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AbstractThe aryl-azaindole-pyrimidine-1,3,4-oxadiazole derivatives (12a–j) were synthesized by Suzuki coupling reaction between bromo-azaindole-1,3,4-oxadiaole intermediate 10 and various aryl boronic acids (11a–j) by using of Pd(dppf)Cl2 and K2CO3 in 1,4-dioxane/H2O. Here, the Suzuki coupling mechanism starts with the oxidative addition followed by transmetallation and ends with reductive elimination. These derivatives were screened in vitro anticancer applications against four human cancer cell lines including MCF-7, A549, Colo-205, and A2780 by employing of MTT method, the well-known chemotherapeutic agent as etoposide used as positive control. Among them, compound 12a bearing 3,4,5-trimethoxy substituent on the aryl moiety displayed good activity as compared with positive control against MCF-7, A549, Colo-205, and A2780 cell lines with IC50 values of 1.10 ± 0.84 µM, 1.07 ± 0.067 µM, 1.20 ± 0.95 µM, and 1.34 ± 0.66 µM respectively. Compounds 12a and 12b primarily engage in hydrophobic interactions such as pi-pi stacked, amide-pi stacked, pi-alkyl, and alkyl interactions. Specifically, nucleotides DG13, DA12, and arg503 display pi-pi stacked and amide-pi stacked interactions. [ABSTRACT FROM AUTHOR]

In this study, we report the first example of acyclic (amino)(N-pyridinium)carbenoid gold(III) complexes synthesized via a coupling reaction between 2-pyridylselenyl chloride and Au(I)-bound isonitriles. The reaction involves an initial oxidative addition of the Se–Cl moiety to Au(I), followed by the nucleophilic addition of the pyridine fragment to the isonitrile's C≡N bond, furnishing a metallacycle. Importantly, this is the first example of the pyridine acting as a nucleophile towards metal-bound isonitriles. Arguably, such an addition is due to the chelate effect. The structures of the gold(III) carbenoid complexes were unambiguously established using X-ray diffraction and NMR spectroscopy. Theoretical calculations, including DFT, Natural Resonance Theory (NRT), and Meyer bond order (MBO) analyses, were used to analyze the different resonance forms. The reaction mechanism was further elucidated using DFT calculations, which identified the oxidative addition as the rate-determining step with a barrier of 29.7 kcal/mol. The nucleophilic addition proceeds with a minimal barrier, making the reaction highly favorable. The antiproliferative activity of new compounds 2a–2e was tested against two human cancer cell lines: A2780 ovarian adenocarcinoma and the A278Cis cisplatin-resistant variant. [ABSTRACT FROM AUTHOR]

Zwitterionic π-allenyl palladium species are newly developed intermediates. A substrate-controlled step existed in the cycloaddition of zwitterionic π-allenyl palladium species with tropsulfimides or tropones. With the assistance of previously experimental studies, zwitterionic allenyl/propargyl palladium species was provenly found by HRMS. Further DFT calculation studies show that zwitterionic π-allenyl palladium species are generated through the oxidative addition of Pd(0), which can be promoted by Lewis acid like Yb(OTf)3, and the cycloaddition more likely undergoes through an outer sphere nucleophilic attack. The isomerization is caused by the difference of dissociation energy between the cycloaddition intermediation of tropsulfimides and tropones, forming the substrate-controlled specificity. [ABSTRACT FROM AUTHOR]

Palladium (Pd) is a 4d transition metal with electronic configuration [Kr] 4d10 5s0, and it is one of the most widely studied metals in the periodic table due to its versatile catalytic role in organic synthesis. The choice of ligands that can coordinate with Pd sites plays a crucial role in the progress of the reaction. Due to the coexistence of multiple oxidation states (Pd(0)/Pd(II)), the active Pd sites of the catalysts can participate in various stages of the coupling reaction. The Pd-catalyzed C-C coupling reactions proceed through four steps: (1) oxidative addition of the reactant to the catalytic site, (2) transmetallation, (3) rearrangements of ligand centers and (4) reductive elimination to the coupling products. For the heterogeneous Pd nanocatalysts, active Pd sites are often strongly bound (chelated) with the solid catalyst surfaces. In this review, we have highlighted the advancements made in the heterogeneous Pd nanocatalysts with an emphasis on the types of different classes of porous solids, which could ligate with the Pd centers via strong covalent bonds. The high specific surface areas and small Pd sites of these nanocatalysts provide a larger number of catalytic sites and thus facilitate the reaction. Mechanistic aspects of the C-C cross-coupling reactions are discussed in the context of the structure–reactivity relationship. [ABSTRACT FROM AUTHOR]

Transition‐metal‐catalyzed hydroamination of unsaturated hydrocarbons is an appealing synthetic tool for the construction of high value‐added chiral amines. Despite significant progress in the asymmetric hydroamination of alkenes, allenes, and 1,3‐dienes, asymmetric hydroamination of 1,6‐enynes or 1,7‐enynes remains rather limited due to the enormous challenges in controlling the chemoselectivity and stereoselectivity of the reaction. Herein, we report a Ni‐catalyzed chemo‐ and enantioselective reductive cyclization/amidation and amination of 1,6‐enynes and 1,7‐enynes using dioxazolones or anthranils as nitrene‐transfer reagents. This mild, modular, and practical protocol provides rapid access to a variety of enantioenriched 2‐pyrrolidone and 2‐piperidone derivatives bearing an aminomethylene group at the 4‐position in good yields (up to 83 %) with excellent enantioselectivities (46 examples, up to 99 % ee). Mechanistic experiments and density functional theory calculations indicate that the reaction is initiated by hydronickelation of alkynes followed by migratory insertion into alkenes, rather than by a [2+2+1] oxidative addition process of nickel to alkenes and alkynes. [ABSTRACT FROM AUTHOR]

A three‐component coupling approach toward structurally complex dialkylsulfides is described via the nickel‐catalyzed 1,2‐carbosulfenylation of unactivated alkenes with organoboron nucleophiles and alkylsulfenamide (N−S) electrophiles. Efficient catalytic turnover is facilitated using a tailored N−S electrophile containing an N‐methyl methanesulfonamide leaving group, allowing catalyst loadings as low as 1 mol %. Regioselectivity is controlled by a collection of monodentate, weakly coordinating native directing groups, including sulfonamides, amides, sulfinamides, phosphoramides, and carbamates. Key to the development of this transformation is the identification of quinones as a family of hemilabile and redox‐active ligands that tune the steric and electronic properties of the metal throughout the catalytic cycle. Density functional theory (DFT) results show that the duroquinone (DQ) ligand adopts different coordination modes in different stages of the Ni‐catalyzed 1,2‐carbosulfenylation‐binding as an η6 capping ligand to stabilize the precatalyst/resting state and prevent catalyst decomposition, binding as an X‐type redox‐active durosemiquinone radical anion to promote alkene migratory insertion with a less distorted square planar Ni(II) center, and binding as an L‐type ligand to promote N−S oxidative addition at a relatively more electron‐rich Ni(I) center. [ABSTRACT FROM AUTHOR]

The preparation of enantioenriched diarylmethanol derivatives is described using nickel‐catalyzed electrochemical cross‐couplings between various alkyl/aryl aldehydes and aryl iodides. Performed in an electrochemical cell equipped with an iron anode and a nickel cathode, this electrocatalytic variant led to the scalemic targeted products in the presence of 2,2‐bis((4 R,5S)‐4,5‐diphenyl‐4,5‐dihydrooxazol‐2‐yl)acetonitrile (L2), as enantiopure cyano‐bis(oxazoline) ligand. X‐ray structure analysis of a pre‐catalyst, for instance the [Ni(II)(L2)2] complex, with L2 as an anionic bisoxazolinate ligand, confirms the chemical formulation of one nickel surrounded by two ligands. The redox behavior of the new Ni complexes generated in situ was first assessed by cyclic voltammetry showing a redox wave at ca. −1.5 V that can be assigned to the two‐electron reduction of the Ni(II) center to the Ni(0) state. Oxidative addition between the electrogenerated Ni(0) complex and aryl iodide was evidenced. An intense current was observed in presence of a mixture of the two substrates pertaining an electrocatalytic process. Interestingly, we found that the sacrificial iron anode plays a crucial role in the catalytic mechanism. [ABSTRACT FROM AUTHOR]

This study presents a Ni‐photoredox method for indole N‐arylation, broadening the range of substrates to include indoles with unprotected C3‐positions and base‐sensitive groups. Through detailed mechanistic inquiries, a Ni(I/III) mechanism was uncovered, distinct from those commonly proposed for Ni‐catalyzed amine, thiol, and alcohol arylation, as well as from the Ni(0/II/III) cycle identified for amide arylation under almost identical conditions. The key finding is the formation of a Ni(I) intermediate bearing the indole nucleophile as a ligand prior to oxidative addition, which is rare for Ni‐photoredox carbon‐heteroatom coupling and has a profound impact on the reaction kinetics and scope. The pre‐coordination of indole renders a more electron‐rich Ni(I) intermediate, which broadens the scope by enabling fast reactivity even with challenging electron‐rich aryl bromide substrates. Thus, this work highlights the often‐overlooked influence of X‐type ligands on Ni oxidative addition rates and illustrates yet another mechanistic divergence in Ni‐photoredox C‐heteroatom couplings. [ABSTRACT FROM AUTHOR]

The kinetic stability provided by the sterically demanding {SiNDipp}2− dianion (SiNDipp = {CH2SiMe2NDipp}2; Dipp = 2,6-i-Pr2C6H3) is intrinsic to the isolation of not only the group 1 alumanyl reagents ([{SiNDipp}AlM]2; M = K, Rb, Cs) but also facilitates the completely selective oxidative addition of a C-H bond of 1,2-C2B10H12 to the aluminium centre. In each case, the resultant compounds comprise a four-coordinate o-carboranyl (hydrido)aluminate anion, [(SiNDipp)Al(H)(1,2-C2B10H11)]−, in which the carboranyl cage is bonded to aluminium by an Al-C σ bond. Although the anions further assemble as extended network structures based on Al-H∙∙∙M, B-H∙∙∙M, and C-H∙∙∙M interactions, each structure is unique due to the significant variation in M+ ionic radius as group 1 is descended. The potassium derivative crystallises as a one-dimensional polymer, its rubidium analogue is a dimer due to the polyhapto-sequestration of a molecule of benzene solvent within the alkali metal coordination sphere, and the caesium species is a two-dimensional assembly of hexameric aggregates. [ABSTRACT FROM AUTHOR]

The alkoxycarbonylation of styrene by palladium chloride is studied employing the density functional theory (DFT). Initially, [PdCl3]– reacts with methanol to form the methoxy-bound intermediate, which undergoes β-hydride elimination to form the key intermediate [PdCl2H]–. Then, a 1,2-insertion reaction to styrene takes place to form linear and branched alkyl coordinated with the PdII. Then, CO coordination followed by a 1,1-insertion reaction leads to the formation of acyl intermediate. Next, the methanolysis leads to the formation of esters. Previous reports with other catalysts suggested the intermolecular/intramolecular transition state (TS) formation with a high activation barrier, and this step was the bottleneck. To the best of our knowledge, this is the first time we have considered a two-step mechanism for the alcoholysis of the ester formation mechanism. After coordination with the metal, the methanol undergoes oxidative addition to form the PdIV square pyramidal intermediate, followed by reductive elimination to form the ester with regeneration of the metal hydride active intermediate. Deeper insight into the nature of bonding at the TSs is obtained through energy decomposition with natural orbital for chemical valence (EDA-NOCV) and quantum theory of atoms in molecules (QTAIM). [ABSTRACT FROM AUTHOR]

Using visible light conditions, we have developed a green protocol to prepare copper oxide‐doped graphitic carbon nitride (Cu2O@g‐C3N4) photocatalysts with varied ratios of g‐C3N4 nanosheets to copper oxide‐dopant (0.1 %, 0.5 %, 0.7 %, and 5 % respectively) and characterized through various physicochemical techniques. These photo‐responsive catalysts were used for the 1,4 radical oxidative addition of trans crotonaldehyde into β‐hydroxybutyric acid (BA) as a major product, utilizing 30 % hydrogen peroxide as an oxidant and a white LED (Light Emitting Diode) source. Under the innoculous eco‐friendly stipulations, Cu2O@g‐C3N4 (5 %) exclusively promoted the aforementioned reaction leading to 99.85 % trans crotonaldehyde conversion with 66.57 %, 24.1 %, and 9.1 % selectivity for β‐hydroxybutyric acid, crotonic acid and subsequent radical synthesis, respectively. [ABSTRACT FROM AUTHOR]

Thomas C. Maier's group has reported a synergistic Ir/Ni catalysis method for the synthesis of C(sp2)–C(sp3) bonds through an amino radical transfer (ART) strategy to generate alkyl radicals. This work employed density functional theory (DFT) to investigate the reaction mechanism, including the redox mechanism of Ir complexes in the generation process of amino radicals, analyzed the role and rationale behind alkyl boronic esters becoming dominant reaction pathways in the ART process, and discussed the competitive reaction mechanisms between oxidative addition and radical capture during C(sp2)–C(sp3) cross-coupling with Ni complexes. Through this theoretical calculation study, we aim to provide a theoretical foundation for constructing key carbon radical intermediates using ART and Ni-complex catalyzed free-radical-involved C(sp2)–C(sp3) cross-coupling reactions. [ABSTRACT FROM AUTHOR]

We disclose herein our evaluation of competitive (hetero)aryl‐X (X: Br>Cl>OTf) reactivity preferences in bisphosphine/Ni‐catalyzed C−N cross‐coupling catalysis, using furfurylamine as a prototypical nucleophile, and employing DalPhos and DPPF as representative ancillary ligands with established efficacy. Beyond this general (pseudo)halide ranking, other intriguing structure‐reactivity trends were noted experimentally, including the unexpected observation that bulky alkyl (e. g. R=tBu) substitution in para‐R‐aryl‐X electrophiles strongly discourages (pseudo)halide reactivity relative to smaller substituents (e. g. nBu, Et, Me), despite being both remote from, and having a similar electronic influence on, the reacting C−X bond; such effects on nickel oxidative addition have not been documented previously and were not observed in our comparator reactions presented herein involving palladium. Density functional theory modeling of such PhPAd‐DalPhos/Ni‐catalyzed C−N cross‐couplings revealed the origins of competitive turnover of C−Br over C−Cl, and possible ways in which bulky para‐alkyl substitution might discourage net electrophile uptake/turnover, leading to inversion of halide selectivity. [ABSTRACT FROM AUTHOR]

Cystathionine beta-synthase deficiency (CBSD) is the most prevalent inherited disorder of homocysteine metabolism in the transsulphuration pathway. Research have suggested oxidative stress and inflammation as candidate pathogenic mechanisms in CBSD. This study aims to evaluate mitochondrial dysfunction and oxidative stress biomarkers in cystathionine beta-synthase deficiency (CBSD) patients, which may aid in understanding the pathogenesis of CBSD and improving treatment. The study group comprised 23 patients with a diagnosis of CBSD and healthy controls. We analysed serum levels of NAD+ and NADH by fluorometric assay, FGF-21 and GDF-15 by ELISA, mitochondrial DAMPs by real time qRT-PCR, total homocysteine levels in plasma by enzymatic test and compared the results in CBSD group with healthy controls. In patient group, a positive correlation was found between the total homocysteine level and both GDF-15 and NAD+/NADH levels. Furthermore, there was a negative correlation between total homocysteine levels and both total NAD++NADH and NADH levels. The alterations in NAD+, FGF-21, GDF-15 levels, and NAD+/NADH ratio in patients suggest that oxidative damage coexists with mitochondrial dysfunction in CBSD. Assessment of oxidative damage and addition of anti-oxidant therapy together with mitochondrial support may have additional benefits in reducing long-term morbidity in CBSD patients. [ABSTRACT FROM AUTHOR]

Herein, we disclose the first report on gold‐catalyzed C(sp2)‐CN cross‐coupling reaction by employing a ligand‐enabled Au(I)/Au(III) redox catalysis. This transformation utilizes acetone cyanohydrin as a nucleophilic cyanide source to convert simple aryl and alkenyl iodides into the corresponding nitriles. Combined experimental and computational studies highlighted the crucial role of cationic silver salts in activating the stable (P,N)‐AuCN complex towards the oxidative addition of aryl iodides to subsequently generate key aryl‐Au(III) cyanide complexes. [ABSTRACT FROM AUTHOR]

The reactivity of [{SiNDipp}AlK]2, which comprises a formally anionic Al(I) centre, has been examined towards a variety of 1,3‐dienic molecules, including 2,3‐dimethylbutadiene, cyclooctatetraene, anthracene and tetracene. In each case, the alumanyl derivative experiences oxidative addition across the Al(I) centre to provide the corresponding potassium aluminacyclopentene, aluminacyclopropene or aluminanorbornadiene products of [4+1] cycloaddition. [ABSTRACT FROM AUTHOR]

Ruthenium‐catalyzed hydrosilylation of aldehydes with hydrooligosilanes is reported. Among the examined ruthenium catalysts, RuH2(CO)(PPh3)3 gave the best results. The reactions proceed with the Si−Si bonds preserved to afford the corresponding alkoxyoligosilanes in good yields. A series of aryl aldehydes with an electron‐withdrawing group is applicable, whereas those with an electron‐donating group are not suitable for the reaction. Mechanistic considerations suggest that the key points for the preservation of the Si−Si bonds are the formation of zero‐valent ruthenium species and the efficient coordination of the aldehyde to the ruthenium center prior to the oxidative addition of the Si−H bond. [ABSTRACT FROM AUTHOR]

Non-noble metals catalyzed carbonylative reactions serve as straightforward and sustainable methods for the synthesis of functionalized carbonyl-containing compounds. Herein, a low-valent-tungsten-catalyzed reaction that enables the coupling of aryl iodides and alcohols or phenols was disclosed, employing the readily available W(CO)6 as the effective catalyst and PPh3 as ligand. Under the optimal reaction conditions, aryl iodides smoothly underwent carbonylative coupling reactions with alcohols or phenols, processing the feature of broad substrate scope and good functional groups tolerance. Furthermore, this conversion can be carried out on a gram scale, showcasing significant promise in the synthesis of pharmaceutical or biologically active compounds. [ABSTRACT FROM AUTHOR]

Carbon-silicon-switch strategy, replacing one specific carbon atom in organic molecules with a silicon, has garnered significant interest for developing new functional molecules. However, the influence of a reaction regarding its selectivity and reactivity by carbon-silicon-switch strategy has far less been investigated. Here we discover an unusual carbon-silicon-switch effect in the enantioselective construction of silicon-stereogenic center. It is found that there has been a significant change in the desymmetrization reaction of silacyclohexadienones using asymmetric conjugate addition or oxidative Heck reaction with aryl/alkyl nucleophiles when compared with their carbon analogues cyclohexadienones. Specifically, the carbon-silicon-switch leads to a reversal in enantioselectivity with arylzinc as the nucleophile by the same chiral catalyst, and results in totally different reactivity with arylboronic acid as the nucleophile. Control experiments and density functional theory (DFT) calculations have shown that the unusual carbon-silicon-switch effect comes from the unique stereoelectronic feature of silicon. Silicon has been incorporated into organic molecules in place of carbon under the principle that, given that they belong to the same periodic group, their reactivity could be similar. Here, the authors perform desymmetrizations on silacyclohexenone and the carbon analogue, with the two substrates yielding opposite enantiomers, showing that our understanding of the similarities of the two atoms is incomplete. [ABSTRACT FROM AUTHOR]

Heavier group 14 carbene analogues, exhibiting transition-metal-like behavior, display remarkable capability for small molecule activation and coordination chemistry. However, their application in redox catalysis remains elusive. In this paper, we report the synthesis and isolation of a stannylene with carbodiphosphorane ligand. The nucleophilic reactivity at the divalent tin center is elucidated by computational and reactivity studies. Moreover, this stannylene exhibits catalytic activity in the hydrodefluorination reaction of fluoroarenes. Mechanistic investigations into the elementary steps confirm a SnII/SnIV redox cycle involving C–F oxidative addition, F/H ligand metathesis, and C–H reductive elimination. This low-valent SnII catalytic system resembles the classical transition metal catalysis. Notably, this represents metallomimetic redox catalysis utilizing carbene analogue with heavier group 14 element as a catalyst. Heavier group 14 carbene analogue display remarkable capability for small molecule activation but their application in redox catalysis remains elusive. Here, the authors report the synthesis and isolation of a stannylene with carbodiphosphorane ligand and characterize its catalytic activity in the hydrodefluorination reaction of fluoroarenes. [ABSTRACT FROM AUTHOR]

We present the photoreaction of newly prepared bis(6,6'‐dimethyl‐2,2'‐bipyridine)(oxalato)rhodium(III) ([Rh(N N)2(ox)]+) in CD3OD. Photoirradiation of this complex causes the dissociation of ox, followed by the formation of the unprecedented Rh(III) complex with Rh−H and Rh−C σ bonds, [Rh(N N)(C N)(H)(CD3OD)]+ (C N=[6,6'‐dimethyl‐2,2'‐bipyridine]‐3‐yl‐κC3,κN1'). This hydride formation and cyclometallation spontaneously proceed owing to the conflict between the steric hindrance arising from the methyl groups of N N and the driving force for the structural change due to [Rh(N N)2]+ formation. Although [Rh(N N)(C N)(H)(CD3OD)]+ is initially converted to [Rh(N N)2]+ by photoirradiation, it is immediately regenerated by the rollover cyclometallation of the [Rh(N N)2]+ complex. [Rh(N N)(C N)(H)(CD3OD)]+ undergoes H/D exchange for the H atoms in the Rh−H bond and at the 3, 3'‐positions of the N N ligand during the photoirradiation. DFT calculations predict with reasonable certainty the spontaneous structural change of [Rh(N N)2]+ to [Rh(N N)(C N)(H)(CD3OD)]+ and the subsequent photodriven Rh−C bond rupture leading to the formation of [Rh(N N)2]+ accompanied by H/D exchange reactions. [ABSTRACT FROM AUTHOR]

We present the photoreaction of newly prepared bis(6,6'‐dimethyl‐2,2'‐bipyridine)(oxalato)rhodium(III) ([Rh(N N)2(ox)]+) in CD3OD. Photoirradiation of this complex causes the dissociation of ox, followed by the formation of the unprecedented Rh(III) complex with Rh−H and Rh−C σ bonds, [Rh(N N)(C N)(H)(CD3OD)]+ (C N=[6,6'‐dimethyl‐2,2'‐bipyridine]‐3‐yl‐κC3,κN1'). This hydride formation and cyclometallation spontaneously proceed owing to the conflict between the steric hindrance arising from the methyl groups of N N and the driving force for the structural change due to [Rh(N N)2]+ formation. Although [Rh(N N)(C N)(H)(CD3OD)]+ is initially converted to [Rh(N N)2]+ by photoirradiation, it is immediately regenerated by the rollover cyclometallation of the [Rh(N N)2]+ complex. [Rh(N N)(C N)(H)(CD3OD)]+ undergoes H/D exchange for the H atoms in the Rh−H bond and at the 3, 3'‐positions of the N N ligand during the photoirradiation. DFT calculations predict with reasonable certainty the spontaneous structural change of [Rh(N N)2]+ to [Rh(N N)(C N)(H)(CD3OD)]+ and the subsequent photodriven Rh−C bond rupture leading to the formation of [Rh(N N)2]+ accompanied by H/D exchange reactions. [ABSTRACT FROM AUTHOR]

A bisphosphirane‐fused anthracene (5) was prepared by treatment of a sterically encumbered amino phosphorus dichloride (3) with MgA ⋅ THF3 (A=anthracene). X‐ray diffraction analysis revealed a pentacyclic framework consisting of 5 with two phosphirane rings fused to the anthracene in a trans‐fashion. Compound 5 has been shown to be an efficient phosphinidene synthon, readily liberating two transient phosphinidene units for subsequent downstream bond activation via the reductive elimination of anthracene under mild conditions. The formal oxidative addition of H2 and E−H (E=Si, N, P) bonds by the liberated phosphinidene provided diphosphine and substituted phosphines. Furthermore, phosphinidene transfer to alkenes and alkynes smoothly yielded the corresponding phosphiranes and phosphirenes. The mechanism of the H2 activation by 5 was investigated by density functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

Polyfluoroaryl ethers represent an important framework of biologically active molecules and materials. Owing to the strong bond dissociation energy of C−F bond, selectivity and other issues, transition metal‐catalyzed synthesis of polyfluoroaryl ethers from perfluoroarenes via the activation of C−F bond is challenging and underdeveloped, as compared to the well‐documented C−O bond formation starting from aryl iodides, aryl bromides or aryl chlorides. Herein, an unprecedented Pd‐catalyzed defluorinative etherification for the synthesis of polyfluoroaryl ether skeletons using hydrobenzoxazoles as phenol surrogate, has been reported. The substrate scope for this protocol is broad, with respect to hydrobenzoxazoles and perfluoroarenes, under mild reaction conditions. More importantly, challenging alkenyl and alkynyl substituted polyfluoroarenes could be successfully used as the cou‐pling component for Pd‐catalyzed etherification reaction. Density functional theory (DFT) calculations were employed to investigate the reaction mechanism, which suggested that oxidative addition between polyfluorobenzene and Pd(0) constituted the rate‐determining step. [ABSTRACT FROM AUTHOR]

A simple and efficient strategy for the synthesis of structurally diverse β,β‐diarylmethine substituted isoxazoline derivatives have been developed. This approach employs a manganese‐promoted oxidative cyclization coupled with a 1,6‐conjugate addition of unsaturated oximes to p‐quinone methides. The key features of this study include the formation of C−O and C−C bonds through intramolecular and intermolecular interactions, facilitated by in situ generated iminoxyl radicals. β,β‐diarylmethine substituted isoxazolines, bearing a wide range of functional groups, were isolated in high yields. [ABSTRACT FROM AUTHOR]

We report a study of solvent effects on the rate, selectivity, and mechanism of (hetero)aryl (pseudo)halide oxidative addition to Pd(PCy3)2 as an exemplar of L2Pd(0) species. First, 2‐chloro‐3‐aminopyridine is observed to undergo faster oxidative addition in toluene compared to more polar solvents, which is not consistent with the trend we observe with many other 2‐halopyridines. We attribute this to solvent basicity hydrogen bonding between solvent and substrate. Greater hydrogen bond donation from the substrate leads to a more electron‐rich aromatic system, and therefore slower oxidative addition. We demonstrate how this affects rate and site‐selectivity for hydrogen bond donating substrates. Second, electron‐deficient multihalogenated pyridines exhibit improved site‐selectivity in polar solvents, which we attribute to different C−X sites undergoing oxidative addition by two different mechanisms. The C−X site that favours the more polar nucleophilic displacement transition state is preferred over the site that favours a less‐polar 3‐centered transition state. Finally, (hetero)aryl triflates consistently undergo faster oxidative addition in more polar solvents, which we attribute to highly polar nucleophilic displacement transition states. This leads to improved site‐selectivity for C−OTf oxidative addition, even in the presence of highly reactive 2‐pyridyl halides. [ABSTRACT FROM AUTHOR]

Quantitative molecular structure‐reactivity models are useful for generating predictions to guide synthesis design, and in formulating and testing mechanistic hypotheses. We report an expanded multivariate linear regression (MLR) model for the rate of (hetero)aryl (pseudo)halide oxidative addition to L2Pd(0), here exemplified by Pd(PCy3)2. This builds on a prior model from our group, with additional substrate classes (aryl chlorides and iodides) and reaction solvents (THF, toluene, THF/DMF mixture). Overall solvent effects across the entire substrate set are minimal under these conditions, enabling a unified MLR model without introduction of new molecular descriptors beyond the original five. Examining the mechanistic origin of the two molecular electrostatic potential (ESP) descriptors led to generation of a simpler, four descriptor model that is suitable for aryl halides, but not for 2‐halopyridines. Using this model we identified a mechanistic outlier, 2‐pyridyl triflate, which undergoes a nucleophilic displacement oxidative addition that does not involve the adjacent nitrogen atom. Finally, we discuss the relationship between C−X bond strength and oxidative addition rates, and compare the intrinsic bond strength index (IBSI) to bond dissociation enthalpy (BDE) as a bond strength descriptor. [ABSTRACT FROM AUTHOR]

ABSTRACT Herein, pyrazinamide (L1) was used as a powerful ligand to promote a CuSO4‐catalyzed reaction between aryl halides and imidazole (HID) under mild conditions, generating various N‐arylation products in good to excellent yields. The findings indicate that CuSO4 was reduced and coordinated with L1 to form [CuIL1], which activated ArX to produce [ArCuIL1X] through oxidative addition. This intermediate subsequently underwent reductive elimination to form N‐arylation products, with [ArCuILID] being generated from a reaction between [ArCuIL1X] and HID. This method was successfully extended to the synthesis of 2‐phenylindole and pyrrolo[1,2‐a]quinoxaline under mild conditions. The method significantly enhances the efficiency and cost effectiveness of C‐N coupling reaction. [ABSTRACT FROM AUTHOR]

One-carbon (1C) metabolism is a complex network of metabolic reactions closely related to producing 1C units (as methyl groups) and utilizing them for different anabolic processes, including nucleotide synthesis, methylation, protein synthesis, and reductive metabolism. These pathways support the high proliferative rate of cancer cells. While drugs that target 1C metabolism (like methotrexate) have been used for cancer treatment, they often have significant side effects. Therefore, developing new drugs with minimal side effects is necessary for effective cancer treatment. Methionine, glycine, and serine are the main three precursors of 1C metabolism. One-carbon metabolism is vital not only for proliferative cells but also for non-proliferative cells in regulating energy homeostasis and the aging process. Understanding the potential role of 1C metabolism in aging is crucial for advancing our knowledge of neoplastic progression. This review provides a comprehensive understanding of the molecular complexities of 1C metabolism in the context of cancer and aging, paving the way for researchers to explore new avenues for developing advanced therapeutic interventions for cancer. [ABSTRACT FROM AUTHOR]

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Aryl fluorosulfates of varying complexities have been used in amination reactions in water using a new Pd oxidative addition complex (OAC‐1) developed specifically to match the needs of the fine chemicals industry, not only in terms of functional group tolerance, but also reflecting time considerations associated with these important C−N couplings. Also especially noteworthy is that they replace both PFAS‐related triflates and nonaflates, which are today out of favor due to recent government regulations. The new complex based on the BippyPhos ligand is used at low loadings and under aqueous micellar conditions. Moreover, it is easily prepared and stable to long term storage. DFT calculations on the OAC precatalyst compare well with the X‐ray structure of the crystals with π‐complexation to the aromatic system of the ligand and also confirm the NMR data showing a mixture of conformers in solution that differ from the X‐ray structure in rotation of the phenyl and t‐butyl ligand substituents. An extensive variety of coupling partners, including pharmaceutically relevant APIs, readily participate under mild and environmentally responsible reaction conditions. [ABSTRACT FROM AUTHOR]

Within the emerging field of bismuth redox catalysis, the catalytic formation of C−C bonds using aryl halides would be highly desirable; yet such a process remains a synthetic challenge. Herein, we present a chemoselective bismuth‐photocatalyzed activation and subsequent coupling of (hetero)aryl iodides with pyrrole derivatives to access C(sp2)−C(sp2) linkages through C−H functionalization. This unique reactivity is the result of the bismuth complex featuring two redox state‐dependent interactions with light, which 1) activates the Bi(I) complex for oxidative addition via MLCT, and 2) promotes the homolytic cleavage of aryl Bi(III) intermediates through a LLCT process. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) calculation has been used to reveal palladium‐catalyzed mode of diaziridinone ring activation. Our theoretical studies found that oxidative addition of di‐tert‐butyldiaziridinone to Pd(II) can give a high valent Pd(IV) intermediate, along with the cleavage of N─N bond in di‐tert‐butyldiaziridinone through a concerted three‐membered‐cyclic transition state. Subsequent transformations via reductive elimination and β‐N elimination give the desired indolo[3,2‐b]indole product. The competitive activation modes such as metathesis and migratory insertion can be excluded in our selected model reaction. The rate‐determining step of this reaction is the oxidative addition of di‐tert‐butyldiaziridinone step. Distortion‐interaction analysis was conducted to reveal that the oxidative addition mode of di‐tert‐butyldiaziridinone is superior to the metathesis mode due to the lower interaction energy. [ABSTRACT FROM AUTHOR]

The ubiquitous nature of amines in drug compounds, bioactive molecules and natural products has fueled intense interest in their synthesis. Herein, we introduce a nickel‐catalyzed enantioconvergent allenylic amination of methanol‐activated allenols. This protocol affords a diverse array of functionalized allenylic amines in high yields and with excellent enantioselectivities. The synthetic potential of this method is demonstrated by employing bioactive amines as nucleophiles and conducting gram‐scale reactions. Furthermore, mechanistic investigations and DFT calculations elucidate the role of methanol as an activator in the nickel‐catalyzed reaction, facilitating the oxidative addition of the C−O bond of allenols through hydrogen‐bonding interactions. The remarkable outcomes arise from a rapid racemization of allenols enabled by the nickel catalyst and from highly enantioselective dynamic kinetic asymmetric transformation of η3‐alkadienylnickel intermediates. [ABSTRACT FROM AUTHOR]

For square-planar late transition metal pyridine, diimine (Rh, Ir) complexes with hydro-xido, methoxido, and thiolato ligands. We could previously establish sizable metal-O- and S π-bonding interactions. Herein, we report the hydrogenation studies of iridium hydroxido and methoxido complexes, which quantitatively lead to the trihydride compound and water/methanol. The iridium trihydride displays a highly fluctional structure with scrambling hydrogen atoms, which can be described as a dihydrogen hydride system based on NMR and DFT investigations. This contrasts the iridium sulfur compounds, which are not reacting with dihydrogen. According to DFT and LNO-CCSD(T) calculations, hydrogenation of the methoxido complex proceeds by a two-step mechanism, i.e., an oxidative addition step of H2 to an Ir(III) dihydride intermediate with consecutive reductive O-H elimination of methanol. Based on PNO-CCSD(T) calculations, the reactivity difference between the O- and S-donors can be traced to the stronger H-O bonds in the water/methanol products compared to the S-H bonds in the sulphur congeners, which serves as a driving force for hydrogenation. [ABSTRACT FROM AUTHOR]

Reforming tar molecules into smaller gaseous molecules has been a critical challenge for biomass energy utilization. Hematite (α-Fe2O3) has been demonstrated as an effective catalyst for the catalytic reforming of tar, nevertheless, the detailed mechanism of α-Fe2O3 catalyzed tar reforming remains unclear. In this work, we apply the density functional theory method to investigate this problem. Specifically, we study both (0001) and (01 2) surface structures of α-Fe2O3 and then use the structures to investigate the adsorption and C–C bond cleavage of benzene on these surfaces. Our results show that the dominant interactions between benzene and a single Fe-terminated (0001) surface are van der Waals forces, yet benzene could be chemisorbed on the Fe and O co-exposed (01 2) surface via strong C–O interactions. As a result, the (0001) surface is not active towards benzene cleavage, whereas the (01 2) surface can promote the aromatic C–C bond breaking. Furthermore, our calculations indicate that chain-like alkene species and carbonyl species are the two types of potential products that form after the C–C bond cleavage of benzene on the α-Fe2O3 (01 2) surface, with the activation energy of 1.78 eV and 2.62 eV, respectively. In summary, we reveal the importance of co-adsorption on both Fe and O centers and oxidative addition on C–C bond cleavage of aromatic compounds on the α-Fe2O3 surface, which provides novel insights into the mechanisms of tar cracking on oxide catalysts. [ABSTRACT FROM AUTHOR]

Cross‐electrophile coupling (XEC) between aryl halides and alkyl halides is a streamlined approach for C(sp2)−C(sp3) bond construction, which is highly valuable in medicinal chemistry. Based on a key NiII aryl amido intermediate, we developed a highly selective and scalable Ni‐catalyzed electrochemical XEC reaction between (hetero)aryl halides and primary and secondary alkyl halides. Experimental and computational mechanistic studies indicate that an amine secondary ligand slows down the oxidative addition process of the Ni‐polypyridine catalyst to the aryl bromide and a NiII aryl amido intermediate is formed in situ during the reaction process. The relatively slow oxidative addition is beneficial for enhancing the selectivity of the XEC reaction. The NiII aryl amido intermediate stabilizes the NiII–aryl species to prevent the aryl–aryl homo‐coupling side reactions and acts as a catalyst to activate the alkyl bromide substrates. This electrosynthesis system provides a facile, practical, and scalable platform for the formation of (hetero)aryl–alkyl bonds using standard Ni catalysts under mild conditions. The mechanistic insights from this work could serve as a great foundation for future studies on Ni‐catalyzed cross‐couplings. [ABSTRACT FROM AUTHOR]

The mechanism of an iron‐catalyzed C—H alkenylation of pivalophenone derivatives with unsymmetric internal alkynes is investigated in details by means of density functional theory calculations. It is shown that the reaction begins with two consecutive ligand exchanges, followed by a fast and reversible oxidative addition C—H activation step. Next, an alkyne insertion into the Fe—H bond, two isomerization steps, and a reductive elimination afford the final product. The reductive elimination is the turnover‐limiting step of the process, and also determines the regiochemical outcome of the reaction. The origin of the regioselectivity is proposed to be the steric repulsion between the bulky trimethylsilyl group and the aromatic fragment in the reductive elimination step leading to the not observed regioisomer. [ABSTRACT FROM AUTHOR]

Chiral allylic alcohols are highly prized in synthetic chemistry due to their versatile reactivity stemming from both alkenyl and hydroxyl functionalities. While the Nozaki–Hiyama–Kishi (NHK) reaction is a widely used method for the synthesis of allylic alcohols, it suffers from drawbacks such as the use of toxic chromium salts, high amounts of metal reductants, and poor enantiocontrol. To address these limitations, we present a novel approach involving a metallaphotoredox‐catalyzed asymmetric NHK reaction for the production of chiral allylic alcohols. This method marries alkenyl (pseudo)halides with aldehydes, leveraging a synergistic blend of a chiral nickel catalyst and a photocatalyst. This innovative technique enables both oxidative addition and insertion just using nickel, diverging significantly from the conventional NHK reaction pathway mediated by nickel and chromium salts. The adoption of this methodology holds immense promise for crafting a spectrum of intricate compounds, particularly those of significance in pharmaceuticals. Detailed experimental investigations have shed light on the metallaphotoredox process, further enhancing our understanding and enabling further advancements. [ABSTRACT FROM AUTHOR]

The mechanistic details of the asymmetric Ni‐catalyzed reductive cyclization/carboxylation of alkenes with CO2 have been revisited using DFT methods. Emphasis was put on the enantioselectivity and the mechanistic role of Lewis acid additives and in situ formed salts. Our results show that oxidative addition of the substrate is rate‐limiting, with the formed Ni(II)‐aryl intermediate preferring a triplet spin state. After reduction to Ni(I), enantioselective cyclization of the substrate occurs, followed by inner sphere carboxylation. Our proposed mechanism reproduces the experimentally observed enantiomeric excess and identifies critical C−H/O and C−H/N interactions that affect the selectivity. Further, our results highlight the beneficial effect of Lewis acids on CO2 insertion and suggest that in situ formed salts influence if the 5‐exo or 6‐endo product will be formed. [ABSTRACT FROM AUTHOR]

Pd‐catalyzed stereoselective glycosylations using unsaturated sugar derivatives, glycals, have been successfully achieved in recent years. This review focuses on approaches to control the stereoselectivities of glycosides via π‐allyl intermediates that mimic the Tsuji–Trost asymmetric allylic alkylation reactions, enabling stereoselectivity control through rational design. In the reaction process, zwitterionic Pd‐π‐allyl complexes, formed after the oxidative addition and decarboxylation, play a crucial role in increasing reactivities and enhancing the stereoselectivities of α‐ and β‐glycosides. We summarized recently developed Tsuji–Trost type glycosylations using 3,4‐carbonate galactals, featuring high efficiency, exclusive stereoselectivities, and a broad reaction scope including O‐, N‐, S‐, and C‐glycosylations. [ABSTRACT FROM AUTHOR]

Effects of different conditions on the reaction of alkenes with phenyl[(trifluoromethanesulfonyl)-imino]-λ3-iodane (PhI=NTf, 1) have been studied. The reaction of PhI=NTf with styrenes in the presence of copper(I) chloride led to the formation of substituted aziridine and bis-trifluorometanesulfonamido derivatives at different ratios. When silver nitrate was used as additive in the same reaction, 1-phenyl-2-(trifluoro-methanesulfonamido)ethyl nitrate was formed. Isomeric amidines were obtained from camphene as substrate in the presence of different activating additives and an oxidant. Potential biological activity of the synthesized compounds was predicted using PASS Online software. [ABSTRACT FROM AUTHOR]

The chemistry of transition‐metal (TM) complexes with monoanionic bidentate (κ2‐L,Si) silyl ligands has considerably grown in recent years. This work summarizes the advances in the chemistry of TM‐(κ2‐L,Si) complexes (L=N‐heterocycle, phosphine, N‐heterocyclic carbene, thioether, ester, silylether or tetrylene). The most common synthetic method has been the oxidative addition of the Si−H bond to the metal center assisted by the coordination of L. The metal silicon bond distances in TM‐(κ2‐L,Si) complexes are in the range of metal‐silyl bond distances. TM‐(κ2‐L,Si) complexes have proven to be effective catalysts for hydrosilylation and/or hydrogenation of unsaturated molecules among other processes. [ABSTRACT FROM AUTHOR]

The adducts 2M,R of general formula trans‐[(L)M{R2P(CH2)2PR2}2{N2B(C6F5)3}] (L=ø or N2, M=Mo or W, R=Et or Ph), formed from Lewis acid‐base pairing of B(C6F5)3 to a dinitrogen ligand of zero‐valent group 6 bis(phosphine) complexes trans‐[M{R2P(CH2)2PR2}2(N2)2] are shown to react with dihydrogen to afford hepta‐coordinated bis(hydride) complexes [M(H)2{R2P(CH2)2PR2}{N2B(C6F5)3}] 3M,R which feature the rare ability to activate both dinitrogen and dihydrogen at a single metal center, except in the case where M=Mo and R=Ph for which fast precipitation of insoluble [Mo(H)4(dppe)2] (dppe=1,2‐bis(diphenylphosphino)ethane) occurs. The frustrated Lewis pair (FLP)‐related reactivity of the B−N linkage in compounds 3W,R was explored and led to distal N functionalization without involvement of the hydride ligands. It is shown in one example that the resulting bis(hydride) diazenido compounds may also be obtained through a sequence involving first FLP‐type N‐functionalization followed by oxidative addition of H2. Those oily compounds were found to have limited stability in solution or in their isolated states. Finally, treatment of 3W,Et with the Lewis base N,N‐dimethylaminopyridine (DMAP) affords the simple but unknown bis(hydride)‐dinitrogen species [W(H)2(depe)2(N2)] 11Et (depe=1,2‐bis(diethylphosphino)ethane) which direct, selective formation from trans‐[W(N2)2(depe)2] is not possible. [ABSTRACT FROM AUTHOR]

The synthesis of three novel [C,N,N′] Pt(IV) cyclometallated compounds containing hydroxo, dichloroacetato or trifluoroacetato axial ligands is reported. Compound [PtCl(OH)2{(CH3)2N(CH2)2N＝CH(4-FC6H3)}] (3) was prepared by the oxidative addition of hydrogen peroxide to [C,N,N′] Pt(II) cyclometallated compound [PtCl{(CH3)2N(CH2)2N＝CH(4-FC6H3)}] (1) and further the reaction of compound 3 with dichloroacetate or trifluoroacetate anhydrides led to the formation of the corresponding compounds [PtCl(CHCl2COO)2{(CH3)2N(CH2)2N＝CH(4-FC6H3)}] (4) and [PtCl(CF3COO)2{(CH3)2N(CH2)2N＝CH(4-FC6H3)}] (5). The properties of the new compounds along with those of the compound [PtCl3{(CH3)2N(CH2)2N＝CH(4-FC6H3)}] (2), including stability in aqueous media, reduction potential using cyclic voltammetry, cytotoxic activity against the HCT116 CRC cell line, DNA interaction, topoisomerase I and cathepsin inhibition, and computational studies involving reduction of the Pt(IV) compounds and molecular docking studies, are presented. Interestingly, the antiproliferative activity of these compounds against the HCT116 CRC cell line, which is in all cases higher than that of cisplatin, follows the same trend as the reduction potentials so that the most easily reduced compound 2 is the most potent. In contrast, according to the electrophoretic mobility and molecular docking studies, the efficacy of these compounds in binding to DNA is not related to their cytotoxicity. The most active compound 2 does not modify the DNA electrophoretic mobility while the less potent compound 3 is the most efficient in binding to DNA. Although compounds 2 and 3 have only a slight effect on cell cycle distribution and apoptosis induction, generation of ROS to a higher extent for the most easily reduced compound 2 was observed. [ABSTRACT FROM AUTHOR]

Mono or bis(tetrazole–thiolato) Pd(II) or Pt(II) complexes were obtained from the reactions of dialkyl Pd(II) or Pt(II) complexes with organic tetrazole–thiones (1-aryl- or 1-alkyl-1H-tetrazole-5-thiones) via deprotonation. In contrast, equimolar reactions of zerovalent Pt(0) or Pd(0) complexes with organic tetrazole–thiones afforded hydrido or bis(tetrazole–thiolato) Pt(II) and Pd(II) complexes, and cyclometallated Pt(II) or Pd(II) complexes bearing a tetrazole–thiolato moiety via oxidative addition, depending on the organic substituents on the tetrazole–thiones. In particular, variable (time and temperature)-dependent 1H-NMR spectra of the hydrido Pt(II) tetrazole–thiolates reveal an upfield shift of the hydride signal, suggesting N,S-coordination behavior of the tetrazole–thiolato ligand. Additionally, the N-CH2 signal corresponds to the six-membered ring of platinacycle or palladacycle exhibiting geminal coupling with multiple protons and PR3 ligands; these coupling values were further determined using 1H{31P} experiments. Finally, treatment of the alkyl Pd(II) tetrazole–thiolate or Pd(II) bis(tetrazole–thiolates) with organic tert-butyl isocyanide, thiophenol, and organic halides caused the selective insertion of the isocyanide into the Pd–C bond or deprotonation to afford a Pd(II) disulfide complex and substitution to afford new organic tetrazolyl sulfides. [ABSTRACT FROM AUTHOR]

Two‐electron oxidative addition is one of the most important elementary reactions for d‐block transition metals but it is uncommon for f‐block elements. Here, we report the first examples of intermolecular oxidative addition of E−H (E=C, N) bonds to uranium(II) centers. The transient U(II) species was formed in‐situ by reducing a heterometallic cluster featuring U(IV)‐Pd(0) bonds with potassium‐graphite (KC8). Oxidative addition of C−H or N−H bonds to the U(II) centers was observed when this transient U(II) species was treated with benzene, carbazole or 1‐adamantylamine, respectively. The U(II) centers could also react with tetracene, biphenylene or N2O, leading to the formation of arene reduced U(IV) products and uranyl(VI) species via two‐ or four‐electron processes. This study demonstrates that the intermolecular two‐electron oxidative addition reactions are viable for actinide elements. [ABSTRACT FROM AUTHOR]