RESUMEN

α-Olefins are very important bulk and fine chemicals and their synthesis from ethylene, an abundantly available and inexpensive feedstock, is highly attractive. Unfortunately, the direct or on-purpose synthesis of olefins from ethylene is limited to three examples, 1-butene, 1-hexene, and 1-octene, all having a linear structure. Herein, the direct synthesis of 3-methylenepentane and 4-ethylhex-1-ene, branched trimerization, and tetramerization products of ethylene, respectively, is reported. Different molecular titanium catalysts, all highly active, with a selectivity toward the formation of the branched ethylene trimer or tetramer, the employment of different activators, and different reaction conditions are the key to selective product formation. The long-time stability of selected catalysts employed permits upscaling as demonstrated for the synthesis of 4-ethylhex-1-ene (52 g isolated, TON(ethylene) 10.7 · 106).

RESUMEN

α-Olefins are important starting materials for the production of plastics, pharmaceuticals, and fine and bulk chemicals. However, the selective synthesis of α-olefins from ethylene, a highly abundant and inexpensive feedstock, is restricted, and thus a broadly applicable selective α-olefin synthesis using ethylene is highly desirable. Here, we report the catalytic reaction of an α-olefin with two ethylene molecules. The first ethylene molecule forms a 4-ethyl branch and the second a new terminal carbon-carbon double bond (C2 elongation). The key to this reaction is the development of a highly active and stable molecular titanium catalyst that undergoes extremely fast ß-hydride elimination and transfer.

RESUMEN

An aminopyridinato ligand stabilized and coordinatively unsaturated dimeric tungsten(0) complex having an electronic structure with six metal centred HOMOs (σ2,π2,π2,δ2,δ2, and δ*2) has been isolated and structurally characterized. Its reaction with a cryptand leads to a C-H bond activation of one of the isopropyl groups of the N-ligand to form a dimeric tungsten(i) complex.

RESUMEN

Four new bis(N,N-dialkylbenzimidazol-2-ylidene)dichlorido platinum(ii) complexes 2 featuring N-alkyl substituents of increasing size (a: Me, b: Et, c: n-butyl, d: n-octyl) were synthesised and oxidised with PhICl2 to give the corresponding [PtIVCl4(N,N-dialkylbenzimidazol-2-ylidene)2] complexes 4 as potential anticancer prodrugs. The known bis(N,N-dibenzylimidazol-2-ylidene)dichlorido platinum(ii) complex 1 was likewise oxidised to [PtIVCl4(N,N-dibenzylimidazol-2-ylidene)2] 3. In contrast, oxidation of complexes 1 and 2 with H2O2 or hypochlorites, or exchange of chlorido for hydroxo ligands in tetrachlorido complexes 4 failed to give isolable complexes of type [PtIVCl4-n(OH)n(NHC)2]. In MTT assays the [PtIICl2(NHC)2]/[PtIVCl4(NHC)2] complex couples 1/3, 2c/4c, and trans-2c/trans-4c, bearing either N-benzyl or N-butyl substituents, each showed similar single-digit micromolar IC50 values against at least three out of five human cancer cell lines, presumably due to an intracellular reduction of the PtIV complexes to their active PtII congeners. Unlike cisplatin, whose anticancer effect requires functional p53, each of them was active both in wildtype and in p53-negative HCT116 colon carcinoma cells. In ethidium bromide saturation assays with isolated DNA, cis-(bis-NHC)PtII complexes such as 1 caused morphological DNA changes more pronounced than those initiated by cisplatin, while the corresponding cis-(bis-NHC)PtIV complexes such as 3 interacted with DNA in a less structure-modifying way.

RESUMEN

Eleven complexes of [(1,3-dialkylbenzimidazol-2-ylidene)LnCl3-n]Pt(n-1)+, with Ln = DMSO (8), Ph3P (9), (Ph3P)2 (10), and alkyl = Me (a), Et (b), Bu (c), octyl (d), were synthesised and tested for cellular accumulation, cytotoxicity, interference with the tumour cell cycle, and interaction with DNA. The delocalised lipophilic cationic bisphosphane complexes 10 were on average found to be more cytotoxic in MTT assays against a panel of seven cancer cell lines than the neutral DMSO and monophosphane complexes 8 and 9. The uptake of complexes 10, at least into HCT116 colon carcinoma cells, was also significantly greater than that of analogues 8 and 9. Their cytotoxicities did not differ significantly with the N-alkyl side chain length. The complexes that were most active, with sub-micromolar IC50 (72 h) values against HCT116wt cells, that is 8b, 9b, 10a-c, worked by a mode of action that was dependent on the functional p53, yet were still far more active than cisplatin in both of the HCT116wt and HCT116-/- variants. In detailed binding analyses 8c, 9c and 10a-c showed a lower affinity to DNA and different binding modes when compared to cisplatin, preferably forming mono-adducts with DNA and distorting it to a lower extent. Also, unlike cisplatin, they arrested the HCT116 cells of both variants predominantly in the G1 phase.

Asunto(s)

Antineoplásicos/farmacología , Bencimidazoles/farmacología , Complejos de Coordinación/farmacología , Platino (Metal)/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Bencimidazoles/síntesis química , Bencimidazoles/química , Bovinos , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , ADN/química , ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Cinética , Estructura Molecular , Plásmidos , Platino (Metal)/química , Relación Estructura-Actividad , Células Tumorales Cultivadas

RESUMEN

Catalysis with earth-abundant transition metals is an option to help save our rare noble-metal resources and is especially interesting when novel reactivity or selectivity patterns are observed. We report here on a novel reaction, namely the dehydrogenative alkylation or α-olefination of alkyl-substituted N-heteroarenes with alcohols. Manganese complexes developed in our laboratory catalyze the reaction with high efficiency whereas iron and cobalt complexes stabilized by the same ligands are essentially inactive. Hydrogen is liberated during the reaction, and bromine and iodine functional groups as well as olefins are tolerated. A variety of alkyl-substituted N-heteroarenes can be functionalized, and benzylic and aliphatic alcohols undergo the reaction.

RESUMEN

The catalytic synthesis of linear α-olefins from ethylene is a technologically highly important reaction. A synthesis concept allowing the formation of selective products and various linear α-olefin product distributions with one catalyst system is highly desirable. Here, we describe a trimetallic catalyst system (Y-Al-Ni) consisting of a rare earth metal polymerization catalyst which can mediate coordinative chain transfer to triethylaluminum combined with a simultaneously operating nickel ß-hydride elimination/transfer catalyst. This nickel catalyst displaces the grown alkyl chains forming linear α-olefins and recycles the aluminum-based chain transfer agent. With one catalyst system, we can synthesize product spectra ranging from selective 1-butene formation to α-olefin distributions centered at 850 gmol-1 with a low polydispersity. The key to this highly flexible linear α-olefin synthesis is the easy tuning of the rates of the Y and Ni catalysis independently of each other. The reaction is substoichiometric or formally catalytic regarding the chain transfer agent.

RESUMEN

The replacement of expensive noble metals by earth-abundant transition metals is a central topic in catalysis. Herein, we introduce a highly active and selective homogeneous manganese-based C=O bond hydrogenation catalyst. Our catalyst has a broad substrate scope, it is able to hydrogenate aryl-alkyl, diaryl, dialkyl, and cycloalkyl ketones as well as aldehydes. A very good functional group tolerance including the quantitative and selective hydrogenation of a ketone in the presence of a non-shielded olefin is observed. In Mn hydrogenation catalysis, the combination of the multidentate ligand, the oxidation state of the metal, and the choice of the right ancillary ligand is crucial for high activity. This observation emphasizes an advantage and the importance of homogeneous catalysts in 3d-metal catalysis. For coordination compounds, fine-tuning of a complex coordination environment is easily accomplished in comparison to enzyme and/or heterogeneous catalysts.

RESUMEN

Based on two well-established ligand systems, the aminopyridinato (Ap) and the phenoxyimine (FI) ligand systems, new Ap-FI hybrid ligands were developed. Four different Ap-FI hybrid ligands were synthesized through a simple condensation reaction and fully characterized. The reaction of hafnium tetrabenzyl with all four Ap-FI hybrid ligands exclusively led to mono(Ap-FI) complexes of the type [(Ap-FI)HfBn2 ]. The ligands acted as tetradentate dianionic chelates. Upon activation with tris(pentafluorophenyl)borane, the hafnium-dibenzyl complexes led to highly active catalysts for the polymerization of 1-hexene. Ultrahigh molecular weights and extremely narrow polydispersities support the living nature of this polymerization process. A possible deactivation product of the hafnium catalysts was characterized by single-crystal X-ray analysis and is discussed. The coordination modes of these new ligands were studied with the help of model titanium complexes. The reaction of titanium(IV) isopropoxide with ligand 1 led to a mono(Ap-FI) complex, which showed the desired fac-mer coordination mode. Titanium (IV) isopropoxide reacted with ligand 4 to give a complex of the type [(ApH-FI)2 Ti(OiPr)2 ], which featured the ligand in its monoanionic form. The two titanium complexes were characterized by X-ray crystal-structure analysis.