Bisphosphonium Salt Research Articles

Bisphosphonium salt catalyzed [3 + 2] annulation of N-tosylimino(iso)quinolinium ylides with aryl olefins under blue LED irradiation

A visible-light-induced [3 + 2] annulation of N-tosylimino(iso)quinolinium ylides with aryl olefins, catalyzed by a bisphosphonium salt has been developed. Furthermore, the synthesis method of the bisphosphonium salts was improved.

New bisphosphonium salt containing a 1,4-dihydroxynaphthalene moiety: molecular and supramolecular structure

Bisphosphonium salt containing a 1,4-dihydroxynaphthyl-substituted moiety was synthesized in high yield by the reaction of 2-methyl-1,4-naphthoquinone with three equivalents of triphenylphosphine and hydrogen bromide. The structure of the synthesized bisphosphonium salt was determined by NMR spectroscopy and X-ray diffraction.

Bisphosphonium salt: an effective photocatalyst for the intramolecular hydroalkoxylation of olefins

A photocatalytic, intramolecular hydroalkoxylation of alkenes has been achieved by utilizing simple and readily available biphosphonium salts as an effective organic photocatalyst. The unique photocatalytic properties of biphosphonium salt enables facile oxidations of substituted alkenes to facilitate the streamline and regioselective synthesis of a series of saturated cyclic ethers from simple alkenes under mild conditions.

Phosphonium salts derived from α-ferrocenylvinyl cation in situ generated in sc-CO2 from ethynylferrocene by Nafion film

A protonation of ethynylferrocene by nafion in sc-CO2 in the presence of triphenylphosphine (PPh3) or 1,2-bis(diphenylphosphino)ethane (DPPE) leads to a formation of novel (1-ferrocenylvinyl)phosphonium or ferrocenyl substituted bisphosphonium salt isolated as tetrafluoroborates 3 and 4, respectively. Ferrocenyl substituted bisphosphonium tetrafluoroborate 4 undergoes the hydrolytic cleavage of the P+-C(Fc) bond in the presence of Al2O3 at 25°C to form ferrocenyl substituted phosphinyl phosphonium tetrafluoroborate 5. Complexes 3–5 were completely characterized by NMR spectra and their molecular structures elucidated by X-ray studies.

Bis-phosphonium salts of pyridoxine: The relationship between structure and antibacterial activity

A series of 23 novel bis-phosphonium salts based on pyridoxine were synthesized and their antibacterial activities were evaluated in vitro. All compounds were inactive against gram-negative bacteria and exhibited the structure-dependent activity against gram-positive bacteria. The antibacterial activity enhanced with the increase in chain length at acetal carbon atom in the order n-Pr>Et>Me. Further increasing of length and branching of alkyl chain leads to the reduction of antibacterial activity. Replacement of the phenyl substituents at the phosphorus atoms in 5,6-bis(triphenylphosphonio(methyl))-2,2,8-trimethyl-4H-[1,3]-dioxino[4,5-c]pyridine dichloride (compound 1) with n-butyl, m-tolyl or p-tolyl as well as chloride anions in the compound 1 with bromides (compound 14a) increased the activity against Staphylococcus aureus and Staphylococcus epidermidis up to 5times (MICs=1–1.25μg/ml). But in practically all cases chemical modifications of compound 1 led to the increase of its toxicity for HEK-293 cells. The only exception is compound 5,6-bis[tributylphosphonio(methyl)]-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine dichloride (10a) which demonstrated lower MIC values against S. aureus and S. epidermidis (1μg/ml) and lower cytotoxicity on HEK-293 cells (CC50=200μg/ml). Compound 10a had no significant mutagenic and genotoxic effects and was selected for further evaluation. It should be noted that all bis-phosphonium salt based on pyridoxine were much more toxic than vancomycin.

Synthesis and structures of non-cyclic and cyclic mono- and bisphosphonium salts derived from 1,8-bis(diphenylphosphino)naphthalene

A monoalkylated 1,8-bis(diphenylphosphino)naphthalene (dppn) was prepared by treating diphosphine with 1,8-bis(bromomethyl)naphthalene. Unprecedented cyclizations of monophosphonium salts in polar solvents, such as DMF or acetonitrile were elucidated. The mechanistic pathway of the cyclization reaction was postulated and X-ray crystal structure analyses of the resulting 2,2-diphenyl-2,3-dihydro-1H-2-phosphoniaphenalene bromide was performed. 1,8-Bis(diphenylphosphino)naphthalene and α,α′-dibromo-o-xylene afforded—despite unfavorable steric strain—the first dialkylation product of 1,8-bis(phosphino)naphthalene, namely corresponding cyclic bisphosphonium salt. The use of acetonitrile as the solvent was the key for this synthesis. The bromide anions were exchanged in metathesis reaction with hexafluorophosphate anions and the new compound was fully characterized including single crystal X-ray diffraction. The large distance between phosphorus atoms of 3.974 Ǻ clearly demonstrate a strong proximity effect in this hindered bisphosphonium salt.

Synthesis of a Novel Bisphosphonium Salt Based on 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (Binap)

The reaction between 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (Binap) and an equimolar amount of [Cu(OTf)2] (where OTf = trifluoromethylsulfonate) in acetonitrile afforded the new bisphosphonium salt 1 by a mechanism that must involve two C−H bond activations and the consequent intramolecular formation of two new C−P bonds. Compound 1 was characterized by spectroscopic and X-ray diffraction methods.

Chemistry and Stereochemistry of the Interaction of the Water-Soluble Phosphine [HO(CH2)3]3P with Cinnamaldehyde in Aqueous Media

To learn more about the bleaching action of pulps by (hydroxymethyl)phosphines, cinnamaldehyde was reacted with tris(3-hydroxypropyl)phosphine, [HO(CH2)3]3P (THPP), in aqueous solution at room temperature under argon. Self-condensation of the aldehyde into two isomeric products, 2-benzyl-5-phenyl-pent-2,4-dienal and 5-phenyl-2-(phenylmethylene)-4-pentenal, is observed; this implies initial nucleophilic attack of the phosphine at the beta-carbon of the alpha,beta-unsaturated aldehyde. Reaction in D2O gives the same products in which all but the phenyl and CHO protons are replaced by deuterons. NMR studies are consistent with carbanion formation and subsequent condensation of two phosphonium-containing aldehyde moieties to generate the products with concomitant elimination of phosphine oxide. In D2O in the presence of HCl, THPP reversibly attacks the aldehyde-C atom to form the (alpha-hydroxy)phosphonium derivative [PhCH=C(H)CH(OD)PR3]Cl (where R=(CH2)3OD), which slowly converts into the deuterated bisphosphonium salt [R3PCH(Ph)CD(H)CH(OD)PR3]Cl2 via the deuterated monophosphonium salt [R3PCH(Ph)CD(H)CHO]Cl. The phosphonium intermediates and phosphonium products in this chemistry, although having up to three chiral carbon centers, are formed with high stereoselectivity just in enantiomeric forms. In acetone-H2O (1:1 v/v), a cross-condensation of cinnamaldehyde with acetone to give 6-phenyl-3,5-hexadien-2-one is promoted by THPP via generation of OH-.

The Total Synthesis of Bistratamides F—I.

Abstract The total synthesis of bistratamides F–I ( 2 – 5 ) have been achieved in overall yields of 3, 10, 13, and 27%, respectively. The thiazole substructure was prepared utilizing a MnO 2 oxidation of a thiazoline, synthesized from a Val-Cys dipeptide using bis(triphenyl)oxodiphosphonium trifluoromethanesulfonate. The serine-based oxazole substructure was prepared from a Val-Ser dipeptide using literature methods. The threonine-derived oxazole substructure was synthesized from a ketoamide dipeptide using the bisphosphonium salt employed for thiazoline preparation. Most of the amide bonds were formed using HBTU and HOBt in the presence of DIEA. The final macrocyclization step was accomplished efficiently by PyBOP and DMAP in all cases.

The total synthesis of bistratamides F–I

The total synthesis of bistratamides F–I ( 2– 5 ) have been achieved in overall yields of 3, 10, 13, and 27%, respectively. The thiazole substructure was prepared utilizing a MnO 2 oxidation of a thiazoline, synthesized from a Val-Cys dipeptide using bis(triphenyl)oxodiphosphonium trifluoromethanesulfonate. The serine-based oxazole substructure was prepared from a Val-Ser dipeptide using literature methods. The threonine-derived oxazole substructure was synthesized from a ketoamide dipeptide using the bisphosphonium salt employed for thiazoline preparation. Most of the amide bonds were formed using HBTU and HOBt in the presence of DIEA. The final macrocyclization step was accomplished efficiently by PyBOP and DMAP in all cases.

Highly Efficient Biomimetic Total Synthesis and Structural Verification of Bistratamides E and J from Lissoclinum bistratum.

The interesting biological activities of heterocycle-containing cyclic peptide-derived natural products, isolated from marine organisms over the past twenty years, have attracted the interest of many synthetic and natural products chemists. Bistratamides E–J, members of this class of natural products that were isolated very recently from Lissoclinum bistratum, exhibited cytotoxic activity against a human colon tumor (HCT-116) cell line. Here we report the first total syntheses of bistratamides E (1) and J (2) in overall yields of 19 and 34 %, respectively. The thiazole substructures have been synthesized by oxidation of their corresponding thiazoline substructures, which were obtained from cysteine containing peptides using a novel biomimetic approach wherein Val-Cys dipeptide units were converted to thiazolines by a bisphosphonium salt. The final macrocyclization was promoted efficiently using the combination of PyBOP and DMAP. This approach allows the use of readily available Fmoc-protected amino acids to make complex thiazole and oxazoline-containing natural products.

Unsymmetrical Double Wittig Olefination on the Syntheses of Insect Pheromones. Part 1. Synthesis of 5,9‐Dimethylpentadecane, the Sexual Pheromone of Leucoptera coffeella.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly efficient biomimetic total synthesis and structural verification of bistratamides E and J from Lissoclinum bistratum.

The interesting biological activities of heterocycle-containing cyclic peptide-derived natural products, isolated from marine organisms over the past twenty years, have attracted the interest of many synthetic and natural products chemists. Bistratamides E-J, members of this class of natural products that were isolated very recently from Lissoclinum bistratum, exhibited cytotoxic activity against a human colon tumor (HCT-116) cell line. Here we report the first total syntheses of bistratamides E (1) and J (2) in overall yields of 19 and 34 %, respectively. The thiazole substructures have been synthesized by oxidation of their corresponding thiazoline substructures, which were obtained from cysteine containing peptides using a novel biomimetic approach wherein Val-Cys dipeptide units were converted to thiazolines by a bisphosphonium salt. The final macrocyclization was promoted efficiently using the combination of PyBOP and DMAP. This approach allows the use of readily available Fmoc-protected amino acids to make complex thiazole and oxazoline-containing natural products.

Unsymmetrical double Wittig olefination on the syntheses of insect pheromones. Part 1: Synthesis of 5,9-dimethylpentadecane, the sexual pheromone of Leucoptera coffeella

An expeditious three-step synthesis of a mixture of stereoisomers of 5,9-dimethylpentadecane 1, the sexual pheromone of the coffee leaf miner Leucoptera coffeella, is described. The route employs an unsymmetrical double Wittig olefination to build the carbon skeleton of the molecule, as the key reaction. The bis-phosphonium salt 3, derived from 1,3-dibromopropane 2, reacted ‘one-pot’ with the ketones 2-octanone and 2-hexanone, affording the asymmetric diene 4. This was readily hydrogenated over Pd/C, furnishing pheromone 1 in 54% overall yield. Synthetic 1 showed high biological activity when tested in field experiments.

C−P and C−H Bond Activations and C−C Coupling in Bis-Phosphonium Salts Induced by Platinum(II) Complexes

The reaction of [Ph3PCH2-(E)-C(Me)C(H)PPh3]Cl2 (1b) with PtCl2(NCPh)2 (1:1 molar ratio) in refluxing 2-methoxyethanol gives the ortho-metalated complex [Pt(C6H3-3-Ph-2-PPh2-CC(Me)CH2PPh2-κC,C,P)Cl] (3). The synthesis of complex 3 formally involves three C−H and one C−P bond activation and one C−C bond coupling. Complex 3 reacts with excess KBr or NaI to give, after halide metathesis, the complexes [Pt(C6H3-3-Ph-2-PPh2-CC(Me)CH2PPh2-κC,C,P)X] (X = Br (4), I (5)). Complex 5 has been characterized by X-ray diffraction methods. The influences of several factors, such as the solvent, the platinum starting complex, and the bis-phosphonium salt, in the synthesis of 3 have been examined, and a plausible reaction mechanism for the synthesis of 3 is proposed. This mechanism is supported by the isolation of the Pt(IV) derivative [Pt(C6H4-4-F){C6H3-5-F-2-P(p-FC6H4)2-CC(Me)CH2P(p-FC6H4)2-κC,C,P}Cl2] (6), obtained by reaction of [(p-FC6H4)3PCH2-(E)-C(Me)C(H)P(p-FC6H4)3]Cl2 (1f) with PtCl2(NCPh)2 in refluxing 2-methoxye...

Synthesis and characterization of Pd II complexes containing cyclic bis-ylides

The reaction of Ph 2PCH 2PPh 2 (dppm) with ClCH 2C(O)CH 2Cl (1:1 molar ratio) in refluxing CHCl 3 gives the new ylide-phosphonium salt 1, through quaternization of the two P atoms of the dppm and spontaneous loss of HCl. Compound 1 reacts with NEt 3 in CHCl 3 or CH 2Cl 2 solution (1:1 molar ratio) giving a mixture of the bis-ylide compound 2a and the ylide-methanide 2b (molar ratio 2a: 2b=1:2). This mixture (prepared in situ) reacts with PdCl 2(NCMe) 2 to give the corresponding dichloride(bis-ylide) complex 3a (coordination through the two ylidic carbons) and the dichloride(ylide-methanide) complex 3b (coordination through the ylide carbon and the methanide carbon), in a molar ratio 3a: 3b=1:2. The reaction of the mixture 3a: 3b with AgClO 4 (1:2 molar ratio, NCMe or Me 2CO) in the presence of neutral ligands L gives the corresponding mixtures of the dicationic complexes [Pd(L) 2(C,C-bis-ylide)](ClO 4) 2 ( 4a, L=NCMe; 5a, L=pyridine) and [Pd(L) 2(C,C-ylide-methanide)](ClO 4) 2 ( 4b, L=NCMe; 5b, L=pyridine) (molar ratio 4a: 4b=1:2; molar ratio 5a: 5b=3:1). On the other hand, the reaction of Ph 2PCH 2PPh 2 (dppm) with ClCH 2C(CH 2)CH 2Cl (1:1 molar ratio) in refluxing ClCH 2CH 2Cl gives the bis-phosphonium salt 6. This salt reacts with Li tBu and PdCl 2(NCMe) 2 (1:2.2:1 molar ratio) in THF affording the ylide-methanide complex 7. The crystal structures of complexes 3b· 3dmso and 7·CHCl 3 have been determined by X-ray diffraction.

Diphosphapodanden,[12]-,[15]- und[18]Diphosphacoronanden, Diphosphacryptand-8 und Alkalimetall-Komplexe

Diphosphapodands, [12]-, [15]-, and [18]Diphosphacoronands, Diphosphacryptand-8, and Alkali-Metal Complexes The cyclizing bis-phosphonium-salt formation of the open-chain bis-phosphine 17a (1,1,7,7-tetrabenzyl〈P.O.P-podand-7〉) with diethylene glycol derived dibromide 13a yields the 12-membered cyclic bis-phosphonium salt 20 (4,4,10,10-tetrabenzyl-12〈O.P.O.P-coronand-4〉-4,10-diium dibromide) in yields as high as 50–60%. The 1,1,10,10-tetrabenzyl〈P.O2.P-podand-10〉 17b forms with 13a the 15-membered cyclic bis-phosphonium salt 21 (7,7,13,13-tetrabenzyl-15〈O2.P.O.P-coronand-5〉-7,13-diium dibromide) with the same high yield. By quaternization of the bis-phosphine 17b with triethylene glycol derived dibromide 13b, the 18-membered 7,7,16,16-tetrabenzyl-18〈O2.P.O2.P-coronand-6〉-7,16-diium dibromide 24 is obtained in 50% yield, too. The Wittig reaction of the cyclic phosphonium salts with benzaldehyde yields the 12-, 15-, and 18-membered cyclic bis-benzylphosphine dioxides 9, 10, and 11 as cis- and trans-isomers beside trans-stilbene. The 7,13-dioxido-7,13-dibenzyl-15〈O2.P.O2.P-coronand-5〉 10 forms a crystalline 1 : 1 Na-complex 23, which exists as a dimer. The structure of 23 was established by an X-ray analysis and spectroscopic data. The 7,16-dibenzyl-18〈O2.P.O2.P-coronand-6〉 28 that is available by reduction of 11 with CeCl3/LiAlH4 reacts with triethylene glycol derived dibromide 13b under RugglyZiegler-dilution conditions to give the bicyclic bis-phosphonium salt 29 (1,10-dibenzyl〈P[O2]3.P-cryptand-8〉-1,10-diium dibromide) in 18% yield. Again, by the Wittig procedure with benzaldehyde, the 7,16-dioxido〈P[O2]3P-cryptand-8〉 12 is obtained as the first diphosphacryptand. The FD-MS (CH2Cl2) of the cyclic bis-phosphine dioxides 10–12 show that they exist as [2M+Na]+ complexes. The complex formation constants Ka of 9–11 with alkali-metal cations are studied and compared with the complex formation of corresponding crown ethers.

Tetraepoxy[32]annulene(4.4.4.4) und `Tetraoxa[30]porphyrin(4.4.4.4)'-Dikationen

Tetraepoxy[32]annulenes(4.4.4.4) and `Tetraoxa[30]porphyrin(4.4.4.4)' Dications Of the tetraepoxy[32]annulenes as well as the `tetraoxa[30]porphyrin' dications, hithertoo only the (8.0.8.0) and the (6.2.6.2) systems are known to exist in several geometric isomers and to possess antiaromatic and aromatic character, respectively. Here we describe the still missing symmetric member of the [32]annulenes, the tetraepoxy[32]annulene(4.4.4.4) 1 and the corresponding `tetraoxa[30]porphyrin(4.4.4.4)' dication 2. The cyclizing Wittig reaction of the dialdehyde 3 with the bis-phosphonium salt 7 at 70° yields the configurational isomers 1a (ZE,EE,EZ,EE), 1b (ZE,EE,EE,EE), and 1c (EZ,EE,EZ,EE). All isomers are antiaromatic; in 1a and 1c, the two (E,E)-buta-1,3-diene-1,4-diyl bridges rotate around the adjacent σ-bonds; the rigidity of 1b with 3 (E,E) bridges prevents any dynamic character. The Wittig reaction of 3 with 7 at 20° only yields the kinetically controlled annulene 1c, and at 120°, an excess of the thermodynamically most stable isomer 1a is formed. The structure of 1 is elucidated mainly by COSY and NOESY experiments, and the dynamic character of 1a and 1c is established by temperature-dependent 1H-NMR spectroscopy. The oxidation of the isomer mixture 1a – c with 4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile (DDQ) gives two isomeric `tetraoxa[30]porphyrin(4.4.4.4)' dications 2′ and 2″, which are frozen conformers with the same (EZ,EE,EZ,EE)-configuration and geometrically related to 1c. Semiempirical calculations of 1 and 2 are in full agreement with the experimental results.

Neutrale aromatische Tetraepoxyannulene: Tetraepoxy[26]annulene(4.2.2.2) und Tetraepoxy[30]annulene(4.4.4.2) - Systeme mit hoher molekularer Dynamik

Neutral Aromatic Tetraepoxyannulenes: Tetraepoxy[26]annulenes(4.2.2.2) and Tetraepoxy[30]annulenes(4.4.4.2) – Systems with High Molecular Dynamics The twofold cyclizing Wittig reaction of the bis-aldehyde 6 with the ylide of the bis-phosphonium salt 7 yields tetraepoxy[26]annulene(4.2.2.2) 4, which exists in the two isomeric forms 4a (EE,Z,E,Z) and 4b (EE,Z,E,E). Annulene 4a is a highly dynamic system down to −80°. Temperature-dependent 1H-NMR spectra of 4a establish that the (E,E)-buta-1,3-dien-1,4-diyl as well as the (E)-ethen-1,2-diyl bridges rotate around the adjacent σ-bonds in a synchronous manner. Isomer 4b, for steric reasons, is rigid. By Wittig reaction of the bis-aldehyde 8 with the ylide of the bis-phosphonium salt 9, the tetraepoxy[30]annulene(4.4.4.2) 5 is obtained, which exists also in two isomeric forms, 5a and 5b. Only 5a (EE,ZE,EE,Z) can be isolated in pure form. Like 4a, 5a is highly dynamic, the (E,E)-buta-1,3-dien-1,4-diyl as well as the opposite (E)-ethen-1,2-diyl bridge being able to rotate down to −80°. The 1H-NMR spectrum at −80° indicates that 5a exists in the stable conformation 5a′. The 26- and 30-membered annulenes belong to the most expanded neutral annulenes known hitherto; their 1H-NMR spectra confirm that they still have diatropic, aromatic character.

C−H Activation in Phosphonium Salts Promoted by Platinum(II) Complexes

The reaction of PtCl2(NCPh)2 with the bis-phosphonium salts {[R2PhPCH2]2C(O)}Cl2 (R2 = Ph2, PhEt, Et2) (1:1 molar ratio) in refluxing 2-methoxyethanol affords the C,C-orthometalated complexes [PtCl2(C6H4-2-PR2C(H)C(O)CH2PPhR2)] (R2 = Ph2 1a, PhEt 1b, Et2 1c). The reaction of PtCl2 with the bis-phosphonium salt {[Ph3PCH2]2C(O)}Cl2 (1:1 molar ratio) gives {[Ph3PCH2]2C(O)}[PtCl4], 2, while treatment of PtCl2 with the perchlorate salts {[R2PhPCH2]2C(O)}(ClO4)2 (1:1 molar ratio) results in the formation of the cationic dinuclear orthometalated derivatives [Pt(μ-Cl)(C6H4-2-PR2C(H)C(O)CH2PPhR2)]2(ClO4)2 (R2 = Ph2 3a, PhEt 3b, Et2 3c). The cycloplatination of the bis-phosphonium salts to give the C,C-orthometalated derivatives implies two C−H bond activation processes at two types of carbon atoms, one arylic and one alkylic. The reaction of PtCl2(NCPh)2 or PtCl2 with the allyl-phosphonium salts [PhR2PCH2CHCH2]Cl (R2 = Ph2, Me2) or [Ph3PCH2CHCHMe]Cl (1:1 molar ratio) in refluxing 2-methoxyethanol gives the orthometalated vinyl-phosphonium derivatives [PtCl2(C6H4-2-PR2-η2-E-C(H)C(H)CH3)] (R2 = Ph2 4a, Me2 4b) or [PtCl2(C6H4-2-PPh2-η2-E-C(H)C(H)CH2CH3)], 7, respectively, while the reaction of PtCl2 with [Ph3PCH2CHCH2]ClO4 (1:1 molar ratio) gives the η2-olefin-bonded derivative [Cl3Pt(η2-CH2CH−CH2PPh3)], 5. The reaction of [Ph3PCH2CHCHPh]Cl with PtCl2 (1:1 molar ratio, 2-methoxyethanol, reflux) gives an easily separable mixture of products: the η2-olefin-bonded [Cl3Pt(η2-CHPhCH−CH2PPh3)], 8, and the orthometalated [PtCl2(C6H4-2-PPh2-η2-E-C(H)C(H)CH2Ph)], 9, while the reaction of [Ph3PCH2CMeCH2]Cl with PtCl2 (1:1 molar ratio) gives a mixture of the cycloplatinated [PtCl2(C6H4-2-PPh2-η2-C(H)CMe2)], 10, and the isomerized vinyl-phosphonium salt [Ph3P−C(H)CMe2]Cl, 11. The synthesis of complexes 4, 7, 9, and 10 implies the activation of one C(aryl)−H bond (instead of the more active methylene group adjacent to the phosphonium unit P−CH2) and the rearrangement of the allyl group into a vinyl group by 1,3-prototropic shift, this shift being produced in the absence of external base. The complexes 4a·CH2Cl2 and 8 have been characterized by X-ray diffraction methods.