Use of Pd-catalyzed Suzuki-Miyaura coupling reaction in the rapid synthesis of 5-aryl-6-(phosphonomethoxy)uracils and evaluation of their inhibitory effect towards human thymidine phosphorylase

A number of new 5-aryl substituted pyrimidine acyclic nucleoside phosphonates were synthesized and tested for their ability to inhibit human TP. Their rapid synthesis using Pd-catalyzed Suzuki-Miyaura coupling reactions of various arylboronic acids with 5-bromo-4-(phosphonomethoxy)-2,6-dibutoxypyrimidine was successfully applied. For a series of 5-aryl-6-phosphonomethoxyuracils, an increased inhibitory effect was determined. This effect is supported by the results found for 4-fluorophenyl (K_i^dThd=4.89±0.62) and 3-nitrophenyl (K_i^dThd=3.98±0.46) substituents.     

An efficient procedure for the synthesis of 3-aryl-4-methoxy-2(5H)-furanones by using the microwave-promoted Suzuki-Miyaura coupling reactions

The Suzuki-Miyaura coupling reactions of 3-bromo-2(5H)-furanones with a variety of arylboronic acids, promoted by microwave heating, efficiently generate 3-aryl-2(5H)-furanones. This remarkably rapid process serves as the foundation for a simple method to rapidly construct 3-aryl-2(5H)-furanone libraries.     

1-(2-羟甲基-1,3-氧硫杂环戊基)吡啶酮类化合物的合成

研究了1,3-氧硫杂环戊烷核苷类似物的合成. 以吡啶酮为碱基, 利用三甲基硅基三氟甲磺酸酯(TMSOTf)催化, 与1,3-氧硫杂环戊烷发生Vorbruggen缩合反应, 合成了一系列的保护的核苷类似物, 经过进一步脱保护或者还原得到目标产物. 并测试了合成化合物的抗菌活性, 发现该类化合物对革兰氏阳性菌具有中等抑制活性.     

A convenient synthesis of 4-aryl-1,8-naphthyridin-2(1H)-ones by the Suzuki coupling

4-Halo-1,8-naphthyridin-2(1H)-ones readily available from 2-chloronicotinic acid were subjected to the Suzuki coupling reaction with arylboronic acids to give a diversity of 4-aryl-1,8-naphthyridin-2(1H)-ones.     

The Silyl Method for the Synthesis of 1[-2(Phenoxy)ethyl]uracils

A modification of the method for the synthesis of N₍₁₎-substituted derivatives of uracil is proposed using the Gilbert-Johnson reaction, which consists of the alkylation of 5-substituted 2,4-bis(trimethylsiloxy)pyrimidines with 1-bromo-2-(phenoxy)ethanes of low reactivity at 180-185° without solvent. The corresponding 1-[2-(phenoxy)ethyl]uracils, which were obtained in 55-74% yield, contained no impurities of the N₍₁₎, N₍₃₎-disubstituted compounds. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, 1071–1075, July, 2005. cf E. Ya. Lukevics and A. E. Zablotskaya. The Silyl Method for the Synthesis of Nucleosides [in Russian], Zinatne, Riga, 1985, 440 p. (Editor's note).     

Facile synthesis and coupling of 3,9-dibromo-6-aryl-5H-dibenzo[d,f][1,3]diazepine derivatives

A route has been developed to prepare 3,9-dibromo-6-aryl-5H-dibenzo[d,f][1,3]diazepine derivatives which undergo facile Suzuki coupling to generate extended conjugated moieties bearing this unit. Single crystal X-ray studies on three of the coupled products provide valuable information on the conformation and bulk packing of these materials.     

2-(Fluorophenyl)pyridines by the Suzuki-Miyaura method: Ag2O accelerates coupling over undesired ipso substitution (SNAr) of fluorine

Problematic ipso substitution was observed in the Suzuki-Miyaura coupling of pentafluorophenylboronic acid to make 2-pentafluorophenylpyridine. Strong bases favored coupling, but under these conditions fluorine in the product tended to undergo nucleophilic substitution. Inclusion of Ag₂O accelerated coupling over ipso substitution.     

Rapid geometrical equilibrium of palladium(II) complexes with tris[2-(diphenylphosphino)ethyl]phosphine disulfide and diselenide and their catalytic activity for Suzuki coupling reaction

Palladium(II) complexes with a tetradentate pseudo-tripodal ligand having two phosphino groups and two phosphine sulfide or selenide groups, pp₃X₂ (pp₃ = tris[2-(diphenylphosphino)ethyl]phosphine, X = S (1) or Se (2)), were prepared from [PdCl(pp₃)]Cl. Both of these phosphine chalcogenide complexes 1 and 2 showed rapid equilibrium between the five-coordinate [PdCl(pp₃X₂)]Cl with two bound phosphine chalcogenide groups and four-coordinate [PdCl₂(pp₃X₂)] with two dissociated pendant ones in chloroform. The thermodynamic parameters for the reaction, [PdCl(pp₃X₂)]⁺ + Cl⁻?[PdCl₂(pp₃X₂)], were obtained by low-temperature ³¹P NMR as follows: K²⁹⁸ = 3.7 × 10³ and 5.4 × 10² mol⁻¹, ΔH^° = 11.3 ± 0.3 and 13.4 ± 0.4 kJ mol⁻¹, and ΔS^° = 106 ± 2 and 97 ± 2 J mol⁻¹ K⁻¹ for 1 and 2, respectively. The rate for the geometrical change at 246.7 K for 1 was appreciably faster than that for 2. These thermodynamic and kinetic results indicate that the phosphine selenide Se atoms can stabilize the five-coordinate structure by effective π-back donation from Pd(II) compared with the phosphine sulfide S atoms. Difference in retention of the catalytic activity for Suzuki coupling, 2 > 1 > [PdCl(pp₃ or p₃)]Cl, was explained by difference in the π-accepting ability that stabilizes the catalytically active Pd(0) species. Considering the rapid dissociation-coordination equilibrium of the phosphine chalcogenide groups on Pd(II), it is probable that the oxidative addition and the subsequent transmetallation of the Pd(II) species are hardly blocked by the phosphine chalcogenide groups.     

Preparation of 3,4-fused-spiro[furan-5(5H),4′-piperidin]-2-one

A general method for the preparation of various 3,4-fused-spiro[furan-5(5H),4′-piperidin]-2-one with high yield is reported. The formation of spiro[furanone-piperidine] structure was achieved by a Suzuki coupling, followed by an iodolactonization reaction.     

A synthesis of 1-substituted 5-[2-(acylamino)ethyl]-1H-pyrazole-4-carboxamides

A seven-step synthesis of 1-substituted 5-(2-acylaminoethyl)-1H-pyrazole-4-carboxamides 20 as the pyrazole analogues of histamine was developed. The synthesis starts with a three-step preparation of N(1)-substituted methyl 5-(2-tert-butoxycarbonylaminoethyl)-1H-pyrazole-4-carboxylates 7 from commercially available Boc-β-alanine (1). Subsequent four-step transformation of the key-intermediates 7 into the final products 20 was performed following two complementary reaction sequences comprising acidolytic removal of the Boc group, hydrolysis of the COOMe group, amidations of the COOH group, and acylations of the NH₂ group. The structures of pyrazole derivatives were determined by spectroscopic methods and by X-ray diffraction.     

(E)-5'-脱氧-5'-N【{[2-(2-苯基)乙烯基]磺酰基}氨基】腺苷的合成

以甲基磺酰胺为起始原料,经Horner和Mitsunobu等反应合成了新型核苷类衍生物——(E)-5'-脱氧-5'-N【{[2-(2-苯基)乙烯基]磺酰基}氨基】腺苷,其结构经1H NMR,13C NMR,IR和LC-MS表征。     

The synthesis of 1-[2-(dimethylamino)ethyl]-7,12-dihydro-3H-[2]-benzoxepino[4,3-e]indole : A potential antidepressant agent

The structures of doxepin and serotonin were overlayed using molecular graphics and 1 - [2-(dimethylamino)ethyl] - 7, 12 - dihydro - 3H - [2] - benzoxepino[4,3-e]indole(1) was proposed as a potential antidepressant agent. This paper deals with the synthesis of the title compound. Key steps in the synthesis include a regioselective electrophilic substitution at C-4 of ethyl 5-hydroxy-1-indolecarboxylate (4) and subsequent modification to 7,12-dihydro-3H-[2]-benzoxepino[4,3-e]indole(12). Standard procedures were then used to construct the dimethylaminoethyl side chain to yeild the title compound (1).     

Synthesis of 1-aryl-2-[2-(dimethylamino)ethyl]-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-diones and their analogs

Methyl o-hydroxybenzoylpyruvate heated with N,N-dimethylethylenediamine and aromatic aldehydes affords in a high yield 5-aryl-3-hydroxy-4-(2-hydroxyphenyl)-1-[2-(dimethylamino)ethyl]-1,5-dihydro-2H-pyrrol-2-ones, which easily split off water at boiling in acetic acid and are converted into 1-aryl-2-[(2-dimethylamino)ethyl]-1,2-dihydrochromeno[2,3-c]pyrrol-3,9-diones. The developed route of synthesis provides a wide range of derivatives of 1-aryl-2-[ω-(dialkylamino)alkyl]-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-diones.     

Iminophosphines: synthesis, formation of 2,3-dihydro-1H-benzo[1,3]azaphosphol-3-ium salts and N-(pyridin-2-yl)-2-diphenylphosphinoylaniline, coordination chemistry and applications in platinum group catalyzed Suzuki coupling reactions and hydrosilylations

The aprotic and protic bi- and multidentate iminophosphines 2-Ph₂PC₆H₄N=CR¹R² (R¹=H, R²=Ph=2a; R¹=Me R²=Ph=2b; R¹=H, R²=2-thienyl=2c; R¹=H, R²=C₆H₄-2-PPh₂=2d; R¹=H, R²=C₆H₄-2-OH=2e, R¹=H, R²=C₆H₄-2-OH-3-Bu^t=2f; R¹=H, R²=CH₂C(O)Me=2g) have been prepared by the acid catalyzed condensation of 2-(diphenylphosphino)aniline with the corresponding aldehyde–ketone. Iminophosphine 2d can be reduced with sodium cyanoborohydride to give the corresponding amino-diphosphine 2-Ph₂PC₆H₄N(H)CH₂C₆H₄-2-PPh₂ (2h). In the presence of a stoichiometric quantity of acid, 2-(diphenylphosphino)aniline reacts in an unexpected manner with benzaldehyde, salicylaldehyde, or acetophenone to give the corresponding 2,3-dihydro-1H-benzo[1,3]azaphosphol-3-ium salts and with pyridine-2-carboxaldehyde to give N-(pyridin-2-ylmethyl)-2-diphenylphosphinoylaniline, the latter of which has been characterized by single-crystal X-ray crystallography, as its palladium dichloride derivative. The attempted condensation of 2-(diphenylphosphino)aniline with pyridine-2-carboxaldehyde to give the corresponding pyridine-functionalized iminophosphine resulted in an unusual transformation involving the diastereoselective addition of two equivalents of aldehyde to give 1,2-dipyridin-2-yl-2-(o-diphenylphosphinoyl)phenylamino-ethanol, which has been characterized by a single-crystal X-ray structure determination. The bidentate iminophosphine 2-Ph₂PC₆H₄N=C(H)Ph reacts with [(cycloocta-1,5-diene)PdClX] X=Cl, Me) to give [Pd{2-Ph₂PC₆H₄N=C(H)Ph}ClX] and the imino-diphosphine 2-Ph₂PC₆H₄N=C(H)C₆H₄-PPh₂ reacts with [(cycloocta-1,5-diene)PdClMe] to give [Pd{2-Ph₂PC₆H₄N=C(H)C₆H₄---PPh₂}ClMe] and each has been characterized by single-crystal X-ray crystallography. The monobasic iminophosphine 2-Ph₂PC₆H₄N=C(Me)CH₂C(O)Me reacts with [Ni(PPh₃)₂Cl₂] in the presence of NaH to give the phosphino–ketoiminate complex [Ni{2-Ph₂PC₆H₄N=C(Me)CHC(O)Me}Cl], which has been structurally characterized. Mixtures of iminophosphines 2a–h and a palladium source catalyze the Suzuki cross coupling of 4-bromoacetophenone with phenyl boronic acid. The efficiency of these catalysts show a marked dependence on the palladium source, catalysts formed from [Pd₂(OAc)₆] giving consistently higher conversions than those formed from [Pd₂(dba)₃] and [PdCl₂(MeCN)₂]. Catalysts formed from neutral bi- and terdentate iminophosphines 2a–d gave significantly higher conversions than those formed from their monobasic counterparts 2e–f. Notably, under our conditions the conversions obtained with 2a–c compare favorably with those of the standards; catalysts formed from tris(2-tolyl)phosphine and tris(2,4-di-tert-butylphenyl)phosphite and a source of palladium. In addition, mixtures of [Ir(COD)Cl]₂ and 2a–h are active for the hydrosilylation of acetophenone; in this case catalysts formed from monobasic iminophosphines 2e–f giving the highest conversions.     

Preparation and characterization of Cu supported on 2-(1H-benzo[d]imidazol-2-yl)aniline-functionalized Fe3O4 nanoparticles as a novel magnetic catalyst for Ullmann and Suzuki cross-coupling reactions

Copper supported on 2-(1H-benzo[d]imidazol-2-yl)aniline (BIA)-functionalized Fe₃O₄ nanoparticles (Cu-BIA-Si-Fe₃O₄) as a novel magnetic catalyst was designed and used for the synthesis of new products via Ullmann and Suzuki cross-coupling reactions. The Ullmann reaction was performed by mixing arylboronic acid with aniline derivatives in dimethylsulfoxide solvent. Also, diaryls were synthesized via Suzuki C–C reactions between aryl halides and phenylboronic acid in the same solvent. The prepared materials and catalyst were characterized with various analytical techniques. The Cu-BIA-Si-Fe₃O₄ catalyst demonstrated catalytic efficiency with good to excellent yields for both types of reactions in comparison with commercial palladium catalysts. Also, the catalyst could be recovered by a simple filtration and retained its activity even after several cycles.     

Mono- and dinuclear Pd(II) complexes of different salicylaldimine ligands as catalysts of transfer hydrogenation of nitrobenzene with cyclohexene and Suzuki-Miyaura coupling reactions

In this study, the synthesis, spectroscopic, catalytic, and electrochemical properties of salicylaldimine Schiff-base ligands (L_n) and their dinuclear Pd(II) complexes for L₁ and L₂ ligands with mononuclear Pd(II) complexes for L₃ and L₄ ligands were investigated. The ligands and their mono- or dinuclear Pd(II) complexes were characterized by FT-IR, UV-Vis, ¹H NMR and elemental analysis, as well as through magnetic susceptibility and spectroelectrochemical techniques. The catalytic studies showed that the introduction of tert butyl groups on the salicyl ring of the molecules increased the catalytic activity towards hydrogenation of nitrobenzene and cyclohexene in DMF at 25 and 45 °C. It was also observed that the steric hindered mono- and dinuclear Pd(II) complexes were thermally stable complexes and were not sensitive to air or the moisture. The complexes were easily prepared from cheap materials that could be used as versatile and efficient catalysts for different C-C coupling reactions (Suzuki-Miyaura reactions).     

4-甲基-苯磺酸-2-氧-2-[3-(5-芳基-[1,3,4]噁二唑-2-基)-硫脲]-乙基酯的合成及生物活性研究

合成了12个未见文献报道的4-甲基-苯磺酸2-氧-2-[3-(5-芳基-[1,3,4]噁二唑-2-基)-硫脲]-乙基酯, 其结构经元素分析、¹H NMR和IR确证. 初步活性测试结果表明: 部分化合物有较好的杀菌活性.