Phosphine Compounds Research Articles

N-Heterocyclic Carbene Enabled Copper Catalyzed Asymmetric Synthesis of Pyrimidinyl Phosphine with both Axial and P-Stereogenicity.

P-stereogenic phosphines, renowned for their utility as ligands and catalysts, have been instrumental in the field of asymmetric catalysis. However, the catalytic asymmetric synthesis of chiral ligands possessing both axial and phosphine chirality remains a significant challenge. Here, we present the successful demonstration of a Cu-catalyzed asymmetric C-P construction using in situ generated secondary phosphine and heteroaryl chloride. By introducing a chiral NHC ligand and an achiral diphosphine auxiliary ligand, we effectively alleviated the poisoning effect caused by phosphine(III) compounds and suppressed the nonenantioselective background reaction. The reaction exhibited excellent enantioselectivity, with up to 96 % ee, and good diastereoselectivity, with up to 14 : 1 dr, when employing less sterically hindered secondary phosphines. This particular substrate poses a significant challenge due to its strong poisoning effect in copper catalysis.

Nickel-Catalyzed Enantioselective Alkylation of Primary Phosphines.

Functional molecules derived from stereogenic phosphorus centers have important applications in the discovery of drugs and agrochemicals. They are also widely utilized as chiral ligands or organocatalysts for diverse asymmetric transformations. However, access to P-stereogenic motifs has always been regarded as a highly challenging yet desirable goal in organic synthesis. The development of general and practical methods for the stereoselective construction of synthetically versatile P(III)-stereogenic phosphines is particularly appealing but remains elusive. Herein, we describe a nickel-catalyzed asymmetric alkylation of primary phosphines with alkyl halides for the synthesis of P-stereogenic secondary phosphine-boranes with high enantioselectivity and broad substrate scope. The resulting optically active secondary phosphine-boranes allow for further stereospecific transformations, thereby establishing a modular and efficient platform for the diversity-oriented construction of P-stereogenic phosphine compounds.

Synthesis of spiroindoline derivatives and biphenyl compounds in green solvent via a “capture–release” mechanism using modified polyacrylonitrile fiber as a catalyst

Green synthesis of critical bioactive molecules and fine chemicals is attracting increasing interest. This study investigates the use of two distinct functionalized polyacrylonitrile (PAN) fibers (PANEDBPF and PANEDBP-Pd0F) as effective catalysts in a green solvent comprising ethanol and water. Firstly, a PAN fiber was modified using 2-(diphenylphosphino) ethylamine, a strongly nucleophilic phosphine compound, to obtain PANEDBPF. Spiroindoline derivatives were obtained in 98 % yields when the reaction was conducted using 5 mol% of PANEDBPF as the catalyst at 70 °C for 30 min. Next, we loaded PdNPs onto PANEDBPF to obtain PANEDBP-Pd0F. When the Suzuki coupling reaction was conducted at room temperature (25 °C) using 0.5 mol% of PANEDBP-Pd0F, the products were obtained in an extremely high yield of 99 %. Additionally, the unique enrichment of the substrate by the functionalized fibers during the reaction and the subsequent release of the product from the microenvironment conform to the “capture–release” reaction mode of catalysis. Both PANEDBPF and PANEDBP-Pd0F demonstrated good gram-scale amplification, repeatability, catalytic activity, and stability. Hence, they are highly promising candidates for green chemistry applications.

Gas‐free initiation for free‐radical frontal polymerization through charge transfer complexes

AbstractFrontal polymerization is a process in which a localized reaction zone propagates through the coupling of thermal transport and the Arrhenius kinetics of exothermic polymerization. Most initiators that have been used produce volatile by‐products, which create bubbles and voids. Tetraalkyl ammonium persulfates have been used but these require synthesis and do not have long shelf lives. A charge transfer complex (CTC) composed of an iodonium salt, and a phosphine compound has been identified as a gas‐free initiator for free‐radical thermal frontal polymerization. This CTC has 4‐(dimethylamino)phenyldiphenly phophine (DMAPDP) as the donor and p‐(octyloxyphenyl)phenyliodonium hexafluoroantimonate as the acceptor (IOC‐8). The CTC was tested with several acrylates, and all were found to support bubble‐free fronts. We determined the CTC mole ratio for some monomers at which the front velocity reaches a plateau.

Ligand-Free Iron-Catalyzed Construction of C-P Bonds via Phosphorylation of Alcohols: Synthesis of Phosphine Oxides and Phosphine Compounds.

An efficient method for the construction of C-P(V) and C-P(III) bonds via the iron-catalyzed phosphorylation of alcohols under ligand-free conditions is disclosed. This strategy represents a straightforward process to prepare a series of phosphine oxides and phosphine compounds in good to excellent yields from the readily available alcohols and P-H compounds. A plausible mechanism is also proposed. We anticipate that this mode of transforming simple alcohols would apply in chemical synthesis widely.

Nitroxyl donating and visualization with a coumarin-based fluorescence probe

Nitroxyl (HNO), the single-electron reduction product of nitric oxide (NO), has attracted great interest in the treatment of congestive heart failure in clinical trials. In this paper, we describe the first coumarin-based compound N-hydroxy-2-oxo-2H-chromene-6-sulfonamide (CD1) as a dualfunctional HNO donor, which can release both an HNO signaling molecule and a fluorescent reporter. Under physiological conditions (pH 7.4 and 37 °C), the CD1 HNO donor can readily decompose with a half-life of ∼90 min. The corresponding stoichiometry HNO from the CD1 donor was confirmed using both Vitamin B12 and phosphine compound traps. In addition to HNO releasing, specifically, the degradation product 2-oxo-2H-chromene-6-sulfinate (CS1) was generated as a fluorescent marker during the decomposition. Therefore, the HNO amount released in situ can be accurately monitored through fluorescence generation. As compared to the CD1 donor, the fluorescence intensity increased by about 4.9-fold. The concentration limit of detection of HNO releasing was determined to be ∼0.13 μM according to the fluorescence generation of CS1 at physiological conditions. Moreover, the bioimaging of the CD1 donor was demonstrated in the cell culture of HeLa cells, where the intracellular fluorescence signals were observed, inferring the site of HNO release. Finally, we anticipate that this novel coumarin-based CD1 donor opens a new platform for exploring the biology of HNO.

Construction of Bidentate Phosphines Enabled by Photoinduced Reductive Diphosphination of Alkenes.

The diphosphination of alkenes through a radical pathway offers a promising approach for the rapid construction of aryl bisphosphines. However, such a synthetic strategy has not been successfully applied to the preparation of alkyl bisphosphines, partially due to the difficulties in the generation of phosphorus-centered radicals from common alkyl phosphine compounds. We herein demonstrate that this challenge can be overcome by hiring Janus-faced chlorophosphine as the phosphine source that can act as not only a radical precursor to generate phosphine-centered radicals but also a radicalphile to capture alkyl radicals. With this novel strategy, a photocatalyzed reductive diphosphination reaction has been established, allowing for a straightforward synthesis of both aryl and alkyl 1,2-bisphosphines from readily accessible alkenes and chlorophosphines.

Synthesis and nitroxyl (HNO) donating properties of benzoxadiazole-based Piloty's acids

Developing functional nitroxyl (HNO) donors play a significant role in the further exploration of endogenous HNO in biochemistry and pharmacology. In this work, two novel Piloty's acids (SBD-D1 and SBD-D2) were proposed by incorporating benzoxadiazole-based fluorophores, in order to achieve the dual-function of releasing both HNO and a fluorophore in situ. Under physiological conditions, both SBD-D1 and SBD-D2 efficiently donated HNO (t1/2 = 10.96 and 8.18 min, respectively). The stoichiometric generation of HNO was determined by both Vitamin B12 and phosphine compound trap. Interestingly, due to the different substitution groups on the aromatic ring, SBD-D1 with the chlorine showed no fluorescence emission, but SBD-D2 was strongly fluorescent due to the presence of the dimethylamine group. Specifically, the fluorescent signal would decrease during the release process of HNO. Moreover, theoretical calculations were performed to understand the emission difference. A strong radiation derived from benzoxadiazole with dimethylamine group due to the large transition dipole moment (∼4.3 Debye), while the presence of intramolecular charge transfer process in the donor with chlorine group caused a small transition dipole moment (<0.1 Debye). Finally, these studies would contribute to the future design and application of novel functional HNO donors for the exploration of HNO biochemistry and pharmacology.

NiII-Catalyzed Enantioselective Anti-Markovnikov Hydrophosphination of Unactivated Alkynes

A mechanism-inspired, reaction mode-controlled enantio- and regioselective anti-Markovnikov hydrophosphination of unactivated alkynes was accomplished by NiII catalysis. Alkenyl phosphine products could be obtained with high regio- and enantioselectivity and easily derivatized to structurally diverse chiral phosphine compounds. Mechanistic studies on both Ni0-catalyzed Markovnikov addition and NiII-catalyzed anti-Markovnikov addition have been carried out by combining experimental and computational methods. In the Ni0 system, an allyl nickel complex was obtained as the catalyst resting state whose structure was unambiguously determined by single-crystal XRD analysis. A sequential hydrometallation, ligand exchange, and reductive elimination mechanism was elucidated corroboratively by DFT calculations. In the NiII system, the cationic secondary phosphine nickel complex serves as the active catalyst. A migratory insertion and protonation sequence was operative to accomplish anti-Markovnikov hydrophosphination.

A Robust HPLC Method for Easily Oxidizable Phosphine Ligand Analysis.

Phosphine ligands are widely used in the manufacture of small molecule active pharmaceutical ingredients, for they play a key role in transition-metal-catalyzed cross-coupling. However, chromatographic analysis of phosphine ligands can be challenging because of the easily oxidizable nature of this class of compounds. This manuscript describes an out-of-specification (OOS) investigation study of XPhos raw material analysis by high performance liquid chromatography (LC). It is concluded that on-column degradation/oxidation is the culprit behind this OOS result. In addition, a slightly modified yet much improved new LC method is developed by adding a trace amount of tris(2-carboxyethyl)phosphine (TCEP) into the aqueous mobile phase. TCEP is also a phosphine compound and is commonly used as a reducing reagent in molecular biology. The trace amount of TCEP serves as a surrogate reagent to passivate the LC column and eliminate the on-column degradation/oxidation. As a result, a much more robust performance is achieved with greatly improved method precision and sensitivity. This is a general approach and can be applied to the LC analysis of many other phosphine ligands in the same manner.

Towards Axially Chiral Pyrazole-Based Phosphorus Scaffolds by Dipeptide-Phosphonium Salt Catalysis.

Given the comparatively lower rotational barriers, the catalytic asymmetric construction of axially chiral biaryl structures, especially those containing a five-membered heterocycle, still remains a challenge. Herein, we described a general and modular protocol to access atropisomeric arylpyrazole scaffolds containing a phosphorus unit by a dipeptide phosphonium salt catalyzed reaction involving an oxidative central-to-axial chirality conversion. This reaction features excellent yields and enantioselectivities, broad substrate scope, and a low catalyst loading, delivering axially chiral phosphine compounds.

Towards Axially Chiral Pyrazole‐Based Phosphorus Scaffolds by Dipeptide‐Phosphonium Salt Catalysis

AbstractGiven the comparatively lower rotational barriers, the catalytic asymmetric construction of axially chiral biaryl structures, especially those containing a five‐membered heterocycle, still remains a challenge. Herein, we described a general and modular protocol to access atropisomeric arylpyrazole scaffolds containing a phosphorus unit by a dipeptide phosphonium salt catalyzed reaction involving an oxidative central‐to‐axial chirality conversion. This reaction features excellent yields and enantioselectivities, broad substrate scope, and a low catalyst loading, delivering axially chiral phosphine compounds.

Dual inhibition of thioredoxin reductase and proteasome is required for auranofin-induced paraptosis in breast cancer cells

Auranofin (AF), a gold (I)-containing phosphine compound, is being investigated for oncological application as a repurposed drug. We show here that 4~5 µM AF induces paraptosis, a non-apoptotic cell death mode characterized by dilation of the endoplasmic reticulum (ER) and mitochondria, in breast cancer cells. Although the covalent inhibition of thioredoxin reductase (TrxR), an enzyme that critically controls intracellular redox homeostasis, is considered the primary mechanism of AF’s anticancer activity, knockdown of TrxR1 did not induce paraptosis. Instead, both TrxR1 knockdown plus the proteasome inhibitor (PI), bortezomib (Bz), and 2 μM AF plus Bz induced paraptosis, thereby mimicking the effect of 5 μM AF. These results suggest that the paraptosis induced by 5 μM AF requires the inhibition of both TrxR1 and proteasome. We found that TrxR1 knockdown/Bz or subtoxic doses of AF and Bz induced paraptosis selectively in breast cancer cells, sparing non-transformed MCF10A cells, whereas 4~5 μM AF killed both cancer and MCF10A cells. GSH depletion was found to be more critical than ROS generation for the paraptosis induced by dual TrxR1/proteasome inhibition. In this process, the ATF4/CHAC1 (glutathione-specific gamma-glutamylcyclotransferase 1) axis leads to GSH degradation, contributing to proteotoxic stress possibly due to the accumulation of misfolded thiol-containing proteins. These results suggest that the paraptosis-inducing strategy of AF plus a PI may provide an effective therapeutic strategy against pro-apoptotic therapy-resistant cancers and reduce the potential side effects associated with high-dose AF.

Electrochemical oxidative intramolecular annulation of aryl phosphine compounds: an efficient approach for synthesizing π-conjugated phosphonium salts

A simple electrochemical oxidation cyclization strategy for the construction of polycyclic phosphonium salts skeletons from trivalent arylphosphines was established.

A Ni-catalyzed asymmetric C(sp)-P cross-coupling reaction for the synthesis of P-stereogenic alkynylphosphines.

Due to the high reactivity of the triple bond, P-stereogenic alkynylphosphines could be easily derivatized, serving as universal building blocks for structurally diverse phosphine compounds. However, the synthesis of alkynylphosphines via direct P-C bond formation was unprecedented. Here, we report an efficient method for the synthesis of P-stereogenic alkynylphosphines with high enantioselectivity via a Ni-catalyzed asymmetric cross-coupling reaction. The reaction could tolerate a variety of functional groups, affording products that can be converted into useful phosphine derivatives.

Secondary Phosphine Sulfide-Enabled Iridium-Catalyzed Asymmetric Allylic Substitution.

An iridium-catalyzed asymmetric synthesis of branched allylic phosphine compounds under mild conditions is reported. Products bearing various functional groups can be synthesized with excellent stereoselectivity (up to 99.9 % ee) and regioselectivity. The employment of phosphine sulfides with relatively low deactivation capacity against metal catalysts is crucial for the success of this reaction.

Secondary Phosphine Sulfide‐Enabled Iridium‐Catalyzed Asymmetric Allylic Substitution

AbstractAn iridium‐catalyzed asymmetric synthesis of branched allylic phosphine compounds under mild conditions is reported. Products bearing various functional groups can be synthesized with excellent stereoselectivity (up to 99.9 % ee) and regioselectivity. The employment of phosphine sulfides with relatively low deactivation capacity against metal catalysts is crucial for the success of this reaction.

Palladium-catalyzed desymmetric hydrophosphination of 3,3-disubstituted cyclopropenes

In this issue of Chem Catalysis , Wang and co-workers report palladium-catalyzed diastereo- and enantioselective desymmetric hydrophosphination of 3,3-disubstituted cyclopropenes. This pathway allows the synthesis of chiral phosphine compounds with two vicinal carbon stereocenters with excellent diastereo- and enantioselectivity. Further, hydrophosphination products can be transformed synthetically for multiple applications. In this issue of Chem Catalysis , Wang and co-workers report palladium-catalyzed diastereo- and enantioselective desymmetric hydrophosphination of 3,3-disubstituted cyclopropenes. This pathway allows the synthesis of chiral phosphine compounds with two vicinal carbon stereocenters with excellent diastereo- and enantioselectivity. Further, hydrophosphination products can be transformed synthetically for multiple applications.

The effect of ligand and acid promoter on hydroesterification of ethylene to methyl propionate and kinetic studies

A new palladium/tris(4-fluorophenyl)phosphine/p-toluenesulfonic acid catalytic system was developed to synthesize methyl propionate from ethylene hydroesterification. The influence of phosphine ligands and acid promoters on catalytic activity was systematically studied. A volcano relationship between the catalytic activity and the electric effect of phosphine ligand was achieved through the characterization of 31P NMR of selenium phosphine compounds. An acid strength range favorable to the hydroesterification of ethylene was found by characterizing the pKa value of Brønsted acid. Then, the effect of phosphine ligand/Pd(OAc)2 ratio, p-toluenesulfonic/Pd(OAc)2 ratio, temperature, time, and pressure on this reaction were investigated. Finally, the elementary reaction-based kinetic model was developed, which indicated that nucleophilic attack of methanol on the Pd-acyl intermediate to give methyl propionate is the rate-determining step. The activation barrier of rate-determining step is 83.1 kJ·mol−1.

Terbium-based phosphine compound: A long-term cycling life material for high-performance supercapacitor

• Tb-based phosphine compound has first been used as an electrode of supercapacitor. • The highest capacitance of 1866 F g −1 at 2 A/g can be obtained. • 81.02% of initial capacitance can be remained after 30,000 cycles at 10 A/g . Herein, a one-step route has been developed for synthesizing terbium-phosphine (Tb-(Ph) 3 P) compound, which exhibited an excellent rate capability and an outstanding long cycling stability. The highest specific capacitance of 1866 F g −1 has been obtained at 2 A/g in 6 M KOH, and the capacitance retention of 81.02% has also been achieved at 10 A/g after 30,000 cycles, resulted in a maximum energy density of 93.3 W h kg −1 and a maximum power density of 6.04 kW kg −1 . Such an excellent performance might be attributed to the insolvability and intrinsic characteristics of the Tb-based phosphine complexes, which provided abundant active sites for the charge storage and conductive networks for electron transport. Moreover, a flexible quasi-solid-state asymmetric supercapacitor composed of Tb-(Ph) 3 P and active carbon has been fabricated, and a specific capacitance of 275 mF cm −2 at a current density of 2 mA cm −2 , and a capacitance retention of 100% after 10,000 cycles at 10 mA cm −2 have been respectively achieved, exhibiting an excellent electrochemical property. Thus, the present work might provide a new strategy for designing new metal–organic complex materials and their applications in energy storage devices.