The selective radical hydroalkylation of 1,3-dienes, particularly using readily available alkyl radical sources, remains a challenging synthetic transformation, primarily due to the high reactivity of radical intermediates and the presence of multiple reactive sites within the 1,3-diene framework. Herein, we disclose a mild and efficient visible-light-driven 1,4-hydroalkylation of conjugated dienes with perfect atom economy. The key steps of this protocol involve catalytic generation of C-radicals from readily available 1,3-dicarbonyls, followed by a radical 1,4-addition to form the benzyl radicals, which then undergo a single-electron-reduction and final protonation. This method features broad substrate scope, operational simplicity and high efficiency. A variety of readily available malonates, β-ketoesters and diversely substituted ary-1,3-dienes were well accommodated, yielding the corresponding 1,4-hydroalkylated products in generally good yields (50%–82% yields). This approach also broadens the synthetic utility of 1,3-dicarbonyl compounds, facilitating gram-scale synthesis, late-stage modifications of drug-like molecules and further synthetic transformations. As a result, numerous high value-added molecules were obtained, showcasing the synthetic potential of this method. Control experiments revealed that visible-light-irradiation, the photocatalyst and the base are all indispensable for the success of this protocol. Preliminary mechanistic studies, encompassing radical-trapping experiment, deuteroxide quenching experiment, light on-off experiments and Stern-Volmer experiments, support the proposed mechanism.
Organofluorine compounds play a critical role in diverse fields such as medicinal chemistry, materials science, and agrochemicals. Due to their scarcity in nature, the construction of C–CF3 bonds has emerged as one of the most actively pursued topics in synthetic chemistry. The direct deoxytrifluoromethylation of alcohols offers a highly attractive route to access valuable C(sp3)-CF3 bonds, leveraging the ubiquity and ready availability of alcohols as feedstocks. Established strategies for such transformations typically require separate reagents for sequential deoxygenation of alcohol substrates and trifluoromethylation of activated intermediates. While dual-function reagents that combine activation and fluorination are well-established in deoxyfluorination chemistry, analogous reagents for deoxytrifluoromethylation have remained largely unexplored. In this study, we address this gap by introducing 2-trifluoromethyl-benzimidazolium salt as a novel dual-function reagent capable of promoting the deoxytrifluoromethylation of benzylic alcohols. This reagent uniquely integrates the ability to activate the alcohol substrate while simultaneously serving as a trifluoromethyl source in a single operational step. The transformation is facilitated by a synergistic system combining photoredox catalysis with a copper promotion. Under mild visible-light irradiation, the photoredox cycle initiates single-electron transfer processes, generating key benzylic radical intermediates from the activated alcohols. Concurrently, the copper species stabilizes the trifluoromethyl moiety and mediates the crucial C–CF3 bond-forming cross-coupling step. This cooperative mechanism enables the efficient one-step conversion of benzylic alcohols into their trifluoromethylated analogues. The reaction demonstrates broad functional group tolerance, accommodating double bonds, aldehydes, ketones, nitro groups, halides, and other sensitive functionalities. Scalability was also confirmed through gram-scale synthesis. In summary, this work establishes the feasibility of a dual-function reagent for deoxytrifluoromethylation, expanding the toolbox for C–CF3 bond formation. The developed methodology offers several advantages, including easy preparation and stability of the reagent, avoidance of substrate pre-functionalization, and excellent functional group compatibility. Furthermore, this study presents a less explored reagent system for copper-catalyzed or promoted trifluoromethylation of aliphatic substrates, opening avenues for further development in radical-mediated trifluoromethylation chemistry.
Mechanically interlocked structures exhibit remarkable adaptability and versatility due to their unique topologies, offering promising applications in molecular machines, smart materials, and energy conversion. In this work, a strategy for directing different topological configuration between metallarectangle and [2]catenane is demonstrated through the incorporation of -Br and -OCH3 groups with distinct steric effects. Their differing size and spatial constraints promote ligand preorganization, facilitating controlled self-assembly and interlocking. Two metallarectangles (2a, 1b) and four [2]catenanes (2b, 3b, 4b, 5b) were synthesized via coordination-driven self-assembly and characterized by single-crystal X-ray diffraction, NMR spectroscopy, and ESI-TOF-MS. The photothermal properties were evaluated, revealing that 2b exhibits the highest performance, achieving a temperature change of 28 °C under 1.5 W irradiation. And the conversion efficiency ranges from 37.74% to 30.13% with varying power, attributing to the strong absorption at 730 nm and enhanced π-stacking interactions within the interlocked architecture. This study provides new insights into the rational design of functional topological complexes and highlights their potential in photothermal energy conversion.
High catalytic efficiency is a fundamental prerequisite for the industrial adoption of catalytic transformations. However, reactions achieving turnover numbers (TONs) exceeding 10,000 remain rare in photocatalytic areas, which is primarily attributed to insufficient photostability and light-absorption capacity of photocatalysts. Metalloporphyrins, featured by extended π-conjugation systems, exhibit distinct advantages including high molar extinction coefficients, long-lived triplet excited states, and exceptional photostability, alongside distinctive Soret and Q absorption bands. Motivated by these advantageous properties, we herein report a photoinduced cobalt(II) porphyrin-catalyzed aerobic oxidative coupling of phosphorus ylides to synthesize 1,4-enediones. This photocatalytic system is distinguished by an exceptionally low catalyst loading (2.5 × 10–3 mol%) and achieves a high turnover number (TON) of up to 19,800. Furthermore, capitalizing on the distinct light absorption of cobalt porphyrin across its Soret and Q bands (corresponding to blue and green light regions), a wavelength-regulated stereoselective synthesis of either (Z)- or (E)-1,4-enediones was realized. Besides, benefiting from the strong absorption at the Soret band of cobalt porphyrin, the reaction for (Z)-1,4-enediones proceeds rapidly within 0.5 h under blue LED irradiation, affording a turnover frequency (TOF) of up to 39,600 h–1. The protocol also demonstrates broad substrate scope, accommodating diverse heterocycles including indoles, thiophenes, and thiazoles. Mechanistic studies implicate the involvement of singlet oxygen (1O2) and superoxide anion (O2•–), supporting a sequential pathway involving initial oxidation of the phosphorus ylide to a 2-oxo-2-arylacetaldehyde intermediate, followed by a Wittig reaction to yield the (E)-alkene. Subsequent blue LED-induced isomerization then furnishes the (Z)-configured isomers. This study underscores the significant potential of metalloporphyrins as highly robust and efficient photocatalysts for advanced organic synthesis.
One of the most profound goals of modern organic chemistry is to enrich synthetic method and compound library serving as the foundation of pharmaceutical and material sciences. Meanwhile, the synthesis of structurally complex compounds necessitates tedious multistep procedures. This is certainly not in line with the requirements of green chemistry. Therefore, there is a strong impetus for the development of more concise and sustainable approaches to obtaining such compounds. So far, a number of state-of-the-art strategies for this purpose have been developed. Among them, molecular skeleton editing stands out for its capability of rapidly building or pruning functional molecules. Given the ubiquity of rings in drugs, skeletal editing leading to the generation of biologically privileged cyclic systems is particularly useful. Presented herein is a concise construction of privileged isoindolone fused CF3-benzooxazocine scaffold based on the cascade reaction of 2-aryl-4H-benzo[d][1,3]oxazine 1 with CF3-ynone 2. This novel reaction is initiated by aryl C−H alkenylation of 1 with 2 followed by intramolecular aza-Michael addition to form the isoindoline ring, water-promoted oxazine ring-opening and intramolecular oxo-nucleophilic addition to form the oxazocine ring. In forming the isoindoline scaffold, 1 acts as a C3N1 synthon and 2 acts as a C1 synthon. In forming the oxazocine skeleton, 1 acts as another version of C3N1 synthon while 2 acts as a C3 synthon and water acts as an O1 synthon. To our knowledge, this is the first example of one-pot tandem generation of both isoindolone and CF3-oxazocine scaffold through directing group-assisted C−H bond activation-initiated skeleton editing of easily obtainable substrates. Importantly, some of the products thus obtained showed excellent in vitro anti-Zika virus (ZIKV) activity and moderate to good anti-proliferative activity against three human cancer cell lines.
Due to the unique physicochemical properties of fluorine atom, the introduction of fluorine or polyfluoroalkyl group has emerged as a pivotal strategy in pharmaceutical and agrochemical design. Radical fluoroalkylation reactions stand out as a particularly efficient and innovative synthetic platform, enabling the construction of a vast array of valuable organofluorine compounds. However, a major synthetic challenge persists─the development of a unified, generalizable methodology capable of selectively forging fluorinated or fluoroalkylated molecular architectures from simple precursors remains highly desirable and challenging. Emerging strategies aim to leverage C–F bond activation, which allows for the transformation of readily available, yet often inert, polyfluorinated feedstocks into versatile fluorinated products. Described herein is a photocatalytic radical-polar crossover [3 + 2 + 1] cyclization reaction from easily available polyfluoroalkyls, enamines and 3-aminoindazole or 3-aminopyrazoles derivatives under mild conditions. Detailed mechanistic investigations reveal a sophisticated cascade pathway involving initial radical fluoroalkylation of the enamine, followed by a defluorination, and culminating in a cyclization sequence. To the best of our knowledge, this platform represents one of the very few examples for the construction of biologically important fluorine or fluoroalkyl-containing fused-ring systems under a uniform reaction condition with high efficiency and compatibility. Key to this methodology is the in-situ generation of a reactive α,β-unsaturated iminium intermediate while enabling subsequent cascade multicomponent cyclization reactions. This transformation proceeds efficiently in simple one-pot protocol with broad substrate scopes, including perfluoroalkyl halides with varying chain lengths and substitution patterns, as well as diverse nucleophilic partners. We anticipate that this transformation will establish a versatile and powerful platform for the highly efficient synthesis of diverse fluorinated scaffolds. By merging radical reactivity with polar crossover and cascade cyclization in a simple operational protocol, it opens practical and streamlined avenues for the discovery and development of diverse fluorinated compounds in medicinal and agricultural chemistry.
The efficient construction of valuable N-heterocycles is one of the most important tasks in organic synthesis. Pyrrolo[2,3-b]indoles represent a privileged skeleton, which are extensively found in natural products, pharmaceuticals and luminescent materials. Nevertheless, their synthesis suffers from pre-functionalized starting materials and multi-step synthesis. On the other hand, despite significant progress in isocyanide insertions, it remains underdeveloped for multiple isocyanide insertion initiated from inert C–O bond activation. Herein, we report an unprecedented TMSOTf-catalyzed domino reaction enabled by C–O bond activation, where double isocyanide insertion with 3-indolylmethanols and sequential intramolecular cyclization are involved to afford cyano-substituted pyrrolo[2,3-b]indoles. Isocyanides, which have generally been utilized as the sole C1 building block, are employed as both C-nucleophiles and masked N-nucleophiles to produce the cyano-substituted pyrrole skeleton. The crucial chloranil oxidant assists the electronic property variation of the indole motif, facilitating the nucleophilic attack at both benzylic and C2 positions of 3-indolylmethanols. This newly established protocol features mild conditions, good functional group tolerance and broad substrate scope. Depending on the substituent of the isocyanide, corresponding amide and cyclopenta[b]indole scaffold could also be accessed. Moreover, diverse transformations of the obtained product are illustrated, including deprotection and hydrolysis. The successful formation of various types of N-containing polycyclic compounds further demonstrates the remarkable synthetic potential inherent of the given protocol. After careful mechanistic studies, the enamine compound, generated from double isocyanide insertion with 3-indolylmethanols, is proposed as the key intermediate for this reaction.
Perovskite solar cells (PSCs) are promising thin-film photovoltaic devices and achieve a high power conversion efficiency (PCE) of 27.3% (certified). Hole transport layer (HTL) composed of nickel oxide (NiOx) and [4-(3,6-dimethyl-9H-carbazol-9-yl)butyl]phosphonic acid (Me-4PACz) is extensively utilized in these devices. However, the dispersion and conductivity of NiOx are suboptimal, and it exhibits energy-level mismatch. Meanwhile, the coverage of Me-4PACz on NiOx is non-uniform. Herein, we synthesized magnesium ion-doped nickel oxide (Mg:NiOx) with more surface hydroxyl groups to address these issues. More surface hydroxyl groups provided more binding sites for Me-4PACz, resulting in a denser and more uniform coverage of Me-4PACz. Consequently, fewer defects were present at the buried interface, and a better environment for the crystallization of perovskite (PVK) was established. Furthermore, Mg:NiOx/Me-4PACz enabled better energy level alignment with PVK. The Mg:NiOx-based PSCs achieved a champion PCE of 25.86%, representing a notable improvement over the NiOx-based devices (24.51%). After 462 h of continuous illumination testing, the PSCs with Mg:NiOx retained 96.8% of their initial PCE, while those with NiOx only maintained 62.9% of their initial PCE. Thus, Mg:NiOx effectively enhanced both the PCE and stability of PSCs.
The catalytic asymmetric synthesis of atropisomers incorporating both axial and central chirality represents an attractive but formidable challenge in synthetic chemistry. We disclose herein a nickel-catalyzed diastereo- and enantioselective silacycloaddition that achieves the atroposelective assembly of multistereogenic aromatic amide-derived atropisomers. This transformation combines dynamic kinetic resolution of racemic aromatic amide atropisomers with asymmetric Si–C bond activation of benzosilacyclobutenes. Employing chiral BINOL-derived phosphoramidite ligand featuring chiral cavity of optimal size, this method provides efficient access to a novel class of phosphorus-containing aromatic amide atropisomers, delivering structurally diverse axially chiral phosphines with concomitant central chirality in good yields, excellent enantioselectivities, and moderate to good diastereoselectivities. This methodology exhibits high configurational stability, as confirmed by both experimental and computational studies, along with remarkable synthetic versatility exemplified by its facile conversion to secondary alcohol-containing atropisomers via desilylation of such organosilicon compounds. Beyond its immediate utility for constructing modular ligand libraries, this work establishes a transformative platform that promises to inspire phosphine substrate-compatible asymmetric transformations, addresses long-standing challenges in the synthesis of stereochemically complex atropisomers, and enables innovative applications across asymmetric catalysis and related fields.
Transition-metal-catalyzed radical-mediated four-component carbonylation reactions offer a sustainable and efficient strategy for modular synthesis of complex carbonyl compounds from simple feedstocks. However, current studies have primarily focused on the alkylcarbonylation of π-bonds in unsaturated hydrocarbons, including alkenes, alkynes and 1,3-enynes. In this study, we report a nickel-catalyzed 1,3-alkylcarbonylation of σ-bonds in bicyclo[1.1.0]butanes (BCBs) using CO as an economical carbonyl source. By leveraging steric hindrance and ring-strain effects, the reaction of BCB-tethered esters, activated alkyl bromides and arylboronic acids proceeded efficiently under nickel catalysis and ambient CO pressure, affording a series of aryl cyclobutyl ketones containing a quaternary carbon center. This protocol is characterized by mild reaction conditions, a broad substrate scope, and excellent functional group compatibility. Control experiments revealed that the steric profile of tertiary alkyl radicals is paramount for the chemoselectivity of this four-component carbonylation cascade.
Despite significant progress in catalytic asymmetric (3+X) cycloadditions of bicyclobutanes (BCBs) for constructing pharmaceutically valuable bicyclo[n.1.1]alkanes, current strategies are limited to using a single catalyst for the separate activation of BCBs or the "X" components. Herein, we report a new strategy that synergistically combines achiral Pd-catalysis for BCB activation with chiral iminium activation of α,β-unsaturated aldehydes, thereby overcoming existing limitations. These limitations include issues of chemo-, diastereo-, and enantioselectivity in the (3+2) cycloadditions of BCBs with enals for the synthesis of multisubstituted all-carbon bicyclo[2.1.1]hexanes (BCHs). Despite these challenges, up to 99% ee, >20 : 1 d.r., and 88% yield have been achieved. Moreover, the protocol demonstrates a wide range of substrates, high tolerance to various functional groups, scalable synthesis and versatile product functionalization, highlighting its practical value in constructing complex chiral BCH structures. Additionally, synergizing transition-metal catalysis and organocatalysis activation principles broadens the mechanistic and synthetic scope of the asymmetric cycloadditions of BCBs.
An expedient organophosphine-mediated skeletal editing of benzodithiol-3-ones is demonstrated herein, which represents the first example for metal-free transformations of benzodithiol-3-ones via S-to-C atom swap. This unprecedented formal [4+1] cycloadditions of benzodithiol-3-ones and α-halocarbonyls enable divergent synthesis of diverse 3-hydroxybenzo[b]thiophenes and benzo[b]thiophen-3(2H)-ones, the products of which were determined by the substitution pattern of the α-halocarbonyls. The newly-developed S-to-C exchange strategy allows for the streamline assembly of valuable sulfur-heterocycles via sulfur-deletion and carbon-insertion. This method is distinguished by its transition-metal-free nature, elimination of inert gas protection requirements, convenient operation, mild conditions, extensive substrate generality and decent yields. Of note, the current protocol could be readily applied to late-stage diversification of structurally varied bioactive molecules, underscoring the potential applicability and practical utility of this metal-free skeletal editing strategy.
End group modification is an effective strategy to modulate the energy levels, molecular packing and intermolecular interactions of small molecule acceptors (SMAs) in organic solar cells (OSCs). However, conventional end group linking site in giant molecule acceptors (GMAs) based on SMA subunits often occupies halogen substitution sites of end group, limiting further modification of GMAs and the improvement of their power conversion efficiency (PCE). Here, we developed a serious of GMAs, G-5H6H, G-5F6H and G-5F6F, by shifting the linking site to the 4-position of the 1,1-dicyanomethylene-3-indanone (IC) unit in the SMAs, enabling stepwise halogenation at the 5- and 6-positions. Due to the di-fluorination of inner IC end group, G-5F6F shows enhanced planarity and intramolecular charge transfer effect, resulting in the red-shifted absorption and highly ordered molecular packing. As a result, the OSCs based on D18:G-5F6F achieve the highest PCE of 18.29%. Furthermore, incorporating G-5F6F as the second acceptor into the D18:BTP-eC9 based OSCs has resulted in a remarkable PCE of 19.52% and enhanced device stability. This work demonstrates a synergistic molecular design strategy integrating linking site relocation and fluorination for high-performance OSCs based on GMAs.
Presently, few methods offer broad applicability for optimizing thick-film organic solar cells (OSCs). Here, we identify and implement a functional aid, 4-iodobiphenyl (IBP), in OSCs to optimize active layer morphology and significantly boost device efficiency. In the PM6:A4T-16 system, the optimized volatility of IBP promotes acceptor recrystallization and ordered molecular alignment during thermal annealing, leading to the formation of large aggregates and a fibrous morphology that facilitates efficient charge transport. As a result, the power conversion efficiency (PCE) of IBP-treated devices increases by 20% compared with those using conventional additives such as DIO and DIB. Notably, IBP exhibits broad compatibility, delivering substantial efficiency enhancements in PM6:BTP-eC9 and PM6:D18:L8-BO systems, with the latter reaching a high PCE of 20%. Furthermore, IBP enables thickness-insensitive performance, maintaining a PCE of ~17% at an active layer thickness exceeding 360 nm. These results demonstrate IBP as a highly effective processing aid for multiple donor:acceptor pairs, offering a promising strategy for morphology engineering and advancing the fabrication of high-performance OSCs.