Phosphine Derivatives Research Articles

Additivity Rule (or Sum Rule) as a Prognostic Tool for Energy Value of Highest Occupied Molecular Orbital (or HOMO) of Organic Molecule

In this review, we consider the possibility of an extended application of the additivity rule, namely, for a theoretical calculation of the energy of a higher filled molecular orbital. The author obtained and checked the reference data for the main functional groups of organic compounds using the example of organic derivatives of phosphine (using the PCGAMESS2009 quantum chemical software package) both for compounds that are prone to and do not have conjugation.

Functional Phosphine Derivatives Having Stationary and Flexible Chiralities: Their Preparation and Chirality Controlling.

Various functional secondary and tertiary phosphines, or their derivatives, containing stationary chiral phosphorus and flexible chiral axis were prepared, which could be further modified to afford diversely chelating ligands. The flexible axial chirality was fixed by stereogenic phosphorus via a cyclic linkage of chemical bonds or coordination with a metallic ion.

Probing non-covalent interactions of phosphine and arsine derivatives: an energy decomposition analysis using localized molecular orbitals

Ab initio (MP2/aug-cc-pVTZ) and density functional theory (DFT) (B3PW91/aug-cc-pVTZ and B3LYP-D3/Def2-TZVPP) analyses have been carried out to characterize the bonding of phosphine and arsine derivatives i.e., M-RH2–HF (M = As or P, R = furan, pyridine, pyrrole, and thiophene) with hydrogen fluoride (HF). Two minima were found on the potential energy surface (PES) for each complex, one in which HF is forming directly an H-bond with pnicogen while the other one in which HF is interacting with the heterocyclic ring in addition to normal H-bond. The latter one is highly stable with MP2/CBS extrapolated binding energies ranging from − 10.67 kcal mol−1 to − 6.33 kcal mol−1. The interaction energies in these complexes follow the order P-PyrHF > P-ThioHF > P-FuHF > P-PyHF > As-PyrHF > As-ThioHF > As-FuHF > As-PyHF. NBO analysis demonstrated that $$ {LP}_{As/P}\to {\sigma}_{H-F}^{\ast } $$ orbital interaction plays a major role in stabilizing these complexes, and the largest charge is transferred in P-type complexes compared with their As-type analogs. The LMO-EDA pointed out that all the partitioning terms are stabilizing in nature with a dominant role carried out by exchange energy while as the repulsion energy is the only term being destabilizing in nature. Many body interaction analysis in ternary complexes M-RH2–(HF)2, in which the other interaction site of heterocyclic rings (N, O, and S) were used for second H-bonding with another HF molecule, revealed that the second H-bond is destabilizing the pnicogen H-bond and showed negative synergetic effects.

Very strong trans effect in ruthenacyclic carbamoyl complexes leads to ligand redistribution in phosphine derivatives

The ruthenacyclic carbamoyl complexes [Ru (2-NHC(O)C5H4N) (CO)2(X) (NCMe)] (X = Cl, Br) (1) and [Ru (2-NHC(O)C5H4N) (CO)2 (2-S-Py)] (2) undergo substitution reactions with organophosphines to afford derivatives which are prone to a redistribution of the phosphine ligand. We have studied these redistribution reactions experimentally and computationally, and proposed an essentially common reaction pathway. The results suggest that the carbamoyl ligand exerts a very strong trans effect.

Chemoselective Reduction of the P=O Bond in the Presence of P–O and P–N Bonds in Phosphonate and Phosphinate Derivatives

Chemoselective reduction of the strong P=O bond in the presence of weaker P–O (ester) and P–N (amide) bonds in phosphonic acid derivatives has constituted an unresolved problem in organophosphorus chemistry for years. This long‐standing problem is now solved for biologically relevant α‐hydroxy and α‐amino phosphonic as well as phosphinic acids esters and amides. The reduction of the P=O bond without concomitant scission of the ester and amide bonds is affected by use of BH3, a mild reducing agent, which affords the corresponding borane protected PIII phosphonite and phosphinite derivatives in one step. A mechanistic rationale is proposed for the role played by neighboring OH and NHR groups in facilitating the reduction, and for the observed chemo‐ and stereoselectivity. The reduction methodology described opens previously unavailable synthetic options in chemistry of α‐functionalized phosphonic and phosphinic acids by offering a unique possibility for direct modifications of oxidation level of the P‐center in these compounds.

New o-substituted diphenylphosphinic amide ligands: synthesis, characterization and complexation with Zn2+, Cu2+ and Y3+

Phosphinic amide derivatives have drawn significant attention in coordination chemistry and have been incorporated into the design and synthesis of new ligands.

Evaluation of ferrocenyl phosphines as potent antimalarials targeting the digestive vacuole function of Plasmodium falciparum.

Owing to their lipophilic nature and chemical stability, ferrocene and its derivatives have been widely explored as antimicrobial agents, in combination with other active chemical 'war heads'. A prime example is ferroquine, an analogue of chloroquine obtained by covalently bonding ferrocene to 4-aminoquinoline, which possesses superior efficacy against multi-drug resistant malaria parasites. Herein, we explored the possibility of combining the ferrocenyl moiety with a phosphine unit and the subsequent inclusion of gold(i) to derive a molecular framework with demonstrated potential in inhibiting parasitic diseases. A library of 24 compounds consisting of 5 non-functionalized ferrocenyl enones and 19 ferrocenyl phosphine derivatives were synthesized, verified and tested against Plasmodium (P.) falciparum, which allowed us to identify compounds with low micromolar potency against both normal and chloroquine-resistant strains. Through flow cytometry combined with microscopic examination of Giemsa-stained thin smears, we observed that most of the active compounds interfered with trophozoite development as well as schizont maturation. The gold complex, namely G3, derived from the hydrophosphination of the terminal furan bearing an enone substrate showed the highest inhibitory potential. We demonstrate that G3 is affecting the parasite's metabolic processes as evident from the swollen digestive vacuole. Furthermore, G3 significantly affected heme de-toxification as determined through the β-hematin assay, which caused apparent oxidative stress on parasites leading to death. Collectively, these results point out the potential of gold-conjugated ferrocenyl phosphine derivatives as antimalarials targeting the digestive vacuole function and metabolism of parasites.

A theoretical study on the coordination behavior of some phosphoryl, carbonyl and sulfoxide derivatives in lanthanide complexation.

The selectivity of phosphoryl P(O)R3, sulfoxide S(O)R2, and carbonyl C(O)R2 (R = NH2, CH3, OH, and F) derivatives with lanthanide cations (La3+, Eu3+, Lu3+) was studied by density functional theory calculations. Theoretical approaches were also used to investigate energy and the nature of metal-ligand interaction in the model complexes. Atoms in molecules and natural bond orbital (NBO) analyses were accomplished to understand the electronic structure of ligands, L, and the related complexes, L-Ln3+. NBO analysis demonstrated that the negative charge on phosphoryl, carbonyl, and sulfoxide oxygen (OP, OC, and OS) has maximum and minimum values when the connected -R groups are -NH2 and -F. The metal-ligand distance declines as, -F > -OH > -CH3 > -NH2. Charge density at the bond critical point and on the lanthanide cation in the L-Ln3+ complexes varies in the order -F < -OH < -CH3 < -NH2, due to greater ligand to metal charge transfer, which is well explained by energy decomposition analysis. It was also illustrated that E(2) values of Lp(N) → σ*(Y-N) vary in the order P=O ˃ S=O ˃ C=O and the related values of Lp(N) → σ*(Y=O) change as C=O ˃ S=O ˃ P=O in (NH2)nYO ligands (Y = P, C, and S). Trends in the L-Ln3+ CP-corrected bond energies are in good accordance with the optimized OY⋯Ln distances. It seems that, comparing the three types of ligands studied, NH2-substituted are the better coordination ligands. Graphical Abstract Density functional theory (B3LYP) calculations were used to compare structural, electronic and energy aspects of lanthanide (La, Eu, Lu) complexes of phosphine derivatives with those of carbonyls and sulfoxides in which the R- groups connected to the P=O, C=O and S=O are -NH2, -CH3, -OH and -F.

Directed ortho-lithiation as a tool for synthesis of chiral 1,2-disubstituted arylsulfonamides

The directed ortho-lithiation is demonstrated as an excellent method for additional functionalization of chiral phenyl and naphthyl sulfonamides. The chirality was introduced through sulfonamide formation with a series of chiral amines prior to the lithiation process. In the case of naphthyl sulfonamides the regioselectivity of the directed ortho-lithiation was studied and optimized. The approach was shown to provide facile ortho-functionalization and was applied for the synthesis of chiral 1,2-sulfonamido phosphine derivatives. The latter were evaluated as P,O-ligands in Pd-catalyzed asymmetric allylic substitution.

Dicopper(I) Complexes Incorporating Acetylide-Functionalized Pyridinyl-Based Ligands: Synthesis, Structural, and Photovoltaic Studies.

Heteroaryl incorporated acetylide-functionalized pyridinyl ligands (L1-L6) with the general formula Py-C≡C-Ar (Py = pyridine and Ar = thiophene-2-yl, 2,2' -bithiophene]-5-yl, 2,2' :5',2″ -terthiophene]-5-yl, thieno[2,3- b]thiophen-2-yl, quinoline-5-yl, benzo[c][1,2,5]thiadiazole-5-yl) have been synthesized by Pd(0)/Cu(I)-catalyzed cross-coupling reaction of 4-ethynylpyridine and the respective heteroaryl halide. Ligands L1-L6 were isolated in respectable yields and characterized by microanalysis, IR spectroscopy, 1H NMR spectroscopy, and ESI-MS mass spectrometry. A series of dinuclear Cu(I) complexes 1-10 have been synthesized by reacting L1-L6 with CuI and triphenylphosphine (PPh3) (R1) or with an anchored phosphine derivative, 4-(diphenylphosphino) benzoic acid (R2)/2-(diphenylphosphino)benzenesulfonic acid (R3), in a stoichiometric ratio. The complexes are soluble in common organic solvents and have been characterized by analytical, spectroscopic, and computational methods. Single-crystal X-ray structure analysis confirmed rhomboid dimeric structures for complexes 1, 2, 4, and 5, and a polymeric structure for 6. Complexes 1-6 showed oxidation potential responses close to 0.9 V vs Fc0/+, which were chemically irreversible and are likely to be associated with multiple steps and core oxidation. Preliminary photovoltaic (PV) results of these new materials indicated moderate power conversion efficiency (PCE) in the range of 0.15-1.56% in dye-sensitized solar cells (DSSCs). The highest PCE was achieved with complex 10 bearing the sulfonic acid anchoring functionality.

Dynamic Kinetic Resolution of Phosphinic Acid Derivatives via Nucleophilic­ Substitution at Phosphorus Center

Reaction of racemic phosphinic acid derivatives with chiral alcohols proceeds with predominant formation of one diastereomer. The highest level of enrichment has been obtained for transesterfication of racemic methyl benzylphenylphosphinate (64% de). The outcome of the reaction depends on both the structure of chiral alcohol and the starting organophosphorus compound. The results strongly suggest that the nature of the observed phenomena is not a classical equilibration of intermediates found in dynamic kinetic resolution process but is a result of a different reactivity of both enantiomers of racemic substrate towards the same chiral nucleophile.

Comparison of Various Phosphine Additives in Zeolite Based Catalytic Isomerization of Oleic Acid

Isostearic acids (ISA) are important bio‐based ingredients for many commercial products such as lubricants, detergents, and cosmetics. This study is targeted to compare the efficacy of various phosphine derivatives in neutralizing the external acidic surface of zeolite which is responsible for the unwanted oligomerization during zeolite based skeletal isomerization reaction producing dimer as byproducts. Sixteen phosphine derivatives were individually evaluated with heat activated ammonium (NH4+) cationic ferrierite zeolite to produce iso‐oleic acid from oleic acid which was converted to ISA through the hydrogenation process. In comparison, eight newly tested phosphine additives were found more effective than the previously reported phosphines (TPP, TPTP) to increase the product yield of iso‐oleic acid, ultimately ISA, either by suppressing the byproducts or accelerating the reaction rate as a whole. The performance depends on the electron donating capacity of central phosphorus atom of phosphine derivative attracting proton from the external surface of zeolite. This phenomenon is resulted from the combination of electronic effects and structural hindrances posed by the different substituents attached to the phosphine derivatives.The effectiveness of sixteen Lewis base phosphine additives were tested in neutralizing the external acidic surface of zeolite. The neutral outer surface of zeolite is ideal for suppressing dimer formation and thus producing the iso‐oleic acid (precursor of isostearic acid) in high yield through Lewis base‐zeolite combination skeletal isomerization reaction.

Direct inclusion of phosphine derivatives in the pores of zeolite β

The thermal treatment of a mixture of phosphines and zeolite β induced the inclusion of the former in zeolite β. The included phosphine molecules were strongly bound by zeolite β, with desorption observed at higher temperatures compared to those of unloaded phosphines. The included amount of methyldiphenylphosphine was much higher than those of other phosphines, including triphenylphosphine, probably because of the small molecular size relative to the other employed phosphines; this tendency opposed that shown by zeolite Y, in which the loaded amount of methyldiphenylphosphine was smaller than that of triphenylphosphine. The inclusion of phosphines occurred in less than 3 h; the inclusion of triphenylphosphine was saturated at the melting point. The Al concentration of zeolite β significantly affected the included number of phosphines. A characteristic shift of the CC stretching band from the benzene rings of the phosphines was observed after their inclusion in zeolite β in infrared spectra. A monotonic decrease in the specific surface area was observed with the inclusion of phosphines, regardless of phosphine species. PdCl2 was introduced into the triphenylphosphine-included zeolite β to form a Pd complex on zeolite β, as confirmed with Pd K-edge extended X-ray absorption fine-structure spectroscopy. Significant improvements in both allylic alkylation and Sonogashira coupling were observed for PdCl2-loaded triphenylphosphine-included zeolite β in the concomitant presence of triphenylphosphine during the loading of PdCl2, probably because of the formation of the active Pd complex near the external surface of zeolite β.

Selective Substitution of POCl3 with Organometallic Reagents: Synthesis of Phosphinates and Phosphonates

The selectivity of the substitution reaction of phosphoryl chloride with organometallic reagents was investigated using NMR spectroscopy. This led to the discovery that the selectivity of the substitution reaction can be tuned by choosing a proper organometallic reagent. A phosphinate could be obtained by using a Grignard reagent whereas an organozinc reagent provided a phosphonate. Based on these results, one-pot synthetic methods for the preparation of phosphinates and phosphonates using commercially available starting materials were developed. Both methods allow the synthesis of a broad range of either phosphinate or phosphonate derivatives in a straightforward and general procedure. Moreover, using these one-pot procedures, mixed systems substituted with different alkyl/aryl groups can be prepared.

Tuning the regioselectivity of (benzimidazolylmethyl)amine palladium(II) complexes in the methoxycarbonylation of hexenes and octenes

Reactions of N-(1H-benzoimidazol-2-ylmethyl-2-methoxy)aniline (L1) and N-(1H-benzoimidazol-2-ylmethyl-2-bromo)aniline (L2) with p-TsOH, Pd(AOc)2 and two equivalents of PPh3 or PCy3 produced the corresponding palladium complexes, [Pd(L1)(OTs)(PPh3)] (1), [Pd(L2)(OTs)(PPh3)] (2) and [Pd(L1)(OTs)(PCy3)] (3), respectively, in good yields. The new palladium complexes 1–3 and the previously reported complexes [Pd(L1)ClMe] (4) and [Pd(L2)ClMe] (5) gave active catalysts in the methoxycarbonylation of terminal and internal olefins to produce branched and linear esters. The effects of complex structure, nature of phosphine derivative, acid promoter and alkene substrate on the catalytic activities and selectivity have been studied and are herein reported.

Synthesis, Characterization, and Electrochemical Analyses of Vanadocene Tetrametaphosphate and Phosphinate Derivatives

The synthesis and characterization of a series of new vanadocene-derived tetrametaphosphate or diphenylphosphinate complexes, [PPN]2[CpV(P4O12)] (1), [Cp2VOP(O)Ph2] (2), [CpV(μ2-O2PPh2)4VCp] (3), and [Cp2V(μ2-O2PPh2)2VCp2][PF6]2 (4), is reported ([PPN]+ = bis(triphenylphosphoranylidene)ammonium; Cp = η5-cyclopentadienyl). The complexes were synthesized from the methyl vanadocene (Cp2VMe) precursor, through protonation of the Me or Cp linkages using the tetrametaphosphate or phosphinate acid precursors [PPN]2[P4O12H2] (for 1) and Ph2P(O)OH (for 2 and 3). Oxidation of 2 with [Fc][PF6] resulted in dimerization, yielding the bimetallic 4 ([Fc]+ = ferrocenium). Electrochemical analysis of this reaction revealed a possible ECE mechanism that includes prior and subsequent electron transfer to this dimerization. The electronic structure of the dimer 4 was probed by SQUID magnetommetry and X-band EPR spectroscopy (100 and 4 K). The dimer was found to contain two antiferromagnetically coupled VIV centers, as well a...

Atom Transfer Radical Addition Catalyzed by Ruthenium–Arene Complexes Bearing a Hybrid Phosphine–Diene Ligand

The synthesis and characterization of a series of arene ruthenium complexes bearing either (3,5-cycloheptadienyl)diphenylphosphine or (cycloheptyl)diphenylphosphine are reported. Upon irradiation or heating, all these complexes lose their arene ligand but then exhibit a different behavior depending on the nature of the phosphine ligand. (Cycloheptadienyl)phosphine complexes 1 and 3 give a cationic dinuclear Ru complex 5 for which the two Ru atoms are bridged by three chlorido ligands and flanked by two tridendate (cycloheptadienyl)phosphines. (Cycloheptyl)diphenylphosphine complexes 2 and 4 undergo arene exchange when toluene is used as solvent or degrade in dichloromethane. ATRA catalytic trials conducted in parallel with these complexes using CCl4 and styrene as standard substrates, highlighted the deep impact of the dienyl moiety on the results. Under smooth conditions (UV irradiation or moderate heating), only (cycloheptyl)phosphine derivatives give Karasch adduct in satisfactory yields. Their perform...

CuI and CuII complexes with phosphine derivatives of fluoroquinolone antibiotics – A comparative study on the cytotoxic mode of action

In this paper, we present a comparative study on the cytotoxic mode of action of copper(I) and copper(II) complexes with phosphine derivatives of fluoroquinolone antibiotics (ciprofloxacin HCp and norfloxacin HNr). The in vitro cytotoxic activity of four new compounds was tested against two selected cancer cell lines. All complexes exhibited much better cytotoxicity against both cell lines than unmodified fluoroquinolone antibiotics, their phosphines (PCp, PNr), chalcogenide derivatives (oxides: OPCp, OPNr; sulfides: SPCp, SPNr and selenides: SePCp, SePNr) and previously described by us complexes with phosphines derived from different fluoroquinolones: lomefloxacin (HLm) and sparfloxacin (HSf) as well as cisplatin. Apoptosis, observed at a great predominance, was induced by all studied complexes. Importantly, it was concluded that coordination compounds with Cu(I) ion ([CuI-PNr] and [CuI-PCp]) were much more active than those with Cu(II) ion ([OPNr-CuII], [OPCp-CuII]), even though the highest efficacy to produce reactive oxygen species, participating in overall cytotoxicity, was proved for copper(II) complexes among all studied compounds. Herein, we discuss not only results obtained for copper(I)/(II) complexes with phosphines derived from HNr and HCp but we also compare them to previously described data for complexes with HLm and HSf derivatives. This is the first insight into a structure–activity relationship of copper complexes with phosphine derivatives of fluoroquinolone antibiotics.

Complexes of phosphonate and phosphinate derivatives of dipicolylamine

Phospho(i)nate derivatives of dipicolylamine show excellent selectivity for Zn(ii) over alkaline earth metal ions.

Influence of the substituent on the phosphine ligand in novel rhenium(i) aldehydes. Synthesis, computational studies and first insights into the antiproliferative activity.

Cyrhetrenyl aldehyde derivatives [(η5-C5H4CHO)Re(CO)2PR3] with R = methyl (Me, 2a), phenyl (Ph, 2b), and cyclohexyl (Cy, 2c) were synthesized by a photochemical reaction from the starting material [(η5-C5H4CHO)Re(CO)3] (1) and the corresponding phosphines. The complexes were fully characterized by FT-IR, 1H, 13C and 31P NMR spectroscopy, elemental analysis and mass spectrometry. The molecular structures of 2a-c have also been determined. Electronic structure calculations by TD-DFT and electrochemical studies are in sound agreement with the effect of the substitution of one carbonyl group by a phosphine ligand. Additionally, the antiproliferative activity of complexes 1 and 2a-c was studied on the human cancer cell lines HT-29 and PT-45 using an MTT assay. Out of all new compounds, only the triphenylphosphine derivative 2b exhibited pronounced cytotoxic effects on both cell lines, being ca. 1.5 times more potent than cisplatin.