Organocatalyzed Asymmetric Conjugate Addition of Alcohols to ß-Fluoroalkyl Vinylsulfones by Bifunctional Phosphonium Salt Catalyst.

Chiral secondary alcohols, serving as essential structural motifs, hold significant potential for diverse applications. The exploration of effective synthetic strategies toward these compounds is both attractive and challenging. Herein, we present an asymmetric oxa-Michael reaction involving aliphatic alcohols as nucleophiles and ß-fluoroalkyl vinylsulfones catalyzed by bifunctional phosphonium salt (BPS), achieving high yields and excellent enantioselectivities (up to 98 % yield and 98 % ee). Additionally, a sequential process including asymmetric oxa-Michael and debenzylation, facilitated by BPS/Lewis acid cooperation, was revealed for synthesizing diverse chiral secondary alcohol compounds in high yields (81-88 %) with consistent stereoselectivities. Furthermore, mechanistic explorations and subsequent results unveiled that the enantioselectivity originates from hydrogen-bonding and ion-pair interactions between the BPS catalyst and the substrates.

α-Umpolung/Michael Addition/Quaternization Tandem Reaction to provide α-Imido-ß-phosphonium Propanoates with Broad Spectrum of Biological Activity.

This paper has been supported by the Kazan Federal University Strategic Academic Leadership Program ('PRIORITY-2030'). HRMS data were obtained in the CSF-SAC FRC KSC RAS by support of the State Assignment of the Federal Research Center "Kazan Scientific Center", Russian Academy of Sciences. A.D.V, conducted studies of anticancer activity with financial support form the government assignment for FRC Kazan Scientific Center of RAS.

The First Example of the Friedel-Crafts Cyclization Leading to (10-Hydroxy-9,10-dihydroanthr-9-yl)phosphonium Salts without the Expected Bradsher Dehydration.

The reaction of (ortho-acetalaryl)arylmethanols with various phosphines PR1R2R3 (R1 = R2 = R3 = Ph; R1 = R2 = Ph, R3 = Me and R1 = R2 = Me, R3 = Ph) under acidic conditions (e.g., HCl, HBF4, TsOH) unexpectedly led to the formation of (10-hydroxy-9,10-dihydroanthr-9-yl)phosphonium salts instead of the corresponding anthryl phosphonium salts. The cyclization occurred according to the Friedel-Crafts mechanism but without the usually observed Bradsher dehydration, giving cyclic products in the form of cis/trans isomers and their conformers. In case of electron-rich and less-hindered dimethylphenylphosphine, all four stereoisomers were recorded in 31P{1H} NMR spectra, while for the other phosphines, only the two most stable cis/trans stereoisomers were detected. This study was supported by DFT and NCI calculations in combination with FT-IR analysis.

Anti Gram-Positive Bacteria Activity of Synthetic Quaternary Ammonium Lipid and Its Precursor Phosphonium Salt.

Organic ammonium and phosphonium salts exert excellent antimicrobial effects by interacting lethally with bacterial membranes. Particularly, quaternary ammonium lipids have demonstrated efficiency both as gene vectors and antibacterial agents. Here, aiming at finding new antibacterial devices belonging to both classes, we prepared a water-soluble quaternary ammonium lipid (6) and a phosphonium salt (1) by designing a synthetic path where 1 would be an intermediate to achieve 6. All synthesized compounds were characterized by Fourier-transform infrared spectroscopy and Nuclear Magnetic Resonance. Additionally, potentiometric titrations of NH3+ groups 1 and 6 were performed to further confirm their structure by determining their experimental molecular weight. The antibacterial activities of 1 and 6 were assessed first against a selection of multi-drug-resistant clinical isolates of both Gram-positive and Gram-negative species, observing remarkable antibacterial activity of both compounds against Gram-positive isolates of Enterococcus and Staphylococcus genus. Further investigations on a wider variety of strains of these species confirmed the remarkable antibacterial effects of 1 and 6 (MICs = 4-16 and 4-64 µg/mL, respectively), while 24 h-time-killing experiments carried out with 1 on different S. aureus isolates evidenced a bacteriostatic behavior. Moreover, both compounds 1 and 6, at the lower MIC concentration, did not show significant cytotoxic effects when exposed to HepG2 human hepatic cell lines, paving the way for their potential clinical application.

Novel Metal-Free Synthesis of 3-Substituted Isocoumarins and Evaluation of Their Fluorescence Properties for Potential Applications.

A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1H-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%). Moreover, the fluorescence properties of isocoumarin derivatives were evaluated at the theoretical and experimental levels to determine their potential application in fluorescent materials. These derivatives have good photoluminescence in THF with a large Stokes shift and an absolute fluorescence quantum yield of up to 14%.

Phosphonium Iodide Featuring Blue Thermally Activated Delayed Fluorescence for Highly Efficient X-Ray Scintillator.

Organic scintillators are praised for their abundant element reserves, facile preparation procedures, and rich structures. However, the weak X-ray attenuation ability and low exciton utilization efficiency result in unsatisfactory scintillation performance. Herein, a new family of highly efficient organic phosphonium halide salts with thermally activated delayed fluorescence (TADF) are designed by innovatively adopting quaternary phosphonium as the electron acceptor, while dimethylamine group and halide anions (I-) serve as the electron donor. The prepared butyl(2-[2-(dimethylamino)phenyl]phenyl)diphenylphosphonium iodide (C4-I) exhibits bright blue emission and an ultra-high photoluminescence quantum yield (PLQY) of 100 %. Efficient charge transfer is realized through the unique n-π and anion-π stacking in solid-state C4-I. Photophysical studies of C4-I suggest that the incorporation of I accounts for high intersystem crossing rate (kISC) and reverse intersystem crossing rate (kRISC), suppressing the intrinsic prompt fluorescence and enabling near-pure TADF emission at room temperature. Benefitting from the large Stokes shift, high PLQY, efficient exciton utilization, and remarkable X-ray attenuation ability endowed by I, C4-I delivers an outstanding light yield of 80721 photons/MeV and a low limit of detection (LoD) of 22.79 nGy ⋅ s-1. This work would provide a rational design concept and open up an appealing road for developing efficient organic scintillators with tunable emission, strong X-ray attenuation ability, and excellent scintillator performance.

From Terminal to Spiro-Phosphonium Acceptors, Remarkable Moieties to Develop Polyaromatic NIR Dyes.

Phosphonium-based compounds gain attention as promising photofunctional materials. As a contribution to the emerging field, we present a series of donor-acceptor ionic dyes, which were constructed by tailoring phosphonium (A) and extended π-NR2 (D) fragments to an anthracene framework. The alteration of the π-spacer of electron-donating substituents in species with terminal -+ PPh2 Me groups exhibits a long absorption wavelength up to λabs =527 nm in dichloromethane and shifted the emission to the near-infrared (NIR) region (λ=805 nm for thienyl aniline donor), although at low quantum yield (Φ<0.01). In turn, the introduction of a P-heterocyclic acceptor substantially narrowed the optical bandgap and improved the efficiency of fluorescence. In particular, the phospha-spiro moiety allowed to attain NIR emission (797 nm in dichloromethane) with fluorescence efficiency as high as Φ=0.12. The electron-accepting property of the phospha-spiro constituent outperformed that of the monocyclic and terminal phosphonium counterparts, illustrating a promising direction in the design of novel charge-transfer chromophores.

Organocatalytic Dynamic Kinetic Resolution Enabled Asymmetric Synthesis of Phosphorus-Containing Chiral Helicenes.

The catalytic asymmetric synthesis of phosphorus-containing helicenes remains a formidable challenge, presumably due to the lack of rational design of substrates, right choice of reactions together with highly effective catalysis systems. Herein, we disclosed an efficient and practical DKR-involving (dynamic kinetic resolution) cascade strategy toward synthesizing a novel family of phosphorus-installing helicenes by peptide-mimic phosphonium salt (PPS) catalysis. The sequential process of PPS-catalyzed phospha-Michael attack and copper salt-facilitated aromatization led to the formation of unprecedented phosphorus-containing oxa[5]helicene scaffolds. A wide variety of substrates bearing an assortment of functional groups were compatible with this protocol, furnishing the expected helical compounds in high yields and excellent stereoselectivities. Additionally, the helical products could be conveniently elaborated to promising phosphine ligands with perfectly retained helical chirality, which turned out to be highly efficient chiral ligands in transition metal-catalyzed reactions. These findings not only expand the current library of phosphorus-containing helicenes but also offer insights to explore other challenging scaffolds with molecular chirality.

Fast and Tunable Phosphorescence from Organic Ionic Crystals.

Crystalline diphosphonium iodides [MeR2 P-spacer-R2 Me]I with phenylene (1, 2), naphthalene (3, 4), biphenyl (5) and anthracene (6) as aromatic spacers, are photoemissive under ambient conditions. The emission colors (λem values from 550 to 880 nm) and intensities (Φem reaching 0.75) are defined by the composition and substitution geometry of the central conjugated chromophore motif, and the anion-π interactions. Time-resolved and variable-temperature luminescence studies suggest phosphorescence for all the titled compounds, which demonstrate observed lifetimes of 0.46-92.23 µs at 297 K. Radiative rate constants kr as high as 2.8×105  s-1 deduced for salts 1-3 were assigned to strong spin-orbit coupling enhanced by an external heavy atom effect arising from the anion-π charge-transfer character of the triplet excited state. These rates of anomalously fast metal-free phosphorescence are comparable to those of transition metal complexes and organic luminophores that utilize triplet excitons via a thermally activated delayed fluorescence mechanism, making such ionic luminophores a new paradigm for the design of photofunctional and responsive molecular materials.

Design and Application of Peptide-Mimic Phosphonium Salt Catalysts in Asymmetric Synthesis.

Chiral phosphonium salt catalysis, traditionally classified as a type of phase transfer catalysis, has proven to be a powerful strategy for the stereoselective preparation of diverse optically active molecules. However, there still remain numerous forbidding issues of reactivity and selectivity in such well-known organocatalysis system. Accordingly, the development of new and high-performance phosphonium salt catalysts with unique chiral backbones is highly desirable, yet challenging. This Minireview describes the prominent endeavours in the development of a new family of chiral peptide-mimic phosphonium salt catalysts with multiple hydrogen-bonding donors and their applications in a plethora of enantioselective synthesis during the past few years. Hopefully, this minireview will pave a way for further developing much more efficient and privileged chiral ligands/catalysts featuring exclusively catalytic ability in asymmetric synthesis.

Comprehensive Review on Synthesis, Properties, and Applications of Phosphorus (PIII, PIV, PV) Substituted Acenes with More Than Two Fused Benzene Rings.

This comprehensive review, covering the years 1968-2022, is not only a retrospective investigation of a certain group of linearly fused aromatics, called acenes, but also a presentation of the current state of the knowledge on the synthesis, reactions, and applications of these compounds. Their characteristic feature is substitution of the aromatic system by one, two, or three organophosphorus groups, which determine their properties and applications. The (PIII, PIV, PV) phosphorus atom in organophosphorus groups is linked to the acene directly by a P-Csp2 bond or indirectly through an oxygen atom by a P-O-Csp2 bond.

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes.

A novel representative of sodium 3,4,5-triaryl-1,2-diphosphacyclopentadienide containing a chloro substituent in the meta-position of the aryl groups was obtained with a high yield based on the reaction of tributyl(1,2,3-triarylcyclopropenyl)phosphonium bromide and sodium polyphosphides. Further reaction of sodium 3,4,5-tris(3-chlorophenyl)-1,2-diphosphacyclopentadienide with [FeCp(η6-C6H5CH3)][PF6] complex gives a new 3,4,5-tris(3-chlorophenyl)-1,2-diphosphaferrocene. The electrochemical properties of 3,4,5-tris(3-chlorophenyl)-1,2-diphosphaferrocene were studied and compared to 3,4,5-tris(4-chlorophenyl)-1,2-diphosphaferrocene. It was found that the position of the chlorine atom on the aryl fragment has an influence on the reduction potential of 1,2-diphosphaferrocenes, while the oxidation potentials do not change.

Rational Design 2-Hydroxypropylphosphonium Salts as Cancer Cell Mitochondria-Targeted Vectors: Synthesis, Structure, and Biological Properties.

It has been shown for a wide range of epoxy compounds that their interaction with triphenylphosphonium triflate occurs with a high chemoselectivity and leads to the formation of (2-hydroxypropyl)triphenylphosphonium triflates 3 substituted in the 3-position with an alkoxy, alkylcarboxyl group, or halogen, which were isolated in a high yield. Using the methodology for the disclosure of epichlorohydrin with alcohols in the presence of boron trifluoride etherate, followed by the substitution of iodine for chlorine and treatment with triphenylphosphine, 2-hydroxypropyltriphenylphosphonium iodides 4 were also obtained. The molecular and supramolecular structure of the obtained phosphonium salts was established, and their high antitumor activity was revealed in relation to duodenal adenocarcinoma. The formation of liposomal systems based on phosphonium salt 3 and L-α-phosphatidylcholine (PC) was employed for improving the bioavailability and reducing the toxicity. They were produced by the thin film rehydration method and exhibited cytotoxic properties. This rational design of phosphonium salts 3 and 4 has promising potential of new vectors for targeted delivery into mitochondria of tumor cells.

Development of New Innovative Synthetic Organic Chemistry Using Lone Pairs of Oxygen Atoms.

Oxygen atoms have a lone pair of electrons, so they have high chelation ability, high nucleophilic ability, stabilizing ability of adjacent cations, and take a chelate or oxocarbenium ion structure with Lewis acids and metals. I took advantage of these properties to develop three new reactions, 1) asymmetric synthesis of chiral quaternary carbon centers, 2) asymmetric synthesis using acetal functions, and 3) organic chemistry using acetal-type reactive salt chemical species, and applied them to biologically active natural products synthesis. New reactions described here are all innovative and useful for natural products synthesis. In particular, the first asymmetric synthesis of fredericamycin A, and concise asymmetric synthesis of anthracycline antibiotics, scyphostatin, (+)-Sch 642305, (-)-stenine, clavolonine, (+)-rubrenolide, (+)-rubrynolide, (+)-centrolobine, and decytospolide A and B, etc., are noteworthy. Furthermore, since reactions using acetal-type reactive salt chemical species allow the coexistence of functional groups that normally cannot coexist, the reactions using reactive salts have potential to change the retrosynthesis planned based on conventional reactions.

Mechanochemical P-derivatization of 1,3,5-Triaza-7-Phosphaadamantane (PTA) and Silver-Based Coordination Polymers Obtained from the Resulting Phosphabetaines.

We have described earlier that in aqueous solutions, the reaction of 1,3,5-triaza-7-phosphaadamantane (PTA) with maleic acid yielded a phosphonium-alkanoate zwitterion. The same reaction with 2-methylmaleic acid (citraconic acid) proceeded much slower. It is reported here, that in the case of glutaconic and itaconic acids (constitutional isomers of citraconic acid), formation of the corresponding phosphabetaines requires significantly shorter reaction times. The new phosphabetaines were isolated and characterized by elemental analysis, multinuclear NMR spectroscopy and ESI-MS spectrometry. Furthermore, their molecular structures in the solid state were determined by single crystal X-ray diffraction (SC-XRD). Synthesis of the phosphabetaines from PTA and unsaturated dicarboxylic acids was also carried out mechanochemically with the use of a planetary ball mill, and the characteristics of the syntheses in solvent and under solvent-free conditions were compared. In aqueous solutions, the reaction of the new phosphabetaines with Ag(CF3SO3) yielded Ag(I)-based coordination polymers. According to the SC-XRD results, in these polymers the Ag(I)-ion coordinates to the N and O donor atoms of the ligands; however, Ag(I)-Ag(I) interactions were also identified. The Ag(I)-based coordination polymer (CP1.2) formed with the glutaconyl derivative of PTA (1) showed considerable antimicrobial activity against both Gram-negative and Gram-positive bacteria and yeast strains.

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita-Baylis-Hillman adducts.

The direct transformation of Morita-Baylis-Hillman (MBH) adducts into molecules of interest is a crucial process wherein allylic hydroxy-protected or halogenated MBH adducts are commonly preferred. Herein, we report an azidophosphonium salt (AzPS)-catalysed straight forward protocol for synthesising structurally demanding (E)/(Z)-cinnamyl-1H-1,2,3-triazoles and halomethylcoumarins from MBH adducts. The novel methodology, efficient catalyst, and direct utilization of MBH adducts under mild reaction conditions qualify the reported procedures as powerful synthetic tools.

Synthesis and Antimicrobial Properties of Novel Phosphonium Salts Bearing 1,4-Dihydroxyaryl Fragment.

A versatile two-step pathway to the synthesis of triaryl(2,5-dihydroxy-6-methyl-3-(propan-2-yl)phenyl)- and triaryl(1,4-dihydroxynaphthyl)phosphonium salts from triarylphosphonium trifluoroacetates was developed. The reaction proceeds under mild conditions (20 °C, CH2 Cl2 ) with high yields (88-95 %). Some representatives of this series possess low hemolytic and high bactericidal activity against Gram-positive bacteria.

A Photo-Triggered Traceless Staudinger-Bertozzi Ligation Reaction.

The use of light to control the course of a chemical/biochemical reaction is an attractive idea because of its ease of administration with high precision and fine spatial resolution. Staudinger ligation is one of the commonly adopted conjugation processes that involve a spontaneous reaction between azides and arylphosphines to form iminophosphoranes, which further hydrolyze to give stable amides. We designed an anthracenylmethyl diphenylphosphinothioester (1) that showed promising Staudinger ligation reactivity upon photo-excitation. Broadband photolysis at 360-400 nm in aqueous organic solvents induced heterolytic cleavage of its anthracenylmethyl-phosphorus bond, releasing a diphenylphosphinothioester (2) as an efficient traceless Staudinger-Bertozzi ligation reagent. The quantum yield of such a photo-induced heterolytic bond-cleavage at the optimal wavelength of photolysis (376 nm) at room temperature is ≥0.07. This work demonstrated the feasibility of photocaging arylphosphines to realize the photo-triggering of the Staudinger ligation reaction.

Synthesis and characterization of n-phosphonium chitosan and its virucidal activity evaluation against coronavirus.

Despite the worldwide vaccination effort against COVID-19, the demand for biocidal materials has increased. One promising solution is the chemical modification of polysaccharides, such as chitosan, which can provide antiviral activity through the insertion of cationic terminals. In this study, chitosan was modified with (4-carboxybutyl) triphenylphosphonium bromide to create N-phosphonium chitosan (NPCS), a quaternized derivative. The resulting NPCS samples with three degrees of substitution (15.6 %, 19.8 % and 24.2 %) were characterized and found to have improved solubility in water and alkaline solutions but reduced thermal stability. The particles zeta potential exhibits positive charges and is directly correlated with the degree of substitution of the derivative. In virucidal assays, all NPCS samples were able to inhibit 99.999 % of the MHV-3 coronavirus within 5 min at low concentrations of 0.1 mg/mL, while maintaining low cytotoxicity to L929 cells. In addition to its potential application against current coronavirus strains, NPCS could also be valuable in combating future pandemics caused by other viral pathogens. The antiviral properties of NPCS make it a promising material for use in coating surface and personal protective equipment to limit the spread of disease-causing viruses.

Magnetic biochar/quaternary phosphonium salt reduced antibiotic resistome and pathobiome on pakchoi leaves.

Antibiotic resistance genes (ARGs) and human pathogenic bacteria (HPB) in leafy vegetable is a matter of concern as they can be transferred from soil, atmosphere, and foliar sprays, and poses a potential risk to public health. While traditional disinfection technologies are effective in reducing the presence of ARGs and HPB in soil. A new technology, foliar spraying with magnetic biochar/quaternary ammonium salt (MBQ), was demonstrated and applied to the leaf surface. High-throughput quantitative PCR targeting 96 valid ARGs and 16 S rRNA sequencing were used to assess its efficacy in reducing ARGs and HPB. The results showed that spraying MBQ reduced 97.0 ± 0.81% of "high-risk ARGs", associated with seven classes of antibiotic resistance in pakchoi leaves within two weeks. Water washing could further reduce "high-risk ARGs" from pakchoi leaves by 19.8%- 24.6%. The relative abundance of HPB closely related to numerous ARGs was reduced by 15.2 ± 0.23% with MBQ application. Overall, this study identified the potential risk of ARGs from leafy vegetables and clarified the significant implications of MBQ application for human health as it offers a promising strategy for reducing ARGs and HPB in leafy vegetables.