Comprehensive Summary Sulfonyl groups represent one of the most encountered structural motifs in medicinal chemistry. They serve as stable linkers that connect pharmacophoric elements within a molecule and as modulators of physicochemical properties, including lipophilicity, conformational flexibility, and metabolic susceptibility. This versatility makes sulfonyl‐containing compounds highly attractive in drug discovery campaigns, particularly for protease inhibitors, kinase modulators, and covalent inhibitors. Among the various sulfonyl derivatives, sulfonyl fluorides have garnered interest due to their stability under ambient conditions and their ability to participate in sulfur(VI) fluoride exchange (SuFEx) reactions. Despite these advantages, the practical synthesis of sulfonyl fluorides remains a significant bottleneck. Conventional methodologies, such as oxidation of thiols or fluorination of sulfonyl chlorides, often suffer from narrow substrate scopes, incompatibility with sensitive functional groups, harsh reaction conditions and unsatisfactory regioselectivity when applied to polyfunctionalized molecules. These limitations severely impede the rapid assembly of sulfonyl fluoride libraries for biological screening and late‐stage functionalization of complex drug candidates. To address this unmet need, we have developed a nickel‐catalyzed Negishi cross‐coupling protocol that utilizes bromomethyl sulfonyl fluoride (BMSF) as a readily available radical precursor. This approach enables the efficient construction of phenylmethylsulfonyl fluorides. The reaction proceeds under remarkably mild conditions, operates with high catalytic efficiency, tolerates a broad array of functional groups and exhibits excellent site selectivity even in the presence of multiple reactive sites. The synthetic utility of this method is further demonstrated by the facile conversion of the obtained products into a diverse range of sulfonamide derivatives through simple nucleophilic substitution reactions. This modular transformation provides a straightforward and scalable route to sulfonyl‐linked molecular architectures, thus offering a versatile platform for medicinal chemistry efforts.
Comprehensive Summary gem ‐Bis(silanes) have attracted significant attention due to their unique reactivity and functionality. Herein, we report a highly efficient Co/Ni‐catalyzed dehydrogenative silylation/hydrosilylation reaction of alkenes for the construction of gem ‐bis(silanes). The unanticipated nickel impurities efficiently drive the key hydrosilylation step, enabling a high turnover number ( TON ) of up to 24,000. This reactivity represents the highest TON achieved for nickel‐catalyzed hydrosilylation of alkenes. Mechanistic studies have revealed that the silicon‐based directing effect plays a crucial role in governing both the reactivity and selectivity of this process. Furthermore, by controlling the nature of the nickel–hydride species, the key hydrosilylation step can be switched between geminal and vicinal pathways.
Comprehensive Summary Achieving an open‐circuit voltage ( V OC ) exceeding 1.2 V in organic solar cells (OSCs) often comes at the cost of limited short‐circuit current density ( J SC ) and power conversion efficiency (PCE). Modulating intermolecular interactions to optimize active layer morphology is an effective strategy to balance exciton dissociation and carrier recombination. In this work, we adopt an asymmetric fluorination strategy on A 2 ‐A 1 ‐D‐A 1 ‐A 2 type nonfullerene acceptors (NFAs) by introducing one fluorine atom on the π‐bridge, aiming to tune molecular dipole moments and stacking behavior. The resulting asymmetric acceptor (HF‐BTA3) shows a larger dipole moment than the symmetric BTA3, promoting tighter π‐π stacking and favorable donor‐acceptor interactions. Using classic D18 or PTQ10 as donors, all devices yield V OC above 1.2 V. Notably, HF‐BTA3‐based devices achieve significantly higher PCE (10.18% for D18:HF‐BTA3, V OC = 1.240 V; 10.05% for PTQ10:HF‐BTA3, V OC = 1.271 V) compared to BTA3‐based ones (8.03% and 6.61%, respectively). Our findings demonstrate that asymmetric fluorination is an effective molecular engineering approach for A 2 ‐A 1 ‐D‐A 1 ‐A 2 type NFAs to modulate intermolecular interactions, enabling high V OC (>1.2 V) and PCE over 10%.
Comprehensive Summary Solvent effects permeate essentially all solution‐phase chemistry. Yet, a unified and generally predictive description remains challenging because solvent effects span multiple length and time scales: bulk dielectric screening and viscosity capture only part of the physics, while first‐shell coordination, ion pairing, hydrophobic aggregation, and heterogeneous structural fluctuations can be decisive near the reaction coordinate; moreover, when solvent relaxation occurs on time scales comparable to chemical events, nonequilibrium solvation and memory effects may invalidate static free energy corrections. This review outlines a practical trajectory from early phenomenology to modern computation and, more recently, data‐driven decision making. We first revisit the conceptual roots of solvent effects and the rise of empirical solvent scales that compress complex microscopic behavior into usable descriptors. We then summarize the logic of implicit, explicit, and hybrid solvent models in contemporary computational chemistry, emphasizing their assumptions, cost‐accuracy trade‐offs, and applicability. Finally, we discuss data standardization and benchmarking for solvation modeling, learning‐based prediction of properties and solvation free energies, machine‐learned potentials that enable scalable explicit solvent simulations, and emerging workflows for solvent/condition recommendation and closed‐loop optimization. Key Scientists
Comprehensive Summary The selective electrooxidation of methanol to formate is a kinetically complex process involving multiple intermediates ( e.g ., *CH 3 O, *CHO, *OH), whose adsorption energies are difficult to regulate simultaneously. Here, we report a conceptually new electric‐field‐directed relay catalysis strategy based on a Ni 4 Mo/MoO 2 Mott‐Schottky heterojunction. Using a combination of UPS, XPS, and XAFS, we demonstrate that the built‐in electric field (BIEF) drives directional electron transfer from metallic Ni 4 Mo to semiconducting MoO 2 , creating spatially separated electron‐deficient Ni sites and electron‐rich MoO 2 interfaces. Operando FTIR and Raman spectroscopy directly visualize the dynamic evolution of intermediates, revealing a relay mechanism: Ni sites promote *CH 3 O adsorption and C–H/O–H bond cleavage, while MoO 2 enhances *OH supply to accelerate *CHO oxidation. DFT calculations confirm that this BIEF‐mediated spatial decoupling lowers the energy barrier of the potential‐determining step (*CHO → *HCOOH) from 1.96 eV (Ni 4 Mo) to only 0.76 eV. Consequently, the obtained catalyst achieves a peak current density of 345.2 mA·cm –2 with >97% Faradaic efficiency for formate. This work establishes a new paradigm for designing heterojunction electrocatalysts that leverage interfacial electric fields to orchestrate multi‐step reaction pathways with high selectivity.
Comprehensive Summary Transition‐metal‐catalyzed C–H borylation is a powerful strategy for constructing C–B bonds, which are valuable intermediates in organic synthesis. However, many existing methods require precious metal catalysts, harsh conditions, or stoichiometric oxidants, and often demand strict exclusion of moisture and oxygen, limiting their practicality. Herein, we report a mild method for direct C(sp 2 )–H borylation of (hetero)arenes and perfluoroarenes using air as a green oxidant. The approach employs inexpensive FeCl 3 as a photocatalyst and chlorine radicals as hydrogen atom transfer (HAT) reagents. The transformation is driven by chlorine radicals generated via ligand‐to‐metal charge transfer (LMCT), which abstract hydrogen atoms from B–H bonds to form boryl radicals, thereby enabling subsequent C–B bond formation. Using only catalytic amounts of FeCl 3 and air as a green terminal oxidant, this strategy overcomes the limitations previously associated with oxygen radical mediated B–H activation. A key advantage of our protocol is its remarkable robustness under ambient conditions, requiring neither anhydrous solvents nor inert‐atmosphere protection. Only a catalytic amount of FeCl 3 is needed, with air serving as the sole stoichiometric oxidant to regenerate the active iron species, thereby rendering the overall process atom‐economical and waste‐minimizing. The synthetic utility of this method was demonstrated by the successful preparation of a broad spectrum of (hetero)aryl and perfluoroaryl boronates bearing diverse functional groups. Furthermore, a one‐pot, two‐step Suzuki–Miyaura cross‐coupling of perfluoroarenes was accomplished without intermediate isolation, affording biaryl products in good overall yields. This tandem procedure highlights the considerable industrial potential of our strategy for the sustainable synthesis of pharmaceuticals, agrochemicals, and advanced functional materials.
Comprehensive Summary The copolymerization of ethylene with functionalized comonomers under industrially relevant high‐temperature conditions remains a great challenge in polyolefin catalysis. Herein, we report a series of arylsilane‐bridged dinuclear half‐titanocene catalysts designed to enhance thermal stability and comonomer incorporation capability. In ethylene/1‐octene copolymerization at 125 °C, the dinuclear catalysts exhibited high activities and achieved 1‐octene incorporations exceeding 20 mol%. By tuning reaction conditions, copolymers with molecular weights ranging from 33,000 to 191,000 and incorporations from 8.2 to 25.2 mol% were obtained, matching the metrics of commercial POE grades. More importantly, these catalysts demonstrated remarkable tolerance toward polar OH‐functionalized α‐olefins, with the dinuclear catalysts showing 2–4 fold higher activities than the mononuclear analogue. The catalysts also enabled efficient copolymerization of ethylene with a carbazole‐containing α‐olefin, achieving high activities (up to 2.11 × 10 7 g·mol Ti –1 ·h –1 ), high molecular weights (>580,000), and tunable carbazole incorporations (2.7–6.0 mol%). The carbazole‐functionalized polyethylenes exhibited unique fluorescence properties, tunable surface wettability, and significantly enhanced ductility. The dinuclear catalyst effect does not follow a universal rule, but is strongly correlated with the specific copolymerization reaction. This work demonstrates that dinuclear half‐titanocenes represent a versatile catalyst platform for high‐temperature synthesis of functional polyolefin materials with tailored properties.
Comprehensive Summary Glycosylation is a fundamental transformation in carbohydrate chemistry that is central to the synthesis of oligosaccharides and glycoconjugates. Glycosyl imidates are widely used glycosyl donors that enable catalytic activation; however, balancing their stability and reactivity remains an ongoing challenge. In this work, we introduce glycosyl N ‐(trifluoromethyl)benzimidates (TFBs) as a new family of glycosyl donors through a connectivity inversion strategy from conventional N ‐phenyl trifluoroacetimidates (PTFAs). TFB donors can be readily prepared from commercially available phenylacetonitrile, leaving space for future optimization. Comprehensive evaluation of TFB donors demonstrates their broad applicability in catalytic glycosylations. These donors are compatible with diverse glycosyl acceptors and challenging substrate classes, including glucuronate and ketosyl donors, and N ‐nucleophiles. Compared with PTFAs, TFB donors exhibit improved spectral resolution and their favorable leaving‐group properties simplify purification procedures. Importantly, TFB donors display enhanced stability while maintaining sufficient glycosylation activity. Computational studies reveal that the reduced reactivity originates from an increased activation barrier during TMSOTf‐mediated donor activation, providing mechanistic insights into how imidate connectivity influences glycosyl donor behavior. The differentiated reactivity profiles of TFB and PTFA donors enable orthogonal one‐pot assembly of oligosaccharides through controlled promoter activation, and enhance chemo‐selective one‐pot synthesis. Overall, this study establishes connectivity inversion as a useful strategy for tuning glycosyl imidate reactivity and provides a new platform for developing stable yet effective glycosyl donors for streamlined carbohydrate synthesis.
Comprehensive Summary Heterobiaryl atropisomers represent a kind of highly valuable scaffolds in drug development and asymmetric catalysis. Although significant progress has been made in atroposelective construction of such kind of scaffolds, exploration of asymmetric synthesis of diverse novel heterobiaryl atropisomers is still desirable. Herein, we report a relay catalytic strategy for the atroposelective synthesis of a kind of novel axially chiral heterobiaryls. By relay catalysis of chiral phosphoric acid and silver nitrate, an atroposelective cascade reaction involving [3+3] cyclization of α‐(3‐isoindolinonyl) propargylic alcohols with 5‐aminoisoxazoles or 5‐aminopyrazole followed by ring‐opening and proton transfer has been accomplished. This transformation allowed the construction of various novel axially chiral 4‐aryl‐isoxazolo[5,4‐ b ]pyridines with low to moderate yields (20%–80%) in moderate to excellent enantioselectivities (38%–98% ee). Afterward, the absolute configurations of one product and the intermediate were determined by X‐ray crystal structural analyses. Subsequently, a series of control experiments revealed a cascade reaction mechanism in which the central‐to axial chirality conversion is the key step of the establishment of the atropisomerism.
Comprehensive Summary Chiral amines are essential structural motifs in pharmaceuticals, fine chemicals, and bioactive natural products. Asymmetric transfer hydrogenation (ATH) of imines represents one of the most straightforward approaches to chiral amine synthesis, yet aqueous ATH of non‐activated acyclic imines remains a longstanding challenge due to the inherent hydrolytic lability of these substrates. Herein, we successfully achieve the aqueous asymmetric transfer hydrogenation of non‐activated acyclic imines via a micellar catalysis strategy, employing an N,O‐chelated half‐sandwich iridium(III) complex as the chiral catalyst. The anionic surfactant sodium dodecyl sulfate (SDS) self‐assembles into micelles in aqueous media, whose hydrophobic core encapsulates both the hydrolytically labile imine substrates and lipophilic metal catalyst. This confined microenvironment effectively isolates acyclic imines from the bulk aqueous phase to suppress the hydrolysis side reaction, while enriching reactants to improve mass transfer efficiency, and also exerts a positive regulatory effect on the stereochemical control of the transformation. After systematic optimization, this protocol has broad substrate scope, affording over 40 chiral amines in good to excellent yields with up to 98% enantiomeric excess (ee). With micellar catalysis suppressing substrate hydrolysis in water, this work provides an efficient green route to chiral amines and expands the scope of aqueous asymmetric transfer hydrogenation.
Comprehensive Summary Efficient interfacial charge transport is essential for achieving high‐performance organic solar cells (OSCs), while conventional cathode interlayers (CILs) often suffer from limited thickness tolerance due to insufficient vertical electron transport. Herein, we develop two hyperbranched CIL molecules, TPA‐PDINNBr and BTT‐PDINNBr, by integrating quaternized perylene diimide (PDI) units with three‐dimensional triphenylamine (TPA) or benzo[1,2‐ b :3,4‐ b ′:5,6‐ b ″]trithiophene (BTT) cores. The three‐dimensional molecular architectures preserve the intrinsic electron‐transporting capability of PDI while constructing multidirectional charge‐transport pathways and regulating molecular packing. Among them, BTT‐PDINNBr exhibits enhanced conductivity (2.03 × 10 –4 S·cm –1 ) and electron mobility (3.36 × 10 –3 cm 2 ·V –1 ·s –1 ), resulting from the optimized balance between molecular ordering and three‐dimensional transport. Incorporation of BTT‐PDINNBr into PM6:D18:L8‐BO OSCs delivers a high power conversion efficiency of 19.68% and maintains ~87% of the optimal efficiency with interlayer thicknesses exceeding 50 nm. This work provides a molecular design strategy for robust CILs by highlighting the importance of three‐dimensional conductive networks and controlled solid‐state packing for scalable and efficient OSCs.
Comprehensive Summary 3‐Hydroxyindanone represents one of the most valuable and privileged cyclic scaffolds in synthetic and medicinal chemistry, which widely exists in a variety of biologically active natural products and pharmaceutical lead molecules. Benefiting from its reactive hydroxyl and carbonyl functional groups, the 3‐hydroxyindanone skeleton also serves as a highly versatile synthetic building block for the modular construction of structurally complex fused and polycyclic ring systems, providing abundant opportunities for molecular diversification and drug molecular modification. Meanwhile, the introduction of fluorinated quaternary stereogenic centers has become a mature and powerful strategy in modern drug discovery. Fluorinated chiral architectures with quaternary C–F stereocenters can effectively optimize the lipophilicity, metabolic stability, and binding affinity of bioactive molecules, endowing them with unique and untapped pharmacological potential compared with their non‐fluorinated counterparts. Despite the tremendous advances in the synthetic chemistry of indanone derivatives and fluorinated chiral compounds, the catalytic asymmetric construction of enantiopure 3‐hydroxyindanones bearing quaternary C–F stereogenic centers remains a long‐standing and unaddressed challenge. The lack of reliable catalytic strategies severely restricts the further development and biological evaluation of such fluorinated chiral 3‐hydroxyindanones. To address this synthetic problem and continue our research interest in asymmetric catalysis and fluorine‐containing chiral heterocycle synthesis, we herein disclose the first example of catalytic asymmetric allylation for the desymmetrization of 2‐fluoro‐1,3‐indanediones, enabling the facile and efficient construction of chiral 3‐hydroxyindanones bearing quaternary C–F stereogenic centers. This newly developed yttrium(III)‐based catalytic system exhibits excellent synthetic performance and stereocontrol ability. A broad range of functionalized 2‐fluoro‐1,3‐indanedione substrates are well tolerated under mild reaction conditions, affording the target enantioenriched fluorinated 3‐hydroxyindanone products in high yields, excellent enantioselectivities, and exclusive diastereoselectivity (>20 : 1 dr). Notably, this desymmetrization strategy not only provides a straightforward and unprecedented approach to forge challenging fluorinated quaternary stereocenters embedded in indanone skeletons but also offers a practical platform for the synthesis of novel fluorinated chiral drug candidates. We believe this work will enrich the synthetic methodology of fluorinated chiral cyclic compounds and provide new insights for the design and synthesis of fluorine‐modified bioactive molecules.
Comprehensive Summary Phase and defect engineering of molybdenum disulfide provides an effective strategy for regulating oxidant activation in heterogeneous advanced oxidation. Herein, a sulfur‐vacancy‐rich 1T/2H‐MoS 2 heterophase catalyst was developed for peroxymonosulfate (PMS) activation and fluoroquinolone degradation. Compared with 1T‐MoS 2 and 2H‐MoS 2 , the 1T/2H‐MoS 2 /PMS system exhibited higher activity, better matrix tolerance, and improved regenerability after ethanol washing. Spectroscopic and quenching analyses revealed that PMS activation proceeds mainly through a non‐radical pathway dominated by singlet oxygen, with a minor contribution from high‐valent molybdenum–oxo species. In situ Raman, EPR, LC‐MS, and frontier‐orbital analysis further suggested a selective degradation route of ofloxacin, initiated by side‐chain oxidation, followed by deeper transformation of the quinolone core. XANES/EXAFS/XPS and DFT calculations showed that the 1T/2H phase boundary and sulfur vacancies cooperatively regulate the local coordination and electronic structure of Mo sites, enabling balanced PMS polarization at interfacial sites while allowing stronger activation at defective motifs. OCTP (organic carbon transfer process) and CRE (catalyst regeneration extent) were further introduced to quantify surface carbon accumulation and catalyst regeneration. This work clarifies how heterophase and vacancy engineering govern selective PMS activation and catalyst durability.
Comprehensive Summary Despite recent breakthroughs in organic solar cell (OSC) efficiency, the trade‐off between broadening spectral response and minimizing non‐radiative energy loss remains a critical bottleneck. While ternary strategies and sequential deposition (SqP) each offer unique benefits, their single‐dimensional optimization often fails to balance efficient photon harvesting with ideal vertical phase separation. Herein, we report a multi‐dimensional synergistic regulation strategy by incorporating polymer acceptor PYF‐T‐ o into the SqP‐processed PM6/eC9 system, where PYF‐T‐ o establishes a cascade energy‐level alignment and forms an alloy‐like acceptor phase with eC9. This unique microstructure broadens spectral absorption, lowers the donor/acceptor surface energy difference, accelerates crystallization kinetics (reducing nucleation time by 60 ms), and refines phase separation. Consequently, the ternary devices exhibit balanced carrier mobilities, ultrafast charge extraction (0.197 μs), and prolonged carrier lifetime (4.54 μs), effectively suppressing trap‐assisted recombination. The energetic disorder is reduced to 23.43 meV, minimizing non‐radiative voltage loss from 0.218 eV to 0.205 eV. By utilizing a 2PACz self‐assembled monolayer, the optimized device achieves a high power conversion efficiency of 20.23% and demonstrates enhanced photostability with the T 80 lifetime extended from 117 h to 260 h. This work establishes a robust paradigm for synchronously reducing energy loss and enhancing device performance via multi‐dimensional synergistic regulation.
Comprehensive Summary Catalytic reduction of unsaturated substrates provides a powerful tool for bulk and fine chemical synthesis. However, very few examples have been reported on the reductive transformation of thioamides, presumably because of the poisoning of catalysts by sulfur‐containing molecules. Herein, we describe an efficient and sustainable hydrogenative coupling of thioamides with olefins under electrocatalytic conditions. The key to success for this reductive process is the application of an earth‐abundant cobalt complex as the cost‐effective and robust molecular electrocatalyst. As only protons (H + ) and electrons (e – ) as the hydrogen source and redox equivalent, this polarity‐reversed electrochemical protocol is showcased by highly selective and straightforward synthesis of a wide range of α‐branched amines, as well as deuterium isotope labeling applications. Over 60 α‐branched amines, including 12 deuterated analogues, have been successfully synthesized. Notably, a variety of functional groups, including aryl halides, esters, and nitriles, are well tolerated under the mild electrochemical conditions. Furthermore, late‐stage modification of complex molecules has also been achieved. Mechanistic studies indicate that the in‐situ generated imines and α‐amino radicals by cobalt‐electrocatalytic desulfurization of thioamides are identified as the key intermediates in this transformation. This work provides an alternative and versatile method for the synthesis of structurally diverse α‐branched amines, with advantages including sustainability, high selectivity, and compatibility with isotope labeling and complex molecular functionalization.
Comprehensive Summary Glycans that are widely distributed in nature possess diverse biological activities. However, the inherent structural microheterogeneity of natural glycans impedes their functional evaluation. Chemical glycosylation serves as a powerful approach to access well‐defined complex glycans for structure‐activity relationship studies. In particular, one‐pot multistep glycosylation enables the efficient assembly of complex glycans by eliminating intermediate purification and minimizing protecting‐group manipulations. Nevertheless, a key limitation of this traditional approach is its inefficient late‐stage coupling, which might result in the loss of valuable advanced donors. Here, we developed a photolabile ester‐mediated one‐pot glycosylation–deprotection–glycosylation strategy for the rapid assembly of both linear and branched oligosaccharides. Based on the photolabile ortho ‐nitro‐benzyloxycarbonyl ( o NBC) ester‐mediated one‐pot strategy from the reducing end to non‐reducing end, efficient and stereoselective synthesis of oligomannoside, oligofucoside, and five types of HBGAs including A tri , B tri , H1, H3 and Le b antigens was achieved. Various glycosyl leaving groups including ynenoates, trichloroacetimidates, N ‐phenyl trifluoroacetimidates, and thioglycosides were successfully employed in these photo‐mediated one‐pot reactions, with solvent and temperature identified as critical factors for stereoselective glycosidic bond formation. In contrast to the photolabile o ‐nitrobenzyl ( o NB) group, the photolabile o NBC group could be readily introduced on the primary and secondary hydroxyls of sugar building blocks under mild basic conditions, which were fully compatible with common ester protecting groups. When installed at the C‐2 position of glycosyl donors, the o NBC group typically favored the formation of β‐glycosidic bonds. The binding results indicated that the H1 receptor exhibited superior binding to norovirus‐like particles relative to the H3 receptor, thereby serving as a valuable tool for assessing norovirus vaccine‐elicited antibodies. The photolabile ester‐mediated one‐pot strategy provides a versatile platform for the streamlined assembly of architecturally complex and branched glycans.
Comprehensive Summary Catalytic hydrogenation of carbon dioxide (CO 2 ) into aromatic hydrocarbons has emerged as a promising route for the high‐value CO 2 utilization and sustainable aromatics production to alleviate fossil resource dependence under the carbon‐neutrality goals. By integrating CO 2 activation/hydrogenation with the downstream C–C coupling and aromatization, bifunctional catalytic systems, typically comprising metal or metal oxide components coupled with acidic zeolites, enable the direct synthesis of valuable aromatics ( e.g. , benzene, toluene, and xylene) from CO 2 . Recently, significant progress has been made in the rational design of such catalysts, particularly through the precise tailoring of the zeolite component for regulating the reaction pathways, product selectivity, and catalyst stability. This minireview summarizes recent advances in CO 2 hydrogenation to aromatics achieved by bifunctional catalysts, with a specific focus on the decisive role of the zeolite properties in governing the aromatization behaviors. Various zeolite modification strategies, such as acidity regulation, metal and non‐metal functionalization, pore‐structure engineering, and morphology control, are systematically discussed in relation to their effects on the intermediate transformation and aromatic selectivity. Finally, perspectives on future research are presented, emphasizing the importance of advanced characterization techniques and theoretical modeling for the rational design of more efficient, selective, and stable CO 2 ‐to‐aromatics catalysts and technologies. Key Scientists
Comprehensive Summary Post‐functionalization of polystyrene (PS) holds a crucial role in creating novel materials from commercially available plastics as it enables the introduction of diverse chemical groups to enhance the material's properties for advanced applications. Despite the ability to introduce various functional groups onto PS, forming C–N bonds on either aromatic ring or aliphatic chain remains a significant challenge. Herein, we present a versatile strategy for site‐selective C–H hydrazination of PS plastics, enabling precise functionalization of both aromatic (sp 2 ) and aliphatic (sp 3 ) bonds under tunable catalytic conditions. Using FeCl 3 / N ‐chlorosuccinimide (NCS) for electrophilic aromatic hydrazination and photoinduced TBAFeCl 4 for radical‐mediated aliphatic C–H cleavage, we achieve the controlled introduction of hydrazine motifs into PS derivatives with high efficiencies. A range of styrene‐based polymers, including PS, SAN, SIS, SEBS, and PMS, can be used to synthesize diverse aminated plastic materials. This method can be also applicable for selective hydrazination of PS from mixed plastic. While the functionalized materials exhibit good ability in being a compatibilizer, the subsequent functional group transformations show great potential for creating (multi)functional materials. And comparative degradation studies reveal that the aliphatic C–H hydrazination might enhance the oxidative degradation of PS materials.
Comprehensive Summary Hybrid antiperovskites have attracted tremendous research interest with unique assembly architecture, holding great promise in ferroelectricity, nonlinear optics, optoelectronic detection, etc . However, constructing hybrid antiperovskite has always been a great challenge, and the ferroelasticity within this family remains unexplored. Here, we report the first case of hybrid antiperovskite ferroelastic, (C 3 H 8 ON) 3 (SnCl 6 )Cl, designed via molecular modification. Through hydrogen‐bond engineering by substituting (C 3 H 6 ON) + cations with (C 3 H 8 ON) + , the stacking arrangement of components in lattice was reconfigured to transform a zero‐dimensional precursor of (C 3 H 6 ON) 2 SnCl 6 into a three‐dimensional hybrid antiperovskite architecture. This structural reorganization successfully induces a ferroelastic phase transition with an Aizu notation of 2 m F222. This work not only enriches the hybrid antiperovskite family, but also sheds new light for designing ferroic materials.
Comprehensive Summary This review systematically details the significant advances from 2019 to 2025 in utilizing difluorocarbene (:CF 2 ) as a minimal perfluorocarbon linker for the efficient synthesis of gem ‐difluoromethylenated compounds (G 1 ‐CF 2 ‐G 2 , G 1 , G 2 ≠ H, F). As the smallest perfluorocarbon linker, :CF 2 has evolved beyond a traditional C1 synthon into a versatile bipolar connective scaffold, enabling modular assembly through innovative methodologies. The progress is systematically categorized into two primary domains: the synthesis of linear and cyclic architectures. For linear molecules, breakthroughs include tunable transition‐metal catalysis ( e.g ., Pd, Cu) that enables controlled three‐component couplings and programmable fluoroalkyl chain elongations, alongside diverse metal‐free strategies utilizing phosphonium ylides, silyl reagents, and oxidative protocols for incorporating heteroatoms (O, S, N, Se, etc .) into the ‐CF 2 ‐ bridge. In cyclic molecule synthesis, beyond the classical [2+1] cycloaddition for the synthesis of gem ‐difluorocyclopropanes, novel annulation paradigms such as [3+1], [4+1], and [1+4] cycloadditions have emerged, providing efficient access to a wide array of medicinally relevant fluorinated heterocycles. Furthermore, complementary difluorocarbene‐like pathways, particularly those employing radical‐based synthons, offer alternative routes for constructing the ‐CF 2 ‐ linkage. Looking forward, the review provides inspiring perspectives, emphasizing the in‐depth fundamental studies of metal‐difluorocarbene coupling reactions, the development of bench‐ stable and externally activated (light, electricity) :CF 2 precursors, the pursuit of enantioselective :CF 2 transfer for constructing chiral G 1 *–CF 2 –G 2 centers, and the exploration of :CF 2 as a repeating linker unit in high‐performance fluorinated polymers and materials. The integration of computational prediction with experimental validation is highlighted as a powerful tool for discovering :CF 2 ‐mediated transformations, while the application of these methodologies in late‐stage diversification of complex pharmaceuticals and agrochemicals underscores their practical utility. This consolidated overview underscores :CF 2 's transformative role as a minimal perfluorocarbon linker in modern synthetic methodology, offering valuable insights for organic, medicinal, and materials chemists to design and access complex fluorinated targets with enhanced efficiency and precision. Key Events Related to Difluorocarbene (:CF 2 ) Chemistry The development of difluorocarbene (:CF 2 ) chemistry has traversed a long journey from a transient reactive intermediate to a powerful synthetic linchpin for constructing G 1 –CF 2 –G 2 architectures. According to our literature survey, the earliest evidence for the generation of :CF 2 dates back to 1933, when it was produced via the high‐temperature pyrolysis of CF 4 [1] and the high‐tension electric discharge decomposition of Cl 2 CF 2 . [2] Since the 1940s, :CF 2 (from ClCF 2 H) has been directly employed in the preparation of polytetrafluoroethylene (Teflon), and ever since, downstream products based on :CF 2 have been widely developed and applied. Concurrently, the discovery and extensive utilization of fluorinated compounds and materials have also spurred the rise and advancement of organofluorine chemistry. [3] Owing to the inherently high reactivity and instability of :CF 2 , synthetic methodologies involving it remained largely unexplored until 1957, when J. Hine successfully captured :CF 2 using sodium methoxide and thiophenoxide to afford the corresponding difluoromethyl (thio)ethers. [4] Subsequently, J. M. Birchall, H. C. Clark, and co‐workers reported the [2+1] cycloaddition of :CF 2 with cyclohexene [5] and tetrafluoroethylene, [6] leading to difluorocyclopropane derivatives. Thereafter, a series of synthetic methods based on free :CF 2 have been continuously developed. In 1978, D. L. Reger and co‐workers reported the first mononuclear metal difluorocarbene complex ([M]=CF 2 , M =Mo), [7] suggesting that [M]=CF 2 may regulate the CF 2 's reactivity. However, although these pioneering discoveries are of great significance, the process of constructing the G 1 –CF 2 –G 2 (G 1 , G 2 ≠ H, F) molecules using :CF 2 was severely hampered by several intrinsic obstacles: harsh reaction conditions (extremely high temperatures or electric discharge), limitations of the available apparatus, [2,8] as well as the tendency of :CF 2 to undergo self‐polymerization and α‐fluoride elimination. [9] Consequently, progress in this area remained sluggish for decades. It was not until the 1990s that a series of reports began to emerge on the use of :CF 2 in consecutive bond‐forming reactions to access both linear and cyclic G 1 –CF 2 –G 2 (G 1 , G 2 ≠ H, F) architectures. [10] The turn of the 21st century witnessed a significant revitalization of :CF 2 chemistry, driven by the extensive development of novel, user‐friendly :CF 2 reagents that enabled efficient fluoroalkylation and gem ‐difluoroalkylation of various substrates. [11] From 2015 onward, the metal difluorocarbenes have been developed by chemists for the selective synthesis of fluorinated compounds, [12] especially metal‐difluorocarbene‐involved catalytic coupling (MeDIC) and cyclization reactions emerged as a powerful regulatory tool for the controlled synthesis of both linear and cyclic G 1 –CF 2 –G 2 (G 1 , G 2 ≠ H, F) compounds, enabling remarkable advances in modular one‐pot consecutive bond‐forming reactions of :CF 2 . In 2018, comprehensive reviews by the groups of A. D. Dilman [13] , X. Zhang, [14] and J. Ichikawa [15] summarized the state‐of‐the‐art in :CF 2 ‐based synthesis of linear and cyclic G 1 –CF 2 –G 2 (G 1 , G 2 ≠ H, F) molecules. Starting in 2019, a series of efficient methods on the synthesis of G 1 –CF 2 –G 2 (G 1 , G 2 ≠ H, F) molecules using :CF 2 as a linker have emerged, especially the isolation and application of highly active [M]=CF 2 . These methods represent the inflection point where :CF 2 evolved into a truly modular, tunable, and catalytic linker for complex gem ‐difluoromethylenated molecules. Building on these seminal contributions and the continuous progress of difluorocarbene chemistry, we have now compiled this review covering the period 2019–2025. Some representative examples of the key developments of free :CF 2 and [M]=CF 2 in this review have been classified and presented in the aforementioned figure, and a brief summary of these representative examples is provided in the following text. The representative examples introduced in this review for the synthesis of linear G 1 ‐CF 2 ‐G 2 (G 1 , G 2 ≠ H, F) compounds: Three recent reports highlight the utility of free :CF 2 as a versatile linker for constructing linear G 1 –CF 2 –G 2 (G 1 , G 2 ≠ H, F) scaffolds under mild conditions. Song and co‐workers achieved deconstructive deuterated difluoromethylation of cyclic ethers with carboxylic acids using :CF 2 at room temperature, delivering RCO 2 (CH 2 ) 4 O–CF 2 –D. [16] Hu's group developed transition‐metal‐free single and double formal CF 2 insertions into aldehyde C–H bonds via 2,2‐difluoroenol silyl ether intermediates, providing ArC(O)CF 2 CF 2 H and ArC(O)CF 2 H with high selectivity. [17] Qing and co‐workers reported a copper‐mediated oxidative chloro‐/bromodifluoromethylation of phenols using TMSCF 2 X/Selectfluor, followed by oxidative coupling to afford ArO–CF 2 –X. [18] Collectively, these methods showcase :CF 2 as a practical and powerful reagent for modular assembly of diverse fluorinated chains. Several recent studies have leveraged [M]=CF 2 as versatile platforms for the modular construction of linear G 1 –CF 2 –G 2 (G 1 , G 2 ≠ H, F) architectures. In 2019, Zhang and co‐workers reported a first example of catalytic controllable difluorocarbene elongation reaction via palladium catalysis, where the nucleophilicity of [Pd 0 ]=CF 2 and the electrophilicity of [Pd II ]=CF 2 could be switched by tuning the oxidation state, enabling selective formation of Ar–CF 2 H, Ar–CF 2 CF 2 H, Ar–COCF 2 H, and Ar–COCF 2 CF 2 H from arylboronic acids and BrCF 2 PO(OEt) 2 . [19] Subsequently, a three‐component Pd‐catalyzed coupling of :CF 2 with arylboronic acids and a sulfonium salt by Xiao et al. provided Ar–CF 2 –Ar’ products, representing the first example of incorporating two aryl groups across a :CF 2 linker. [20] In 2022, Hu's group achieved controllable single and double CF 2 insertions into CuCF 2 H using TMSCF 2 Br, generating CuCF 2 CF 2 H and Cu(CF 2 ) 2 CF 2 H; subsequent coupling with aryl iodides delivered ArCF 2 CF 2 H and Ar(CF 2 ) 2 CF 2 H, respectively. [21] Thereafter, in 2024, Hu and co‐workers developed another controllable double :CF 2 insertion into ArS–Cu bonds (via [ArS–Cu=CF 2 ]). [22] The resulting ArSCF₂CF₂Cu species undergoes efficient cross‐coupling with diverse aryl iodides to afford ArSCF 2 CF 2 Ar’ products. The first isolation and characterization of well‐defined [Cu I ]=CF 2 complexes ligated an externally added bulky dinitrigen ligand by Zhang in 2023 enabled a Cu‐catalyzed modular difluoroalkylation of silyl enol ethers with allyl bromides, affording CF 2 ‐linked ketones. [23] Most recently, Zhang group revealed that thermolytic homolysis of the ArCF 2 –Pd bond in a [Pd II ]=CF 2 ‐derived intermediate generates difluoroalkyl radicals, allowing for a three‐component coupling of aryl iodides, ClCF 2 H, and alkenes to produce diverse Ar–CF 2 –CH 2 C(=O)R products. [24] Collectively, these works demonstrate that [M]=CF 2 species serve as powerful and tunable linchpins for the precise assembly of linear G 1 –CF 2 –G 2 frameworks under mild, catalytic conditions. The representative examples introduced in this review for the synthesis of cyclic G 1 ‐CF 2 ‐G 2 (G 1 , G 2 ≠ H, F) compounds: Several studies have successfully harnessed free :CF 2 as a versatile linker for the construction of cyclic G 1 –CF 2 –G 2 (G 1 , G 2 ≠ H, F) frameworks. In 2019, Wang and co‐workers generated the previously unknown difluoroketenimine from the reaction of :CF 2 with an isocyanide, which underwent a [2+2] cycloaddition with imines to afford α,α‐difluoro‐β‐lactams. [25] Dilman and co‐workers trapped :CF 2 with an intramolecular frustrated Lewis pair (phosphine/borane), yielding stable zwitterionic phosphonium‐borate adducts containing a P–CF 2 –B linkage within a five‐membered ring. [26] Most notably, Mita, Maeda and co‐workers employed in silico reaction screening using the artificial force induced reaction method to predict and then realize a diverse N ‐difluoroalkylative dearomatization of pyridines with :CF 2 and various electrophiles (aldehydes, ketones, imines, alkenes, alkynes). This multicomponent cycloaddition proceeds via a pyridinium ylide intermediate and delivers a wide array of α,α‐difluorinated N ‐heterocycles. [27] In 2024, Hu and co‐workers developed a controllable fluorocarbon chain elongation (CFCE) strategy using TMSCF 2 Br as the sole fluorocarbon source. The reaction proceeds via Fe/Zn‐mediated homocoupling of TMSCF 2 Br to generate TMSCF 2 CF 2 TMS, which undergoes TBAT‐initiated trifluorovinylation with aldehydes to afford trifluorovinyl alcohols (C 1 to C 2 ). Subsequently, in situ generated free :CF 2 adds to the trifluorovinyl intermediate via [2+1] cycloaddition, delivering pentafluorocyclopropanols (C 1 to C 3 ). [28] Collectively, these approaches showcase the power of free :CF 2 for the modular and efficient synthesis of medicinally relevant fluorinated heterocycles. Recent advances have demonstrated that well‐defined [M]=CF 2 complexes serve as powerful platforms for constructing cyclic G 1 –CF 2 –G 2 (G 1 , G 2 ≠ H, F) frameworks. Koh and co‐workers developed a Cu‐catalyzed skeletal expansion of epoxides using :CF 2 , where an electrophilic [Cu]=CF 2 promotes regioselective C–O bond cleavage and ring closure to afford α,α‐difluoro‐oxetanes. [29] Bourissou and co‐workers isolated the first genuine [Au I ]=CF 2 complexes stabilized by chelating P,P or P,N ligands, which exhibit unprecedented reactivity with alkenes and 1,3‐dienes. The reaction proceeds via formation of Au(III) metallacyclobutanes or metallacyclohexenes, and the subsequent reductive elimination delivers either difluorocyclopropanes or difluorocyclopentenes, respectively. [30] Toste and co‐workers also demonstrated that free :CF 2 inserts into the Au–C bond of organogold(I) complexes to give isolable R–CF 2 –Au(I) species, while with alkynylgold(I), cycloaddition occurs exclusively to form the first κ 1 ‐difluorocyclopropenylgold(I) complex. [31] Collectively, these works highlight the versatility of [M]=CF 2 intermediates in enabling diverse ring‐forming reactions.
