Radical C−H Trifluoromethoxylation of (Hetero)arenes with Bis(trifluoromethyl)peroxide

Trifluoromethoxylated (hetero)arenes are of great interest for several disciplines, especially in agro- and medicinal chemistry. Radical C−H trifluoromethoxylation of (hetero)arenes represents an attractive approach to prepare such compounds, but the high cost and low atom economy of existing ^. OCF₃ radical sources make them unsuitable for the large-scale synthesis of trifluoromethoxylated building blocks. Herein, we introduce bis(trifluoromethyl)peroxide (BTMP, CF₃OOCF₃) as a practical and efficient trifluoromethoxylating reagent that is easily accessible from inexpensive bulk chemicals. Using either visible light photoredox or TEMPO catalysis, trifluoromethoxylated arenes could be prepared in good yields under mild conditions directly from unactivated aromatics. Moreover, TEMPO catalysis allowed for the one-step synthesis of valuable pyridine derivatives, which have been previously prepared via multi-step approaches.     

“Golden” Cascade Cyclization to Benzo[c]-Phenanthridines

Herein, we describe a gold-catalyzed cascade cyclization of Boc-protected benzylamines bearing two tethered alkyne moieties in a domino reaction initiated by a 6-endo-dig cyclization. The reaction was screened intensively, and the scope was explored, resulting in nine new Boc-protected dihydrobenzo[c]phenanthridines with yields of up to 98 %; even a π-extension and two bidirectional approaches were successful. Furthermore, thermal cleavage of the Boc group and subsequent oxidation gave substituted benzo[c]phenanthridines in up to quantitative yields. Two bidirectional approaches under the optimized conditions were successful, and the resulting π-extended molecules were tested as organic semiconductors in organic thin-film transistors.     

Ethiopian Medicinal Plants Traditionally Used for the Treatment of Cancer; Part 3: Selective Cytotoxic Activity of 22 Plants against Human Cancer Cell Lines

Medicinal plants have been traditionally used to treat cancer in Ethiopia. However, very few studies have reported the in vitro anticancer activities of medicinal plants that are collected from different agro-ecological zones of Ethiopia. Hence, the main aim of this study was to screen the cytotoxic activities of 80% methanol extracts of 22 plants against human peripheral blood mononuclear cells (PBMCs), as well as human breast (MCF-7), lung (A427), bladder (RT-4), and cervical (SiSo) cancer cell lines. Active extracts were further screened against human large cell lung carcinoma (LCLC-103H), pancreatic cancer (DAN-G), ovarian cancer (A2780), and squamous cell carcinoma of the esophagus (KYSE-70) by using the crystal violet cell proliferation assay, while the vitality of the acute myeloid leukemia (HL-60) and histiocytic lymphoma (U-937) cell lines was monitored in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) microtiter assay. Euphorbia schimperiana, Acokanthera schimperi, Kniphofia foliosa, and Kalanchoe petitiana exhibited potent antiproliferative activity against A427, RT-4, MCF-7, and SiSo cell lines, with IC₅₀ values ranging from 1.85 ± 0.44 to 17.8 ± 2.31 µg/mL. Furthermore, these four extracts also showed potent antiproliferative activities against LCLC-103H, DAN-G, A2780, KYSE-70, HL-60, and U-937 cell lines, with IC₅₀ values ranging from 0.086 to 27.06 ± 10.8 µg/mL. Hence, further studies focusing on bio-assay-guided isolation and structural elucidation of active cytotoxic compounds from these plants are warranted.     

Biomimetic Ketone Reduction by Disulfide Radical Anion

The conversion of ribonucleosides to 2′-deoxyribonucleosides is catalyzed by ribonucleoside reductase enzymes in nature. One of the key steps in this complex radical mechanism is the reduction of the 3′-ketodeoxynucleotide by a pair of cysteine residues, providing the electrons via a disulfide radical anion (RSSR^•−) in the active site of the enzyme. In the present study, the bioinspired conversion of ketones to corresponding alcohols was achieved by the intermediacy of disulfide radical anion of cysteine (CysSSCys)^•− in water. High concentration of cysteine and pH 10.6 are necessary for high-yielding reactions. The photoinitiated radical chain reaction includes the one-electron reduction of carbonyl moiety by disulfide radical anion, protonation of the resulting ketyl radical anion by water, and H-atom abstraction from CysSH. The (CysSSCys)^•− transient species generated by ionizing radiation in aqueous solutions allowed the measurement of kinetic data with ketones by pulse radiolysis. By measuring the rate of the decay of (CysSSCys)^•− at λ_max = 420 nm at various concentrations of ketones, we found the rate constants of three cyclic ketones to be in the range of 10⁴–10⁵ M⁻¹s⁻¹ at ~22 °C.     

Complexes formed between nitrilotris(methylenephosphonic acid) and M(2+) transition metals: isostructural organic-inorganic hybrids

Nitrilotris(methylenephosphonic acid) (NTP, [N(CH(2)PO(3)H(2))(3)]) recently has been found to form three-dimensional porous structures with encapsulation of templates as well as layered and linear structures with template intercalation. It was, therefore, of interest to examine the type of organic-inorganic hybrids that would form with metal cations. Mn(II) was found to replace two of the six acid protons, while a third proton bonds to the nitrilo nitrogen, forming a zwitter ion. Two types of compounds were obtained. When the ratio of acid to Mn(II) was less than 10, a trihydrate, Mn[HN(CH(2)PO(3)H)(3)(H(2)O)(3)] (2) formed. Compound 2 is monoclinic P2(1)/c, with a = 9.283(2) A, b = 16.027(3) A, c = 9.7742(2) A, beta = 115.209(3) degrees, V = 1315.0(5) A(3), and Z = 4. The Mn atoms form zigzag chains bridged by two of the three phosphonate groups. The third phosphonate group is only involved in hydrogen bonding. The metal atoms are octahedrally coordinated with three of the sites occupied by water molecules. Adjacent chains are hydrogen-bonded to each other through POH and HN donors, and the additional participation of all the water hydrogens in H-bonding results in a corrugated sheet-like structure. Use of excess NTP at a ratio to metal of 10 to 1 yields an anhydrous compound Mn[HN(CH(2)PO(3)H)(3)] (1), P2(1)/n, a = 9.129(1) A, b = 8.408(1) A, c = 13.453(1) A, beta = 97.830(2) degrees, V = 1023.0(2) A(3), and Z = 4. Manganese is five coordinate forming a distorted square pyramid with oxygens from five different phosphonate groups. The sixth oxygen is 2.85 A from an adjacent Mn, preventing octahedral coordination. All the protonated atoms, three phosphonate oxygens and N, form moderately strong hydrogen bonds in a compact three-dimensional structure. The open-structured trihydrate forms a series of isostructural compounds with other divalent transition metal ions as well as with mixed-metal compositions. This is indicative that the hydrogen bonding controls the type of structure formed irrespective of the cation.     

Control of Metal–Organic Framework Crystallization by Metastable Intermediate Pre‐equilibrium Species

There is an increasing amount of interest in metal–organic frameworks (MOFs) for a variety of applications, from gas sensing and separations to electronics and catalysis. However, the mechanisms by which they crystallize remain poorly understood. Herein, an important new insight into MOF formation is reported. It is shown that, prior to network assembly, crystallization intermediates in the canonical ZIF‐8 system exist in a dynamic pre‐equilibrium, which depends on the reactant concentrations and the progress of reaction. Concentration can, therefore, be used as a synthetic handle to directly control particle size, with potential implications for industrial scale‐up and gas sorption applications. These findings enable the rationalization of apparent contradictions between previous studies of ZIF‐8 and opens up new opportunities for the control of crystallization in network solids more generally.     

Nylon Intermediates from Bio‐Based Levulinic Acid

Use of ZrO₂/SiO₂ as a solid acid catalyst in the ring‐opening of biobased γ‐valerolactone with methanol in the gas phase leads to mixtures of methyl 2‐, 3‐, and 4‐pentenoate (MP) in over 95 % selectivity, containing a surprising 81 % of M4P. This process allows the application of a selective hydroformylation to this mixture to convert M4P into methyl 5‐formyl‐valerate (M5FV) with 90 % selectivity. The other isomers remain unreacted. Reductive amination of M5FV and ring‐closure to ?‐caprolactam in excellent yield had been reported before. The remaining mixture of 2‐ and 3‐MP was subjected to an isomerising methoxycarbonylation to dimethyl adipate in 91 % yield.     

Real‐time Probing the Formation of [M(2,2‐bipyridine)2(NO3)3] (M = Ce,La, Tb) Complexes and Influence of Synthesis Parameters

Despite the strong technological importance of lanthanide complexes, their formation processes are rarely investigated. This work is dedicated to determining the influence of synthesis parameters on the formation of [Ce(bipy)₂(NO₃)₃] as well as Ce³⁺‐ and Tb³⁺‐substituted [La(bipy)₂(NO₃)₃] (bipy = 2,2′‐bipyridine) complexes. To this end, we performed in situ luminescence measurements, synchrotron‐based X‐ray diffraction (XRD) analysis, infrared spectroscopy (IR), and measured pH value and/or ion conductivity during their synthesis process under real reaction conditions. For the [Ce(bipy)₂(NO₃)₃] complex, the in situ luminescence measurements initially presented a broad emission band at 490 nm, assigned to the 5d→4f Ce³⁺ ions within the ethanolic solvation shell. Upon the addition of bipy, a red shift to 700 nm was observed. This shift was attributed to the changes in the environment of the Ce³⁺ ions, indicating their desolvation and incorporation into the [Ce(bipy)₂(NO₃)₃] complex. The induction time was reduced from 8 to 3.5 min, by increasing the reactant concentration by threefold. In contrast, [La(bipy)₂(NO₃)₃] crystallized within days instead of minutes, unless influenced by high Ce³⁺ and Tb³⁺ concentrations. Monitoring and controlling the influence of the reaction parameters on the structure of emissive complexes is important for the development of rational synthesis approaches and optimization of their structure‐related properties like luminescence.