Regioselective synthesis of cytotoxic 4-(1-alkynyl)-substituted 2-(5H)-furanones

4-(1-Alkynyl)-3-bromo- and 4-(1-alkynyl)-3-chloro-2(5H)-furanones have been regioselectively synthesized in moderate to good yields by a new version of the Pd/Cu-catalyzed Sonogashira reaction involving treatment of 1-alkynes with 3,4-dibromo- and 3,4-dichloro-2(5H)-furanone, respectively, in the presence of KF as a base. 4-(1-Alkynyl)-3-bromo-2(5H)-furanones have been found to be able to undergo Stille-type and Suzuki-type reactions with aryl(tributyl)tins and arylboronic acids, respectively, to give 4-(1-alkynyl)-3-aryl-2(5H)-furanones in modest to satisfactory yields. Some 4-(1-alkynyl)-substituted 2(5H)-furanones so prepared have been found to exhibit significant cytotoxic activities, especially against human leukemia cell lines.     

Pyridazines. Part 34: Retro-ene-assisted palladium-catalyzed synthesis of 4,5-disubstituted-3(2H)-pyridazinones

The efficient one-pot bis-functionalization of the 4,5-positions of the 3-pyridazinone ring has been performed using Suzuki, Sonogashira and Stille cross-coupling reactions assisted by a retro-ene fragmentation. This route allows access in a shorter synthetic sequence to several pharmacologically useful 3(2H)-pyridazinones.     

Pyridazine derivatives. Part 33: Sonogashira approaches in the synthesis of 5-substituted-6-phenyl-3(2H)-pyridazinones

Several 6-phenyl-3(2H)-pyridazinones bearing different alkynyl groups at position 5 have been prepared by a palladium-catalysed Sonogashira cross-coupling reaction. An interesting base-promoted electronically permitted isomerization has been observed during the coupling of 1-phenyl-2-propyn-1-ol. This rearrangement afforded the E-chalcone 6 in excellent yield.     

(BeDABCO)2Pd2Cl6 as an efficient homogeneous catalyst for copper‐free Sonogashira cross‐coupling reaction

An efficient catalytic system using 1‐benzyl‐4‐aza‐1‐azoniabicyclo[2.2.2]octane chloride and palladium chloride ((BeDABCO)₂Pd₂Cl₆) was developed for the Sonogashira reaction. In the presence of a catalytic amount of this efficient, stable homogeneous catalytic system that is non‐sensitive to air and moisture, various aryl halides were efficiently coupled with phenylacetylene in good yields in H₂O at 50°C under copper‐free conditions. Benzyl dabco as an efficient ligand and also a quaternary ammonium salt had an efficient stabilizing effect on the Pd(0) species. Copyright © 2014 John Wiley & Sons, Ltd.     

Polymer-supported palladium (II) containing N2O2: An efficient and robust heterogeneous catalyst for C–C coupling reactions

A new polymer was prepared from 1,3,5-triformylphloroglucinol (noted as TDTB) and o-phenylenediamine through Schiff base condensation reaction, and palladium (II) was immobilized on the polymer (noted as TbPo-Pd(II)). This process was easy to work-up and cost-effective. The structure and composition of TbPo-Pd(II) were fully characterized by FTIR, TGA, XPS, AAS, SEM, and TEM analyses. Meanwhile, this catalyst showed desired thermal stability and excellent performance in water/methanol system for Suzuki and Sonogashira coupling reactions. In addition, this heterogeneous catalyst can be readily recovered by simple filtration with no appreciable Pd leaching in the reaction. This work provides a powerful protocol for rapid access to asymmetrical biphenyls and aryl alkynes. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2344–2353     

Reductive electrochemical formation of 6H-dibenzo[b,d]pyran-6-one and 2-benzopyran-1(1H)-one

In the present Letter several carbolactones (oxidative products) are obtained under aprotic cathodic conditions in the preparative scaled electrolysis of 1,2-quinones in a divided electrochemical cell and in the presence of oxygen. When 9,10-phenanthrenequinone is reduced 6H-dibenzo[b,d]pyran-6-one and [1,1′-biphenyl]-2,2′-dicarboxylic acid are obtained as major products. In the reduction of 1,2-naphthoquinone, 2-benzopyran-1(1H)-one, and 2-(2-carboxyethenyl)-benzoic acid were formed as main products. The proposed mechanism to explain the formation of these and other products, that involves an electron-transfer reaction to the oxygen in air, is now discussed.     

Ceria/vinylpyridine polymer nanocomposite: an ecofriendly catalyst for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones

The three-component condensation of aldehydes, β-ketoesters and urea has been carried out in water using ceria (cerium oxide, CeO₂) nanoparticles supported on poly(4vp-co-dvb) as a catalyst for the preparation of 3,4-dihydropyrimidin-2(1H)-ones in good yields. The catalyst was recovered easily and reused without loss of its activity.     

Divergent synthesis of arylated pyridin-2(1H)-one derivatives via metal-catalysed cross-coupling processes

1,5-Di(hetero)arylated-pyridin-2(1H)-one derivatives have been readily obtained in good yields starting from 2-fluoro-5-pyridylboronic acid. The sequence comprises three steps: (i) palladium-catalysed Suzuki-Miyaura reaction; (ii) base-catalysed hydrolysis; (iii) copper-catalysed C-N coupling. X-ray crystal structures are reported for selected pyridin-2(1H)-one derivatives. These compounds are of interest as new scaffolds for drug discovery.     

2,5-Dimethoxy-2,5-dihydrofuran chemistry: a new approach to 2(5H)-furanone derivatives

2,5-Dimethoxy-2,5-dihydrofuran is a synthetic equivalent of 2(5H)-furanone or 2-trimethylsilyloxyfuran, useful C₄ synthons in the preparation of 5-substituted-2(5H)-furanone derivatives. The reaction conditions adopted allow to obtain different classes of complex and biologically interesting compounds, in only one step, with high yields.     

Facile access to 4-(1-alkynyl)-2(5H)-furanones by Sonogashira coupling of terminal acetylenes with β-tetronic acid bromide: efficient synthesis of cleviolide

A mild and convenient synthesis of 4-(1-alkynyl)-2(5H)-furanones has been achieved by Sonogashira or Heck-type alkynylation of β-tetronic acid bromide. As an illustration of this methodology, the natural product cleviolide was prepared in two steps and 78% overall yield.     

The Thorpe-Ziegler-type reaction of 3-cyanopyridine-2(1H)-thiones with Biginelli 6-bromomethyl-3,4-dihydropyrimidin-2(1H)-ones: cascade assembling of tetra- and pentacyclic heterocyclic scaffolds

3-Cyanopyridine-2(1H)-thiones have been shown to react with Biginelli-type ethyl 4-aryl-6-(bromomethyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates upon heating in DMF giving rise to ethyl 4-aryl-6-{[(3-cyanopyridin-2-yl)thio]methyl}-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates. The latter upon treatment with an excess of NaH or t-BuOK in boiling DMF undergo a tandem Thorpe-Ziegler-type heterocyclization to give pyrido[3″,2″:4′,5′]thieno[2′,3′:5,6]pyrido[4,3-d]pyrimidine derivatives in good yields. Selected compounds were tested for antibacterial and antifungal activity.     

A valuable heterocyclic ring transformation: from isoxazolin-5(2H)-ones to quinolines

A new synthesis of quinoline derivatives was achieved by catalytic hydrogenation of 3,4-disubstituted 2-(2-formylphenyl)-isoxazolin-5(2H)-ones. In the same way, 2,3-disubstituted [1,8]naphthyridine was obtained.     

N-Heterocyclic carbene-Pd(II)-PPh3 complexes as a new highly efficient catalyst system for the Sonogashira cross-coupling reaction: Synthesis,characterization and biological activities

A novel series of N-heterocyclic carbene-phosphine palladium(II) complexes has been synthesized and fully characterized by IR, ¹H NMR, ¹³C NMR, and ³¹P NMR spectroscopies, and elemental analysis. The new N-heterocyclic carbene (NHC)-phosphine palladium(II) complexes 3a–h have been easily prepared by the reaction of the corresponding PEPPSI (pyridine-enhanced precatalyst preparation stabilization and initiation) complexes 2a–h and triphenylphosphine in dichloromethane in high yields. These complexes were applied as catalyst precursors which efficiently catalyzed Sonogashira reactions between aryl bromides and phenylacetylene to afford the corresponding products in good yields. The bulky NHC-Pd-PPh₃ complexes 3 were tested against Gram-positive and Gram-negative bacteria to study their biological activity. All the complexes exhibit antibacterial against these organisms. Investigation of the anti-acetylcholinesterase activity of the studied complexes showed that compounds 3a and 3b exhibited moderate activity at 100 μg mL^?1 and product 3b is the most active.     

Water mediated catalyst-free efficient domino synthesis of 9-(quinolin-2(1H)-one)-xanthene-1,8(5H,9H)-diones using parallel synthesizer

A facile and efficient method for the preparation of 3,4,6,7-tetrahydro-9-(1,2-dihydro-2-oxoquinolin-3-yl)-2H-xanthene-1,8(5H,9H)-diones from substituted 2-chloro-3-formylquinoline and 1,3-cyclohexanedione or dimedone in water at 90 °C using parallel synthesizer is reported. The present methodology offers a tandem-cascade methodology, high yield, and operational simplicity.     

MCM-41-supported bidentate phosphine palladium(0) complex: a highly active and recyclable catalyst for the Sonogashira reaction of aryl iodides

The first MCM-41-supported bidentate phosphine palladium(0) complex has been prepared. This complex is a highly efficient catalyst for Sonogashira reaction and can be reused at least 10 times without any decrease in activity.     

A convenient one-pot synthesis of 2-(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one derivatives and their further transformations

The trifluoromethyl containing heterocycles, 2-hydroxy-4-aryl-3-(thien-2-oyl)-2-(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one derivatives 4, were synthesized via a one-pot three-component reaction of aldehyde 1 with 1,3-cyclohexanedione 2 and 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-dione 3 in the presence of a catalytic amount of Et₃N. The effect of bases and solvents on the reaction efficiency and yield was briefly investigated. Treatment of 4 with an excess amount of NH₄OAc in ethanol afforded 2-trifluoromethyl-1H-quinolin-5-one derivatives 5. Refluxing of 4 with TsOH in CHCl₃ gave the corresponding dehydrated products 8.     

Unexpected behavior of 6H,13H-5:12,7:14-dimethanedibenzo[d,i][1,3,6,8]tetraazecine (DMDBTA) toward phenols

A new 20-membered octaazamacrocyclic compound named 1:4,6:9,11:14,16:19-tetramethylentetrabenzo[b,g,l,q][1,4,6,9,11,14,16,19]octaazaeicocine (TTBOE) (9) has been prepared by means of in situ one-pot synthesis between the aminal 6H,13H-5:12,7:14-dimethanedibenzo[d,i][1,3,6,8]tetraazecine (DMDBTA) (3) and electron-deficient phenols. Otherwise, electron-rich phenols such as 4-chloro-3,5-dimethylphenol or 2-naphthol produce an ortho-regioselective aminomethylation resulting in 2-(1H-benzimidazol-1-ylmethyl)-4-chloro-3,5-dimethylphenol (7) and 1-(1H-benzimidazol-1-ylmethyl)-2-naphthol (8) in a Mannich type reaction in a basic medium. Moreover, obtainment of 1,1′-methylenbis(1H-benzimidazole) (15) from TTBOE is discussed.     

Highly convenient amine-free sonogashira coupling in air in a polar mixed aqueous medium by trans- and cis-[(NHC)2PdX2] (X=Cl, Br) complexes of N/O-functionalized N-heterocyclic carbenes

Two new trans- and cis-[(NHC)(2)PdX(2)] (X=Cl, Br) complexes of N/O-functionalized N-heterocyclic carbenes employed in a highly convenient amine-free Sonogashira cross-coupling reaction in air in a polar mixed aqueous medium are reported. Specifically, the trans-[{1-benzyl-3-(3,3-dimethyl-2-oxobutyl)imidazol-2-ylidene}(2)PdBr(2)] (3) and cis-[{1-benzyl-3-(N-tert-butylacetamido)imidazol-2-ylidene}(2)PdCl(2)] (4) complexes effectively catalyzed the Sonogashira cross-coupling reaction of aryl iodides with substituted acetylenes in air in a mixed solvent (DMF/H(2)O, 3:1 v/v) under amine-free conditions. Interestingly, these trans- and cis-[(NHC)(2)PdX(2)] (X=Cl, Br) complexes, with two N-heterocyclic carbene ligands, exhibited superior activity compared with the now popular PEPPSI (pyridine enhanced precatalyst preparation, stabilization and initiation)-themed analogues, trans-[(NHC)Pd(pyridine)X(2)] (X=Cl, Br), 3 a and 4 a, with one N-heterocyclic carbene ligand and a "throw away" pyridine ligand in a trans disposition to each other. The higher activities of 3 and 4 compared with PEPPSI analogues 3 a and 4 a are attributed to more-electron-rich metal centers, as revealed by DFT studies, in the former complexes and is in concurrence with a more electron-rich metal center being effective in facilitating the oxidative addition of aryl halide, often a rate-determining step in palladium-mediated cross-coupling reactions. Complexes 3 and 4 were prepared from the corresponding silver analogues by transmetalation with [(cod)PdCl(2)], whereas the corresponding PEPPSI analogues 3 a and 4 a were obtained directly from the imidazolium halide salts by reaction with PdCl(2) in pyridine in the presence of K(2)CO(3) as base.     

Highly selective hydrogenation of carbon-carbon multiple bonds catalyzed by the cation [(C(6)Me(6))(2)Ru(2)(PPh(2))H(2)](+): molecular structure of [(C(6)Me(6))(2)Ru(2)(PPh(2))(CHCHPh)H](+), a possible intermediate in the case of phenylacetylene hydrogenation

The dinuclear cation [(C(6)Me(6))(2)Ru(2)(PPh(2))H(2)](+) (1) has been studied as the catalyst for the hydrogenation of carbon-carbon double and triple bonds. In particular, [1][BF(4)] turned out to be a highly selective hydrogenation catalyst for olefin functions in molecules also containing reducible carbonyl functions, such as acrolein, carvone, and methyljasmonate. The hypothesis of molecular catalysis by dinuclear ruthenium complexes is supported by catalyst-poisoning experiments, the absence of an induction period in the kinetics of cyclohexene hydrogenation, and the isolation and single-crystal X-ray structure analysis of the tetrafluoroborate salt of the cation [(C(6)Me(6))(2)Ru(2)(PPh(2))(CHCHPh)H](+) (2), which can be considered as an intermediate in the case of phenylacetylene hydrogenation. On the basis of these findings, a catalytic cycle is proposed which implies that substrate hydrogenation takes place at the intact diruthenium backbone, with the two ruthenium atoms acting cooperatively in the hydrogen-transfer process.