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Described herein are studies toward the core modificationof cyclicaliphatic amines using either a riboflavin/photo-irradiation approachor Cu-(I) and Ag-(I) to mediate the process. Structural remodeling ofcyclic amines is explored through oxidative C-N and C-Cbond cleavage using peroxydisulfate (persulfate) as an oxidant. Ring-openingreactions to access linear aldehydes or carboxylic acids with flavin-derivedphotocatalysis or Cu salts, respectively, are demonstrated. A complementaryring-opening process mediated by Ag-(I) facilitates decarboxylativeCsp(3)-Csp(2) coupling in Minisci-type reactionsthrough a key alkyl radical intermediate. Heterocycle interconversionis demonstrated through the transformation of N-acyl cyclic aminesto oxazines using Cu-(II) oxidation of the alkyl radical. These transformationsare investigated by computation to inform the proposed mechanisticpathways. Computational studies indicate that persulfate mediatesoxidation of cyclic amines with concomitant reduction of riboflavin.Persulfate is subsequently reduced by formal hydride transfer fromthe reduced riboflavin catalyst. Oxidation of the cyclic aliphaticamines with a Cu-(I) salt is proposed to be initiated by homolysisof the peroxy bond of persulfate followed by alpha-HAT from thecyclic amine and radical recombination to form an alpha-sulfateadduct, which is hydrolyzed to the hemiaminal. Investigation of thepathway to form oxazines indicates a kinetic preference for cyclizationover more typical elimination pathways to form olefins through Cu-(II)oxidation of alkyl radicals., Journal of the American Chemical Society, 145 (20), ISSN:0002-7863, ISSN:1520-5126

Rhodium catalyzes double hydroboration of pyridine via an unique mechanism involving a Rh-1,2-dihydropyridine adduct to give a mixture of unprecedented tetrahydropyridines bearing a sp3 C–B bond in a specific position.

We illuminate that cytochrome c (Cyt c) directly interacts with amyloid-β (Aβ) and alters Aβ amyloidogenesis in a peroxide-dependent manner, which demonstrates its new role towards the amyloid pathology associated with Alzheimer's disease.

Highly modular and rational syntheses of titanium compounds containing ditelluride, terminal telluride, and bis(telluride) structural motifs are disclosed in this study. Titanate anions bearing two

The role of a phosphine-free SNS-pincer ligand in metal–ligand cooperative hydroboration catalysis was investigated. The bifunctional thiolate donor and spin-state change to high-spin Mn are crucial to accessing low-energy activation barriers.

We employed the chemical potential neutralization principle to demonstrate that fractional electrons are involved in the electro-inductive effect as well as the vibrational Stark effect. By the chemical potential model, we were able to deduce that the frontier molecular orbitals of immobilized molecules can provide valuable insight into these effects. To further understand and quantify these findings, we introduced fractional charge density functional theory (FC-DFT), a canonical ensemble approach for open systems. This method allows for the calculation of electronic energies, nuclear gradients, and the Hessian matrix of fractional electronic systems. To correct the spurious delocalization error commonly found in approximate density functionals for small systems, we imposed the Perdew-Parr-Levy-Balduz (PPLB) condition through linear interpolation of two adjacent integer points (LI-FC-DFT). Although this approach is relatively simple in terms of molecular modeling, the results obtained through LI-FC-DFT calculations predict the same trend seen in experimental reactivity and the frequency change of immobilized molecules.

AdN

A low-spin and mononuclear vanadium complex, ((Me)nacnac)V(CO)(η(2)–P≡C(t)Bu) (2) ((Me)nacnac(−) = [ArNC(CH(3))](2)CH, Ar = 2,6-(i)Pr(2)C(6)H(3)), was prepared upon treatment of the vanadium neopentylidyne complex ((Me)nacnac)V≡C(t)Bu(OTf) (1) with Na(OCP)(diox)(2.5) (diox = 1,4-dioxane) while the isoelectronic ate-complex [Na(15–crown–5)]{([ArNC(CH(2))]CH[C(CH(3))NAr])V(CO)(η(2)–P≡C(t)Bu)} (4), was obtained via the reaction of Na(OCP)(diox)(2.5) and ([ArNC(CH(2))]CH[C(CH(3))NAr])V≡C(t)Bu(OEt(2)) (3) in the presence of crown–ether. Computational studies suggest the P–atom transfer to proceed by [2+2]–cycloaddition of the P≡C bond across the V≡C(t)Bu moiety, followed by a reductive decarbonylation to form V–C≡O linkage. The nature of the electronic ground state in diamagnetic complexes, 2 and 4, was further investigated both theoretically and experimentally, using a combination of Density Functional Theory (DFT) calculations, UV-Vis and NMR spectroscopies, cyclic voltammetry, X-ray Absorption Spectroscopy (XAS) measurements, and comparison of salient bond metrics derived from X-ray single-crystal structural characterization. In combination, these data are consistent with a low-valent vanadium ion in complexes 2 and 4. This study represents the first example of a metathesis reaction between the P-atom of [PCO](‒) and an alkylidyne ligand.

Decarbonylation along with P-atom transfer from the phosphaethynolate anion, PCO

Oxidative carbene organocatalysis, which proceeds via single electron transfer (SET) pathways, has been limited by the moderately reducing properties of deprotonated Breslow intermediates BI−s derived from thiazol-2-ylidene 1 and 1,2,4-triazolylidene 2. Using computational methods, we assess the redox potentials of BI−s based on ten different types of known stable carbenes and report our findings concerning the key parameters influencing the steps of the catalytic cycle. From the calculated values of the first oxidation potential of BI−s derived from carbenes 1 to 10, it appears that apart from the diamidocarbene 7, all the others are more reducing than thiazol-2-ylidene 1 and the 1,2,4-triazolylidene 2. We observed that while the reducing power of BI−s significantly decreases with increasing solvent polarity, the redox potential of the oxidant can increase at a greater rate, thus facilitating the reaction. The cation, associated with the base, also plays an important role when a non-polar solvent is used; large and weakly coordinating cations such as Cs+ are beneficial. The radical-radical coupling step is probably the most challenging step due to both electronic and steric constraints. Based on our results, we predict that mesoionic carbene 3 and abnormal NHC 4 are the most promising candidates for oxidative carbene organocatalysis.

A transition metal-catalyzed ring expansion and C–H functionalization of azulene were developed. This work constitutes the first example of the ring expansion of azulene using Cu(hfacac)2 with diazo compound and chemoselectivity for C–H functionalization of azulene controlled by changing to AgOTf. A chemoselectivity can be controlled simply by changing the metal frame. This approach does not demand the addition of phosphine, NHC or related ligands and prefunctionalization of azulenes. In addition, the excellent functional group tolerance allows the synthesis of a wide range of 6,7-bicyclic compounds and C–H functionalized azulenes. A theoretical study was able to explain the experimental observations that copper catalysts afford the ring expansion product while silver catalysts result in the formation of C–H alkylation product.

A neutral and mononuclear niobium nitride complex (PNP)NbN(N[tBu]Ar) (PNP− = N[2-PiPr2-4-methylphenyl]2) can be isolated using the redox-active properties of the [PNP]− ligand.

The cationic Ru-H complex [(C6H6)(PCy3)(CO)RuH]+BF4- (1) was found to be an effective catalyst for the dehydrative C-H coupling reaction of phenols and aldehydes to form 2-alkylphenol products. The coupling reaction of phenols with branched aldehydes selectively formed 1,1-disubstituted benzofurans, while the coupling reaction with salicylaldehydes yielded xanthene derivatives. A normal deuterium isotope effect was observed from the coupling reaction of 3-methoxyphenol with benzaldehyde and 2-propanol/2-propanol-d8 (kH/kD = 2.3 ± 0.3). The carbon isotope effect was observed on the benzylic carbon of the alkylation product from the coupling reaction of 3-methoxyphenol with 4-methoxybenzaldehyde (C(3) 1.021(3)) and on both benzylic and ortho-arene carbons from the coupling reaction with 4-trifluorobenzaldehdye (C(2) 1.017(3), C(3) 1.011(2)). The Hammett plot from the coupling reaction of 3-methoxyphenol with para-substituted benzaldehydes p-X-C6H4CHO (X = OMe, Me, H, F, Cl, CF3) displayed a V-shaped linear slope. Catalytically relevant Ru-H complexes were observed by NMR from a stoichiometric reaction mixture of 1, 3-methoxyphenol, benzaldehyde, and 2-propanol in CD2Cl2. The DFT calculations provided a detailed catalysis mechanism featuring an electrophilic aromatic substitution of the aldehyde followed by the hydrogenolysis of the hydroxy group. The calculations also revealed a mechanistic rationale for the strong electronic effect of the benzaldehdye substrates p-X-C6H4CHO (X = OMe, CF3) in controlling the turnover-limiting step. The catalytic C-H coupling method provides an efficient synthetic protocol for 2-alkylphenols, 1,1-disubstituted benzofurans, and xanthene derivatives without employing any reactive reagents or forming wasteful byproducts.

Aldehyde and ketone hydrosilylation turnover frequencies of up to 330 s−1 have been achieved using a phosphine-substituted aryl diimine cobalt catalyst.

Wir berichten über eine Dichtefunktionaltheorie (DFT)-basierte Entdeckung von Ethinyl-Triazolyl-Phosphinaten (ETP) als eine neue Klasse elektrophiler Verbindungen für die selektive Biokonjugation von Cystein. Mit Hilfe der CuI-katalysierten Azid-Alkin-Cycloaddition (CuAAC) in wässrigem Puffer konnten wir eine Vielzahl funktioneller elektrophiler Bausteine, darunter auch Proteine, aus Diethynylphosphinat herstellen. Wir verwendeten diese ETP-Reagenzien, um fluoreszierende Peptid-Konjugate für die Markierung von Rezeptoren auf lebenden Zellen sowie ein stabiles und biologisch aktives Antikörper-Wirkstoff-Konjugat zu erhalten. Darüber hinaus konnten wir ETP-Elektrophile unter nativen Bedingungen in ein Azid-haltiges Ubiquitin einbauen und ihr Potenzial für die Protein-Protein-Konjugation demonstrieren. Schließlich zeigen wir die exzellente Cystein-Selektivität dieser neuen Klasse von Elektrophilen in Massenspektrometrie basierten, proteomweiten Reaktivitätsstudien und unterstreichen damit die generelle Anwendbarkeit in homogenen Biokonjugationsstrategien zur Verknüpfung zweier komplexer Biomoleküle.

Refluxing Mo(CO)6 in the presence of the phosphine-functionalized α-diimine ligand Ph2PPrDI allowed for substitution and formation of the dicarbonyl complex, (Ph2PPrDI)Mo(CO)2. Oxidation with I2 followed by heating resulted in further CO dissociation and isolation of the corresponding diiodide complex, (Ph2PPrDI)MoI2. Reduction of this complex under a N2 atmosphere afforded the corresponding bis(dinitrogen) complex, (Ph2PPrDI)Mo(N2)2. The solid-state structures of all three compounds were found to feature a tetradentate chelate and cis-monodentate ligands. Notably, the addition of CO2 to (Ph2PPrDI)Mo(N2)2 is proposed to result in head-to-tail CO2 coupling to generate the corresponding metallacycle and ultimately a mixture of (Ph2PPrDI)Mo(CO)2 and the bis(oxo) dimer, [(κ3-Ph2PPrDI)Mo(O)(μ-O)]2. Computational studies have been performed to gain insight into the reaction and evaluate the importance of cis-coordination sites for selective head-to-tail CO2 reductive coupling, CO deinsertion, disproportionation, and stepwise CO2 deinsertion.

We disclose herein a directing group-assisted nickel-catalyzed intermolecular C(sp3)–H amidation using organic azides as nitrene precursors. With the installation of an electronically tailored dire...

We report a copper-catalyzed enatiotopic-group-selective allylation of gem-diborylalkanes with allyl bromides. The combination of copper(I) bromide and H8-BINOL derived phosphoramidite ligand proved to be the most effective catalytic system to provide various enantioenriched homoallylic boronate esters, containing a boron-substituted stereogenic center that is solely derived from gem-diborylalkanes, in good yields with high enantiomeric ratios under mild conditions. Experimental and theoretical studies have been conducted to elucidate the reaction mechanism, revealing how the enatiotopic-group-selective transmetalation of gem-diborylalkanes with chiral copper complex occurs to generate chiral α-borylalkyl-copper species for the first time. Additional synthetic applications to the synthesis of various chiral building blocks are also included.

Purely organic phosphorescent emitters have been developed with the incorporation of alkyl substituents into the N-phenylphenoselenazine core. The new emitter displayed efficient phosphorescence in amorphous film and featured pure phosphorescence in electroluminescence devices due to strong spin–orbit coupling for triplet to singlet transition. The steric bulk of the alkyl substituent, which could hamper triplet-exciton-quenching, is found to be essential for high efficiency of the device, and the tert-butyl group induces the highest external quantum efficiency (EQE) of 9.0%.

It was recently discovered that (

We report the density functional theory (DFT) guided discovery of ethynyl‐triazolyl‐phosphinates (ETPs) as a new class of electrophilic warheads for cysteine selective bioconjugation. By using CuI‐catalysed azide alkyne cycloaddition (CuAAC) in aqueous buffer, we were able to access a variety of functional electrophilic building blocks, including proteins, from diethynyl‐phosphinate. ETP‐reagents were used to obtain fluorescent peptide‐conjugates for receptor labelling on live cells and a stable and a biologically active antibody‐drug‐conjugate. Moreover, we were able to incorporate ETP‐electrophiles into an azide‐containing ubiquitin under native conditions and demonstrate their potential in protein–protein conjugation. Finally, we showcase the excellent cysteine‐selectivity of this new class of electrophile in mass spectrometry based, proteome‐wide cysteine profiling, underscoring the applicability in homogeneous bioconjugation strategies to connect two complex biomolecules. Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659 Leibniz-Gemeinschaft http://dx.doi.org/10.13039/501100001664 Studienstiftung des Deutschen Volkes http://dx.doi.org/10.13039/501100004350 Alexander von Humboldt-Stiftung http://dx.doi.org/10.13039/100005156 Institute for Basic Science in Korea

Summary Due to the existing challenges in the synthesis of covalently linked large organic cages, the potential benefits of such gigantic structures have been less explored, comparatively. Here, we present a one-pot, template-free strategy to construct a porphyrin-based gigantic organic cage P12L24, built with 12 square-shaped porphyrins (P) and 24 bent linkers (L). Single crystal X-ray analysis of P12L24 revealed a cuboctahedron structure with a diameter of ∼5.3 nm reminiscent of the COPII protein with a cuboctahedral geometry. To the best of our knowledge, it represents the largest, pure organic synthetic cage reported so far. By virtue of its large voids facilitating mass transport of substrates, 3a efficiently catalyzes the photooxidation of dihydroxynaphthalene derivatives in a heterogeneous setting, corroborating the benefits of these structures. Additionally, we demonstrate the insertion of a linear guest molecule into Zn-metallated cage Zn-3b in solution, which may facilitate the synthesis of multivariate gigantic cages in the future.

A potential method to tune reactivity In organic chemistry, reaction rates are often sensitive to substituents that either donate or withdraw electron density from a reactive carbon center. Heo et al. now report that when reactants are tethered to an electrode, the polarization effect of an applied potential can exert an analogous influence, essentially acting as a tunable functional group. The authors demonstrate rate modulations in ester hydrolysis and arene cross-coupling, as well as a two-step acid-to-amide conversion that benefits from inversion of the polarization midway through the reaction. Science , this issue p. 214

Copper-catalyzed [5 + 1] cycloadditions of N-aromatic zwitterions have been accomplished by chelation-assisted 1,2-dearomative addition of electron-deficient terminal alkynes. The unique modular sk...

Summary Poor solubility of π-conjugated two-dimensional polymers (C2Ps) has been a significant roadblock in incorporating these emergent materials into electronic devices by simple solution processing. Here, we report a rational design of triphenylene-based building blocks that condense via a series of reversible reactions for self-error-correction and a final irreversible fixation to form a pyrazine motif, which leads to the formation of crystalline C2Ps in solution without any aid of template or preorganization. Unlike typical covalent organic frameworks, remarkably, these materials remain dispersed as single- to few-layer films in solution, presumably because of protonation of pyrazine motifs by the strong acid employed in the synthesis. The C2Ps can be easily drop-cast onto solid surfaces for characterization and fabrication of electronic devices. The thin polymer films display a long-range internal order and exhibit high hole mobility up to 4 cm2V−1s−1, the highest among C2Ps, which paves the way to design high-performance optoelectronic devices.

The utilizations of omnipresent, thermodynamically stable amides and aliphatic C(sp3 )-H bonds for various functionalizations are ongoing challenges in catalysis. In particular, the direct coupling between the two functional groups has not been realized. Here, we report the synergistic activation of the two challenging bonds, the amide C-N and unactivated aliphatic C(sp3 )-H, via metallaphotoredox catalysis to directly acylate aliphatic C-H bonds utilizing amides as stable and readily accessible acyl surrogates. N-acylsuccinimides served as efficient acyl reagents for the streamlined synthesis of synthetically useful ketones from simple C(sp3 )-H substrates. Detailed mechanistic investigations using both computational and experimental mechanistic studies were performed to construct a detailed and complete catalytic cycle. The origin of the superior reactivity of the N-acylsuccinimides over other more reactive acyl sources such as acyl chlorides was found to be an uncommon reaction pathway which commences with C-H activation prior to oxidative addition of the acyl substrate.

Herein we report the synthesis of substituted indolizidines and related N-fused bicycles from simple saturated cyclic amines through sequential C─H and C─C bond functionalizations. Inspired by the Norrish–Yang Type II reaction, C─H functionalization of azacycles is achieved by forming α-hydroxy-β-lactams from precursor α-ketoamide derivatives under mild, visible light conditions. Selective cleavage of the distal C(sp(2))─C(sp(3)) bond in α-hydroxy-β-lactams using a Rh-complex leads to α-acyl intermediates which undergo sequential Rh-catalyzed decarbonylation, 1,4-addition to an electrophile, and aldol cyclization, to afford N-fused bicycles including indolizidines. Computational studies provide mechanistic insight into the observed positional selectivity of C─C cleavage, which depends strongly on the groups bound to Rh trans to the phosphine ligand.

The regioselective, direct alkylation of electron-deficient N-heteroarenes is, in principle, a powerful and efficient way of accessing alkylated N-heteroarenes that are important core structures of many biologically active compounds and pharmaceutical agents. Herein, we report a ZnMe2-promoted, direct C2- or C4-selective primary and secondary alkylation of pyridines and quinolines using 1,1-diborylalkanes as alkylation sources. While substituted pyridines and quinolines exclusively afford C2-alkylated products, simple pyridine delivers C4-alkylated pyridine with excellent regioselectivity. The reaction scope is remarkably broad, and a range of C2- or C4-alkylated electron-deficient N-heteroarenes are obtained in good yields. Experimental and computational mechanistic studies imply that ZnMe2 serves not only as an activator of 1,1-diborylalkanes to generate (α-borylalkyl)methylalkoxy zincate, which acts as a Lewis acid to bind to the nitrogen atom of the heterocycles and controls the regioselectivity, but also as an oxidant for rearomatizing the dihydro-N-heteroarene intermediates to release the product.

Korea Hydro & Nuclear Power Company, Ltd., has operated the Wolsong Tritium Removal Facility (WTRF) since 2007 to reduce tritium concentrations in the moderator and coolant of the Wolsong nuclear p...

Multiple pathogenic elements, including reactive oxygen species, amyloidogenic proteins, and metal ions, are associated with the development of neurodegenerative disorders. We report minimalistic redox-based principles for preparing compact aromatic compounds by derivatizing the phenylene moiety with various functional groups. These molecular agents display enhanced reactivities against multiple targets such as free radicals, metal-free amyloid-β (Aβ), and metal-bound Aβ that are implicated in the most common form of dementia, Alzheimer's disease (AD). Mechanistic studies reveal that the redox properties of these reagents are essential for their function. Specifically, they engage in oxidative reactions with metal-free and metal-bound Aβ, leading to chemical modifications of the Aβ peptides to form covalent adducts that alter the aggregation of Aβ. Moreover, the administration of the most promising candidate significantly attenuates the amyloid pathology in the brains of AD transgenic mice and improves their cognitive defects. Our studies demonstrate an efficient and effective redox-based strategy for incorporating multiple functions into simple molecular reagents.