should be a useful method for creating actuators with designable deformation properties.     

Remote Regulation of Membrane Channel Activity by Site‐Specific Localization of Lanthanide‐Doped Upconversion Nanocrystals

The spatiotemporal regulation of light‐gated ion channels is a powerful tool to study physiological pathways and develop personalized theranostic modalities. So far, most existing light‐gated channels are limited by their action spectra in the ultraviolet (UV) or visible region. Simple and innovative strategies for the specific attachment of photoswitches on the cell surface without modifying or genetically encoding channel structures, and more importantly, that enable the remote activation of ion‐channel functions within near‐infrared (NIR) spectral window in living systems, remain a challenging concern. Herein, metabolic glycan biosynthesis is used to achieve site‐specific covalent attachment of near‐infrared‐light‐mediated lanthanide‐doped upconversion nanocrystals (UCNs) to the cell surface through copper‐free click cyclization. Upon irradiation with 808 nm light, the converted emission at 480 nm could activate a light‐gated ion channel, channelrhodopsins‐2 (ChR2), and thus remotely control the cation influx. This unique strategy provides valuable insights on the specific regulation membrane‐associated activities in vivo.     

Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides

SuFEx is a new‐generation click chemistry transformation that exploits the unique properties of S?F bonds and their ability to undergo near‐perfect reactions with nucleophiles. We report here the first SuFEx‐based procedure for the efficient synthesis of pharmaceutically important triflones and bis(trifluoromethyl)sulfur oxyimines from sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new process involves rapid S?F exchange with trifluoromethyltrimethylsilane (TMSCF₃) upon activation by potassium bifluoride in anhydrous DMSO. The reaction tolerates a wide selection of substrates and proceeds under mild conditions without need for chromatographic purification. A tentative mechanism is proposed involving nucleophilic displacement of S?F by the trifluoromethyl anion via a five‐coordinate intermediate. The utility of late‐stage SuFEx trifluoromethylation is demonstrated through the synthesis and selective anticancer properties of a bis(trifluoromethyl)sulfur oxyimine.     

Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF4 Hub

Sulfur(VI) fluoride exchange (SuFEx) is a new family of click chemistry based transformations that enable the synthesis of covalently linked modules via S^VI hubs. Here we report thionyl tetrafluoride (SOF₄) as the first multidimensional SuFEx connector. SOF₄ sits between the commercially mass‐produced gases SF₆ and SO₂F₂, and like them, is readily synthesized on scale. Under SuFEx catalysis conditions, SOF₄ reliably seeks out primary amino groups [R‐ NH₂ ] and becomes permanently anchored via a tetrahedral iminosulfur(VI) link: R−N=(O=)S(F)₂. The pendant, prochiral difluoride groups R−N=(O=) SF₂ , in turn, offer two further SuFExable handles, which can be sequentially exchanged to create 3‐dimensional covalent departure vectors from the tetrahedral sulfur(VI) hub.