Palladium-catalyzed Suzuki–Miyaura cross-coupling with α\alpha -aminophosphonates based on 1,3,4-oxadiazole as ligands

The synthesis of a palladium complex bearing two diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-nitrophenyl)methyl]phosphonates as ligands has demonstrated the ability of this type of $\alpha$-aminophosphonates to coordinate to the palladium(II) ion via their electronically enriched nitrogen atom of the 1,3,4-oxadiazole ring. The complex was fully characterized by elemental analysis, infrared, NMR and mass spectrometry. A solid-state structure revealed the trans coordination of the two nitrogenated ligands. The presence of a hemilabile P(O)(OEt)$_{2}$ moiety in the $\alpha$-aminophosphonates was exploited into palladium-catalyzed Suzuki–Miyaura cross-coupling of aryl halides. The formation of ($N{,}O$)-chelate intermediates may increase the steric hindrance and the electronic density of the metal, which should favor the oxidative addition and the reductive elimination/product decoordination elementary steps. With our catalytic systems, good activities for the formation of ortho-di/trisubstituted biphenyl compounds were observed from aryl bromides using only 0.5 mol% of palladium. Cross-coupling of aryl chlorides required a catalyst loading of 1 mol% to generate ortho-substituted biphenyls

Palladium-catalyzed Suzuki–Miyaura cross-coupling with α\alpha -aminophosphonates based on 1,3,4-oxadiazole as ligands

The synthesis of a palladium complex bearing two diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-nitrophenyl)methyl]phosphonates as ligands has demonstrated the ability of this type of $\alpha$-aminophosphonates to coordinate to the palladium(II) ion via their electronically enriched nitrogen atom of the 1,3,4-oxadiazole ring. The complex was fully characterized by elemental analysis, infrared, NMR and mass spectrometry. A solid-state structure revealed the trans coordination of the two nitrogenated ligands. The presence of a hemilabile P(O)(OEt)$_{2}$ moiety in the $\alpha$-aminophosphonates was exploited into palladium-catalyzed Suzuki–Miyaura cross-coupling of aryl halides. The formation of ($N{,}O$)-chelate intermediates may increase the steric hindrance and the electronic density of the metal, which should favor the oxidative addition and the reductive elimination/product decoordination elementary steps. With our catalytic systems, good activities for the formation of ortho-di/trisubstituted biphenyl compounds were observed from aryl bromides using only 0.5 mol% of palladium. Cross-coupling of aryl chlorides required a catalyst loading of 1 mol% to generate ortho-substituted biphenyls

Synthesis, spectroscopic, and structural characterization of new functionalized gem-bisphosphonate complexes of tin(IV) chloride

The authors are grateful to the Tunisian Ministry of High Education and Scientific Research and Technology for financial support of this researchBisphosphonates of the types X(P(O)(OEt)2)2 (X = CH2=C (1a), CNCH2CH (1b) and PhCH2NCH2CH (1c)) react with SnCl4 in anhydrous dichloromethane to produce the new tin(IV) adducts [SnCl4(1a)] (2a), [SnCl4(1b)] (2b) and [SnCl4(1c)] (2c) in 72-80% yields. These complexes were characterized using IR, multinuclear (1H, 13C, 31P, 119Sn) NMR spectroscopy, elemental analysis, and in one case by single crystal X-ray diffraction. The NMR data show that the bisphosphonate ligands are coordinated to the tin center in a bidentate fashion forming cis octahedral tin complexes. Furthermore, the X-ray structure of complex 2b reveals that the bisphosphonate ligand is coordinated in a bidentate manner to the metal center in a distorted octahedral arrangement with Sn-O-P bond angles in the range 135.95(16)–137.99(18)°. The P=O and Sn-O bond lengths of 1.495(3)-1.497(3) and 2.134(3)-2.146(2) Å, respectively are in the order expected for phosphonate tin(IV) complexes. The results are discussed and compared with closely related analogues.PostprintPeer reviewe

Intramolecular Phospholithiation of alkynes and its application in synthesis of a novel phosphorus heterocycles

International audienc

Direct Functionalization of Lithium Phosphine Oxides Bearing an Alkyne Chain

International audienc

Selective Substitution Reactions at the Phosphorus Atom of 1,3-Dienyl Phosphonates

International audienc

Design, synthesis, antimicrobial evaluation, and molecular docking studies of novel symmetrical 2,5‐difunctionalized 1,3,4‐oxadiazoles

International audienceA series of novel symmetrical 2,5-difunctionalized 1,3,4-oxadiazole derivatives of pharmacological significance have been synthesized. The obtained compounds were screened for their in vitro antimicrobial activities against Gram-negative (Escherichia coli and Salmonella typhimurium) and Gram-positive bacteria (Staphylococcus aureus, Enterococcus feacium and Streptococcus agalactiae or group B Streptococcus), as well as against the fungus Candida albicans. Although the synthesized compounds showed moderate antifungal activity against C. albicans, they exhibited good to excellent antibacterial activities against several strains, compared with standard drugs Ampicillin and Nystatin. In silico molecular docking in FabI enzyme active site, gave information regarding the binding mode of the drug candidate at molecular level

Silver(I) Complexes Based on Oxadiazole-Functionalized α-Aminophosphonate: Synthesis, Structural Study, and Biological Activities

Two silver(I) complexes, bis{diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-κN3:κN4-amino) (4-trifluoromethylphenyl)methyl]phosphonate-(tetrafluoroborato-κF)}-di-silver(I) and tetrakis-{diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-κN3-amino)(4-trifluoromethylphenyl)methyl]phosphonate} silver(I) tetrafluoroborate, were prepared starting from the diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-amino)(4-trifluoromethylphenyl)methyl]phosphonate (1) ligand and AgBF4 salt in Ag/ligand ratios of 1/1 and 1/4, respectively. The structure, stoichiometry, and geometry of the silver complexes were fully characterized by elemental analyses, infrared, single-crystal X-ray diffraction studies, multinuclear NMR, and mass spectroscopies. The binuclear complex ([Ag2(1)2(BF4)2]; 2) crystallizes in the monoclinic asymmetric space group P21/c and contains two silver atoms adopting a {AgN2F} planar trigonal geometry, which are simultaneously bridged by two oxadiazole rings of two ligands, while the mononuclear complex ([Ag(1)4]BF4; 3) crystallizes in the non-usual cubic space group Fd-3c in which the silver atom binds to four distinct electronically enriched nitrogen atoms of the oxadiazole ring, in a slightly distorted {AgN4} tetrahedral geometry. The α-aminophosphonate and the monomeric silver complex were evaluated in vitro against MCF-7 and PANC-1 cell lines. The silver complex is promising as a drug candidate for breast cancer and the pancreatic duct with half-maximal inhibitory concentration (IC50) values of 8.3 ± 1.0 and 14.4 ± 0.6 μM, respectively. Additionally, the interactions of the ligand and the mononuclear complex with Vascular Endothelial Growth Factor Receptor-2 and DNA were evaluated by molecular docking methods

Lateral Deprotometallation-Trapping Reactions on Methylated Pyridines, Quinolines and Quinoxalines Using Lithium Diethylamide

International audienceThe functionalization of methylated azines and diazines has aroused the interest of chemists given the structural diversity that it affords. Hindered lithium dialkylamides have been used to deprotometallate these substrates chemoselectively. In contrast, it can be observed that, despite some promising work, lithium diethylamide has been used very little for this purpose. Our objective here is on the one hand to make an inventory of what reagents have been used to deprotometallate methylpyridines, -quinolines and -quinoxalines, and on the other hand to describe the results obtained by seeking to functionalize a series of substrates with lithium diethylamide (picolines, 2,4-lutidine, methylquinolines and 2-methylquinoxaline). Our efforts to take advantage of the use of an in-situ trap (a zinc chloride chelate) in these reactions are also described