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Molecules (Basel, Switzerland) Jul 2022A Knoevenagel based redox-reaction promoted by intramolecular phosphine sources is presented for the first time. The influence of different diketones, aldehydes, bases...
A Knoevenagel based redox-reaction promoted by intramolecular phosphine sources is presented for the first time. The influence of different diketones, aldehydes, bases and acids was investigated. The effects of different substituents were evaluated based on their electronical influence on the diketone structure. With the obtained results a mechanism is proposed, giving information about transition states formed during the reaction, which can lead to different products. This type of an internal redox transformation with a phosphine oxide moiety remaining in the molecule after the redox reaction represents a new type of reaction.
Topics: Catalysis; Ketones; Oxidation-Reduction; Phosphines; Stereoisomerism
PubMed: 35956825
DOI: 10.3390/molecules27154875 -
Nature Jul 2023The chemical activation of water would allow this earth-abundant resource to be transferred into value-added compounds, and is a topic of keen interest in energy...
The chemical activation of water would allow this earth-abundant resource to be transferred into value-added compounds, and is a topic of keen interest in energy research. Here, we demonstrate water activation with a photocatalytic phosphine-mediated radical process under mild conditions. This reaction generates a metal-free PR-HO radical cation intermediate, in which both hydrogen atoms are used in the subsequent chemical transformation through sequential heterolytic (H) and homolytic (H) cleavage of the two O-H bonds. The PR-OH radical intermediate provides an ideal platform that mimics the reactivity of a 'free' hydrogen atom, and which can be directly transferred to closed-shell π systems, such as activated alkenes, unactivated alkenes, naphthalenes and quinoline derivatives. The resulting H adduct C radicals are eventually reduced by a thiol co-catalyst, leading to overall transfer hydrogenation of the π system, with the two H atoms of water ending up in the product. The thermodynamic driving force is the strong P=O bond formed in the phosphine oxide by-product. Experimental mechanistic studies and density functional theory calculations support the hydrogen atom transfer of the PR-OH intermediate as a key step in the radical hydrogenation process.
PubMed: 37380779
DOI: 10.1038/s41586-023-06141-1 -
Chemical Science May 2024Nickel-catalyzed cross-couplings of (hetero)aryl electrophiles with a diversity of nucleophiles (nitrogen, oxygen, carbon, and others) have evolved into competitive... (Review)
Review
Nickel-catalyzed cross-couplings of (hetero)aryl electrophiles with a diversity of nucleophiles (nitrogen, oxygen, carbon, and others) have evolved into competitive alternatives to well-established palladium- and copper-based protocols for the synthesis of (hetero)aryl products, including (hetero)anilines and (hetero)aryl ethers. A survey of the literature reveals that the use of cage phosphine (CgP) 'DalPhos' (DALhousie PHOSphine) bisphosphine-type ligands operating under thermal conditions currently offers the most broad substrate scope in nickel-catalyzed cross-couplings of this type, especially involving (hetero)aryl chlorides and phenol-derived electrophiles. The development and application of these DalPhos ligands is described in a ligand-specific manner that is intended to serve as a guide for the synthetic chemistry end-user.
PubMed: 38784740
DOI: 10.1039/d4sc01253d -
Journal of the American Chemical Society Sep 2022Template-directed synthesis of nucleic acids in the polymerase chain reaction is based on the use of a primer, which is elongated in the replication process. The...
Template-directed synthesis of nucleic acids in the polymerase chain reaction is based on the use of a primer, which is elongated in the replication process. The attachment of a high affinity primer to the end of a template chain has been implemented for templating the synthesis of triazole oligomers. A covalent ester base-pair was used to attach a primer to a mixed sequence template. The resulting primed template has phenol recognition units on the template, which can form noncovalent base-pairs with phosphine oxide monomers via H-bonding, and an alkyne group on the primer, which can react with the azide group on a phosphine oxide monomer. Competition reactions between azides bearing phosphine oxide and phenol recognition groups were used to demonstrate a substantial template effect, due to H-bonding interactions between the phenols on the template and phosphine oxides on the azide. The largest rate acceleration was observed when a phosphine oxide 2-mer was used, because this compound binds to the template with a higher affinity than compounds that can only make one H-bond. The P NMR spectrum of the product duplex shows that the H-bonds responsible for the template effect are present in the product, and this result indicates that the covalent ester base-pairs and noncovalent H-bonded base-pairs developed here are geometrically compatible. Following the templated reaction, it is possible to regenerate the template and liberate the copy strand by hydrolysis of the ester base-pair used to attach the primer, thus completing a formal replication cycle.
Topics: Alkynes; Azides; Esters; Nucleic Acids; Oxides; Phenol; Phosphines; Templates, Genetic; Triazoles
PubMed: 36082527
DOI: 10.1021/jacs.2c08119 -
ChemistryOpen Nov 2022The substitution reaction of phosphinates with a binaphthyloxy group at the phosphorus atom with lithium alkoxides proceeded with good to high efficiencies to give...
The substitution reaction of phosphinates with a binaphthyloxy group at the phosphorus atom with lithium alkoxides proceeded with good to high efficiencies to give P-chirogenic phosphinates with a high enantiomeric ratio. As alcohols, primary, secondary, and tertiary alcohols could be used, and the use of tert-butyl alcohol yielded the products with a higher enantiomeric ratio. A substrate with two different alkyl groups on the phosphorus atom could also participate in the substitution reaction to give the corresponding products in good yields with excellent selectivity. The molecular structures of one of the substrates and the corresponding products, determined by X-ray analyses, proved that the substitution reaction at the phosphorus atom proceeded with inversion of the absolute configuration. The usefulness of the reaction was demonstrated by using it to prepare a drug candidate for Duchenne muscular dystrophy. Finally, thionation of the resulting phosphinates was carried out to form P-chirogenic phosphinothioates.
Topics: Stereoisomerism; Molecular Structure; Alcohols; Phosphorus; Esterification
PubMed: 35261188
DOI: 10.1002/open.202100294 -
International Journal of Molecular... May 2021Phosphinate pseudopeptide are analogs of peptides containing phosphinate moiety in a place of the amide bond. Due to this, the organophosphorus fragment resembles the...
Phosphinate pseudopeptide are analogs of peptides containing phosphinate moiety in a place of the amide bond. Due to this, the organophosphorus fragment resembles the tetrahedral transition state of the amide bond hydrolysis. Additionally, it is also capable of coordinating metal ions, for example, zinc or magnesium ions. These two properties of phosphinate pseudopeptides make them an ideal candidate for metal-related protease inhibitors. This research investigates the influence of additional residue in the P2 position on the inhibitory properties of phosphinopeptides. The synthetic strategy is proposed, based on retrosynthetic analysis. The N-C-P bond formation in the desired compounds is conveniently available from the three-component condensation of appropriate amino components, aldehydes, and hypophosphorous acid. One of the crucial synthetic steps is the careful selection of the protecting groups for all the functionals. Determination of the inhibitor activity of the obtained compounds has been done using UV-Vis spectroscopy and standard substrate -Leu--nitroanilide toward the enzymes isolated from the porcine kidney (SsLAP, Leucine aminopeptidase) and barley seeds (HvLAP, Leucine aminopeptidase). An efficient procedure for the preparation of phosphinotripeptides has been performed. Activity test shown that introduction of additional residue into P2 position obtains the micromolar range inhibitors of SsLAP and HvLAP. Moreover, careful selection of the residue in the P2 position should improve its selectivity toward mammalian and plant leucyl aminopeptidases.
Topics: Animals; Enzyme Inhibitors; Leucyl Aminopeptidase; Models, Molecular; Peptide Fragments; Phosphines; Protein Conformation; Swine
PubMed: 34065004
DOI: 10.3390/ijms22105090 -
Journal of the American Chemical Society May 2022Fluorogenic bioorthogonal reactions enable biomolecule visualization in real time. These reactions comprise reporters that "light up" upon reaction with complementary...
Fluorogenic bioorthogonal reactions enable biomolecule visualization in real time. These reactions comprise reporters that "light up" upon reaction with complementary partners. While the spectrum of fluorogenic chemistries is expanding, few transformations are compatible with live cells due to cross-reactivities or insufficient signal turn-on. To address the need for more suitable chemistries for cellular imaging, we developed a fluorogenic reaction featuring cyclopropenone reporters and phosphines. The transformation involves regioselective activation and cyclization of cyclopropenones to form coumarin products. With optimal probes, the reaction provides >1600-fold signal turn-on, one of the highest fluorescence enhancements reported to date. The bioorthogonal motifs were evaluated in vitro and in cells. The reaction was also found to be compatible with other common fluorogenic transformations, enabling multicomponent, real-time imaging. Collectively, these data suggest that the cyclopropenone-phosphine reaction will bolster efforts to track biomolecule targets in their native settings.
Topics: Cyclopropanes; Fluorescent Dyes
PubMed: 35442034
DOI: 10.1021/jacs.2c02058 -
Chemistry (Weinheim An Der Bergstrasse,... Jan 2022We report the synthesis and properties of the much sought-after tris(1,1,3,3-tetramethylguanidinyl) phosphine P(tmg) , a crystalline, superbasic phosphine accessible...
We report the synthesis and properties of the much sought-after tris(1,1,3,3-tetramethylguanidinyl) phosphine P(tmg) , a crystalline, superbasic phosphine accessible through a short and scalable procedure from the cheap and commercially available bulk chemicals 1,1,3,3-tetramethylguanidine, tris(dimethylamino)-phosphine and phosphorus trichloride. The new phosphine exhibits exceptional electron donor properties and readily forms transition metal complexes with gold(I), palladium(II) and rhodium(I) precursors. The formation of zwitterionic Lewis base adducts with carbon dioxide and sulfur dioxide was explored. In addition, the complete series of phosphine chalcogenides was prepared from the reaction of P(tmg) with N O and the elemental chalcogens.
PubMed: 34793627
DOI: 10.1002/chem.202104021 -
Molecules (Basel, Switzerland) Mar 2022For decades, various plants have been studied as sources of biologically active compounds. Compounds with anticancer and antimicrobial properties are the most frequently... (Review)
Review
For decades, various plants have been studied as sources of biologically active compounds. Compounds with anticancer and antimicrobial properties are the most frequently desired. Cruciferous plants, including Brussels sprouts, broccoli, and wasabi, have a special role in the research studies. Studies have shown that consumption of these plants reduce the risk of lung, breast, and prostate cancers. The high chemopreventive and anticancer potential of cruciferous plants results from the presence of a large amount of glucosinolates, which, under the influence of myrosinase, undergo an enzymatic transformation to biologically active isothiocyanates (ITCs). Natural isothiocyanates, such as benzyl isothiocyanate, phenethyl isothiocyanate, or the best-tested sulforaphane, possess anticancer activity at all stages of the carcinogenesis process, show antibacterial activity, and are used in organic synthesis. Methods of synthesis of sulforaphane, as well as its natural or synthetic bifunctional analogues with sulfinyl, sulfanyl, sulfonyl, phosphonate, phosphinate, phosphine oxide, carbonyl, ester, carboxamide, ether, or additional isothiocyanate functional groups, and with the unbranched alkyl chain containing 2-6 carbon atoms, are discussed in this review. The biological activity of these compounds are also reported. In the first section, glucosinolates, isothiocyanates, and mercapturic acids (their metabolites) are briefly characterized. Additionally, the most studied anticancer and antibacterial mechanisms of ITC actions are discussed.
Topics: Isothiocyanates; Sulfoxides
PubMed: 35268851
DOI: 10.3390/molecules27051750 -
Chemical Science Feb 2022Chiral bisphosphine ligands are of key importance in transition-metal-catalyzed asymmetric synthesis of optically active products. However, the transition metals...
Chiral bisphosphine ligands are of key importance in transition-metal-catalyzed asymmetric synthesis of optically active products. However, the transition metals typically used are scarce and expensive noble metals, while the synthetic routes to access chiral phosphine ligands are cumbersome and lengthy. To make homogeneous catalysis more sustainable, progress must be made on both fronts. Herein, we present the first catalytic asymmetric hydrophosphination of α,β-unsaturated phosphine oxides in the presence of a chiral complex of earth-abundant manganese(i). This catalytic system offers a short two-step, one-pot synthetic sequence to easily accessible and structurally tunable chiral 1,2-bisphosphines in high yields and enantiomeric excess. The resulting bidentate phosphine ligands were successfully used in asymmetric catalysis as part of earth-abundant metal based organometallic catalysts.
PubMed: 35222914
DOI: 10.1039/d1sc06694c