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Based on the relationship between average local ionization energy I ̄ (r) and average local electron affinity A ̄ (r) with the electronic Fukui functions, i.e., f−(r) and f+(r), respectively, in this paper, we establish a connection between nuclear and electronic Fukui functions beyond frontier molecular orbitals. As a consequence of this connection, we obtain expressions of average nuclear Fukui functions interpreted as a variation of average nucleophilicity or electrophilicity (weighted by the electronic orbital Fukui functions) with respect to nuclear displacements, which goes beyond the highest occupied molecular orbital/or lowest unoccupied molecular orbital consideration. Furthermore, from this connection and considering the frontier molecular orbital approximation, we derive expressions of nuclear Fukui functions in terms of the atom-condensed electronic Fukui functions, which imply a locality in the chemical reactivity and could be used to study the variation of local nucleophilicity or electrophilicity with respect to nuclear displacements. Finally, this new way to interpret the nuclear Fukui function could be useful in the future to study the chemical reactivity related to molecular vibrations, internal rotations, bond dissociation, chemical reaction along the model of reaction coordinate, and so on. [ABSTRACT FROM AUTHOR]

(E)-6-Methoxy-1-methyl-3-(2-(3-methyl-4-nitroisoxazol-5-yl)vinyl)quinolin-2(1H)-one dye (MQI) has been synthesized, and its structural and electronic properties have been characterized by employing UV-vis spectroscopy in combination with computational methods. The MQI dye has been assessed as an activated Michael acceptor-type probe toward bisulfite ions. This reaction was kinetically tested in different mild, cationic (cetyltrimethylammonium bromide, cetyltrimethylammonium chloride, and cetylpyridinium bromide), and zwitterionic (N-decyl-N,N-dimethyl-3-ammonio-1-propanesulfonate, N-tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate, and N-hexacyl-N,N-dimethyl-3-ammonio-1-propanesulfonate) micellar solutions at pH ∼ 5.5. Both micellar media remarkably allow the addition reactions, increasing the reactivity of MQI towards bisulfite ions, the biggest effects were found in the presence of cationic micelles. The binding constants of MQI with the micelles and the rate constants were determined from kinetic data, which were interpreted on the basis of the pseudophase kinetic model. The kinetic study and the product analysis allow us to highlight the relevant role of the association between MQI dye and the micellized surfactant, allowing efficient nucleophilic addition of bisulfite ions. The findings of this work will be valuable for the use of micellar solutions as an alternative medium to replace the use of toxic solvents to carry out organic reactions to perform nucleophilic addition reactions of bisulfite. [ABSTRACT FROM AUTHOR]

A unique direct asymmetric synthesis of α‐aminoimines is realized, through rapid and exclusive mono‐allylation of chiral bis‐N‐sulfinylimines using allylboronic acids. The highly selective allylation was possible as electrophilic imine functional group in the product α‐aminoimines remained unreactive towards allyl boronic acid nucleophiles. Notably, by varying the geometry and chiral auxiliary, all four isomers of the α‐aminoimines were accessed from readily available precursors. A range of allyl nucleophiles, which are tricky to generate by other means possessing highly reactive functional groups also took part in this reaction, expanding the scope further. The applicability of the products α‐aminoimines were further demonstrated by accessing a range of structurally diverse chiral cyclic and acyclic 1,2‐diamines bearing adjacent stereocenters through addition of a second nucleophile or Prins‐type cyclization by exploiting the nucleophilicity of the tethered alkene moiety. Moreover, the leaving group aptitude of sulfinyl auxiliary attached to imine, was exploited to access valuable chiral α‐aminonitriles under thermal conditions without employing any reagents. Detailed DFT calculation revealed a chair‐like transition state, arising from corresponding allylboroxine species, likely operating for the allylboration reaction across imine. [ABSTRACT FROM AUTHOR]

We have developed a TfOH-catalyzed, highly efficient protocol for the synthesis of biologically active β-acylamino ketones from aldehyde, ketone, and nitrile by avoiding the use of acetyl chloride. The reaction proceeds through a sequential aldol reaction followed by a nucleophilic attack of nitrile and hydrolysis of nitrile in one pot. The attractive features of this tandem process are mild reaction conditions, high atom economy, broad substrate scope with 51–87% yield, gram-scale reaction, and ease of operation. [ABSTRACT FROM AUTHOR]

The small, lipophilic tetrafluoroborate anion is ubiquitous in the imidazol(in)ium and iminium precursors to N‐heterocyclic carbenes (NHCs), including cyclic (alkyl)(amino)carbenes (CAACs). Its symmetrical distribution of charge over four highly electronegative fluorine atoms confers high stability, attenuating basicity while shielding the boron center. Here we report that this inertness does not withstand the nucleophilicity of free carbenes, when combined with a polarizing lithium cation. Reaction of CAAC ⋅ HBF4 salts with LiN(SiMe3)2, a protocol widely used to liberate free CAACs, generates zwitterionic CAAC‐BF3 adducts within minutes at 80 °C, or hours at room temperature, even for bulky N‐diisopropylphenyl (DIPP) CAACs. Imidazol(in)ium tetrafluoroborates likewise form NHC‐BF3 adducts in excellent yields. [ABSTRACT FROM AUTHOR]

Sets of electrophilic probes are generally prepared using a narrow toolkit of robust reactions, which tends to limit both their structural and functional diversity. A unified synthesis of skeletally-diverse sulfonyl fluorides was developed that relied upon photoredox-catalysed dehydrogenative couplings between hetaryl sulfonyl fluorides and hydrogen donor building blocks. A set of 32 diverse probes was prepared, and then screened against Trypanosoma brucei. Four of the probes were found to have sub-micromolar anti-trypanosomal activity. A chemical proteomic approach, harnessing an alkynylated analogue and broad-spectrum fluorophosphonate tools, provided insights into the observed anti-trypanosomal activity, which likely stems from covalent modification of multiple protein targets. It is envisaged that the unified diversity-oriented approach may enable the discovery of electrophilic probes that have value in the elucidation of biological and biomedical mechanisms. Electrophilic bioactive compounds are useful chemical tools for identifying and modulating protein targets through reaction with nucleophilic amino acid side chain residues. Here, the authors report a modular synthesis of electrophilic sulfonyl fluoride probes, and evaluate their anti-trypanosomal activity using a chemoproteomics approach [ABSTRACT FROM AUTHOR]

Chiral tertiary alcohols are an important structural motif, however, the general and efficient methodologies for their synthesis are less reported. Herein, we report a Ni(ІІ)-catalyzed asymmetric alkenylation and arylation of aryl ketones with organoborons under air via a 1,5-metalate shift strategy to obtain chiral tertiary allylic alcohols and diaryl alcohols. The reaction demonstrates good functional group tolerance and delivers chiral tertiary alcohols with good to excellent results. Furthermore, this method can be applied to the late-stage modification of drugs and the efficient synthesis of natural products. Notably, the reaction proceeds through an outer-sphere mechanism. The Ni(II) complex functions both as a Lewis acid to activate the ketone and create a chiral environment, and as coordination bridge linking the ketone and the organoboron-derived "ate" complex, facilitating the 1,5-metalate shift without forming a C-Ni bond. This approach contrasts with traditional transition metal-catalyzed nucleophilic addition reactions that involve carbon-metal bond formation. Chiral tertiary alcohols are an important structural motif, but the general methodologies for the synthesis are less reported. Herein, the authors report a Ni(ІІ)-catalyzed asymmetric alkenylation and arylation of aryl ketones with organoborons under air via a 1,5-metalate shift to obtain chiral tertiary allylic alcohols and diaryl alcohols. [ABSTRACT FROM AUTHOR]

The intrinsic correlation between depression and serotonin (5‐HT) is a highly debated topic, with significant implications for the diagnosis, treatment, and advancement of drugs targeting neurological disorders. To address this important question, it is of utmost priority to understand the action mechanism of serotonin in depression through fluorescence imaging studies. However, the development of efficient molecular probes for serotonin is hindered by the lack of responsive sites with high selectivity for serotonin at the present time. Herein, we developed the first highly selective serotonin responsive site, 3‐mercaptopropionate, utilizing thiol‐ene click cascade nucleophilic reactions. The novel responsive site was then employed to construct the powerful molecular probe SJ‐5‐HT for imaging the serotonin level changes in the depression cells and brain tissues. Importantly, the imaging studies reveal that the level of serotonin in patients with depression may not be the primary factor, while the ability of neurons in patients with depression to release serotonin appears to be more critical. Additionally, this serotonin release capability correlates strongly with the levels of mTOR (intracellular mammalian target of rapamycin). These discoveries could offer valuable insights into the molecular mechanisms underpinning depression and furnish mTOR as a novel direction for the advancement of antidepressant therapies. [ABSTRACT FROM AUTHOR]

Context: Electrophilicity and nucleophilicity are two vastly important chemical concepts gauging the capability of atoms in molecules to accept and donate the maximal number of electrons. In our earlier studies, we proposed to simultaneously quantify them using the Kullback–Leibler divergence from the information-theoretic approach in density functional theory. However, several issues with this scheme remain to be clarified such as its general validity, predictability, and relationship with other information-theoretic quantities. In this work, we revisit the matter with bigger datasets and deeper theoretical insights. Five information-theoretic quantities including Kullback–Leibler divergence, Hirshfeld charge, Ghost-Berkowitz-Parr entropy, and second and third orders of relative Onicescu information energy are found to be reliable and robust descriptors of electrophilicity and nucleophilicity propensities. Employing these five descriptors, we design a list of new compounds and predict their electrophilicity and nucleophilicity scales. This work should markedly improve our confidence and capability in applying information-theoretic quantities to evaluate electrophilicity and nucleophilicity propensities and henceforth pave the route for more applications of these quantities from information-theoretic approach in density functional theory in the future. Methods: All structures were fully optimized at the M06-2X/6–311 + G(d) level of DFT functional using the Gaussian 16 package (version C01) with integration grids and tight self-consistent-field convergence. The solvent effect was taken into account by using the implicit solvent model (CPCM) in the CH2Cl2 solvent, and all 3D contour surfaces of Fukui function, local temperature, and ITA (information-theoretic approach) quantities were generated by GaussView. The Multiwfn 3.8 program was used to calculate the ITA indexes and atomic charges. [ABSTRACT FROM AUTHOR]

Objective: The study commenced with the conversion of 4-(1H-indol-3-yl)butanoic acid (I) into ethyl 4-(1H-indol-3-yl)butanoate (II), succeeded by the synthesis of the hydrazide nucleophile, 4-(1H-indol-3-yl)butanohydrazide (III). Methods: Following this, nucleophilic addition reactions of (III) with various electrophilic aldehydes (IVa–IVg) were conducted to yield the targeted derivatives (Va–Vg/Vʹa–Vʹg). The structural elucidation of all synthesized compounds relied on IR, 1H, 13C NMR, HMBC, and CHN analysis. Results and Discussion: Evaluation of the inhibitory effects of these heterocyclic butanohydrazides (Va–Vg/Vʹa–Vʹg) against the α-glucosidase enzyme revealed significant inhibition by compounds (Vg/Vʹg) compared to the standard. Conclusions: Hemolytic analysis indicated mild cytotoxicity towards red blood cell membranes, indicating the potential of these molecules as nontoxic medicinal scaffolds for skin pigmentation and related disorders. [ABSTRACT FROM AUTHOR]

The role of MA in FAMA mixed perovskite remains far from being fully understood, due to the intricate chemical evolutions in the precursor solutions. Adjusting the content of MA in FAMA mixed perovskite arbitrarily remains a great challenge. This study elucidates a synergistic effect between H+ and I− oxidation which helps to reduce the content of MA in FA‐dominated perovskite. Briefly, excessive H+ boosts the balanced and rapid assembly of MA and FA components in FA‐dominated perovskite and hampers unfavorable chemical evolution induced by nucleophilic reaction between MA and FA in the precursor solution, while I− oxidation accelerates the in situ crystallization of perovskite. Leveraging this synergistic effect, centimeter‐scaled FAxMA(1‐x)PbI3 single crystals with arbitrarily adjustable values of x are successfully fabricated. In addition, peroxyacetic acid is introduced as the additive, enabling the blade‐coated FA0.9MA0.1PbI3 perovskite solar cells (PSCs) to achieve an impressive efficiency of 23.7%. The efficiency achieved here is among the highest values for blade‐coated PSCs with FA content exceeding 90% so far. The optimized solution developed in this study achieved exceptional stability, allowing it to be stored under air conditions for over 2 months without significant degradation in cell efficiency. This outcome satisfies the requirements for commercialization. [ABSTRACT FROM AUTHOR]

Polyacrylonitrile (PAN) is a promising polymer for solid‐state lithium (Li) metal batteries (SSLMBs). However, the low ionic conductivity of PAN‐based solid polymer electrolytes (SPEs) and unstable Li/PAN interface hinder the applications of PAN in SSLMBs. Herein, a strategy of ring‐opening polymerization is proposed to reconfigure the PAN‐based SPE network. Triggered by the alkaline species from Li6.4La3Zr1.4Ta0.6O12 nanoparticles, ethylene carbonate (EC) undergoes nucleophilic ring‐opening reaction, and subsequently forms dipole–dipole interaction with the PAN chain. This polymerization process consequently reconfigures PAN segment, endowing the SPE with rapid Li+ transport channels and enhanced interfacial stability with Li metal. As a result, the designed PAN‐based SPE demonstrates high ionic conductivity of 2.96 × 10−4 S cm−1 and Li+ transference number of 0.56 at 25 °C. The Li/Li symmetric cells with the reconfigured PAN network deliver a high critical current density of 1.8 mA cm−2 and maintain stable Li plating/stripping for 1200 h. A high‐capacity retention of 90.1% after 1000 cycles at 2 C is achieved in LiFePO4 (LFP)/Li solid‐state cells with PAN‐based SPEs. Moreover, the LFP/Li and LiNi0.8Co0.1Co0.1O2/Graphite pouch batteries both present good cycling and safety performances. This strategy provides new insights into designing high‐performance PAN‐based SPE for SSLMBs. [ABSTRACT FROM AUTHOR]

A transition metal‐free Se‐catalyzed C−H amination protocol for α'‐amination of enol derivatives has been developed. This reaction can be used to functionalize a wide variety of oxygen‐ and halogen‐substituted alkenes spanning a vast range of nucleophilicities, giving α'‐aminated enol derivatives with high regioselectivity. Amination of E/Z mixtures of alkenes proceeds stereoconvergently to give the (Z)‐enol derivatives exclusively. Mechanistic studies revealed that the relative reactivity and α'‐regioselectivity of these transformations is determined by substantial resonance donation to the heteroatom‐bound carbon in the transition state. These products participate in traditional reactions of enol derivatives, allowing for efficient functionalization of both α‐ and α'‐positions from a single enol derivative with high diastereocontrol. [ABSTRACT FROM AUTHOR]

ABSTRACT Herein, a new hybrid inorganic–organic ligand was designed and synthesized to form a series of transition metal (II) complexes as potential substrate towards cytotoxicity studies. The inorganic heterocycle, cyclotriphosphazene (N3P3Cl6, CTP) was chosen as the core unit to synthesize geminal hydrazone Schiff bases as multisite coordination ligand via substitution of six reactive chlorine. Herein, CTP was substituted by nucleophilic reaction at six chlorine atoms that exist on three phosphorus (V) centers of CTP with salicylaldehyde to form hexakis salicylaldehyde derivative. Further, salicylic hydrazide tethered with terminal amine group was condensed with above hexakis salicylaldehyde derivative of CTP at ratio of 1:6 afforded SBCTP ligand. Indeed, a series of M (II) complexes (M = Co, Ni, Mn, Cu and Zn) were obtained from SBCTP ligand with characteristic functional groups to manifest the cytotoxic activity, in order to venture as the active anticancer agent in pharmaceutics. Despite the Schiff base of aromatic rings tend to exhibit inherent cytotoxic properties, the complementary influence of CTP appended with two consecutive salicylic units in SBCTP found to show unique properties. In particular, metal (II) complexes via imine bonds of SBCTP oriented from CTP ring found to reveal essential properties to treat cancerous cells. The above ligand and prospective metal complexes were investigated individually for the cytotoxic activity with normal and cancerous cells at five different concentrations, with/without addition of the above samples into MTT assay. Structural characterization of above samples was conducted by multinuclear NMR, 1H, 13C, and 31P as well as ESI, HRMS, FTIR, EDS, and TGA data. [ABSTRACT FROM AUTHOR]

We describe the transition-metal-free coupling for polyfluoroalkoxy arenes using polyfluoroalkoxy borates, which serve as counterions to diaryliodonium salts and transferring mediators of polyfluoroalkoxy groups. This strategy demonstrates high functional group compatibility owing to the low nucleophilicity of the borate mediator, thus offering a practical approach for synthesizing diverse polyfluoroalkoxy arenes. [ABSTRACT FROM AUTHOR]

Appreciating reactivity in terms of physicochemical effects for chemical processes is one of the most important undertakings in chemistry. While transition state (TS) theory provides the framework enabling the reliable calculation of the barrier height for a given elementary step, analytical tools are necessary to gain insight into key factors governing the different processes during chemical reactions. In this contribution, we partition the potential energy surface of an elementary step along the intrinsic coordinate into three segments, the so‐called Pre‐TS, TS, and Post‐TS regions, and then determine the most important factors dictating each segment. This analysis is based on the use of both reactivity descriptors from conceptual density functional theory and concepts from the information‐theoretic approach in density functional theory. We found that in both Pre‐TS and Post‐TS regions, steric effects are the dominant factors, whereas in the TS region, it is the intrinsic electrophilic and nucleophilic propensity of the transition state structure that governs the reactivity. The wide applicability of our approach is shown by a validation for a total of 37 organic and inorganic reactions. Different partition approaches from density functional theory, energy decomposition analysis and wavefunction‐based resonance theory are employed to support our main conclusions. [ABSTRACT FROM AUTHOR]

A practical and efficient trifluoromethylation of readily available and bench stable N‐Thiophthalimides and N‐Thioimides with Ruppert‐Prakash reagent (TMS‐CF3) is described. The reaction proceeds at room temperature and only requires NaOAc as the mild promoter to prepare a series of trifluoromethyl thioethers in good to excellent yields. Both aryl and alkyl derivates are well trifluoromethylated under transition‐metal‐free reaction conditions. Moreover, the reaction features with scale‐up synthesis and late‐stage modification of bioactive molecule. [ABSTRACT FROM AUTHOR]

In this paper, a two‐step process is described for the chemoselective synthesis of highly fluorescent polycyclic chromeno[4,3,2‐ij]isoquinoline‐3‐carbonitriles using a sequential nucleophilic addition reaction involving 4‐chloro‐3‐vinyl coumarins, α,α‐dicyanoolefins and ammonium acetate as a source of nitrogen. In this process, it is believed that ammonium acetate is converted into ammonia and acetic acid during the reaction. Ammonia is the source of nitrogen, and the acid produced can catalyze the progress of the reaction. Single‐crystal X‐ray analysis was performed to confirm the structure of one of the typical products. In addition, the photophysical characteristics of the product 3 a were investigated through absorption and emission spectroscopy. This analysis reveals that the new heterocyclic system has impressive fluorescence characteristics. Several advantages of the presented synthetic strategy can be found in its simplicity, readily available starting materials, high‐efficiency products, highly chemoselective route, metal‐free catalyst, and ability to purify products by washing them with EtOH (96 %), a technique called GAP (Group‐Assisted‐Purification) chemistry. [ABSTRACT FROM AUTHOR]

A truly organocatalytic approach to the Darzens reaction affording α,β-epoxy carbonyl compounds in good yields was developed taking advantage of the high basic strength and low nucleophilicity of cyclopropenimine superbases. The catalytic active free base can easily be generated in situ from its hydrochloride salt and maintained in the active deprotonated form by performing the reactions in a heterogeneous reaction system in the presence of excess potassium carbonate as a sacrificial base. [ABSTRACT FROM AUTHOR]

Conformational freedom-restricted peptides, such as stapled peptides, play a crucial role in the advancement of functional peptide development. We synthesized stapled octapeptides using α-carbocyclic α,α-disubstituted α-amino acids, particularly 3-allyloxy-1-aminocyclopentane-1-carboxylic acid, as the crosslink motifs. The organocatalytic capabilities of the synthesized stapled peptides were assessed in an asymmetric nucleophilic epoxidation reaction because the catalytic activities are known to be proportional to α-helicity. Despite incorporating side-chain crosslinks, the enantioselectivities of the epoxidation reaction catalyzed by stapled octapeptides were found to be comparable to those obtained using unstapled peptides. Interestingly, the stapled peptides using α-carbocyclic α,α-disubstituted α-amino acids demonstrated higher reactivities and stereoselectivities (up to 99% ee) compared to stapled peptides derived from (S)-α-(4-pentenyl)alanine, a commonly used motif for stapled peptides. These differences could be attributed to the increased α-helicity of the former stapled peptide in contrast to the latter, as evidenced by the X-ray crystallographic structures of their N-tert-butoxycarbonyl derivatives. [ABSTRACT FROM AUTHOR]

The catalytic decarboxylation of malonic acid half oxy‐ and thioesters, β‐ketocarboxylic acids, and their related compounds is a straightforward, powerful, and atom‐economical strategy for the in‐situ formation of enolates, which are important and well‐studied synthons for various functional materials and natural products. This strategy, inspired by the biosynthesis of polyketides and fatty acids, is an attractive method for synthesizing enols from carboxyl compounds with less reactive α‐hydrogen atoms under mild conditions. In addition, these reactions are environmentally friendly and are of great interest to chemists because the use of a stoichiometric amount of base can be avoided, and the only byproduct is CO2. Thus far, remarkable progress has been made, especially in the field of organocatalytic enantioselective decarboxylation reactions, allowing for the stereocontrolled formation of new C−H, C−C, C−heteroatom, and C−X bonds. This review provides a comprehensive overview of organocatalytic enantioselective decarboxylation reactions and highlights the significant progress made since 2020. In particular, it focuses on chiral catalyst systems and transition states as key parameters for decarboxylation reactions. [ABSTRACT FROM AUTHOR]

The chemical reactivity of 3-formylchromones toward several carbon and nitrogen nucleophiles is collected in this review. Certain annulated chromones and 3-heteroaryl chromones were synthesized. A diversity of three component reactions including 3-formylchromones was also summarized. [ABSTRACT FROM AUTHOR]

After extensive computations, novel trinitro compounds, triethyl ammonium 2,4,6-trinitro phenoxide (TEA-TNP) and tetramethyl guanidinium 2,4,6-trinitro phenoxide (TMG-TNP), are designed, synthesized, and identified. The Geometrical parameters, electronic properties, and spectroscopic analysis have been investigated by comparison of theoretical and experimental methods. Spectrum features that include IR and Raman have been calculated, and 1H and 13C NMR spectra are compared to experimental data. Electronic analysis has been investigated through NLO, FMO, UV-Vis, NBO, and MEP calculations. B3LYP/6-311++G(d,p) is highly successful and dependable for predicting ionic liquid stability, electrical characteristics, and spectroscopy. Both TEA-TNP and TMG-TNP are introduced as suitable candidates for NLO material. TMG-TNP with greater nucleophilicity (N) is a noncorrosive lubricant additive that reduces friction and wear for tribological performance. [ABSTRACT FROM AUTHOR]

Six novel brominated bis-pyridinium oximes were designed and synthesized to increase their nucleophilicity and reactivation ability of phosphorylated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Their pKa was valuably found lower to parent non-halogenated oximes. Stability tests showed that novel brominated oximes were stable in water, but the stability of di-brominated oximes was decreased in buffer solution and their degradation products were prepared and characterized. The reactivation screening of brominated oximes was tested on AChE and BChE inhibited by organophosphorus surrogates. Two mono-brominated oximes reactivated AChE comparably to non-halogenated analogues, which was further confirmed by reactivation kinetics. The acute toxicity of two selected brominated oximes was similar to commercially available oxime reactivators and the most promising brominated oxime was tested in vivo on sarin- and VX-poisoned rats. This brominated oxime showed interesting CNS distribution and significant reactivation effectiveness in blood. The same oxime resulted with the best protective index for VX-poisoned rats. [ABSTRACT FROM AUTHOR]

Reaction of a nucleophilic germylene Ge[CH(SiMe3)2]2 with the phosphanyl phosphaketene [{(H2C)(NDipp)}2P]PCO induces decarbonylation to form a phosphanyl phosphagermene [{(H2C)(NDipp)}2P]P=Ge[CH(SiMe3)2]2 (1; Dipp=2,6‐diisopropyl‐phenyl). Addition of CO2 or MeCN to 1 results in [3+2]‐cycloaddition reactions to afford five‐membered heterocycles. This mode of reactivity is reminiscent of that observed for frustrated Lewis pairs, with the pendant phosphanyl group acting as a base and the germanium center as a Lewis acid. Contrastingly, 1,2‐addition across the P=Ge bond was observed when using ammonia, small primary amines (NH2nP), or metal complexes (e. g. Au(PPh3)Cl and ZnEt2). These latter reactions allow for the one‐step synthesis of metal phosphide complexes. [ABSTRACT FROM AUTHOR]

Coumalic acid methyl ester (methyl coumalate), a biomass‐derived building block, was converted into (E)‐enaminoesters by an original uncatalyzed stereoselective 1,6‐addition/fragmentation cascade involving secondary amines. The transformation occurred under useful experimental conditions as a simple heating of a stoichiometric mixture of the starting compounds led to the desired products. The reaction could be extended to a range of alkyl coumalates and a variety of secondary amines. Given the original character of the transformation, the reaction mechanism was discussed. Therefore, the cascade is supposed to involve a 1,6‐conjugate addition followed by a fragmentation sequence leading ultimately to the decarboxylative elimination of (E)‐enaminoesters. Using this procedure, renewable coumalic acid proved to be a valuable alternative to fossil fuel‐based propiolates for the preparation of enaminoesters. [ABSTRACT FROM AUTHOR]

N-Furfuryl allylamines react with a broad range of isocyanates, isothiocyanates, isoselenocyanates with the formation of a 3a,6-epoxyisoindole core in one synthetic stage. The interaction sequence involves two consecutive steps: the nucleophilic addition reaction and the intramolecular Diels–Alder furane (IMDAF) reaction. The scope and limitations of the proposed method were thoroughly investigated, and it was revealed that the key [4+2] cycloaddition step proceeds through an exo-transition state, giving rise to the exclusive formation of a single diastereomer of the target heterocycle. Dynamic temperature NMR analysis allowed to fully investigating a case of coalescence of NMR signals and determined the coalescence temperature during the transition O → Se. The antimicrobial properties of the obtained compounds against sensitive strains of yeast Candida albicans, fungus Aspergillus niger and bacteria including Staphylococcus aureus, Micrococcus luteus, Pseudomonas fluorescens were identified. [ABSTRACT FROM AUTHOR]

Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential to mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf)3‐catalyzed [3+2] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding a diverse array of polysubstituted 2‐amino‐bicyclo[2.1.1]hexenes in good to excellent yields. These products offer valuable starting materials for the construction of novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that the reaction involves a nucleophilic addition of ynamides to bicyclo[1.1.0]butanes, followed by an intramolecular cyclization of in situ generated enolate and keteniminium ion. We expect that these findings will encourage utilization of complex bioisosteres and foster further investigation into BCB‐based cycloaddition chemistry. [ABSTRACT FROM AUTHOR]

Isatin-derived spirocyclic cores are found in several biologically active molecules. Here, we report nucleophilic domino reactions for the synthesis of α-methylene-γ-butyrolactone/lactam containing spirocyclic oxindoles. The Zn-mediated one-step reaction accommodates a range of substrates and can be used to rapidly generate focused libraries of highly substituted spirocyclic compound. [ABSTRACT FROM AUTHOR]

Piperazines constitute an important structural feature of many pharmaceuticals. For the discovery of new drugs, the ability to modify the lead compound's structure is crucial. Herein, we provide an efficient method for the synthesis of chiral 2,3,5-trisubstituted piperazine structures. Our route enables the synthesis of several novel chiral aryl aziridinyl ketones that could be converted into aziridine-fused bicyclic imines. The reduction of these imines and the nucleophilic ring-opening reaction of the aziridine ring allowed us to synthesize highly functionalized piperazine derivatives. [ABSTRACT FROM AUTHOR]

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The mechanism of the Rh‐catalyzed oxidative coupling cyclization of 2,3‐allenols has been studied by DFT calculations. The whole process of the current reaction involves the nucleophilic cyclic oxyrhodation/ stereodefined carborhodation/ β‐H elimination/ reductive elimination. Calculated results reveal that the carborhodation step is not only the rate‐limiting step but also determines the stereo‐selectivity. [ABSTRACT FROM AUTHOR]

Oximes, belonging to imines with the general formula of RR'C=NOH, are produced by the nucleophilic addition reaction between hydroxylamine with ketones or aldehydes, yielding corresponding aldoxime and ketoxime. The presence of hydrogen bond acceptor and donor is the classical feature of oxime‐containing structural framework. This review presents a summary of the role of oximes and its structure activity relationships including antimicrobial, anticancer, anti‐inflammatory, antihyperglycemic, insecticidal agents, along with their involvement in the treatment of organophosphorus poisoning. The review also focused on the pharmacological profile of lead molecules of several classes of oxime‐containing compounds. [ABSTRACT FROM AUTHOR]

Profiting from the dual high basicity and nucleophilicity of organosodium complexes, here we report the stepwise lateral metalation of a wide range of alkyl arenes (MeAr), mediated by hydrocarbon‐soluble NaCH2SiMe3 ⋅ PMDETA (PMDETA=N,N,N',N",N"‐pentamethyldiethylenetriamine), followed by nucleophilic addition to diarylethenes of the newly generated NaCH2Ar ⋅ PMDETA complexes. This method grants access to a range of functionalised hydrocarbons in excellent yields and can be upgraded to catalytic regimes when using trans‐stilbene, a 10 mol% of the alkyl sodium base and toluene as a solvent. Extending this approach to aromatic ketones leads to the formation of stilbenes under mild reaction conditions, resulting from the deprotonative coupling of toluenes with ketones. Combining spectroscopic studies with the trapping and characterisation of key reaction intermediates, mechanistic insights have been gained, advancing the understanding of coordination effects in organosodium chemistry, and shedding light on their special reactivity profiles. [ABSTRACT FROM AUTHOR]

Carbon dioxide (CO2) is a greenhouse gas, and its resource use is vital for carbon reduction and neutrality. Herein, the nucleophilic addition reaction of calcium carbide (CaC2) to CO2 was studied for the first time to synthesize propiolic and butynedioic acids by using CuI or AgNO3 as catalyst, Na2CO3 as additive, and triphenylphosphine as ligand in the presence/absence of a hydrogen donor. The effects of the experimental conditions and intensification approach on the reaction were investigated. The reactivity of CaC2 is closely associated with its synergistic activation by the catalysts, solvent, and external intensification, such as the ultrasound and mechanical force. Ultrasound helps to promote the reaction by enhancing the interfacial mass transfer of CaC2 particulates. Mechanochemistry can effectively promote the reaction, yielding 29.8% of butynedioic acid and 74.8% of propiolic acid after 2 h ball milling at 150 rpm, arising from the effective micronization and interfacial renewal of calcium carbide. The present study sheds a light on the high-value uses of CO2 and CaC2 and is of reference significance for the nucleophilic reaction of CaC2 with other carbonyl compounds. [ABSTRACT FROM AUTHOR]

Context: Understanding and predicting the nucleophilic reactivity are paramount in elucidating organic chemical reactions and designing new synthetic pathways. In this study, we propose a nucleophilicity index within the framework of Conceptual Density Functional Theory (CDFT). Through rigorous theoretical formulations, we introduce an original quantum reactivity descriptor that captures the nucleophilic propensity of molecules based on their electronic structure and chemical environment. Subsequently, this proposed index is applied to a series of nucleophiles (pyrrolidines derivatives), spanning a diverse range of chemical functionalities. Our computational assessments reveal insightful correlations between the predicted nucleophilicity index and experimental observations of nucleophilic behavior. Thereby, they offer a promising avenue for advancing the understanding of organic reactivity and guiding synthetic efforts. Methods: Experimentally, Mayr's experimental parameters accounting for nucleophilicity were selected for the pyrrolidines. This study used DFT calculations at the B3LYP/Aug-cc-pVTZ level of theory using the Gaussian 16 program. Geometry optimization was thus performed, and the methodology employed for the computation of quantum reactivity descriptor is presented. Solvent effect was also taken into account using IEFPCM, and empirical dispersion correction (GD3) was employed. [ABSTRACT FROM AUTHOR]

The synthesis of novel 5-(2-((1(E/Z),2E)-1,3-disubstitutedallylidene)hydrazinyl)-1,3-dimethyl-4-nitro-1H-pyrazole (4a–k) was attempted via reaction involves a nucleophilic attack which takes place at the carbonyl group of the α,β-unsaturated carbonyls. The transformation proceeds via an effective addition-elimination reaction in the presence of catalytic amount of concentrated H2SO4. The cytotoxicity of synthesized compounds was evaluated against two tumor cell lines, MCF-7 and MDA-MB-231, via MTT assay. The compounds 4a–d showed better toxicity than tamoxifen on MCF-7 cells, ranging from 26.28 to 12.96 µM with 4b having the lowest IC50 among the compounds tested. On the other hand, the compounds have moderate toxicity on MDA-MB-231 with 4c showing the lowest IC50. The docking study suggests that these Schiff bases chalcone scaffolds might facilitate the further development of investigated compounds as anticancer agents. [ABSTRACT FROM AUTHOR]

In general, the P-centered ring-opening of quaternary phosphirenium salts (QPrS) predominantly leads to hydrophosphorylated products, while the C-centered ring-opening is primarily confined to intramolecular nucleophilic reactions, resulting in the formation of phosphorus-containing cyclization products instead of difunctionalized products generated through intermolecular nucleophilic processes. Here, through the promotion of ring-opening of three-member rings by iodine anions and the quenching of electronegative carbon atoms by iodine cations, we successfully synthesize β-functionalized vinylphosphine oxides by the P-addition of QPrS intermediates generated in situ. Multiple β-iodo-substituted vinylphosphine oxides can be obtained with exceptional regio- and stereo-selectivity by reacting secondary phosphine oxides with unactivated alkynes. In addition, a variety of β-functionalized vinylphosphine oxides converted from C-I bonds, especially the rapid construction of benzo[b]phospholes oxides, demonstrates the significance of this strategy. P-centered ring-opening of quaternary phosphirenium salts (QPrS) predominantly leads to hydrophosphorylated products, while the C-centered ring-opening results mainly in the formation of phosphorus-containing cyclization products. Here the authors synthesize β-functionalized vinylphosphine oxides by the P addition of QPrS intermediates generated in situ. [ABSTRACT FROM AUTHOR]

Oxime ethers are attractive compounds in medicinal scaffolds due to the biological and pharmaceutical properties, however, the crucial and widespread step of industrial oxime formation using explosive hydroxylamine (NH2OH) is insecure and troublesome. Herein, we present a convenient method of oxime ether synthesis in a one‐pot tandem electrochemical system using magnesium based metal‐organic framework‐derived magnesium oxide anchoring in self‐supporting carbon nanofiber membrane catalyst (MgO‐SCM), the in situ produced NH2OH from nitrogen oxides electrocatalytic reduction coupled with aldehyde to produce 4‐cyanobenzaldoxime with a selectivity of 93 % and Faraday efficiency up to 65.1 %, which further reacted with benzyl bromide to directly give oxime ether precipitate with a purity of 97 % by convenient filtering separation. The high efficiency was attributed to the ultrafine MgO nanoparticles in MgO‐SCM, effectively inhibiting hydrogen evolution reaction and accelerating the production of NH2OH, which rapidly attacked carbonyl of aldehydes to form oximes, but hardly crossed the hydrogenation barrier of forming amines, thus leading to a high yield of oxime ether when coupling benzyl bromide nucleophilic reaction. This work highlights the importance of kinetic control in complex electrosynthetic organonitrogen system and demonstrates a green and safe alternative method for synthesis of organic nitrogen drug molecules. [ABSTRACT FROM AUTHOR]

The article discusses the challenges and strategies involved in the dearomatization of ¿-unsubstituted ß-naphthols in organic synthesis. It explores various methods, including catalytic reduction reactions, Lewis acid catalysis, transition-metal-catalyzed reactions, and gold-catalyzed reactions, which offer efficient ways to synthesize complex spirocyclic molecules and functional spiro polymers. The article also acknowledges the limitations and challenges associated with these reactions. It concludes by suggesting that new strategies for catalytic asymmetric dearomatization reactions will likely be discovered in the future. [Extracted from the article]

Functional group compatibility in an amide bond cleavage reaction with hydrazine was evaluated for 26 functional groups in the functional group evaluation (FGE) kit. Accurate and rapid evaluation of the compatibility of functional groups, such as nitrogen-containing heterocycles important in drug discovery research, will enhance the application of this reaction in drug discovery research. These data will be used for predictive studies of organic synthesis methods based on machine learning. In addition, these studies led to discoveries such as the unexpected positive additive effects of carboxylic acids, indicating that the FGE kit can propel serendipitous discoveries. [ABSTRACT FROM AUTHOR]

Fabrication of versatile hydrogels in a facile and effective manner represents a pivotal challenge in the field of biomaterials. Herein, a novel strategy is presented for preparing on‐demand degradable hydrogels with multilevel responsiveness. By employing selenol‐dichlorotetrazine nucleophilic aromatic substitution (SNAr) to synthesize hydrogels under mild conditions in a buffer solution, the necessity of additives or posttreatments can be obviated. The nucleophilic and redox reactions between selenol and tetrazine culminate in the formation of three degradable chemical bonds—diselenide, aryl selenide, and dearomatized selenide—in a single, expeditious step. The resultant hydrogel manifests exceptional adaptability to intricate environments in conjunction with self‐healing and on‐demand degradation properties. Furthermore, the resulting material demonstrated light‐triggered antibacterial activity. Animal studies further underscore the potential of integrating metformin into Se‐Tz hydrogels under green light irradiation, as it effectively stimulates angiogenesis and collagen deposition, thereby fostering efficient wound healing. In comparison to previously documented hydrogels, Se‐Tz hydrogels exhibit controlled degradation and drug release, outstanding antibacterial activity, mechanical robustness, and bioactivity, all without the need for costly and intricate preparation procedures. These findings underscore Se‐Tz hydrogels as a safe and effective therapeutic option for diabetic wound dressings. [ABSTRACT FROM AUTHOR]

Investigating the reactivity of small nucleophilic scaffolds is a strategic approach for the design of new catalysts aiming at effective detoxification processes of organophosphorus compounds. The drug methimazole (MMZ) is an interesting candidate featuring two non‐equivalent nucleophilic centers. Herein, phosphoryl transfer reactions mediated by MMZ were assessed by means of spectrophotometric kinetic studies, mass spectrometry (MS) analyses, and density functional theory (DFT) calculations using the multi‐electrophilic compound O,O‐diethyl 2,4‐dinitrophenyl phosphate (DEDNPP). MMZ anion acts primarily as an S‐nucleophile, exhibiting a nucleophilic activity comparable to that of certain oximes featuring alpha‐effect. Selective nucleophilic aromatic substitution was observed, consistent with the DFT prediction of a low energy barrier. Overall, the results bring important advances regarding the mechanistic understanding of nucleophilic dephosphorylation reactions, which comprises a strategic tool for neutralizing toxic organophosphates, hence promoting chemical security. [ABSTRACT FROM AUTHOR]

The review summarizes literature data on new nucleophilic functionalization reactions of tropylium salts with heterocyclic amines and monocarboxylic acid amides and hydrazides over the past decade. [ABSTRACT FROM AUTHOR]

Radical substitution is a useful method to functionalize heterocycles, as in the venerable Minisci reaction. Empirically observed regiochemistries indicate that the CF2H radical has a nucleophilic character similar to alkyl radicals, but the CF3 radical is electrophilic. While the difference between •CH3 and •CF3 is well understood, the reason that one and two Fs make little difference but the third has a large effect is puzzling. DFT calculations with M06-2X both reproduce experimental selectivities and also lead to an explanation of this difference. Theoretical methods reveal how the F inductive withdrawal and conjugative donation alter radical properties, but only CF3 becomes decidedly electrophilic toward heterocycles. Here, we show a simple model to explain the radical orbital energy trends and resulting nucleophilicity or electrophilicity of fluorinated radicals. Empirically observed regiochemistries indicate that the CF2H radical has a nucleophilic character similar to alkyl radicals, but the CF3 radical is electrophilic in reactions with heterocycles. Here, the authors report DFT calculations, reproducing experimental selectivities and leading to an explanation of this difference. [ABSTRACT FROM AUTHOR]

We describe here the synthesis of isoselenochromenes via a nucleophilic selenocyclization reaction of benzodiynes with sodium selenide. The central parameters that affect this cyclization reaction were studied, and the best reaction conditions were applied to different substrates to determine the scope of the method. The results indicated that isoselenochromenes were obtained in higher yields when the reactions were performed by the addition of NaBH4 (3 equiv), at room temperature, under nitrogen atmosphere, to a solution of elemental selenium (2 equiv) in dimethylformamide (2 mL). After 1 h, a benzodiynes (0.25 mmol) solution in EtOH (3 mL) was added at room temperature. The reaction was stirred at 75 °C until the starting material was consumed. The best conditions were applied to benzodiynes having electron‐rich, electron poor aromatic rings, and alkyl groups directly bonded to the alkynes. The same reaction condition was extended to isothiochromene derivatives but failed to prepare isotelurochromenes. The isoselenochromenes were easily transformed into three new classes of organoselenium compounds using classical methods available in the literature. We also conducted several control experiments to propose a reaction mechanism. [ABSTRACT FROM AUTHOR]

The given text provides a detailed account of the synthesis and characterization of several chemical compounds. The compounds synthesized include 1-(2,4-Dichlorophenyl)-3-(2,4-dimethoxyphenyl)-5-(trimethylsilyl)-1,4-pentadiyne, Hexacarbonyl[μ-[(1,2-η:1,2-η)-1-(2,4-dichlorophenyl)-1,4-pentadiyn-3-ol]]dicobalt, Hexacarbonyl[μ-[(1,2-η:1,2-η)-1-(2,4-dichlorophenyl)-3-(2,4-dimethoxyphenyl)-1,4-pentadiyne]], 1-(2,4-Dichlorophenyl)-3-(2,4-dimethoxyphenyl)-1,4-pentadiyne, (Z)-1-(2,4-Dichlorophenyl)-3-(2,4-dimethoxyphenyl)-1,4-pentadiene, and (E)-1-(2,4-Dichlorophenyl)-3-(2,4-dimethoxyphenyl)-1,4-pentadiene. The synthesis procedures and characterization data, including IR, NMR, and HRMS spectra, are provided for each compound. The supporting information for the article is also [Extracted from the article]

The C--H bond activation catalyzed by a manganese(I) complex has achieved significant development but is limited to C(sp²)--H bonds. In this work, an efficient manganese(I)-catalyzed direct nucleophilic addition reaction of C(sp³)--H bonds to aromatic aldehydes has been developed. This is the first example of manganese(I)-catalyzed C(sp³)--H bond transformation. A manganacycle complex was isolated and proved to be the key active intermediate in the catalytic cycle. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl substances (PFASs) are persistent and toxic to human health. It is demanding for high‐efficient and green technologies to remove PFASs from water. In this study, a novel PFAS treatment technology was developed, utilizing polytetrafluoroethylene (PTFE) particles (1–5 μm) as the catalyst and a low frequency ultrasound (US, 40 kHz, 0.3 W/cm2) for activation. Remarkably, this system can induce near‐complete defluorination for different structured PFASs. The underlying mechanism relies on contact electrification between PTFE and water, which induces cumulative electrons on PTFE surface, and creates a high surface voltage (tens of volts). Such high surface voltage can generate abundant reactive oxygen species (ROS, i.e. O2⋅−, HO⋅, etc.) and a strong interfacial electrostatic field (IEF of 109~1010 V/m). Consequently, the strong IEF significantly activates PFAS molecules and reduces the energy barrier of O2⋅− nucleophilic reaction. Simultaneously, the co‐existence of surface electrons (PTFE*(e−)) and HO⋅ enables synergetic reduction and oxidation of PFAS and its intermediates, leading to enhanced and thorough defluorination. The US/PTFE method shows compelling advantages of low energy consumption, zero chemical input, and few harmful intermediates. It offers a new and promising solution for effectively treating the PFAS‐contaminated drinking water. [ABSTRACT FROM AUTHOR]

Amine modification through nucleophilic attack of the amine functionality is a very common chemical transformation. Under biorelevant conditions using acidic-to-neutral pH buffer, however, the nucleophilic reaction of alkyl amines (pKa ≈ 10) is not facile due to the generation of ammonium ions lacking nucleophilicity. Here, we disclose a unique molecular transformation system, catalysis driven by amyloid-substrate complex (CASL), that promotes amine modifications in acidic buffer. Ammonium ions attached to molecules with amyloid-binding capability were activated through deprotonation due to the close proximity to the amyloid catalyst formed by Ac-Asn-Phe-Gly-Ala-Ile-Leu-NH2 (NL6), derived from islet amyloid polypeptide (IAPP). Under the CASL conditions, alkyl amines underwent various modifications, i.e., acylation, arylation, cyclization, and alkylation, in acidic buffer. Crystallographic analysis and chemical modification studies of the amyloid catalysts suggested that the carbonyl oxygen of the Phe-Gly amide bond of NL6 plays a key role in activating the substrate amine by forming a hydrogen bond. Using CASL, selective conversion of substrates possessing equivalently reactive amine functionalities was achieved in catalytic reactions using amyloids. CASL provides a unique method for applying nucleophilic conversion reactions of amines in diverse fields of chemistry and biology. [ABSTRACT FROM AUTHOR]