Pd(II)/LA-catalyzed acetanilide olefination with dioxygen.

Transition-metal-catalyzed aromatic olefination through direct C-H activation represents an atom and step-economic route for versatile pharmaceutical syntheses, and in many cases, different stoichiometric oxidants are frequently employed for achieving a reasonable catalytic efficiency of the transition metal ions. Herein, we report a Lewis acid promoted Pd(II)-catalyzed acetanilide olefination reaction with atmospheric dioxygen as the oxidant source. The linkage of the Lewis acid to the Pd(II) species through a diacetate bridge significantly improved its catalytic efficiency, and independent kinetic studies on the olefination step revealed that adding the Lewis acid significantly accelerated the olefination rate as well as the C-H activation step. A strong basicity of the internal base in the Pd(II) salt also benefited the olefination reaction plausibly through base-assisted ß-hydride elimination.

Nickel(II)/Lewis acid catalysed olefin hydroamination and hydroarylation under mild conditions.

Aniline derivatives are important nitrogen-containing compounds with wide applications in chemicals, pharmaceuticals and agrochemicals. In the work described herein, nickel(II)/Lewis acid (LA) catalysed olefin hydroamination with anilines was explored for use in aniline derivative syntheses. The Ni(II)/LA catalysis proceeded smoothly under mild conditions, whereas using Ni(OAc)2 alone, the catalyst was inactive. Remarkably, the Markovnikov addition type products were obtained when substituted styrenes were used as the olefin source, while the anti-Markovnikov addition type products were obtained when the electron-deficient olefins such as acrylonitrile and acrylates were used. The mechanistic studies revealed that hydroamination of the styrene derivates proceeded via the amino-Ni(II)/LA attacking the carbocation intermediate which was generated by the protonation of the olefin, whereas for acrylonitrile and acrylates, it proceeded by a direct amino-Ni(II)/LA attack on the olefin by nucleophilic addition. In addition, the hydroarylation product was generated by the Hofmann-Martius rearrangement of the hydroamination product.

Correction: Lewis acid improved dioxygen activation by a non-heme iron(II) complex towards tryptophan 2,3-dioxygenase activity for olefin oxygenation.

Correction for 'Lewis acid improved dioxygen activation by a non-heme iron(II) complex towards tryptophan 2,3-dioxygenase activity for olefin oxygenation' by Guangjian Liao et al., Dalton Trans., 2022, https://doi.org/10.1039/d2dt02769k.

Observing the Agostic Hydrogen in Pd(II)-Catalyzed Aromatic C-H Activation.

Direct C-H activation and functionalization offer a convenient protocol for pharmaceutical and material syntheses. Although versatile mechanisms have been proposed to depict transition-metal-catalyzed C-H activation, to date, the shared key agostic hydrogen intermediate in several major mechanisms has not been observed yet, which apparently puzzles the mechanism-based catalyst design. This work reports the direct observations of this intermediate in Pd(II)/Sc(III)-catalyzed C-H activation of acetanilides, and its stability and reactivity in C-H activation are investigated. Remarkably, this intermediate is only observed in electron-rich acetanilides, and the meta-substituent with increased σm constant generally accelerates C-H activation, a characteristic of the base-assisted C-H activation mechanism. This study has unveiled the masks of this intermediate with an understanding of its first-hand physicochemical properties, shedding new light on mechanism-based catalyst design.

Lewis acid improved dioxygen activation by a non-heme iron(II) complex towards tryptophan 2,3-dioxygenase activity for olefin oxygenation.

Dioxygen activation and catalysis around ambient temperature is a long-standing challenge in chemistry. Inspired by the significant roles of the hydrogen bond network in dioxygen activation and catalysis by redox enzymes, this work presents a Lewis acid improved dioxygen activation by an FeII(BPMEN)(OTf)2 complex towards tryptophan 2,3-dioxygenase (TDO) activity for 3-methylindole and common olefinic CC  bond oxygenation and cleavage (enzymatic Brønsted acid vs. chemical Lewis acid). It was found that the presence of a Lewis acid such as Sc3+ could substantially improve olefinic CC  bond oxygenation and cleavage activity through FeII(BPMEN)(OTf)2 catalyzed dioxygen activation. Notably, a more negative ρ value in the Hammett plot of para-substituted styrene oxygenations was observed in the presence of a stronger Lewis acid, disclosing the enhanced electrophilic oxygenation capability of the putative iron(III) superoxo species through its electrostatic interaction with a stronger Lewis acid. Thereof, this work has demonstrated a new strategy in catalyst design for dioxygen activation and catalysis for olefin oxygenation, a significant process in the chemical industry.

Pd(II)/Lewis Acid Catalyzed Intramolecular Annulation of Indolecarboxamides with Dioxygen through Dual C-H Activation.

Transition-metal ion catalyzed intramolecular dual C-H activation to construct polycyclic heteroarene skeletons is merited for its step and atom-economic advantages in organic synthesis. However, in most cases, stoichiometric oxidants, elevated temperature, and other harsh conditions were commonly faced for this reaction, which apparently block the synthetic applications. Herein, we report a Pd(II)/LA (LA: Lewis acid) catalyzed intramolecular dual C-H activation to construct indoloquinolinone derivatives under mild conditions with dioxygen as the sole oxidant. It was found that adding LA such as Sc3+ to Pd(OAc)2 sharply improved its catalytic efficiency, whereas Pd(OAc)2 alone was very sluggish. The activity improvement was attributed to the linkage of the Sc3+ cation to the Pd(II) species through a diacetate bridge that significantly enhanced the electrophilic properties of Pd(II) for dual C-H activation.

Configuration-Dependent Liquid Crystal and Gel Behaviors of Tetraphenylethene-Containing Main-Chain Copolyesters.

The construction of aggregation-induced emission-active (AIE-active) gelators with liquid crystal properties remains a challenge. Moreover, the effects of AIE configuration on liquid crystal, gel and AIE behaviors in one system are unclear. Herein, two main-chain liquid crystalline copolyester gelators with a single configuration of AIEgen TPE, mesogen biphenyl, and pendent amide groups are synthesized through melt polycondensation. Both copolyesters display smectic phase, while E-P20 possesses a wider temperature range of liquid crystal and a narrower layer distance owing to the more serious nonlinear "defect" of Z-TPE than E-TPE units. In addition, E-P20 and Z-P20 can form AIE-active gels with the minimum gelation concentration (MGC) values of 10 and 4 wt% in ethyl acetate mainly via hydrogen bonds between the pendent amide groups, respectively. These AIE-active gels show potential applications in temperature sensor, information storage, and so on.

Palladium(II)/Lewis Acid-Catalyzed Olefination of Arylacetamides with Dioxygen.

The present work introduces Pd(II)/LA-catalyzed (LA: Lewis acid) olefination of arylacetamides with dioxygen as the oxidant source. This protocol tolerates with different functional groups on the substrates, and the catalytic efficiency is highly Lewis acidity-dependent on added LA, that is, a stronger LA provided a better promotional effect. The 1H NMR studies of the semireaction between the arylacetamide and the Pd(II)/Sc(III) catalyst in HOAc-d4 disclosed the formation of a palladacycle intermediate, and the C-H activation step was reversible, which led to the formation of the deuterated arylacetamide substrate and the palladacycle intermediate. Further semireaction between the palladacycle intermediate and the olefin disclosed that it was a clean and much faster reaction than the C-H activation step, thus revealing multiple mechanistic information for Pd(II)-catalyzed C-H activation.

Pd(II)/Lewis acid catalyzed regioselective olefination of indole with dioxygen.

Transition metal ion catalyzed indole olefination through C-H activation is a convenient protocol to synthesize versatile bioactive vinylindole compounds; however, in most cases, stoichiometric amounts of oxidants were necessary to accomplish the catalytic cycle. The present study describes a Pd(II)/LA (LA: Lewis acid) catalyzed indole olefination with dioxygen as the sole oxidant. The olefination reaction with electron-rich olefins proceeded smoothly through the pyrrolyl N-carboxamide group directed remote C-H activation at the C3 position of the indole with the Pd(II)/LA catalyst, whereas Pd(II) alone was a very sluggish catalyst under identical conditions. For the electron-deficient olefins, the directing N-carboxamide group was not essential for olefination with this Pd(II)/LA catalyst, demonstrating a different olefination pathway from that of electron-rich olefins. Remarkably, 1H NMR kinetics disclosed that olefination proceeded much faster with electron-rich olefins than with electron-deficient ones.

Decarboxylative Addition of Propiolic Acids with Indoles to Synthesize Bis(indolyl)methane Derivatives with a Pd(II)/LA Catalyst.

Exploring new protocols for efficient organic synthesis is crucial for pharmaceutical developments. The present work introduces a Pd(II)/LA-catalyzed (LA: Lewis acid) decarboxylative addition reaction for the synthesis of bis(indolyl)methane derivatives. The presence of Lewis acid such as Sc(OTf)3 triggered Pd(II)-catalyzed decarboxylative addition of propiolic acids with indoles to offer the bis(indolyl)methane derivatives in moderate to good yields, whereas neither Pd(II) nor Lewis acid alone was active for this synthesis. The catalytic efficiency of Pd(OAc)2 was highly dependent on the Lewis acidity of the added Lewis acid, that is, a stronger Lewis acid provided a higher yield of the bis(indolyl)methane derivatives. Meanwhile, this Pd(II)/LA-catalyzed decarboxylative addition reaction showed good tolerance toward versatile electron-rich or -deficient substituents on the indole skeleton and on the benzyl ring of propiolic acids. The studies on the in situ 1H NMR kinetics of this Pd(II)/Sc(III) catalysis disclosed the formation of a transient vinyl-Pd(II)/Sc(III) intermediate generated by the pyrrole addition to the alkynyl-Pd(II)/Sc(III) species after decarboxylation, which was scarcely observed before.

The oxidative reactivity of three manganese(III) porphyrin complexes with hydrogen peroxide and nitrite toward catalytic nitration of protein tyrosine.

Understanding the toxicological properties of MnIII-porphyrins (MnTPPS, MnTMPyP, or MnTBAP) can provide important biochemical rationales in developing them as the therapeutic drugs against protein tyrosine nitration-induced inflammation diseases. Here, we present a comprehensive understanding of the pH-dependent redox behaviors of these MnIII-porphyrins and their structural effects on catalyzing bovine serum albumin (BSA) nitration in the presence of H2O2 and NO2-. It was found that both MnTPPS and MnTBAP stand out in catalyzing BSA nitration at physiologically close condition (pH 8), yet they are less effective at pH 6 and 10. MnTMPyP was shown to have no ability to catalyze BSA nitration under all tested pHs (pH 6, 8, and 10). The kinetics and active intermediate determination through electrochemistry method revealed that both the pH-dependent redox behavior of the central metal cation and the antioxidant capability of porphin derivative contribute to the catalytic activities of three MnIII-porphyrins in BSA nitration in the presence of H2O2/NO2-. These comprehensive studies on the oxidative reactivity of MnIII-porphyrins toward BSA nitration may provide new clues for searching the manganese-based therapeutic drugs against the inflammation-related diseases.

Palladium(II)/Lewis Acid-Catalyzed Oxidative Olefination/Annulation of N-Methoxybenzamides: Identifying the Active Intermediates through NMR Characterizations.

Although Pd(II)-catalyzed C-H activation in arenes has been widely successful in organic synthesis with many palladacycle compounds isolated as the intermediates in ligand-directed C-H activation, direct identification of the reaction intermediates such as the π-complex prior to the C-H activation is still not successful because of their instability. In the present study, we introduce a Pd(II)/LA (LA: Lewis acid)-catalyzed oxidative olefination/annulation reaction between N-methoxybenzamides and acrylates with oxygen as the oxidant source, in which two intermediates, including an unsymmetrical η6-complex and a palladacycle species without the proton releasing to the environment, were identified through NMR characterizations. The in situ formation of the heterobimetallic Pd(II)/LA species such as Pd(II)/Sc(III) may have enhanced the electrophilic properties of the Pd2+ cation, thus improving the stability of the π-complex, herein, an unsymmetrical η6-complex, and improving its catalytic efficiency. The observed insensitive electronic effect preferred the concerted metalation-deprotonation (CMD) mechanism for this C-H activation, and the detected palladacycle intermediate without the proton releasing to the environment offered an experimental clue to support the proposed CMD mechanism.

Lewis Acid Promoted Aerobic Oxidative Coupling of Thiols with Phosphonates by Simple Nickel(II) Catalyst: Substrate Scope and Mechanistic Studies.

Exploring new catalysts for efficient organic synthesis is among the most attractive topics in chemistry. Here, using Ni(OAc)2/LA as catalyst (LA: Lewis acid), a novel catalyst strategy was developed for oxidative coupling of thiols and phosphonates to phosphorothioates with oxygen oxidant. The present study discloses that when Ni(OAc)2 alone was employed as the catalyst, the reaction proceeded very sluggishly with low yield, whereas adding non-redox-active metal ions such as Y3+ to Ni(OAc)2 dramatically promoted its catalytic efficiency. The promotional effect is highly Lewis acidity dependent on the added Lewis acid, and generally, a stronger Lewis acid provided a better promotional effect. The stopped-flow kinetics confirmed that adding Y(OTf)3 can obviously accelerate the activation of thiols by Ni(II) and next accelerate its reaction with phosphonate to generate the phosphorothioate product. ESI-MS characterizations of the catalyst disclosed the formation of the heterobimetallic Ni(II)/Y(III) species in the catalyst solution. Additionally, this Ni(II)/LA catalyst can be applied in the synthesis of a series of phosphorothioate compounds including several commercial bioactive compounds. This catalyst strategy has clearly supported that Lewis acid can significantly improve the catalytic efficiency of these traditional metal ions in organic synthesis, thus opening up new opportunities in their catalyst design.

Nonredox Metal Ions Promoted Olefin Epoxidation by Iron(II) Complexes with H2O2: DFT Calculations Reveal Multiple Channels for Oxygen Transfer.

Nonredox metal ions play significant roles in a wide range of biological and chemical oxidations in which they can modulate the oxidative reactivity of those redox metal ions. With environmentally benign H2O2 as oxidant, the influence of nonredox metal ions on an iron(II) complex mediated olefin epoxidation was investigated through experimental studies and theoretical calculations. It was found that adding nonredox metal ions like Sc3+ can substantially improve the oxygen transfer efficiency of the iron(II) complex toward cyclooctene epoxidation even in the presence of certain amount of water. In 18O-labeling experiments with 18O water, the presence of Sc3+ provided a higher 18O incorporation in epoxide. In UV-vis studies, it was found that the presence of Sc3+ makes both FeIII-OOH and FeIV═O species unstable. Density functional theory calculations further disclosed that, in the presence of Sc(OTf)3, the Sc3+ adducts of FeIII-OOH and FeIV═O species are capable of epoxidizing olefin as well as FeV═O species, thus opening multiple channels for oxygenation. In particular, in the pathway of cyclooctene epoxidation, the FeIV═O/Sc3+ adduct-mediated epoxidation is more energetically favorable than that of the FeV═O species (12.2 vs 17.2 kcal/mol). This information may implicate that the presence of certain nonredox metal ions can facilitate these redox metal ions mediating biological and chemical oxidations happening at a relatively low oxidation state, which is more energetically accessible.

Transformation of Unsaturated Fatty Acids/Esters to Corresponding Keto Fatty Acids/Esters by Aerobic Oxidation with Pd(II)/Lewis Acid Catalyst.

Utilization of renewable biomass to partly replace the fossil resources in industrial applications has attracted attention due to the limited fossil feedstock with the increased environmental concerns. This work introduced a modified Wacker-type oxidation for transformation of unsaturated fatty acids/esters to the corresponding keto fatty acids/esters, in which Cu2+ cation was replaced with common nonredox metal ions, that is, a novel Pd(II)/Lewis acid (LA) catalyst. It was found that adding nonredox metal ions can effectively promote Pd(II)-catalyzed oxidation of unsaturated fatty acids/esters to the corresponding keto fatty acids/esters, even much better than Cu2+, and the promotional effect is highly dependent on the Lewis acidity of added nonredox metal ions. The improved catalytic efficiency is attributed to the formation of heterobimetallic Pd(II)/LA species, and the oxidation mechanism of this Pd(II)/LA catalyst is also briefly discussed.

Support-dependent active species formation for CuO catalysts: Leading to efficient pollutant degradation in alkaline conditions.

Redox metal ions play the crucial role in versatile advanced oxidation technologies, in which controlling the active species formation through catalyst design is one of the key challenges in oxidant utilization. This work describes an example of different active species formations in CuO-mediated degradation just because of supporting material differences. Although three CuO catalysts were prepared by similar procedures, it was found that CuO-MgO catalyst demonstrated high efficiency in phenol degradation with bicarbonate activated H2O2, in which the superoxide radical is crucial, while hydroxyl radical and singlet oxygen are ignorable. For the CuO-MgO-Al2O3 and CuO-Al2O3 catalysts, the degradation proceeds by popular hydroxyl radical based process, however, the efficiency was poor. The EPR experiments also confirmed the absence of hydroxyl radical in CuO-MgO system but its presence in CuO-MgO-Al2O3 and CuO-Al2O3 system. The high catalytic efficiency with ignorable hydroxyl radical in the CuO-MgO system leads us to propose that an alternative Cu(III) species dominates the degradation. The basic MgO support may facilitate the formation of the Cu(III) species, whereas the neutral MgO-Al2O3 and acidic Al2O3 supports are unable to stabilize the high valent Cu(III) species, leading to the common hydroxyl radical mechanism with low efficiency of H2O2 in alkaline conditions.

Nonredox Metal-Ions-Enhanced Dioxygen Activation by Oxidovanadium(IV) Complexes toward Hydrogen Atom Abstraction.

Dioxygen activation toward efficient catalysis at ambient temperature is still a big challenge for industrial oxidations, while it proceeds smoothly in nature. This work presents an example of that adding nonredox metal ions as Lewis acid can enhance dioxygen activation by oxidovanadium(IV) complex, [VIV(O)Cl(TPA)]PF6 (where TPA is tris-[(2-pyridy)methyl]amine), which leads to efficient hydrogen abstraction at ambient temperature, whereas, in the absence of a Lewis acid, the catalytic hydrogen abstraction of the oxidovanadium(IV) complex is very sluggish. Ultraviolet-visible light (UV-vis), electron paramagnetic resonance (EPR), mass, and nuclear magnetic resonance (NMR) studies have provided informative clues to indicate the interaction between the Lewis acid and vanadium complexes, including assisting the dissociation of the chloride from the oxidovanadium(IV) complex, interacting with the vanadium oxido group, and stabilizing the vanadium(V) superoxo species. These interactions enhanced the dioxgyen activation efficiency of oxidovanadium(IV) complex, and improved the hydrogen abstraction ability of vanadium(V) oxido species, which leads to efficient hydrogen abstraction in a catalytic process. A brief mechanism has also been proposed for dioxygen activation toward hydrogen abstraction by an oxidovanadium(IV) complex.

Synergistic oxygen atom transfer by ruthenium complexes with non-redox metal ions.

Non-redox metal ions can affect the reactivity of active redox metal ions in versatile biological and heterogeneous oxidation processes; however, the intrinsic roles of these non-redox ions still remain elusive. This work demonstrates the first example of the use of non-redox metal ions as Lewis acids to sharply improve the catalytic oxygen atom transfer efficiency of a ruthenium complex bearing the classic 2,2'-bipyridine ligand. In the absence of Lewis acid, the oxidation of ruthenium(ii) complex by PhI(OAc)2 generates the Ru(iv)[double bond, length as m-dash]O species, which is very sluggish for olefin epoxidation. When Ru(bpy)2Cl2 was tested as a catalyst alone, only 21.2% of cyclooctene was converted, and the yield of 1,2-epoxycyclooctane was only 6.7%. As evidenced by electronic absorption spectra and EPR studies, both the oxidation of Ru(ii) by PhI(OAc)2 and the reduction of Ru(iv)[double bond, length as m-dash]O by olefin are kinetically slow. However, adding non-redox metal ions such as Al(iii) can sharply improve the oxygen transfer efficiency of the catalyst to 100% conversion with 89.9% yield of epoxide under identical conditions. Through various spectroscopic characterizations, an adduct of Ru(iv)[double bond, length as m-dash]O with Al(iii), Ru(iv)[double bond, length as m-dash]O/Al(iii), was proposed to serve as the active species for epoxidation, which in turn generated a Ru(iii)-O-Ru(iii) dimer as the reduced form. In particular, both the oxygen transfer from Ru(iv)[double bond, length as m-dash]O/Al(iii) to olefin and the oxidation of Ru(iii)-O-Ru(iii) back to the active Ru(iv)[double bond, length as m-dash]O/Al(iii) species in the catalytic cycle can be remarkably accelerated by adding a non-redox metal, such as Al(iii). These results have important implications for the role played by non-redox metal ions in catalytic oxidation at redox metal centers as well as for the understanding of the redox mechanism of ruthenium catalysts in the oxygen atom transfer reaction.

Non-redox metal ion promoted oxidative coupling of indoles with olefins by the palladium(ii) acetate catalyst through dioxygen activation: experimental results with DFT calculations.

Developing new catalytic technologies through C-H bond activation to synthesize versatile pharmaceuticals has attracted much attention in recent decades. This work introduces a new strategy in catalyst design for Pd(ii)-catalyzed C-H bond activation in which non-redox metal ions serving as Lewis acids play significant roles. In the oxidative coupling of indoles with olefins using dioxygen, it was found that Pd(OAc)2 alone as the catalyst is very sluggish at ambient temperature which provided a low yield of the olefination product, whereas adding non-redox metal ions to Pd(OAc)2 substantially improves its catalytic efficiency. In particular, it provided bis(indolyl)methane derivatives as the dominant product, a category of pharmacological molecules which could not be synthesized by Pd(ii)-catalyzed oxidative coupling previously. Detailed investigations revealed that the reaction proceeds by heterobimetallic Pd(ii)/Sc(iii)-catalyzed oxidative coupling of an indole with an olefin followed by Sc(iii)-catalyzed addition with a second indole molecule. DFT calculations disclosed that the formation of heterobimetallic Pd(ii)/Sc(iii) species substantially decreases the C-H bond activation energy barrier, and shifts the rate determining step from C-H bond activation of indole to the olefination step. This non-redox metal ion promoted Pd(ii)-catalyzed C-H bond activation may offer a new opportunity for catalyst design in organic synthesis, which has not been fully recognized yet.

Non-redox metal ions can promote Wacker-type oxidations even better than copper(II): a new opportunity in catalyst design.

In Wacker oxidation and inspired Pd(ii)/Cu(ii)-catalyzed C-H activations, copper(ii) is believed to serve in re-oxidizing of Pd(0) in the catalytic cycle. Herein we report that non-redox metal ions like Sc(iii) can promote Wacker-type oxidations even better than Cu(ii); both Sc(iii) and Cu(ii) can greatly promote Pd(ii)-catalyzed olefin isomerization in which the redox properties of Cu(ii) are not essential, indicating that the Lewis acid properties of Cu(ii) can play a significant role in Pd(ii)-catalyzed C-H activations in addition to its redox properties. Characterization of catalysts using UV-Vis and NMR indicated that adding Sc(OTf)3 to the acetonitrile solution of Pd(OAc)2 generates a new Pd(ii)/Sc(iii) bimetallic complex having a diacetate bridge which serves as the key active species for Wacker-type oxidation and olefin isomerization. Linkage of trivalent Sc(iii) to the Pd(ii) species makes it more electron-deficient, thus facilitating the coordination of olefin to the Pd(ii) cation. Due to the improved electron transfer from olefin to the Pd(ii) cation, it benefits the nucleophilic attack of water on the olefinic double bond, leading to efficient olefin oxidation. The presence of excess Sc(iii) prevents the palladium(0) black formation, which has been rationalized by the formation of the Sc(iii)H-Pd(ii) intermediate. This intermediate inhibits the reductive elimination of the H-Pd(ii) bond, and facilitates the oxygen insertion to form the HOO-Pd(ii) intermediate, and thus avoids the formation of the inactive palladium(0) black. The Lewis acid promoted Wacker-type oxidation and olefin isomerization demonstrated here may open up a new opportunity in catalyst design for versatile C-H activations.