Insertion Reactions Research Articles

Lithium Bromide-Promoted Formal C(sp3)-H Bond Insertion Reactions of β-Carbonyl Esters with Sulfoxonium Ylides to Synthesize 1,4-Dicarbonyl Compounds.

A LiBr-promoted formal C(sp3)-H bond insertion reaction between β-carbonyl esters and sulfoxonium ylides is established. This practical reaction has a wide range of substrate scope for both β-carbonyl esters and sulfoxonium ylides to give a variety of 1,4-dicarbonyl compounds with 43-94% yields. The reaction features transition-metal-free reaction conditions and exclusive C-alkylation chemselectivity. The use of bench-stable sulfoxonium ylides overcomes previous methods that require transition metal as catalysts and unstable diazo compounds or toxic haloketones as alkylation reagents.

Spin-Phonon Coupling in Iron-Doped Ultrathin Bismuth Halide Perovskite Derivatives.

Spin in semiconductors facilitates magnetically controlled optoelectronic and spintronic devices. In metal halide perovskites (MHPs), doping magnetic ions is proven to be a simple and efficient approach to introducing a spin magnetic momentum. In this work, we present a facile metal ion doping protocol through the vapor-phase metal halide insertion reaction to the chemical vapor deposition (CVD)-grown ultrathin Cs3BiBr6 perovskites. The Fe-doped bismuth halide (Fe:CBBr) perovskites demonstrate that the iron spins are successfully incorporated into the lattice, as revealed by the spin-phonon coupling below the critical temperature Tc around 50 K observed through temperature-dependent Raman spectroscopy. Furthermore, the phonons exhibit significant softening under an applied magnetic field, possibly originating from magnetostriction and spin exchange interaction. The spin-phonon coupling in Fe:CBBr potentially provides an efficient way to tune the spin and lattice parameters for halide perovskite-based spintronics.

Catalyst-free electro-photochemical insertion reactions of carbene anion radicals by convergent paired electrolysis

Catalyst-free electro-photochemical insertion reactions of carbene anion radicals by convergent paired electrolysis

P(III)-Mediated Formal Reductive N-H Bond Insertion Reaction of Hydrazones to α-Keto Esters.

A diazo-, metal-, and base-free multi-substituted hydrazone synthesis via a formal reductive N-H bond insertion reactions of hydrazones to α-keto esters has been developed. The protocol features a broad substrate scope and good functional group tolerance, providing N-H bond insertion products in moderate to excellent yields. Moreover, P(III)-mediated N-H functionalization of pharmaceutical containing hydrazone moiety was also successfully achieved.

Mechanistic Insights into Rare-Earth-Catalyzed Alternating Copolymerization through C-H Polyaddition of Functionalized Organic Compounds to Unconjugated Dienes.

Density functional theory (DFT) calculations have been conducted to elucidate the detailed mechanisms of yttrium-catalyzed C-H polyaddition of 1,4-dimethoxybenzene (DMB) to 1,4-divinylbenzene (DVB). It was computationally determined that DMB not only serves as a substrate but also performs a crucial role as a ligand, stabilizing the catalytically active species and promoting alkene insertion. Side pathways involving Cβ-H activation and C═C continuous insertion were excluded due to steric and electronic factors, respectively, explaining why the reaction occurred efficiently and selectively to give perfectly alternating DMB-DVB polymers. Interestingly, the theoretical prediction of the reactivity of N,N-dimethyl-1,4-phenylenediamine and 2,2'-biethyl-4,4'-bipyridine reveals significant differences in the coordination effects of these substrates, leading to distinct mechanisms, primarily influenced by their steric effects. These findings shed new light on the previously overlooked role of substrate ligand effects in rare-earth-catalyzed step-growth copolymerization reactions.

Nickel‐Catalyzed Branch Selective C‐H Alkylation of Indoles and Azoles with Alkenes: An Additive‐ and Solvent‐Free Approach

The development of sustainable protocols for the synthesis of alkylated heteroarenes is crucial owing to their widespread existence in medicinally relevant and bioactive natural products. Herein, we describe an efficient, additive‐ and solvent‐free approach for the regioselective C−H alkylation of indoles and azoles with alkenes using a nickel catalyst, which proceeds through a chelation‐assistance strategy. The reaction exclusively provided branched alkylated products with the compatibility of alkyl, alkoxy, fluoro, trifluoromethyl, alkene, cyano, ester, and carbonyl groups. This protocol is applicable to other heteroarenes, such as imidazoles and benzimidazoles, providing the desired alkylated products with exclusive Markovnikov selectivity. The synthetic utility and scale‐up of the reaction are demonstrated, and the protocol is in concord with the principles of green chemistry. Alkylation proceeds through facile and reversible C−H nickelation and alkene insertion processes, presumably involving rate‐limiting reductive elimination.

Front Cover: Intermolecular Insertion Reactions into the P−P Bond of Oligophosphorus Compounds (Eur. J. Inorg. Chem. 14/2024)

Front Cover: Intermolecular Insertion Reactions into the P−P Bond of Oligophosphorus Compounds (Eur. J. Inorg. Chem. 14/2024)

Cyclic (Alkyl)(Amino)Carbene-Iminoboryl Compounds with Three Formal Oxidation States.

BN/CC isosterism is an effective strategy to build hybrid functional molecules with unique properties. In contrast to the alkynyl iminium salts derived from cyclic (alkyl)(amino)carbenes (CAACs) that feature only one reversible reduction wave, the isoelectronic cationic CAAC-iminoboryl adducts could be singly and doubly reduced smoothly. Both the resultant neutral radical and anionic azaborataallenes bear NBC-mixed allenic structures. The former radical has a high spin-density of 0.55e at CCAAC carbon, yet exhibits formal boron-centered radical reactivity. The latter azaborataallenes feature the nucleophilic CCAAC center and polar N(δ-)═B(δ+)═C(δ-) unit, and readily undergo nucleophilic substitution, isocyanide insertion, dipolar addition and cycloaddition reactions etc. The N-substituents have been shown to have a significant influence on the solid-state structure, thermal stability, and reactivity of azaborataallenes. This work showcases the allenic BN-unsaturated species as versatile building blocks in organic synthesis.

Heterogeneous Rhodium Single-Atom-Site Catalyst Enables Chemoselective Carbene N-H Bond Insertion.

Transition-metal-catalyzed carbene insertion reactions of a nitrogen-hydrogen bond have emerged as robust and versatile methods for the construction of C-N bonds. While significant progress of homogeneous catalytic metal carbene N-H insertions has been achieved, the control of chemoselectivity in the field remains challenging due to the high electrophilicity of the metal carbene intermediates. Herein, we present an efficient strategy for the synthesis of a rhodium single-atom-site catalyst (Rh-SA) that incorporates a Rh atom surrounded by three nitrogen atoms and one phosphorus atom doped in a carbon support. This Rh-SA catalyst, with a catalyst loading of only 0.15 mol %, exhibited exceptional catalytic performance for heterogeneous carbene insertion with various anilines and heteroaryl amines in combination with diazo esters. Importantly, the heterogeneous catalyst selectively transformed aniline derivatives bearing multiple nucleophilic moieties into single N-H insertion isomers, while the popular homogeneous Rh2(OAc)4 catalyst produced a mixture of overfunctionalized side products. Additionally, similar selectivities for N-H bond insertion with a set of stereoelectronically diverse diazo esters were obtained, highlighting the general applicability of this heterogeneous catalysis approach. On the basis of density functional theory calculations, the observed selectivity of the Rh-SA catalyst was attributed to the insertion barriers and the accelerated proton transfer assisted by the phosphorus atom in the support. Overall, this investigation of heterogeneous metal-catalyzed carbene insertion underscores the potential of single-atom-site catalysis as a powerful and complementary tool in organic synthesis.

Designing MnO2@amorphous carbon core-shell structure as a cathode to enhance rate performance and cycling stability of aqueous zinc-ion batteries

Manganese dioxide has received significant attention as a prospective cathode material in aqueous zinc-ion batteries (ZIBs) owing to its elevated working voltage and commendable energy density. Nevertheless, challenges such as structural instability, manganese dissolution, and poor electrical conductivity remain significant barriers to the practical application of research. Here, the MnO2 nanorods encapsulated in the amorphous carbon (MnO2@C) with core-shell structure are prepared by a special hard template method, and investigated as cathode materials for ZIBs. The amorphous carbon, characterized by its structural defects and disorder, manifests heightened active site density, thereby establishing an efficient conduit for charge transport. Concurrently, the nano-dimensional interstitial spaces augment the active sites available for zinc insertion reactions, thereby effectively curtailing the ion diffusion path and, consequently, engendering heightened electrochemical performance. Moreover, the distinctive core-shell architecture of MnO2@C not only furnishes substantial spatial accommodation but also serves to alleviate volume alterations throughout charge and discharge events. Consequently, MnO2@C demonstrates outstanding electrochemical performance, with reversible capacities of 210 mAh·g−1 and 50 mAh·g−1 at 0.1 A·g−1 and 1.6 A·g−1, respectively. Furthermore, even after 600 cycles at 0.8 A·g−1, it maintains exceptional cycling performance, reaching 102 mAh·g−1, endowing MnO2@C cathodes with robust competitiveness in aqueous ZIBs.

Mechanism and Origins of Enantioselectivity in the Nickel-catalyzed Asymmetric Synthesis of Silicon-Stereogenic Benzosiloles.

As important π-skeletons, benzosiloles often possess unique electronic and optical properties and have been widely used in semiconductor materials. Therefore, great attention has been drawn to the area of developing novel synthetic methods for various benzosiloles. However, the synthesis of enantioenriched silicon-stereogenic benzosiloles is still at an early stage and remains to be explored. Herein, we performed systematic density functional theory studies on the recently reported nickel-catalyzed asymmetric synthesis of silicon-stereogenic benosiloles, which was enabled by an enantioselective desymmetrization of (2-alkenyl)aryl-substituted silacyclobutanes. Our computational study shows that the reaction mechanism involves ligand exchange, oxidative addition, alkene insertion, and hydrogen-transfer coupled reductive-demetalation steps. The proposed transmetalation and β-hydride elimination mechanism was not found, which might be due to the unfavorable ring strain of the multicyclic intermediates. The novel hydrogen-transfer coupled reductive-demetalation mechanism was shown to be reasonable for the generation of the silicon-stereogenic benzosilole. Noncovalent interactions (including C-H···π and hydrogen bonding) in the rate-determining alkene insertion transition state account for the origins of the enantioselectivity. Our computational study sheds light on the detailed reaction mechanism and also provides insights for the development of novel approaches for synthesis of high-value silicon-stereogenic compounds.

Rotational Spectrum and First Interstellar Detection of 2-methoxyethanol Using ALMA Observations of NGC 6334I

We use both chirped-pulse Fourier transform and frequency-modulated absorption spectroscopy to study the rotational spectrum of 2-methoxyethanol (CH3OCH2CH2OH) in several frequency regions ranging from 8.7 to 500 GHz. The resulting rotational parameters permitted a search for this molecule in Atacama Large Millimeter/submillimeter Array (ALMA) observations toward the massive protocluster NGC 6334I, as well as source B of the low-mass protostellar system IRAS 16293−2422. A total of 25 rotational transitions are observed in the ALMA Band 4 data toward NGC 6334I, resulting in the first interstellar detection of 2-methoxyethanol. A column density of 1.3−0.9+1.4×1017 cm−2 is derived at an excitation temperature of 143−39+31 K. However, molecular signal is not observed in the Band 7 data toward IRAS 16293−2422B, and an upper-limit column density of 2.5 × 1015 cm−2 is determined. Various possible formation pathways—including radical recombination and insertion reactions—are discussed. We also investigate physical differences between the two interstellar sources that could result in the observed abundance variations.

A comparison of anesthesia induction by two different administration routes and doses of ketamine and medetomidine in red-eared sliders (Trachemys scripta elegans)

This study aimed to assess the efficiency of ketamine and medetomidine by two different doses and routes on anesthesia depth and cardiac stability in red-eared sliders. Each turtle was anesthetized two times, with seven days wash-out period. Induction of anesthesia consisted of a bolus combination of ketamine (10 mg/kg) and medetomidine (0.2 mg/kg) administered in the left brachial biceps in the intramuscular protocol, or a bolus combination of ketamine (20 mg/kg) and medetomidine (0.2 mg/kg) administered in subcarapacial sinus after clear blood presence confirmation in the intravenous protocol. Vital signs, reaction on the skin palpation, manual mouth opening for endotracheal intubation, palpebral and cloacal reflex, and the withdrawal reflex of the front and hind limbs were measured and recorded every 5 minutes for 60 minutes after anesthesia injection. Atipamezole (1 mg/kg) was administered in the right brachial biceps one hour after ketamine and medetomidine administration. Needle insertion and possible painful reactions to drug administration were also evaluated and recorded. Obtained data were analyzed for normality and paired t-tests, Wilcoxon, or McNamar tests were performed where appropriate. The values of P≤0.05 were considered significant. A significantly less pronounced decrease in heart rate was observed with intravenous anesthesia protocol. Both protocols recorded complete anesthesia recovery 60 minutes after intramuscular atipamezole administration. A ketamine-medetomidine dose combination administered intravenously provides a more stable and consistent anesthetic plane in red-eared sliders than ketamine-medetomidine administered intramuscularly.

Systematic Studies of Functional Group Tolerance and Chemoselectivity in Carbene-Mediated Intramolecular Cyclopropanation and Intermolecular C-H Functionalization.

Generating reliable data on functional group compatibility and chemoselectivity is essential for evaluating the practicality of chemical reactions and predicting retrosynthetic routes. In this context, we performed systematic studies using a functional group evaluation kit including 26 kinds of additives to assess the functional group tolerance of carbene-mediated reactions. Our findings revealed that some intermolecular heteroatom-hydrogen insertion reactions proceed faster than intramolecular cyclopropanation reactions. Lewis basic functionalities inhibited rhodium-catalyzed C-H functionalization of indoles. While performing these studies, we observed an unexpected C-H functionalization of a 1-naphthol variant used as an additive.

A Comparison of β–Phenyl Elimination in Nickel and Palladium Alkyl Complexes: A Potentially Relevant Process in the Mizoroki–Heck Reaction

There is currently much interest in avoiding precious metals in catalysis. The development of nickel catalysts to replace palladium in the Mizoroki–Heck reaction is a relevant case in this line of research, since both elements share many chemical features. This contribution focuses on β–phenyl (β–Ph) elimination in alkyl—nickel complexes. This is the microscopic reverse of olefin insertion (or carbometallation), a fundamental step in the Heck cycle that is usually considered irreversible and selectivity-determining. However, the potential reversibility of carbometallation is generally concealed by the facile β–hydrogen (β–H) elimination that follows. Where β–hydrogen elimination is hindered, β–aryl elimination may ensue. We have previously shown that cationic 2–methyl–2–phenylpropyl (neophyl) palladium complexes supported by bidentate ligands experience β–Ph elimination, which can be seen as an example of olefin de-insertion. In this contribution, we report that β–Ph elimination can also occur in their nickel analogs, in which case fast hydrolyses of the resulting phenyl product can follow the reaction. We investigated the mechanism of these processes and compared their feasibility for nickel and palladium catalysts using DFT calculations. These results are relevant information for the design of nickel-based catalysts for the Heck reaction.

Light-Driven Three-Component Carbonylation of Aryl Halides Using Abundant Metal Carbonyl.

Carbonyl compounds are widely found in various pharmaceutical intermediates and synthetic precursors. Herein we report a simple light-driven three-component aryl halide process for synthesizing a variety of carbonylation products, utilizing Co2(CO)8 as an abundant solid carbonyl source, in good to excellent yields. The products can easily be subjected to further functionalization in synthesis. Mechanism studies indicated that this reaction is enabled by aryl radical generation and the subsequent CO insertion, alkene insertion, and protonation process.

Enantioselective functionalization of unactivated C(sp3)–H bonds through copper-catalyzed diyne cyclization by kinetic resolution

Site- and stereoselective C–H functionalization is highly challenging in the synthetic chemistry community. Although the chemistry of vinyl cations has been vigorously studied in C(sp3)–H functionalization reactions, the catalytic enantioselective C(sp3)–H functionalization based on vinyl cations, especially for an unactivated C(sp3)–H bond, has scarcely explored. Here, we report an asymmetric copper-catalyzed tandem diyne cyclization/unactivated C(sp3)–H insertion reaction via a kinetic resolution, affording both chiral polycyclic pyrroles and diynes with generally excellent enantioselectivities and excellent selectivity factors (up to 750). Importantly, this reaction demonstrates a metal-catalyzed enantioselective unactivated C(sp3)–H functionalization via vinyl cation and constitutes a kinetic resolution reaction based on diyne cyclization. Theoretical calculations further support the mechanism of vinyl cation-involved C(sp3)–H insertion reaction and elucidate the origin of enantioselectivity.

Computational Exploration of 1,2-Carboamine Carbonylation Catalyzed by Nickel.

Nickel-catalyzed carbonylation of alkenes is a stereoselective and regioselective method for the synthesis of amide compounds. Theoretical predictions with density functional theory calculations revealed the mechanism and origin of stereoselectivity and regioselectivity for the nickel-catalyzed carbonylation of norbornene. The carbonylation reaction proceeds through oxidative addition, migration insertion of alkenes, and subsequent reduction elimination to afford cis-carbonylation product. The C-N bond activation of amides is unfavorable because the oxidative addition ability of the C-C bond is stronger than that of the C-N bond. The determining step of stereoselectivity is the migratory insertion of the strained olefin. The structural analysis shows that steroselectivity is controlled by the steric hindrance of methyl groups to olefins and substituents to IMes in ligands.

Intermolecular Insertion Reactions into the P−P Bond of Oligophosphorus Compounds

AbstractThe insertion of unsaturated organic molecules into a P−P bond of oligophosphorus compounds has the potential to expand the organophosphorus and organometallic chemistry and to make it more variable with the selective formation of desirable products. This article reviews the insertion reaction for oligophosphorus compounds and focuses in particular on non‐metals, unsaturated organic substrates, carbenes and carbene analogues as starting reagents.

Theoretical prediction on the insertion reactions of stannylenoid H2SnLiF with CH3X and SiH3X (X = F, Cl, Br)

Density functional theory was used to study the insertion reaction of stannylenoid H2SnLiF with CH3X, SiH3X (X = F, Cl, Br). Comparing the reaction barrier of H2SnLiF with CH3X, SiH3X, it can be found that the order of the difficulty of insertion reaction is F > Cl > Br. The insertion reaction potential barrier of SiH3X is lower than that of CH3X, which means that SiH3X is easier to react. According to the calculation results, the reaction law in THF solvent is consistent with that in vacuum, while in THF solvent, the barrier is lower and therefore more prone to reactions. This work provides theoretical support for the reaction properties of stannylenoids.