Phosphination of aryl/alkyl bromides Mn-mediated reductive C-P coupling.

Mn-mediated reductive cross-coupling of organic bromides with 2-bromo-1,3,2-diazaphospholene was developed for efficient construction of C-P bonds under mild conditions. Mechanistic studies suggested that bromides are activated by formed bis-diazaphospholene hybrid radical and polar mechanisms.

Metal-Carbon Bond Heterolysis Energy Scale for Model Palladium Catalysts.

Thermodynamic studies of transition-metal intermediates are crucial for understanding of metal-catalyzed transformations. Herein, a series of arylpalladium cyanomethanides were synthesized and characterized. Their palladium-carbon bond heterolysis energies (Δ(Pd-C)) were determined in DMSO for the first time by equilibrium methods.

Organocatalytic Hydrogen Evolution Reaction by Diazaphospholenes.

The electrochemical hydrogen evolution reaction (HER) is currently recognized as a prospective way to obtain clean energy. The electrocatalysts used currently are dominantly based on transition metals. In this work, we have demonstrated a diazaphospholene (-heterocyclic phosphine (NHP))-type small molecular organocatalyst that can catalyze the HER with a maximum current density of 130 mA·cm, an overpotential of 354 mV, and a faradaic efficiency of 90%.

Hydroxylamine-Mediated C(sp)-H Trifluoromethylation of Terminal Alkenes.

Introduction of the trifluoromethyl (CF) group into organic compounds has garnered substantial interest because of its significant role in pharmaceuticals and agrochemicals. Here, we report a hydroxylamine-mediated radical process for C(sp)-H trifluoromethylation of terminal alkenes. The reaction shows good reactivity, impressive E/Z selectivity (up to >20 : 1), and broad functional group compatibility.

Phosphonium-Catalyzed Monoreduction of Bisphosphine Dioxides: Origin of Selectivity and Synthetic Applications.

Controlling product selectivity in successive reactions of the same type is challenging owing to the comparable thermodynamic and kinetic properties of the reactions involved. Here, the synergistic interaction of the two phosphoryl groups in bisphosphine dioxides (BPDOs) with a bromo-phosphonium cation was studied experimentally to provide a practical tool for substrate-catalyst recognition. As the eventual result, we have developed a phosphonium-catalyzed monoreduction of chiral BPDOs to access an array of synthetically useful bisphosphine monoxides (BPMOs) with axial, spiro, and planar chirality, which are otherwise challenging to synthesize before.

Deoxygenation of Phosphine Oxides by P/P═O Redox Catalysis via Successive Isodesmic Reactions.

Deoxygenation of phosphine oxides is of great significance to synthesis of phosphorus ligands and relevant catalysts, as well as to the sustainability of phosphorus chemistry. However, the thermodynamic inertness of P═O bonds poses a severe challenge to their reduction. Previous approaches in this regard rely primarily on a type of P═O bond activation with either Lewis/Brønsted acids or stoichiometric halogenating reagents under harsh conditions.

Revisiting the Electrochemistry of TEMPOH Analogues in Acetonitrile.

Hydroxylamines, represented by 1-hydroxy-2,2,6,6-tetramethylpiperidine (TEMPOH), are widely involved as active species in various chemical and electrochemical oxidations. The electrochemical behavior of TEMPOH is crucial to understanding the mechanisms of TEMPO-mediated redox sequences. However, compared to abundant studies on TEMPOH electrochemistry in aqueous solutions, the sole value of its oxidation potential (TEMPOH) in organic solutions was reported to be 0.

Catalytic Vilsmeier-Haack Reactions for C1-Deuterated Formylation of Indoles.

The Vilsmeier-Haack reaction is a powerful tool to introduce formyl groups into electron-rich arenes, but its wide application is significantly restricted by stoichiometric employment of caustic POCl. Herein, we reported a catalytic version of the Vilsmeier-Haack reaction enabled by a P(III)/P(V)═O cycle. This catalytic reaction provides a facile and efficient route for the direct construction of C1-deuterated indol-3-carboxaldehyde under mild conditions with stoichiometric DMF-d7 as the deuterium source.

Synthetic applications of NHPs: from the hydride pathway to a radical mechanism.

The unique heterocyclic skeletons of N-heterocyclic phosphines (NHPs) endow them with excellent hydridic reactivity, which has enabled NHPs to be applied in a great array of catalytic hydrogenations of unsaturated substrates in the past few decades. Recently, applications of NHPs in radical reductions, especially in a catalytic fashion, have emerged as a promising forefront area. This new reaction pattern, distinctive from but complementary to the well-established hydride pathway, can greatly expand the reaction scope to σ-bond scission.

LncRNA TUG1 Promoted Stabilization of BAG5 by Binding DDX3X to Exacerbate Ketamine-Induced Neurotoxicity.

As a clinically widely used anesthetic, ketamine (KET) has been reported to cause neurotoxicity in patients. Our work aimed to probe the function of long-chain non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) in KET-induced neurotoxicity. HT22 cells were subjected to KET to build the cell model.

Diazaphospholene-Catalyzed Hydrodefluorination of Polyfluoroarenes with Phenylsilane via Concerted Nucleophilic Aromatic Substitution.

The metal-free catalytic C-F bond activation of polyfluoroarenes was achieved with diazaphospholene as the catalyst and phenylsilane as the terminal reductant. Density functional theory calculations suggested a concerted nucleophilic aromatic substitution mechanism.

Recent progress in reactivity study and synthetic application of N-heterocyclic phosphorus hydrides.

N-heterocyclic phosphines (NHPs) have recently emerged as a new group of promising catalysts for metal-free reductions, owing to their unique hydridic reactivity. The excellent hydricity of NHPs, which rivals or even exceeds those of many metal-based hydrides, is the result of hyperconjugative interactions between the lone-pair electrons on N atoms and the adjacent σ(P-H) orbital. Compared with the conventional protic reactivity of phosphines, this umpolung P-H reactivity leads to hydridic selectivity in NHP-mediated reductions.

Diazaphosphinyl radical-catalyzed deoxygenation of α-carboxy ketones: a new protocol for chemo-selective C-O bond scission mechanism regulation.

C-O bond cleavage is often a key process in defunctionalization of organic compounds as well as in degradation of natural polymers. However, it seldom occurs regioselectively for different types of C-O bonds under metal-free mild conditions. Here we report a facile chemo-selective cleavage of the α-C-O bonds in α-carboxy ketones by commercially available pinacolborane under the catalysis of diazaphosphinane based on a mechanism switch strategy.

Chemoselective catalytic hydrodefluorination of trifluoromethylalkenes towards mono-/gem-di-fluoroalkenes under metal-free conditions.

Fluorine-containing moieties show significant effects in improving the properties of functional molecules. Consequently, efficient methods for installing them into target compounds are in great demand, especially those enabled by metal-free catalysis. Here we show a diazaphospholene-catalyzed hydrodefluorination of trifluoromethylalkenes to chemoselectively construct gem-difluoroalkenes and terminal monofluoroalkenes by simple adjustment of the reactant stoichiometry.

Bonding Energetics of Palladium Amido/Aryloxide Complexes in DMSO: Implications for Palladium-Mediated Aniline Activation.

Thermodynamic knowledge of the metal-ligand (M-L) σ-bond strength is crucial to understanding metal-mediated transformations. Here, we developed a method for determining the Pd-X (X=OR and NHAr) bond heterolysis energies (ΔG (Pd-X)) in DMSO taking [(tmeda)PdArX] (tmeda=N,N,N',N'-tetramethylethylenediamine) as the model complexes. The ΔG (Pd-X) scales span a range of 2.

Holistic Prediction of the pK in Diverse Solvents Based on a Machine-Learning Approach.

While many approaches to predict aqueous pK values exist, the fast and accurate prediction of non-aqueous pK values is still challenging. Based on the iBonD experimental pK database (39 solvents), a holistic pK prediction model was established using machine learning. Structural and physical-organic-parameter-based descriptors (SPOC) were introduced to represent the electronic and structural features of the molecules.

Exploiting the radical reactivity of diazaphosphinanes in hydrodehalogenations and cascade cyclizations.

The remarkable reducibility of diazaphosphinanes has been extensively applied in various hydrogenations, based on and yet limited by their well-known hydridic reactivity. Here we exploited their unprecedented radical reactivity to implement hydrodehalogenations and cascade cyclizations originally inaccessible by hydride transfer. These reactions feature a broad substrate scope, high efficiency and simplicity of manipulation.

Predicting Absolute Rate Constants for Huisgen Reactions of Unsaturated Iminium Ions with Diazoalkanes.

The kinetics and stereochemistry of the reactions of iminium ions derived from cinnamaldehydes and MacMillan's imidazolidinones with diphenyldiazomethane and aryldiazomethanes were investigated experimentally and with DFT calculations. The reactions of diphenyldiazomethane with iminium ions derived from MacMillan's second-generation catalysts gave 3-aryl-2,2-diphenylcyclopropanecarbaldehydes with yields >90 % and enantiomeric ratios of ≥90:10. Predominantly 2:1 products were obtained from the corresponding reactions with monoaryldiazomethanes.

Diazaphosphinanes as hydride, hydrogen atom, proton or electron donors under transition-metal-free conditions: thermodynamics, kinetics, and synthetic applications.

Exploration of new hydrogen donors is in large demand in hydrogenation chemistry. Herein, we developed a new 1,3,2-diazaphosphinane , which can serve as a hydride, hydrogen atom or proton donor without transition-metal mediation. The thermodynamics and kinetics of these three pathways of , together with those of its analog , were investigated in acetonitrile.

Counterintuitive solvation effect of ionic-liquid/DMSO solvents on acidic C-H dissociation and insight into respective solvation.

How would acidic bond dissociation be affected by adding a small quantity of a weakly polar ionic liquid IL (the "apparent" or "measured" dielectric constant of the IL is around 10-15) into a strongly polar molecular solvent (, of DMSO: 46.5), or ? The answer is blurred, because no previous investigation was reported in this regard. Toward this, we, taking various IL/DMSO mixtures as representatives, have thoroughly investigated the effects of the respective solvent in ionic-molecular binary systems on self-dissociation of C-H acid phenylmalononitrile PhCH(CN) p determination.

Toward Rational Understandings of α-C-H Functionalization: Energetic Studies of Representative Tertiary Amines.

Functionalization of α-C-H bonds of tertiary amines to build various α-C-X bonds has become a mainstream in synthetic chemistry nowadays. However, due to lack of fundamental knowledge on α-C-H bond strength as an energetic guideline, rational exploration of new synthetic methodologies remains a far-reaching anticipation. Herein, we report a unique hydricity-based approach to establish the first integrated energetic scale covering both the homolytic and heterolytic energies of α-C-H bonds for 45 representative tertiary amines and their radical cations.

Understanding the role of thermodynamics in catalytic imine reductions.

The past decade has witnessed a booming growth of research activity in catalytic imine reduction, due to the ongoing motivation to find more efficient conversions of the rather unreactive C[double bond, length as m-dash]N bonds to the desired C-N segments found in many pharmaceuticals. While several timely reviews have well documented various C[double bond, length as m-dash]N reduction methodologies with respect to the type of catalyst (acid, base, or transition metal), a detailed discussion of the core role of thermodynamic driving forces in governing these catalyses is still lacking, however. Hence, this tutorial review describes some of the most practical considerations for adjusting reduction thermodynamics by choosing appropriate catalytic strategies, in order to make the target reduction energetically feasible.

A Nucleophilicity Scale for the Reactivity of Diazaphospholenium Hydrides: Structural Insights and Synthetic Applications.

Nucleophilicity parameters (N, s ) of a group of representative diazaphospholenium hydrides were derived by kinetic investigations of their hydride transfer to a series of reference electrophiles with known electrophilicity (E) values, using the Mayr equation log k =s (N+E). The N scale covers over ten N units, ranging from the most reactive hydride donor (N=25.5) to the least of the scale (N=13.

Exploration of the Synthetic Potential of Electrophilic Trifluoromethylthiolating and Difluoromethylthiolating Reagents.

The electrophilicity parameters (E) of some trifluoromethylthiolating and difluoromethylthiolating reagents were determined by following the kinetics of their reactions with a series of enamines and carbanions with known nucleophilicity parameters (N, s ), using the linear free-energy relationship log k =s (N+E). The electrophilic reactivities of these reagents cover a range of 17 orders of magnitude, with Shen and Lu's reagent 1 a being the most reactive and Billard's reagent 1 h being the least reactive electrophile. While the observed electrophilic reactivities (E) of the amido-derived trifluoromethylthiolating reagents correlate well with the calculated Gibbs energies for heterolytic cleavage of the X-SCF bonds (Tt DA), the cumol-derived reagents 1 f and 1 g are more reactive than expected from the thermodynamics of the O-S cleavage.

Recent Advances and Advisable Applications of Bond Energetics in Organic Chemistry.

Most organic transformation involves cleavage and formation of various covalent bonds, and naturally, can be regarded as a process of bond reorganization, which should be intrinsically related to bond energies (e.g., p K, BDE, etc.