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Comprehensive Summary: A copper‐catalyzed cyanation/diarylmethylation of formamides has been developed for the synthesis of α‐cyano functionalized tetra‐substituted olefins by utilizing para‐quinone methides (p‐QMs) and trimethylcyanosilane as functionalization sources. Various kinds of p‐QMs and formamides are well tolerated, delivering the desired products with 72%—94% yields, demonstrating broad functional group tolerance. Notably, the reaction does not require noble metals and proceeds regioselectively under mild conditions. Based on step‐by‐step control experiments, Hammett studies and DFT calculation, a plausible mechanism is proposed. [ABSTRACT FROM AUTHOR]

An efficient Rh(III)-catalyzed C-H activation of azobenzenes and subsequent [4+1] cascade annulation with CF3-imidoyl sulfoxonium ylides was developed, yielding diverse CF3-indazoles. This protocol featured easily available starting materials, excellent functional group tolerance and high efficiency. Moreover, the antitumor activities of selected CF3-indazoles against human cancer cell lines were also studied, and the results indicated that several compounds displayed considerable antiproliferative activities. [ABSTRACT FROM AUTHOR]

An efficient “one pot” direct N-α-C(sp3)-H functionalization of arylmethylamines towards synthesis of substituted 2,4,6-triarylpyridines has developed. Fascinatingly, this method features O2 as an oxidant, metal-free simple reaction operation and the dual role of arylmethylamines. The self-oxidative coupling of readily available simple methylamines followed by their sequential deamination/cyclization cascade with arylmethylketones has accomplished anticipated 2,4,6-triarylpyridines (20 examples) up to 95% yield with good functional groups tolerance. The straightforward reaction condition in the presence of an oxidant O2 and generated H2O as a sole byproduct made this process environmentally friendly. [ABSTRACT FROM AUTHOR]

Comprehensive Summary We synthesized a dialane(4) compound (2) stabilized by double‐layer N‐P ligands. Upon reduction with KC8, compound 2 demonstrates solvent‐dependent reactivity: in THF, it undergoes C—O bond cleavage to yield product [MeN(CH2CH2NPiPr2)2Al(CH2)4O]2K2; whereas in a THF/toluene mixture, it results in the activation of the methyl C—H bond in toluene, forming product [MeN(CH2CH2NPiPr2)2AlH]2K2. We propose that these reactions involve an “Al(I)” intermediate, which facilitates oxidative addition with either the C—O bond of THF or the C—H bond of toluene. [ABSTRACT FROM AUTHOR]

Herein, an atom-economic method for the synthesis of fused-ring pyrrolizine derivatives by a cycloaddition reaction of easily accessible N -substituted pyrrole-2-carboxaldehydes with N -substituted maleimides in the presence of di- tert -butyl peroxide has been successfully developed. A total of 23 compounds were obtained by using this method, with a maximum yield of 72%, providing a practical and efficient method for the synthesis of tricyclic pyrrolizine frameworks. [ABSTRACT FROM AUTHOR]

Oxidative C–H bond activated palladium-catalyzed aromatic cross-coupling reactions offer advantages of fewer required synthetic steps but disadvantages of loss of inherent regioselectivity and selectivity. In one proposed catalytic cycle, each arene adds to a palladium carboxylate catalyst according to a concerted metalation deprotonation mechanism, followed by reductive elimination to couple the arenes and the replenishment of the catalyst by an oxidant. Using this proposed mechanism, molecular structures and free energy profiles were calculated for coupling of benzene with a range of heteroarenes containing various substituents and with several Pd-carboxylate catalysts. Reaction kinetics were analysed using the energetic span model, predicting turnover frequencies (TOFs) of heterocoupling (HB and BH) and homocoupling (HH and BB) pathways and assessing degrees of turnover frequency control (XTOFs). More electron-withdrawing carboxylate ligands and more electron-donating heteroarene substituents decrease activation and reaction free energies of addition steps, with C-2 more favourable than C-3. When heteroarene and catalyst choice are particularly favourable, the first association can become exergonic, causing a significant change in catalytic kinetics. When not exergonic, free energy for addition of benzene is almost always higher, leading to large energetic spans and slower TOFs (BB < HB < BH < HH). Non-exergonic pathways are also faster with more electron-withdrawing ligands and more electron-donating heteroarene substituents because of lower energy addition steps and a smaller energetic span. For exergonic associations, the low-energy arene–catalyst intermediate creates a larger energetic span, slowing down the HH and HB pathways. More electron-withdrawing ligands and more electron-donating substituents increase the relative TOF for BH, and the reaction requires only small excesses of benzene to induce heterocoupling. [ABSTRACT FROM AUTHOR]

The hypervalent iodine-mediated formation of steroidal 5/5-spiroiminals and 5/5-spiroaminals from steroidal amines is presented. Under the influence of excess PhI(OAc)2 and iodine in acetonitrile at 0 °C, steroidal amines smoothly underwent cyclization to give a mixture of 5/5-spiroiminals and 5/5-spiroaminals. This reaction represents the first example of a C-H-activation-mediated formation of a spiroiminal. Presumably, the formation of 5/5-spiroiminals occurs through aminyl radical-mediated cyclization followed by amine-to-imine oxidation. [ABSTRACT FROM AUTHOR]

The development of efficient synthetic procedures to access fused N, O-heterocyclic skeletons has been a pivotal research topic in organic synthesis for several years. Owing to the applications of N, O-fused heterocycles in organic synthesis, material sciences, and medicinal chemistry, significant efforts have been dedicated to design novel methods for their construction. To this end, 1,3-benzoxazin-4-ones are privileged candidates for N, O-heterocyclic molecules often found in natural products, agrochemicals, and materials science applications. In this review, we aim to summarize the existing literature on the synthesis of 1,3-benzoxazin-4-ones from 2010 onwards. Moreover, 1,3-benzoxazin-4-ones have also been identified as an excellent native directing group for the ortho-functionalization via C-H activation, which is often a strenuous task requiring pre-functionalized substrates. In the latter part of this report, we compiled several interesting examples of N-directed functionalizations of 1,3-benzoxazin-4-ones. Additionally, to emphasize biological importance, recent developments on the anticancer evaluations of benzoxazine-4-one core are included. We believe that by harnessing the methodologies discussed herein, new possibilities could be unlocked for the synthesis of fused N, O-heterocycles, leading to the development of novel biologically active compounds and functional materials. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The first total synthesis of neopetromin, featuring the highly strained Tyr C‐6‐to‐Trp N‐1' linkage, is hereby reported. This modular synthetic strategy, employing C—H arylation and Larock macrocyclization, offers a novel approach to the synthesis of various RiPPs natural product families. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The first total synthesis of neopetromin, featuring the highly strained Tyr C‐6‐to‐Trp N‐1' linkage, is hereby reported. This modular synthetic strategy, employing C—H arylation and Larock macrocyclization, offers a novel approach to the synthesis of various RiPPs natural product families. [ABSTRACT FROM AUTHOR]

ABSTRACT A highly regioselective approach for constructing 4‐cyclobutene‐isoquinoline derivatives through ruthenium‐catalyzed domino C–H activation/cyclization of aryl imidates has been demonstrated. This new transformation tolerates various substituted functional groups on imidates and propargylic monofluoroalkynes, resulting in the corresponding products being delivered in moderate yields. [ABSTRACT FROM AUTHOR]

The activation of inert C–H bonds remains a challenge in current chemistry. Here, we report the excellent reactivity of the anionic gallylene species [LGa:][Na(THF)3] (L = [(2,6-iPr2C6H3)NC(CH3)]22−, 1) that allows the selective activation one ortho sp2 C–H bond of several azobenzene and azide derivatives at ambient temperature, with the transfer of the hydrogen atom to one of the nitrogen atoms. The process leads to the formation of the aryl amido products [LGa-κ2N,C-PhNN(H)(p-R-C6H3)][Na(solvent)3] (2, R = H solvent = DME (1,2-Dimethoxyethane); 3, R = –OMe, solvent = DME; 4, R = –NMe2 solvent = THF), [LGa-κ2N,C-(m-CH3-C6H4)NN(H)(m-CH3-C6H3)][Na(15-C-5)2] (5) with new Ga–C and Ga–N bonds. Moreover, 1 is also effective for the C–H activation of two azides RN3 (R = 2,4,6-Me3C6H2 or 2,6-iPr2C6H3), resulting in the formation of gallium amides [LGa(NH-2-(CH2)-4,6-Me2C6H2)][Na(15-C-5)2] (6) and [LGa(NH-2,6-iPr2C6H3)2][Na(THF)5] (7) through intra- or intermolecular sp3 C–H amination. Significantly, these reactions occur for the highly challenging activation of inert C(sp2)–H and C(sp3)–H bonds, thus demonstrating the excellent reactivity of the Ga(I) species 1. The products 2–7 were characterized by X-ray crystallography, 1H and 13C NMR, UV–vis spectroscopy, and density functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: We herein describe a Cp*RhIII‐catalyzed C(sp3)–H mono‐arylation of 8‐methylquinolines with benign arylsilanes. The use of 1‐adamantane carboxylic acid can benefit the efficiency in this transformation, and AgF was both activator and reoxidant. Control experiments indicated inability of C—H cleavage in determining the rate of the reaction. [ABSTRACT FROM AUTHOR]

Selective functionaliz0ation of C(sp3)–H bonds is a straightforward and practical method to construct complex molecule skeletons. In this field, direct transformation of unactivated C(sp3)–H bonds into C(sp3)–SCF3 architectures is still a great challenge. We report a highly selective trifluoromethylthiolation of unactivated aliphatic C(sp3)–H bonds by combination of proton-coupled electron transfer (PCET) and hydrogen atom transfer (HAT) strategy. A wide range of structurally diverse alkyl trifluoromethyl sulfides are obtained. Furthermore, the use of two different photocatalysts can realize an unprecedented trifluoromethylthiolation and amidation cascade of different C(sp3)–H bonds. It can afford a good access to bifunctionalized molecules in synthetically useful yields. [ABSTRACT FROM AUTHOR]

The peroxygenases are ideal biocatalysts for the selective oxyfunctionalisation of stable C–H bonds. However, the catalytic efficiency of this approach is limited due to enzyme lability toward oxidant H2O2. Although the reported in-situ H2O2 generation system enables the stable biocatalytic process without deactivating the enzyme, the greatest catalytic potential of peroxygenases still cannot be fulfilled effectively. To address the above issue, a H2O2 generation-detection-regulation platform that integrated an effective organocatalyst-driven H2O2 generation system, a precise electrochemical H2O2 real-time detection device, and a convenient H2O2 regulation strategy was first developed. The suitable range of H2O2 generation rate for maximizing the catalytic efficiency of peroxygenases while minimizing inactivation of the enzyme was firstly obtained by simply adjusting the amount of organocatalyst. According to the determined suitable range, the C–H oxyfunctionalisation efficiency of peroxygenases for each substrate was significantly boosted, achieving ∼3-fold of the reported highest turnover frequency.

We developed a redox-neutral synthesis of isoindoloindolone via intramolecular arylation of 2-(1 H -indole-1-carbonyl)benzoic acids. This protocol facilitates the formation of various substituted isoindoloindolones in yields ranging from 17% to 80%. Our mechanistic investigations indicate the pivotal role of NaI: the iodide anion promotes the formation of the desired isoindoloindolone, and the sodium cation suppresses the formation of acylated byproducts, thereby enabling the selective formation of isoindoloindolones in acceptable yields. [ABSTRACT FROM AUTHOR]

A biomass-based catalyst, CuxOy@CS-400, was employed as an excellent recyclable heterogeneous catalyst to realize the sulfonylation reaction of aniline derivatives with sodium sulfinates. Various substrates were compatible, giving the desired products moderate to good yields at room temperature. In addition, this heterogeneous copper catalyst was also easy to recover and was recyclable up to five times without considerably deteriorating in catalytic efficiency. Importantly, these sulfonylation products were readily converted to the corresponding 4-sulfonyl anilines via a hydrolysis step. The method offers a unique strategy for synthesizing arylsulfones and has the potential to create new possibilities for developing heterogeneous copper-catalyzed C-H functionalizations. [ABSTRACT FROM AUTHOR]

Installing fluoroalkyl motifs into biorelevant indoles is particularly interesting due to their ubiquitous presence in drug molecules. Herein, we demonstrate the regioselective C4 fluoroalkoxylation of indoles using fluoroalcohols via palladium‐catalyzed chelation‐assisted C─H activation. The weak chelating benzoyl moiety at the C3 position acts as a directing group for remote C(4)─H fluoroalkoxylation of diversely substituted indoles. This methodology demonstrates a high level of regioselectivity and tolerates a range of crucial functional groups, yielding diverse trifluoroalkoxylated indoles in moderate to good yields. Removal of directing/protecting groups and further functionalization established the synthetic utility of the methodology. A preliminary mechanistic investigation is conducted by isolating the palladacycle intermediate and performing the deuterium scrambling study. [ABSTRACT FROM AUTHOR]

A new approach for the preparation of a variety of 3-arylated 2-furoic acid derivatives has been developed. The approach involves selective Ru-catalyzed C3-H arylation of the furan moiety of readily available 2-furoyl-1-methylimidazole (using imidazole as a removable N-donor directing group), subsequent N-methylation, and nucleophilic substitution of the imidazole moiety with N, O, S, and C nucleophiles. [ABSTRACT FROM AUTHOR]

Fluorinated molecules are widely used in pharmaceutical and agrochemical industries. Multifluoroalkyl-containing compounds have attracted increasing attention for their unique ability to alter the activity of drugs and bioactive molecules. Herein, we report an efficient Rh(III)-catalyzed, redox-neutral, C–H multifluoroalkenylation of benzamides with multifluoroalkenes, which provides a versatile protocol for accessing a wide range of multifluoroalkenylated arenes. [ABSTRACT FROM AUTHOR]

A library of neutral and cationic palladium complexes of cis‐chelating hetero‐dicarbene ligands have been prepared. These ligands contain two different NHC donors allowing for a wider degree of variation, and the impact of the distinct NHC units has been compared using various spectroscopic means. In addition, the catalytic activities of these complexes in the direct C‐H arylation of thiophenes with aryl halides were studied leading to the finding that the neutral dibromido complexes of the type [PdBr2(diNHC)] generally outperformed their cationic [Pd (NCMe)2(diNHC)](OTf)2 counterparts. More importantly, complexes containing more distinct NHC units give rise to superior catalysts due to an amplified "stereoelectronic asymmetry" within the complex. A preliminary photophysical study of some selected thiophene reaction products has been conducted as well. The ability to individually change each NHC donor in such dicarbene ligands allows for a better fine‐tuning of complex properties in search for superior catalysts. [ABSTRACT FROM AUTHOR]

The indole moiety, a prevalent and versatile heterocyclic scaffold, plays a pivotal role in the realm of organic synthesis, underpinning the structural basis of myriad natural products, pharmaceuticals and advanced materials. This review comprehensively surveys the landscape of methodologies for indole synthesis, highlighting the evolution of techniques from classical to contemporary strategies. We investigate the Fischer Indole Synthesis, emphasizing its historical significance and mechanistic nuances and transition to discussing the Reissert Indole Synthesis, detailing its unique contributions to the synthesis of indole derivatives. Furthermore, the review explores advanced methodologies including metal-catalyzed reactions, C-H activation processes and green synthesis approaches, offering insights into their mechanisms, scope and limitations. Through this review, we aim to provide a holistic overview of indole synthesis, furnishing researchers with a detailed understanding of its complex mechanisms and the broad utility of the indole moiety in synthesizing biologically active compounds. The synthesis methods reviewed not only underscore the chemical diversity and adaptability of indole chemistry but also highlight ongoing challenges and future directions in the synthesis and transformation of derivatives of indole. This comprehensive examination serves as a valuable resource for chemists seeking to harness the indole scaffold's potential in novel synthetic applications. [ABSTRACT FROM AUTHOR]

The pursuit of high-performance narrowband blue organic light-emitting diodes (OLEDs) is of paramount importance in both academic research and industrial applications. While obvious strides have been made in the design of narrowband blue emitters, the development of appropriate host materials has evidently trailed behind. Herein, we introduce a medium-ring strategy for crafting host molecules based on the heptagonal tribenzo[b,d,f]azepine (TBA) unit. The twisted three-dimensional (3D) architecture of the TBA framework not only endows the host molecules with fast hole-transporting pathways but also effectively reduces exciton quenching. Equipped with two TBA units, DTBA, synthesized with ease, demonstrates a huge horizontal orientation factor (Θ//) of 93.5% and a broad emission spectrum for accelerating the energy transfer process in the emitting layer, which contributes to enhancing device performance. We have fabricated high-performance narrowband blue OLEDs using DTBA as the host, FIrpic as the phosphor sensitizer, and the widely used boron-nitrogen-containing multiple resonance emitter BCz-BN. These devices exhibit a maximum external quantum efficiency (EQEmax) as high as 31.0% with an impressively low-efficiency roll-off. Even at a high luminance level of 10,000 cd m−2, the EQE value remains noteworthy at 20.3%, marking a significant advancement in BCz-BN-based devices. [ABSTRACT FROM AUTHOR]

A novel methodology for the synthesis of 2-pyridones bearing a 2-pyridyl group on nitrogen and carbon atoms, starting from 2-bromopyridines, was developed employing a simple Ru(II)–KOPiv–Na2CO3 catalytic system. Unsubstituted 2-bromopyridine was successfully converted to the penta-heteroarylated 2-pyridone product using this method. Preliminary mechanistic studies revealed a possible synthetic pathway leading to the multi-heteroarylated 2-pyridone products, involving consecutive oxygen incorporation, a Buchwald–Hartwig-type reaction, and C–H bond activation. [ABSTRACT FROM AUTHOR]

Reported here is the iridium-catalyzed regio- and enantio-selective secondary benzylic C–H borylation using benzothiazole as the directing group. Various monosubstituted 2-arylalkylbenzo[ d ]thiazole were well-tolerated, affording the corresponding products in moderate to good yields with good enantioselectivity. The C–B bond in one boryl-ated product could undergo stereospecific transformations to form a series of C–C and C–heteroatom bonds. [ABSTRACT FROM AUTHOR]

A novel route for C(sp3)-N bond formation via C(sp2)−H activation/reduction by metal-free which uses (E)- N ′-benzylideneacetohydrazide and (vinylsulfonyl)benzene to synthesize derivatives of (E)- N ′-benzylidene- N -(2-(phenylsulfonyl)ethyl)acetohydrazide has been reported. This methodology features good functional group tolerance and convenient operation. In addition, it uses inexpensive and insensitive chemical reagents as raw materials and provides an atom- and efficient method for the preparation of (E)- N ′-benzylidene- N -(2-(phenylsulfonyl)ethyl)acetohydrazides. [ABSTRACT FROM AUTHOR]

In this study, Pd nanoparticles encapsulated in the copper‐based mesoporous metal–organic framework (Cu2(BDC)2DABCO) and used as a reusable heterogeneous catalyst to establish a method for the direct benzylation of carboxylic acids through C‐H (sp3) bond activation. The catalyst structure was characterized by scanning electron microscope (SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD), Brunauer–Emmett–Teller (BET), and inductively coupled plasma (ICP). This catalyst showed high catalytic activity, selectivity, and good functional group tolerance for the direct benzylation of carboxylic acids. [ABSTRACT FROM AUTHOR]

A new approach to the alkylation of azoles with alkenes catalyzed by the nickel complexes with N-heterocyclic carbenes (Ni/NHC) was developed. The catalytically active Ni/NHC complexes are formed in situ from the air-stable precursors: the nickel chloride complex with pyridine (NiCl2Py2), imidazolium salt IMes•HCl (IMes is 1,3-bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene) as the carbene source, and sodium tert-butoxide (ButONa). The advantages of the developed approach are availability of the components of the catalytic system, no necessity to apply special agents for the reduction of NiII to Ni0, and simplification of the synthesis procedure. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The rhodium‐catalyzed C—H bond activation and cyclization of 3‐oxopent‐4‐enenitriles with alkynes proceed efficiently. Various 2H‐pyrans with multiple substituents are achieved in good yields through regioselective formation of C—O and C—C bonds. Transformations involving hydroxy‐alkynoates resulted in products with a furo[3,4‐b]pyran skeleton via further intramolecular ester exchange processes. Different from the traditional "1‐oxatrienes pathway", this method for the synthesis of useful 2H‐pyrans possesses certain highlights in terms of readily available substrates, stable and easily derivatized products, gentle and convenient operation process, and step and atom economy. [ABSTRACT FROM AUTHOR]

This short review showcases the developing field of C–H activation reactions, with a particular focus on green catalysis through the use of environmentally friendly solvents. It evaluates the effects of these solvents on reaction outcomes, environmental aspects and general efficacy, highlighting their advantages that lead to greater selectivity, lower levels of toxicity and enhanced reaction rates. Water and biobased alternatives such as polyethylene glycols, glycerol, 2-methyltetrahydrofuran, γ-valerolactone, methanol, ethanol, p -cymene and diethyl carbonate are representative examples of such solvents. The scope of this short review encompasses studies of different methodologies, catalysts, and reaction conditions that help to develop C–H activation reactions utilizing green solvents. 1 Introduction 2 Water 3 Polyethylene Glycols (PEGs) 4 Glycerol 5 2-Methyltetrahydrofuran (2-MeTHF) 6 γ-Valerolactone (GVL) 7 Methanol 8 Ethanol 9 p -Cymene 10 Diethyl Carbonate 11 Conclusion [ABSTRACT FROM AUTHOR]

C–H bond activation is a crucial synthetic strategy widely utilized in both academic and industrial settings. Due to the strong and kinetically inert nature of the C–H bond, its functionalization typically requires metal-based catalysts. This review highlights the most significant advancements in homogeneously catalyzed reactions using pincer complexes with metals from groups 8–10, capable of promoting challenging C–H activation, published since 2010. In particular, it focuses on C–H bond activation for borylation, isomerization, and dehydrogenation, among other processes, discussing their scope and mechanistic insights. [ABSTRACT FROM AUTHOR]

Transition-metal-catalyzed directed C–H functionalization with various carbene precursors has been widely employed for constructing a wide range of complex and diverse active molecules through metal carbene migratory insertion processes. Among various carbene precursors, iodonium ylides serve as a novel and emerging carbene precursor with features including easy accessibility, thermal stability and high activity, which have attracted great attention from organic chemists and have achieved tremendous success in organic transformation. In this review, recent progress on the application of iodonium ylides with multifunctional coupling characteristics in C–H bond activation reactions is summarized, and the potential of iodonium ylides is discussed. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A new, selective Ru(II)‐catalyzed alkynylation reaction of isoquinolones, quinazolones and phthalazinones with readily available bromoalkynes has been developed. This reaction enables the selective construction of a new C(sp2)‐C(sp) bond through C—H activation and C—Br functionalization, and offers an effective and selective route to synthesizing highly valuable alkynylated isoquinolone, quinazolone and phthalazinone derivatives with a wide substrate scope and high selectivity. [ABSTRACT FROM AUTHOR]

The peroxygenases are ideal biocatalysts for the selective oxyfunctionalisation of stable C-H bonds. However, the catalytic efficiency of this approach is limited due to enzyme lability toward oxidant H2O2. Although the reported in-situ H2O2 generation system enables the stable biocatalytic process without deactivating the enzyme, the greatest catalytic potential of peroxygenases still cannot be fulfilled effectively. To address the above issue, a H2O2 generation-detection-regulation platform that integrated an effective organocatalyst-driven H2O2 generation system, a precise electrochemical H2O2 real-time detection device, and a convenient H2O2 regulation strategy was first developed. The suitable range of H2O2 generation rate for maximizing the catalytic efficiency of perox-ygenases while minimizing inactivation of the enzyme was firstly obtained by simply adjusting the amount of organocatalyst. According to the determined suitable range, the C-H oxyfunctionalisation efficiency of peroxygenases for each substrate was significantly boosted, achieving ~3-fold of the reported highest turnover frequency. [ABSTRACT FROM AUTHOR]

Organic azides are convenient and versatile intermediates for the synthesis of various nitrogen-containing scaffolds, including biologically active compounds, approved drugs, functional materials, etc. Designing general approaches to deliberately chemo-, regio-, and steroselective synthesis of aliphatic azides is an urgent task of synthetic chemistry. Particularly challenging is direct azidation of non-activated C(sp3)−H groups, capable of providing ready access to remote and late-stage functionalization of complex targets without need for re-designing existing multistep synthetic procedures. This contribution surveys the C(sp3)−H azidation approaches known to date, both non-catalytic and catalytic, including enzyme-mediated ones, with the major focus on the synthetic perspective of these transformations. Essential mechanistic details are briefly discussed.

A novel palladium(II) catalyzed C–H annulation strategy has been developed for the synthesis of a diverse range of furo[3′,4':5,6]pyrido[3,4-b]indole-1,5(3H)-dione scaffolds. This is the first report on the construction of polycyclic carboline frameworks from indole-2-carboxamides and 4-hydroxy-2-alkynoates. This method provides a direct access to fused carbolines that are closely resemble to biologically active β-carboline frameworks.

Poly(ionic liquids) (PILs) combined with the macromolecular structure and unique properties of ionic liquids show unlimited potential in catalysis. In this work, a series of metal-based PIL with different ionic ratios were prepared for the selective oxidation of cyclohexane. Characterization analysis reveals that different degrees of ionization could adjust the Co–N sites of the catalysts efficiently, leading to significant changes in their electronic structure, which strongly relate to catalytic performance in oxidation. 20.07% cyclohexane conversion and 13.06% cyclohexanone and cyclohexanol (KA oil) yield can be achieved by metal-based PILs that are better than other commercial catalysts. Compared with CoCl2, metal-based PILs perform well, with superior conversion and KA oil yield. More interestingly, the catalyst created in this study features a malleable Co–N site, which may potentially have an impact on how oxygen species adsorb and desorb from the catalyst. Therefore, the catalyst studied in this work is used as molecular oxygen for the selective oxidation of cyclohexane to produce KA oil, and its application prospect is promising.

Biocatalytic C-H activation has the potential to merge enzymatic and synthetic strategies for bond formation. FeII/αKG-dependent halogenases are particularly distinguished for their ability both to control selective C-H activation as well as to direct group transfer of a bound anion along a reaction axis separate from oxygen rebound, enabling the development of new transformations. In this context, we elucidate the basis for the selectivity of enzymes that perform selective halogenation to yield 4-Cl-lysine (BesD), 5-Cl-lysine (HalB), and 4-Cl-ornithine (HalD), allowing us to probe how site-selectivity and chain length selectivity are achieved. We now report the crystal structure of the HalB and HalD, revealing the key role of the substrate-binding lid in positioning the substrate for C4 vs C5 chlorination and recognition of lysine vs ornithine. Targeted engineering of the substrate-binding lid further demonstrates that these selectivities can be altered or switched, showcasing the potential to develop halogenases for biocatalytic applications.