Concerted Process Research Articles

Modular Synthesis of Polycarbonyl Compounds via Regioselective Hydration of Oxo-Alkynes.

A novel protocol has been developed for the modular synthesis of polycarbonyl compounds by catalytic hydration of 1,3-diketone-tethered alkynes. The hydration process exhibits good regioselectivity and high yields at room temperature, avoiding the use of strong acids and noble metals and the requirement for elevated temperatures. Mechanistic insights suggest that the hydration proceeds through a concerted process of alkyne protonation and remote carbonyl participation. This approach provides direct access to tandem heterocycle dyads and triads.

C-H Activation of Pyridines by Boryl Pincer Complexes: Elucidation of Boryl-Directed C-H Oxidative Addition to Ir and Discovery of Transition Metal-Assisted Reductive Elimination from Boron at Rh.

Experimental and theoretical techniques were used to investigate the mechanism of pyridine C-H activation by diarylboryl/bis(phosphine) PBP pincer complexes of Ir. The critical intermediate (PBP)IrCO (4) contains a three-coordinate, Ir-bound boron that retains Lewis acidity in the perpendicular direction. Coordination of pyridine to this boron center in 4 leads to fast insertion of Ir into the 2-CH bond of pyridine, providing a different topology of direction than the conventional directed C-H activation where both the directing group coordination and C-H activation happen at the same metal center. Beyond this critical sequence, the system possesses significant complexity in terms of possible isomers and pathways, which have been thoroughly explored. Kinetic and thermodynamic preferences for the activation of differently substituted pyridines were also investigated. In experimental work, the key intermediate 4 is accessed via elimination of benzene from a phenyl/hydride containing precursor (PBPhP)IrHCO (3). Density functional theory (DFT) investigations of the mechanism of benzene loss from 3 revealed the possibility of a genuinely new type of mechanism, whereby the Ph-H bond is made in a concerted process that is best described as C-H reductive elimination from boron, assisted by the transition metal (TMARE). For Ir, this pathway was predicted to be competitive with the more conventional pathways involving C-H reductive elimination from Ir, but still higher in energy barrier. However, for the Rh analog 3-Rh, TMARE was calculated to be the preferred pathway for benzene loss and this prediction was experimentally corroborated through the study of reaction rates and the kinetic isotope effect.

Copper(II)-Catalyzed Regioselective H/D Exchange Based on Reversible C-H Activation.

Despite the increasing use of copper in C-H functionalizations, the Cu-catalyzed direct deuteration of C-H bonds remains a significant challenge due to its inherent low reactivity in inverse C-H bond reconstruction. In this paper, a novel strategy had been developed to reverse the copper-catalyzed concerted metalation-deprotonation process by inhibiting the unexpected disproportionation of Cu(II) to Cu(III). Picolinic acid was identified as a powerful ligand for facilitating this H/D exchange with D2O as deuterium source, and its inhibition activity was supported by preliminary control experiments and DFT studies.

"Marriage" of Inorganic to Organic Chemistry as Motivation for a Theoretical Study of Chloroform Hydrolysis Mechanisms.

Incorporation of chlorides in coordination complexes, prepared by reactions in CHCl3, stimulated MP2 and DFT studies of its complete hydrolysis mechanisms. In excellent agreement with previous experimental results, the most important mechanism for CHCl3 basic hydrolysis at room temperature is the radical one producing :CCl2. The latter inserts into the H-O bond of H2O yielding dichloromethanol (1). The hydrolysis mechanism of α-H-lacking PhCCl3 to the corresponding dichloro(phenyl)methanol (3) was also studied. 1 decomposes by H2O to formyl chloride (2) and HCl. 2, following a variety of pathways, leads to known CHCl3 hydrolysis products, such as CO (4) and formic acid (6), via the intermediates chloromethanediol (5), s-cis, s-trans-dihydroxycarbene (ct-7), and s-trans, s-trans-dihydroxycarbene (tt-7). Interestingly, both ct-7 and tt-7 intermediates have recently been implicated in the reduction of CO2 with H2 to 6. The conversion of CO to HCOOH was studied. Most of the reactions studied are asynchronous concerted processes, the radical mechanism being a multistep one. The synthetic utility of this mechanism is briefly mentioned. To avoid chloride ions when performing reactions in CHCl3, we should use the solvent at room temperature even in the presence of water. This has been verified further by coordination chemistry reactions in progress.

Zn-doped tubular graphene nitride for visible light and sacrificial-agent-free H2O2 photosynthesis in water

Graphitic carbon nitride (g-C3N4) has become a favored universal photocatalyst. Despite its numerous advantages, the photocatalytic efficiency of g-C3N4 is hindered by the substantial recombination of photoexcited charge carriers and holes. In this work, we demonstrate that Zn-doped tubular carbon nitride photocatalyst (Zn-tCN) can serve as highly efficient catalysts for H2O2 photosynthesis. Mechanism studies confirm that the presence of Zn in g-C3N4 prolongs the lifetimes of photogenerated carriers and inhibits their recombination, which triggers the reduction of O2 to reaction intermediates (O2−), as supported by in situ electron paramagnetic resonance (EPR) spectroscopy. More importantly, sacrificial agent experiments coupled with in situ EPR results confirmed that the reaction mechanism involves a concerted two-electron transfer process. The optimal catalyst displays a H2O2 productivity of 162.4μmol g–1h−1 under visible-light irradiation without a sacrificial agent, which is 11.7 times higher than that of pristine g-C3N4 (13.8μmol g–1h−1). This work proposes a synthetic strategy for the preparation of high-performance Zn-doped g-C3N4, which offers insights and perspectives for developing highly active photocatalysts and deepening the understanding of photocatalytic mechanisms.

Distance-Independent Efficiency of Triplet Energy Transfer from π-Conjugated Organic Ligands to Lanthanide-Doped Nanoparticles.

Lanthanide-doped nanoparticles (LnNPs) possess unique optical properties and are employed in various optoelectronic and bioimaging applications. One fundamental limitation of LnNPs is their low absorption cross-section. This hurdle can be overcome through surface modification with organic chromophores with large absorption cross-sections. Controlling energy transfer from organic molecules to LnNPs is crucial for creating optically bright systems, yet the mechanisms are not well understood. Using pump-probe spectroscopy, we follow singlet energy transfer (SET) and triplet energy transfer (TET) in systems comprising different length 9,10-bis(phenylethynyl)anthracene (BPEA) derivatives coordinated onto ytterbium and neodymium-doped nanoparticles. Photoexcitation of the ligands forms singlet excitons, some of which convert to triplet excitons via intersystem crossing when coordinated to the LnNPs. The triplet generation rate and yield are strongly distance-dependent. Following their generation, TET occurs from the ligands to the LnNPs, exhibiting an exponential distance dependence, independent of solvent polarity, suggesting a concerted Dexter-type process with a damping coefficient of 0.60 Å-1. Nevertheless, TET occurs with near-unity efficiency for all BPEA derivatives due to the lack of other triplet deactivation pathways and long intrinsic triplet lifetimes. Thus, we find that close coupling is primarily important to ensure efficient triplet generation rather than efficient TET. Although SET is faster, we find its efficiency to be lower and more strongly distance-dependent than the TET efficiency. Our results present the first direct distance-dependent energy transfer measurements in LnNP@organic nanohybrids and establish the advantage of using the triplet manifold to achieve the most efficient energy transfer and best sensitization of LnNPs with π-conjugated ligands.

Harnessing Gold(I)-Catalyzed Hydroamination/1,3-Sulfonyl Migration Cascade for Divergent Synthesis of Isoxazolidine and Isoxazoline from O-Alkynyl Hydroxylamine.

Gold-catalyzed 5-exo-dig hydroamination on O-homopropargylic hydroxylamine gave expeditious access to methylene isoxazolidine. Excess catalyst loading led to facile 1,3-sulfonyl migration in a cascade fashion to furnish the isoxazoline. Mechanistic studies using react-IR and NMR as well as crossover experiments indicated that 1,3-sulfonyl group migration is an intramolecular concerted process. The ene-hydroxylamine moiety also underwent dipolar cycloaddition reactions with nitrile oxide and nitrones leading to the first examples of spirocyclic bis-isoxazolidine derivatives.

A Cytochrome P450 Enzyme Catalyses Oxetane Ring Formation in Paclitaxel Biosynthesis

AbstractOxetane synthase (TmCYP1), a novel cytochrome P450 enzyme from Taxus×media cell cultures, has been functionally characterized to efficiently catalyse the formation of the oxetane ring in tetracyclic taxoids. Transient expression of TmCYP1 in Nicotiana benthamiana using 2α,5α,7β,9α,10β,13α‐hexaacetoxytaxa‐4(20),11(12)‐diene (1) as a substrate led to the production of a major oxetane derivative, 1β‐dehydroxybaccatin IV (1 a), and a minor 4β,20‐epoxide derivative, baccatin I (1 b). However, feeding the substrate decinnamoyltaxinine J (2), a 5‐deacetylated derivative of 1, yielded only 5α‐deacetylbaccatin I (2 b), a 4β,20‐epoxide. A possible reaction mechanism was proposed on the basis of substrate‐feeding, 2H and 18O isotope labelling experiments, and density functional theory calculations. This reaction could be an intramolecular oxidation‐acetoxyl rearrangement and the construction of the oxetane ring may occur through a concerted process; however, the 4β,20‐epoxide might be a shunt product. In this process, the C5‐O‐acetyl group in substrate is crucial for the oxetane ring formation but not for the 4(20)‐epoxy ring formation by TmCYP1. These findings provide a better understanding of the enzymatic formation of the oxetane ring in paclitaxel biosynthesis.

A Cytochrome P450 Enzyme Catalyses Oxetane Ring Formation in Paclitaxel Biosynthesis.

Oxetane synthase (TmCYP1), a novel cytochrome P450 enzyme from Taxus×media cell cultures, has been functionally characterized to efficiently catalyse the formation of the oxetane ring in tetracyclic taxoids. Transient expression of TmCYP1 in Nicotiana benthamiana using 2α,5α,7β,9α,10β,13α-hexaacetoxytaxa-4(20),11(12)-diene (1) as a substrate led to the production of a major oxetane derivative, 1β-dehydroxybaccatin IV (1 a), and a minor 4β,20-epoxide derivative, baccatin I (1 b). However, feeding the substrate decinnamoyltaxinine J (2), a 5-deacetylated derivative of 1, yielded only 5α-deacetylbaccatin I (2 b), a 4β,20-epoxide. A possible reaction mechanism was proposed on the basis of substrate-feeding, 2H and 18O isotope labelling experiments, and density functional theory calculations. This reaction could be an intramolecular oxidation-acetoxyl rearrangement and the construction of the oxetane ring may occur through a concerted process; however, the 4β,20-epoxide might be a shunt product. In this process, the C5-O-acetyl group in substrate is crucial for the oxetane ring formation but not for the 4(20)-epoxy ring formation by TmCYP1. These findings provide a better understanding of the enzymatic formation of the oxetane ring in paclitaxel biosynthesis.

Nitridation of diamond(111) surface by density functional theory.

Density functional theory was employed to examine the adsorption and thermal evolution of nitrogen species on diamond(111) impacted by microwave N2 plasma. On bare domains of diamond, as represented by the models of C(111)-2 × 1 and graphite-like C(111), N2(ad) is identified as the major surface species; the desorption of N2(ad) proceeds on both models via a concerted process of breaking two C-N bonds. By contrast, there is evidence of the formation of (NH)2(ad) via the insertion reaction of microwave N2 plasma on hydrogenated domains of diamond, as represented by the models of C(111)-2 × 1-H and C(111)-1 × 1-H. Interestingly, contrasting dynamics of desorption of (NH)2(ad) are presented on these two models, that is, via sequential breaking of two C-N bonds on C(111)-2 × 1-H and via concerted breaking of both C-N bonds on C(111)-1 × 1-H. Our results demonstrate that the observed diversity of surface nitrogen species in composition, bonding, vibration, and desorption in prior experiments is linked to domains of a variety of surface terminations and reconstructions on diamond(111).

N‒N hydrazonyl bond cleavage in benzothiazolyl-hydrazino-phenathrenequinone mediated by ruthenium(II) via an anion radical intermediate

The complexes [Ru(LBenz)H(CO)(PPh3)2] 2, [Ru(LBenz)Cl(CO)(PPh3)2] 3, (ligand behaving as bidentate monoanionic) and [Ru(LBenz)Cl(CO)(PPh3)] 4, (ligand is tridentate monoanionic) have been synthesized starting from benzothiazolyl-hydrazino-phenathrenequinone (HL) 1 and [RuH(CO)Cl(PPh3)3]. These are characterized by electrochemical and spectral methods as well as single crystal X-ray diffractometry (SCXRD). Upon treating with NaBH4, 3 accepts an electron within the coordinated ligand framework and the anionic hydrazonyl-N takes up a proton to be transformed to meta-stable hydrazinoquinone anion radical complex of ruthenium(II) [Ru(HLBenz•‒)Cl(CO)(PPh3)2] 5, possibly via concerted proton electron transfer process (CPET). Thus, the redox non-innocent character of the ligand upon complexation with ruthenium(II), has been disclosed and it is attributed to presence of low lying π* orbitals of almost entirely of phenanthraquinone and hydrazone character. In 5, the π‒acceptor ability of the ligand donor centres are reduced due to the existence of an odd electron in SOMO and hence the M-L distances around the coordination sphere are altered. The N‒N (hydrazonyl bond length increases from 1.296(6) Å in 3 to 1.429 Å in 5, leading to lesser thermodynamic stability of the latter and upon standing, the N‒N bond is cleaved to be transformed to 6+, possibly via the formation of iminoquinone anion radical complex, [6] (reported elsewhere). Also, it is via the dissociation of N‒N (hydrazonyl) bond, the biologically important molecule 2-aminobenzothiazole is formed along with 6+, so as to provide a novel route for its synthesis.

N-coordinated single cobalt atoms catalyst triggering concerted radical-nonradical process in catalytic ozonation for efficient water decontamination

Heterogeneous catalytic ozonation (HCO) has been developed as a promising technology for wastewater treatment, while traditional radical-based HCO process still suffers from insufficient mineralization of organic pollutants. Herein, we constructed a N-coordinated single cobalt atoms catalyst (CoSAC-N-C) triggering concerted radical-nonradical process in catalytic ozonation for efficient decontamination of pollutants. Experiments and theoretical calculations proved that mediate O in O3 obtained electrons from electron-rich N sites for hydroxyl radical (·OH) production, and the terminal O in O3 was attracted on electron-deficient Co sites for nonradical *O generation by O-O cleavage. The synergistic oxidation of ·OH and *O enabled excellent pollutants mineralization, surpassing most of conventional HCO catalysts. CoSAC-N-C exhibited excellent treatment performance for the coking wastewater in a continuous-flow reactor with COD reducing from 86 mg/L to less than 50 mg/L. This work provided a viable strategy of developing dual-site HCO catalysts to promote concerted radical-nonradical oxidations for wastewater treatment.

2:1 Adducts Arising from Reactions between Benzynes and 1,3,4-Oxadiazoles.

2:1 adducts arise from the reaction of 2,5-diaryl-1,3,4-oxadiazoles and benzynes generated from the hexadehydro-Diels-Alder (HDDA) reaction. Density functional theory computations support a mechanistic manifold that includes a concerted SNAr process. Additionally, the benzyne trapping reaction of 2,5-dimethyl-1,3,4-oxadiazole affords an unusual acylimine-containing 2:1 adduct, which is the first case in which a dearomatized product has arisen from a HDDA reaction.

Alternative strategies for the recombinant synthesis, DOPA modification and analysis of mussel foot proteins – A case study for Mefp-3 from Mytilus edulis

Mussel foot proteins (Mfps) possess unique binding properties to various surfaces due to the presence of L-3,4-dihydroxyphenylalanine (DOPA). Mytilus edulis foot protein-3 (Mefp-3) is one of several proteins in the byssal adhesive plaque. Its localization at the plaque-substrate interface approved that Mefp-3 plays a key role in adhesion. Therefore, the protein is suitable for the development of innovative bio-based binders. However, recombinant Mfp-3s are mainly purified from inclusion bodies under denaturing conditions. Here, we describe a robust and reproducible protocol for obtaining soluble and tag-free Mefp-3 using the SUMO-fusion technology. Additionally, a microbial tyrosinase from Verrucomicrobium spinosum was used for the in vitro hydroxylation of peptide-bound tyrosines in Mefp-3 for the first time. The highly hydroxylated Mefp-3, confirmed by MALDI-TOF-MS, exhibited excellent adhesive properties comparable to a commercial glue. These results demonstrate a concerted and simplified high yield production process for recombinant soluble and tag-free Mfp3-based proteins with on demand DOPA modification.

Multiscale calculations reveal new insights into the reaction mechanism between KRASG12C and α, β-unsaturated carbonyl of covalent inhibitors

Utilizing α,β-unsaturated carbonyl group as Michael acceptors to react with thiols represents a successful strategy for developing KRASG12C inhibitors. Despite this, the precise reaction mechanism between KRASG12C and covalent inhibitors remains a subject of debate, primarily due to the absence of an appropriate residue capable of deprotonating the cysteine thiol as a base. To uncover this reaction mechanism, we first discussed the chemical reaction mechanism in solvent conditions via density functional theory (DFT) calculation. Based on this, we then proposed and validated the enzymatic reaction mechanism by employing quantum mechanics/molecular mechanics (QM/MM) calculation. Our QM/MM analysis suggests that, in biological conditions, proton transfer and nucleophilic addition may proceed through a concerted process to form an enolate intermediate, bypassing the need for a base catalyst. This proposed mechanism differs from previous findings. Following the formation of the enolate intermediate, solvent-assisted tautomerization results in the final product. Our calculations indicate that solvent-assisted tautomerization is the rate-limiting step in the catalytic cycle under biological conditions. On the basis of this reaction mechanism, the calculated kinact/ki for two inhibitors is consistent well with the experimental results. Our findings provide new insights into the reaction mechanism between the cysteine of KRASG12C and the covalent inhibitors and may provide valuable information for designing effective covalent inhibitors targeting KRASG12C and other similar targets.

Umpolung reactivity of strained C–C σ-bonds without transition-metal catalysis

Umpolung is an old and important concept in organic chemistry, which significantly expands the chemical space and provides unique structures. While, previous research focused on carbonyls or imine derivatives, the umpolung reactivity of polarized C–C σ-bonds still needs to explore. Herein, we report an umpolung reaction of bicyclo[1.1.0]butanes (BCBs) with electron-deficient alkenes to construct the C(sp3)-C(sp3) bond at the electrophilic position of C–C σ-bonds in BCBs without any transition-metal catalysis. Specifically, this transformation relies on the strain-release driven bridging σ-bonds in bicyclo[1.1.0]butanes (BCBs), which are emerged as ene components, providing an efficient and straightforward synthesis route of various functionalized cyclobutenes and conjugated dienes, respectively. The synthetic utilities of this protocol are performed by several transformations. Preliminary mechanistic studies including density functional theory (DFT) calculation support the concerted Alder-ene type process of C–C σ-bond cleavage with hydrogen transfer. This work extends the umpolung reaction to C–C σ-bonds and provides high-value structural motifs.

An ensemble of excited molecules collectively emits multiple-frequency real and virtual photons.

The interplay of molecules gives rise to collective phenomena absent in a single molecule. Many examples of collective phenomena have been reported as their knowledge is essential for understanding the behavior of matter. Here, we consider molecules sufficiently separated from each other to not form chemical bonds. If these molecules are excited, e.g., by a weak laser, can they concertedly relax by emitting a single high-energy photon possessing the total energy of all the relaxing molecules? We show that this concerted emission process is indeed possible. We estimate its probability and analyze its dependence on molecular properties, intermolecular distances, and relative orientations of the molecules. A numerical example on two pyridine molecules is given. The concerted emission found is a fundamental process expected to be operative in gas phase and clusters. Its true relevance lies in its intimate relationship to concerted emission of virtual photons and thus to collective energy transfer ionizing neighboring systems. The estimated rates and examples discussed of this collective intermolecular Coulombic decay shed much light on recent puzzling experiments.

A Ruthenophosphanorcaradiene as a Synthon for an Ambiphilic Metallophosphinidene.

Reaction of the ruthenium carbene complex Cp*(IPr)RuCl (1) (IPr = 1,3-bis(Dipp)imidazol-2-ylidene; Dipp = 2,6-diisopropylphenyl) with sodium phosphaethynolate (NaOCP) led to intramolecular dearomatization of one of the Dipp substituents on the Ru-bound carbene to afford a Ru-bound phosphanorcaradiene, 2. Computations by DFT reveal a transition state characterized by a concerted process whereby CO migrates to the Ru center as the P atom adds to the π system of the aryl group. The phosphanorcaradiene possesses ambiphilic properties and reacts with both nucleophilic and electrophilic substrates, resulting in rearomatization of the ligand aryl group with net P atom transfer to give several unusual metal-bound, P-containing main-group moieties. These new complexes include a metallo-1-phospha-3-azaallene (Ru─P═C═NR), a metalloiminophosphanide (Ru─P═N─R), and a metallophosphaformazan (Ru─P(═N─N═CPh2)2). Reaction of 2 with the carbene 2,3,4,5-tetramethylimidazol-2-ylidene (IMe4) produced the corresponding phosphaalkene DippP═IMe4.

“Concerted Process between Humans and AI” to Explore New Horizons in Materials Science

“Concerted Process between Humans and AI” to Explore New Horizons in Materials Science

Competing radical and molecular channels in the unimolecular dissociation of methylformate

The thermal dissociation of methylformate has been characterized by numerous experimental and theoretical studies that all seem to agree that the lowest energetically accessible process is a 3-center H-atom transfer that leads to the molecular products CH3OH + CO. However, these literature studies seem to be at odds with regards to the role of other competing molecular eliminations and bond-fission processes and therefore a complete and resolved mechanistic picture of methylformate thermal dissociation still eludes us. In this work, we have performed high-level electronic structure theory calculations to characterize the energetics of other overlooked molecular and radical processes that can originate on the complex CH3OCHO potential energy surface (PES). The present calculations do indeed confirm that the lowest energy process accessible on this PES is molecular elimination to form CH3OH + CO. However, unlike prior theoretical studies, the present calculations reveal that the second lowest energy process is a 5-center concerted elimination process that leads to the direct formation of H2 + CH2O + CO. We also note that HCO2 from the lowest-lying bond fission has two energetically comparable electronic states (of 2B2 and 2A1 symmetry). Furthermore, the barrier for H-atom migration of CH3OCHO to form the carbene (CH3OCOH) is similar to that for the direct 4-center elimination process leading to CH2O + CH2O characterized in prior literature studies. Radical and molecular pathways to CH3 + HOCO and CH4 + CO2 can also be facilitated from this carbene. Master equation calculations were performed to characterize the competition between the various molecular and radical processes on this more elaborate CH3OCHO PES. The results of the present theoretical analyses were used to resolve outstanding questions on the role of secondary radical-initiated reactions in characterizing prior literature experimental studies.