Insights into the Activation Mode of α-Carbonyl Sulfoxonium Ylides in Rhodium-Catalyzed C−H Activation: A Theoretical Study

A computational study has been performed to investigate the mechanism of Rh^III-catalyzed C−H bond activation using sulfoxonium ylides as a carbene precursor. The stepwise and concerted activation modes for sulfoxonium ylides were investigated. Detailed theoretical results showed that the favored stepwise pathway involves C−H bond activation, carbonization, carbene insertion, and protonation. The free energy profiles for dialkylation of 2-phenylpyridine were also calculated to account for the low yield of this reaction. Furthermore, the substituent effect was elucidated by comparing the energy barriers for the protonation of meta- and para-substituted sulfoxonium ylides calculated by density functional theory.     

Organocatalytic asymmetric synthesis of α-amino esters from sulfoxonium ylides

Described here is the first organocatalytic asymmetric N–H insertion reaction of α-carbonyl sulfoxonium ylides. Without a metal catalyst, this reaction represents an attractive complement to the well-established carbene insertion reactions. As a stable surrogate of diazocarbonyl compounds, sulfoxonium ylides reacted with a range of aryl amines to provide efficient access to α-aryl glycines with excellent enantiocontrol in the presence of a suitable chiral phosphoric acid catalyst. The high stability and weak basicity of sulfoxonium ylides not only enable this protocol to be user-friendly and practically useful, but also preclude catalyst decomposition, which is crucial to the excellent amenability to electron-poor amine nucleophiles. Detailed mechanistic studies indicated that the initial protonation is reversible and the C–N bond formation is rate-determining.

An organocatalytic asymmetric N–H insertion reaction of α-carbonyl sulfoxonium ylides has been developed to provide efficient access to α-amino esters without involving a metal carbenoid intermediate.     

Cd2+ and Zn2+ Complexes with 2,4,6‐Tri(2‐pyridyl)‐s‐Triazine and Terephthalate for Rapid,High‐Capacity Adsorption of Congo Red

Three crystal complexes were designed and synthesised through the solvothermal method, with Cu²⁺, Zn²⁺, and Cd²⁺ ions as the metal centres and 2,4,6‐tri(2‐pyridyl)‐s‐triazine (TPTZ) and terephthalate (BDC²⁻) as the ligands. Their compositions were determined to be Cd(TPTZ)Cl₂ (Cd‐MOF), {[Zn(TPTZ)(BDC)] ⋅ 3H₂O}_n (Zn‐MOF), and Cu₂(PCA)₂(BDC)(H₂O)₂ (Cu‐MOF) (PCA⁻=2‐pyridinium amide), respectively. Cd‐MOF can adsorb 90 % of Congo red (CR) in 10 s at room temperature and atmospheric pressure, and CR removal was complete at 20 s over a wide pH range. The adsorption capacity for CR reached 1440 mg g⁻¹ in 5 min. Selective adsorption was demonstrated in mixed dyes. The adsorption kinetic data agree well with the pseudo‐second‐order kinetic model. The Temkin model was successfully used to evaluate the adsorption isotherms of CR on Cd‐MOF at room temperature, suggesting that adsorption occurs through a hybrid of monolayer and multilayer mechanisms.     

Rh(III)-catalyzed [4 + 1]-annulation of azobenzenes with α- carbonyl sulfoxonium ylides toward 3-acyl-(2H)-indazoles

A Rh(III)-catalyzed [4?+?1]-annulation of azobenzenes with α- carbonyl sulfoxonium ylides was developed to access 2H-indazoles in moderate to excellent yields with good functional group compatibilities. It proceeded with the sequential insertion of the Rh(III) carbene to the C?H bond and cyclization steps, where sulfoxonium ylides served as efficient and stable carbene precursor.     

Characterization of Diastereomeric Equilibria of Pseudotetrahedral Bis[(R or S)‐N‐1‐(Ar)Ethylsalicylaldiminato‐κ2N,O]zinc(II) with Λ/Δ‐Chirality‐At‐Metal Induction

A family of bis[(R or S)‐N‐1‐(Ar)ethylsalicylaldiminato‐κ²N,O]‐Δ/Λ‐zinc(II) {Ar=C₆H₅ (ZnRL¹ or ZnSL¹), p‐CH₃OC₆H₄ (ZnRL² or ZnSL²) and p‐ClC₆H₄ (ZnRL³ or ZnSL³)} compounds was synthesized and investigated by multiple methods. They feature Λ/Δ‐chirality‐at‐metal induction along the pseudo‐C ₂ axis of the molecules. The chirality induction is quantitative in the solid state, explored by X‐ray crystallography and powder X‐ray diffraction (PXRD), where R or S‐ligated complexes diastereoselectively yield Λ or Δ‐configuration at the metal. On the other hand, Λ and Δ‐diastereomers co‐exist in solution. The Λ⇆Δ equilibrium is solvent‐ and temperature‐dependent. Electronic circular dichroism (ECD) spectra confirm the existence of a diastereomeric excess of Λ‐ZnRL¹⁻³ or Δ‐ZnSL¹⁻³ in solution. DSC analysis reveals thermally induced irreversible phase transformation from a crystalline solid to an isotropic liquid phase. ECD spectra were reproduced by DFT geometry optimizations and time‐dependent DFT (TD‐DFT) calculations, providing ultimate proof of the dominant chirality atmetal in solution.     

An efficient method to prepare sulfoxonium ylides and their reactivity studies using copper powder and Sc(III) as catalysts: Molecular and electronic structure analysis

Sulfoxonium ylides are the viable alternatives for diazo compounds as carbene precursors. Unlike diazo compounds, these are bench-stable and crystalline solids. However, the existing methods for the synthesis of sulfoxonium ylides have disadvantages related to the yields, substrate scope, and usage of expensive catalysts. Therefore, it is necessary to develop efficient and competitive protocols for the preparation of sulfoxonium ylides. In this study, we developed an economically affordable protocol for the synthesis of sulfoxonium ylides from diazo compounds using copper powder as a catalyst. This protocol leads to the efficient multigram-scale synthesis of a wide range of sulfoxonium ylides in good yields. Further, we demonstrated scandium triflate–catalyzed carbene insertion into the N−H bond from sulfoxonium ylide. A variety of anilines and sulfoxonium ylides with various functional groups reacted well and produced the corresponding α-amino esters in good yields. All the synthesized compounds were characterized using various standard spectroscopic and analytical techniques. We also used computational methods to understand the electronic structure of all the sulfoxonium ylides using geometry optimization, frequency calculation, molecular orbital and natural bond orbital analysis, and energy decomposition analysis. Our computational results revealed that the interaction between carbene and dimethyl sulfoxide is covalent in nature and stable enough to handle in the absence of any catalyst.     

C(sp3)–H cyanation by a formal copper(iii) cyanide complex

High-valent metal oxo complexes are prototypical intermediates for the activation and hydroxylation of alkyl C–H bonds. Substituting the oxo ligand with other functional groups offers the opportunity for additional C–H functionalization beyond C–O bond formation. However, few species aside from metal oxo complexes have been reported to both activate and functionalize alkyl C–H bonds. We herein report the first example of an isolated copper(iii) cyanide complex (LCu^IIICN) and its C–H cyanation reactivity. We found that the redox potential (E_ox) of substrates, instead of C–H bond dissociation energy, is a key determinant of the rate of PCET, suggesting an oxidative asynchronous CPET or ETPT mechanism. Among substrates with the same BDEs, those with low redox potentials transfer H atoms up to a million-fold faster. Capitalizing on this mechanistic insight, we found that LCu^IIICN is highly selective for cyanation of amines, which is predisposed to oxidative asynchronous or stepwise transfer of H⁺/e⁻. Our study demonstrates that the asynchronous effect of PCET is an appealing tool for controlling the selectivity of C–H functionalization.

A formal copper(iii) cyanide complex and its C–H cyanation reactivity are reported. The redox potentials of substrates, instead of C–H bond dissociation energies, were found to be the key determinant of the rates of PCET.     

Organocatalytic asymmetric azidation of sulfoxonium ylides: mild synthesis of enantioenriched α-azido ketones bearing a labile tertiary stereocenter

Disclosed here is a catalytic asymmetric azidation reaction for the efficient synthesis of α-azido ketones bearing a labile tertiary stereocenter. With a superb chiral squaramide catalyst, a mild asymmetric formal H–N₃ insertion of α-carbonyl sulfoxonium ylides proceeded with excellent efficiency and enantioselectivity. This organocatalytic process not only complements the previous α-azidation approaches for the formation of quaternary stereocenters and mostly for 1,3-dicarbonyl compounds, but also has advantages over the well-known metal-catalyzed asymmetric carbene insertion chemistry using α-diazocarbonyl compounds. Detailed mechanistic studies via control reactions and NMR studies provided important insights into the reaction pathway, which features reversible protonation and dynamic kinetic resolution. The curiosity in mechanism also led to the development of a simplified alternative protocol with a cheaper HN₃ source.

An organocatalytic asymmetric H–N₃ insertion of α-carbonyl sulfoxonium ylides has been developed, providing efficient access to α-azido ketones bearing labile tertiary stereocenters and complementing the metal carbene insertion chemistry.     

亚砜叶立德在C—H键活化反应中的应用研究进展

过渡金属催化的导向C—H键活化反应具有反应效率高、选择性好、原子经济等优点,特别是卡宾前体参与的C—H活化反应已经发展为一种新颖的构筑碳碳键的合成策略.相比于传统的重氮化合物等卡宾前体,亚砜叶立德作为一种新型的卡宾前体,具有易于制备、性质稳定、操作安全等诸多优点,被广泛应用于C—H活化反应,可以便捷地转化成各种酰甲基化...     

Cross‐Coupling of α‐Carbonyl Sulfoxonium Ylides with C−H Bonds

The functionalization of carbon–hydrogen bonds in non‐nucleophilic substrates using α‐carbonyl sulfoxonium ylides has not been so far investigated, despite the potential safety advantages that such reagents would provide over either diazo compounds or their in situ precursors. Described herein are the cross‐coupling reactions of sulfoxonium ylides with C(sp²)−H bonds of arenes and heteroarenes in the presence of a rhodium catalyst. The reaction proceeds by a succession of C−H activation, migratory insertion of the ylide into the carbon–metal bond, and protodemetalation, the last step being turnover‐limiting. The method is applied to the synthesis of benz[c]acridines when allied to an iridium‐catalyzed dehydrative cyclization.     

Catalyst control of selectivity in the C–O bond alumination of biomass derived furans

Non-catalysed and catalysed reactions of aluminium reagents with furans, dihydrofurans and dihydropyrans were investigated and lead to ring-expanded products due to the insertion of the aluminium reagent into a C–O bond of the heterocycle. Specifically, the reaction of [{(ArNCMe)₂CH}Al] (Ar = 2,6-di-iso-propylphenyl, 1) with furans proceeded between 25 and 80 °C leading to dearomatised products due to the net transformation of a sp² C–O bond into a sp² C–Al bond. The kinetics of the reaction of 1 with furan were found to be 1st order with respect to 1 with activation parameters ΔH^‡ = +19.7 (±2.7) kcal mol⁻¹, ΔS^‡ = −18.8 (±7.8) cal K⁻¹ mol⁻¹ and ΔG^‡_{298 K} = +25.3 (±0.5) kcal mol⁻¹ and a KIE of 1.0 ± 0.1. DFT calculations support a stepwise mechanism involving an initial (4 + 1) cycloaddition of 1 with furan to form a bicyclic intermediate that rearranges by an α-migration. The selectivity of ring-expansion is influenced by factors that weaken the sp² C–O bond through population of the σ*-orbital. Inclusion of [Pd(PCy₃)₂] as a catalyst in these reactions results in expansion of the substrate scope to include 2,3-dihydrofurans and 3,4-dihydropyrans and improves selectivity. Under catalysed conditions, the C–O bond that breaks is that adjacent to the sp²C–H bond. The aluminium(iii) dihydride reagent [{(MesNCMe)₂CH}AlH₂] (Mes = 2,4,6-trimethylphenyl, 2) can also be used under catalytic conditions to effect a dehydrogenative ring-expansion of furans. Further mechanistic analysis shows that C–O bond functionalisation occurs via an initial C–H bond alumination. Kinetic products can be isolated that are derived from installation of the aluminium reagent at the 2-position of the heterocycle. C–H alumination occurs with a KIE of 4.8 ± 0.3 consistent with a turnover limiting step involving oxidative addition of the C–H bond to the palladium catalyst. Isomerisation of the kinetic C–H aluminated product to the thermodynamic C–O ring expansion product is an intramolecular process that is again catalysed by [Pd(PCy₃)₂]. DFT calculations suggest that the key C–O bond breaking step involves attack of an aluminium based metalloligand on the 2-palladated heterocycle. The new methodology has been applied to important platform chemicals from biomass.

Non-catalysed and catalysed reactions of aluminium reagents with furans, dihydrofurans and dihydropyrans were investigated and lead to ring-expanded products due to the insertion of the aluminium reagent into a C–O bond of the heterocycle.     

Ruthenium Catalyzed C−H Acylmethylation of N‐Arylphthalazine‐1,4‐diones with α‐Carbonyl Sulfoxonium Ylides: Highway to Diversely Functionalized Phthalazino‐fused Cinnolines

A direct ortho‐Csp²‐H acylmethylation of 2‐aryl‐2,3‐dihydrophthalazine‐1,4‐diones with α‐carbonyl sulfoxonium ylides is achieved through a Ru^II‐catalyzed C?H bond activation process. The protocol featured high functional group tolerance on the two substrates, including aryl‐, heteroaryl‐, and alkyl‐substituted α‐carbonyl sulfoxonium ylides. Thereafter, 2‐(ortho‐acylmethylaryl)‐2,3‐dihydrophthalazine‐1,4‐diones were used as potential starting materials for the expeditious synthesis of 6‐arylphthalazino[2,3‐a]cinnoline‐8,13‐diones and 5‐acyl‐5,6‐dihydrophthalazino[2,3‐a]cinnoline‐8,13‐diones under Lawesson's reagent and BF₃?OEt₂ mediated conditions, respectively. Of these, the BF₃?OEt₂‐mediated cyclization proceeded in DMSO as a solvent and a methylene source via dual C?C and C?N bond formations.     

Formation of a C–C double bond from two aliphatic carbons. Multiple C–H activations in an iridium pincer complex

The search for novel, atom-economic methods for the formation of C–C bonds is of crucial importance in synthetic chemistry. Especially attractive are reactions where C–C bonds are formed through C–H activation, but the coupling of unactivated, alkane-type C_sp³–H bonds remains an unsolved challenge. Here, we report iridium-mediated intramolecular coupling reactions involving up to four unactivated C_sp³–H bonds to give carbon–carbon double bonds under the extrusion of dihydrogen. The reaction described herein is completely reversible and the direction can be controlled by altering the reaction conditions. With a hydrogen acceptor present a C–C double bond is formed, while reacting under dihydrogen pressure leads to the reverse process, with some of the steps representing net C_sp³–C_sp³ bond cleavage. Mechanistic investigations revealed a conceptually-novel overall reactivity pattern where insertion or deinsertion of an Ir carbene moiety, formed via double C–H activation, into an Ir–C bond is responsible for the key C–C bond formation and cleavage steps.     

Activation of perfluoroalkyl iodides by anions: extending the scope of halogen bond activation to C(sp3)–H amidation,C(sp2)–H iodination,and perfluoroalkylation reactions

A simple, efficient, and convenient activation of perfluoroalkyl iodides by tBuONa or KOH, without expensive photo- or transition metal catalysts, allows the promotion of versatile α-sp³ C–H amidation reactions of alkyl ethers and benzylic hydrocarbons, C–H iodination of heteroaryl compounds, and perfluoroalkylations of electron-rich π bonds. Mechanistic studies show that these novel protocols are based on the halogen bond interaction between perfluoroalkyl iodides and tBuONa or KOH, which promote homolysis of perfluoroalkyl iodides under mild conditions.

A simple activation of perfluoroalkyl iodides by tBuONa or KOH allows the promotion of α-sp³ C–H amidation reactions of alkyl ethers and benzylic hydrocarbons, C–H iodination of heteroaryl compounds, and perfluoroalkylations of electron-rich π bonds.     

Ni(0)-promoted activation of Csp2–H and Csp2–O bonds

A dinickel(0)–N₂ complex, stabilized with a rigid acridane-based PNP pincer ligand, was studied for its ability to activate C(sp²)–H and C(sp²)–O bonds. Stabilized by a Ni–μ–N₂–Na⁺ interaction, it activates C–H bonds of unfunctionalized arenes, affording nickel–aryl and nickel–hydride products. Concomitantly, two sodium cations get reduced to Na(0), which was identified and quantified by several methods. Our experimental results, including product analysis and kinetic measurements, strongly suggest that this C(sp²)–H activation does not follow the typical oxidative addition mechanism occurring at a low-valent single metal centre. Instead, via a bimolecular pathway, two powerfully reducing nickel ions cooperatively activate an arene C–H bond and concomitantly reduce two Lewis acidic alkali metals under ambient conditions. As a novel synthetic protocol, nickel(ii)–aryl species were directly synthesized from nickel(ii) precursors in benzene or toluene with excess Na under ambient conditions. Furthermore, when the dinickel(0)–N₂ complex is accessed via reduction of the nickel(ii)–phenyl species, the resulting phenyl anion deprotonates a C–H bond of glyme or 15-crown-5 leading to C–O bond cleavage, which produces vinyl ether. The dinickel(0)–N₂ species then cleaves the C(sp²)–O bond of vinyl ether to produce a nickel(ii)–vinyl complex. These results may provide a new strategy for the activation of C–H and C–O bonds mediated by a low valent nickel ion supported by a structurally rigidified ligand scaffold.

A structurally rigidified nickel(0) complex was found to be capable of cleaving both C(sp²)–H and C(sp²)–O bonds.     

Switch From Pauli‐Lowering to LUMO‐Lowering Catalysis in Brønsted Acid‐Catalyzed Aza‐Diels‐Alder Reactions

Brønsted acid‐catalyzed inverse‐electron demand (IED) aza‐Diels‐Alder reactions between 2‐aza‐dienes and ethylene were studied using quantum chemical calculations. The computed activation energy systematically decreases as the basic sites of the diene progressively become protonated. Our activation strain and Kohn‐Sham molecular orbital analyses traced the origin of this enhanced reactivity to i) “Pauli‐lowering catalysis” for mono‐protonated 2‐aza‐dienes due to the induction of an asynchronous, but still concerted, reaction pathway that reduces the Pauli repulsion between the reactants; and ii) “LUMO‐lowering catalysis” for multi‐protonated 2‐aza‐dienes due to their highly stabilized LUMO(s) and more concerted synchronous reaction path that facilitates more efficient orbital overlaps in IED interactions. In all, we illustrate how the novel concept of “Pauli‐lowering catalysis” can be overruled by the traditional concept of “LUMO‐lowering catalysis” when the degree of LUMO stabilization is extreme as in the case of multi‐protonated 2‐aza‐dienes.     

Biomimetic catalytic aerobic oxidation of C–sp(3)–H bonds under mild conditions using galactose oxidase model compound CuIIL

Developing highly efficient catalytic protocols for C–sp(3)–H bond aerobic oxidation under mild conditions is a long-desired goal of chemists. Inspired by nature, a biomimetic approach for the aerobic oxidation of C–sp(3)–H by galactose oxidase model compound Cu^IIL and NHPI (N-hydroxyphthalimide) was developed. The Cu^IIL–NHPI system exhibited excellent performance in the oxidation of C–sp(3)–H bonds to ketones, especially for light alkanes. The biomimetic catalytic protocol had a broad substrate scope. Mechanistic studies revealed that the Cu^I-radical intermediate species generated from the intramolecular redox process of Cu^IILH₂ was critical for O₂ activation. Kinetic experiments showed that the activation of NHPI was the rate-determining step. Furthermore, activation of NHPI in the Cu^IIL–NHPI system was demonstrated by time-resolved EPR results. The persistent PINO (phthalimide-N-oxyl) radical mechanism for the aerobic oxidation of C–sp(3)–H bond was demonstrated.

A biomimetic catalytic approach for the aerobic oxidation of C–sp(3)–H bonds using galactose oxidase model compound was developed. EPR showed that the Cu^I-radical intermediate species was critical for O₂ activation.     

Evaluating Zn‐Porphyrin‐Based Near‐IR‐Sensitive Non‐Fullerene Acceptors for Efficient Panchromatic Organic Solar Cells

Porphyrin‐based non‐fullerene acceptors (NFAs) have shown pronounced potential for assembling low‐bandgap materials with near‐infrared (NIR) characteristics. Herein, panchromatic‐type porphyrin‐based molecules (POR1–POR5) are proposed by modulating end‐capped acceptors of a highly efficient porphyrin‐based NFA PORTFIC(POR) for organic solar cells (OSCs). Quantum chemical structure‐property relationship has been studied to discover photovoltaic and optoelectronic characteristics of POR1–POR5. Results show that optoelectronic properties of the POR1–POR5 are better in all aspects when compared with the reference POR. All proposed NFAs particularly POR5 proved to be the preferable porphyrin‐based NIR sensitive NFA for OSCs applications owing to lower energy gap (1.56 eV), transition energy (1.11 eV), binding energy (E_b =0.986 eV), electron mobility (λ_e=0.007013E_h ), hole mobility (λ_h =0.004686 E_h), high λ_max =1116.27 nm and open‐circuit voltage (V_oc =1.96 V) values in contrast to the reference POR and other proposed NFAs. This quantum chemical insight provides sufficient evidence about excellent potential of the proposed porphyrin‐based NIR sensitive NFA derivatives for their use in OSCs.     

The Activating Effect of Strong Acid for Pd-Catalyzed Directed C–H Activation by Concerted Metalation-Deprotonation Mechanism

A computational study on the origin of the activating effect for Pd-catalyzed directed C–H activation by the concerted metalation-deprotonation (CMD) mechanism is conducted. DFT calculations indicate that strong acids can make Pd catalysts coordinate with directing groups (DGs) of the substrates more strongly and lower the C–H activation energy barrier. For the CMD mechanism, the electrophilicity of the Pd center and the basicity of the corresponding acid ligand for deprotonating the C–H bond are vital to the overall C–H activation energy barrier. Furthermore, this rule might disclose the role of some additives for C–H activation.     

Enantioselective S−H Insertion Reactions of α‐Carbonyl Sulfoxonium Ylides

The first example of enantioselective S?H insertion reactions of sulfoxonium ylides is reported. Under the influence of thiourea catalysis, excellent levels of enantiocontrol (up to 95 % ee) and yields (up to 97 %) are achieved for 31 examples in S?H insertion reactions of aryl thiols and α‐carbonyl sulfoxonium ylides.