Redox‐Controlled Olefin (Co)Polymerization Catalyzed by Ferrocene‐Bridged Phosphine‐Sulfonate Palladium Complexes

The facile and reversible interconversion between neutral and oxidized forms of palladium complexes containing ferrocene‐bridged phosphine sulfonate ligands was demonstrated. The activity of these palladium complexes could be controlled using redox reagents during ethylene homopolymerization, ethylene/methyl acrylate copolymerization, and norbornene oligomerization. Specifically in norbornene oligomerization, the neutral complexes were not active at all whereas the oxidized counterparts showed appreciable activity. In situ switching between the neutral and oxidized forms resulted in an interesting “off” and “on” behavior in norbornene oligomerization. This work provides a new strategy to control the olefin polymerization process.     

Alkaline Earth–Olefin Complexes with Secondary Interactions

Strontium and calcium (alkaline earth: Ae) olefin complexes stabilised by secondary Ae???F?C and β‐agostic Ae???H?Si interactions are presented. Olefin coordination onto the alkaline earths is plain in the solid state, and it is thermodynamically favoured over the coordination of THF. The existence of the Ae???olefin interactions is corroborated by solution NMR data and DFT computations. The coordination mode of the olefin varies with steric effects and, if enforced, olefin dissociation can be compensated by the other non‐covalent interactions, as supported by DFT computations.     

Hetaryl- and heteroarylvinyl-substituted nitrofurans identified as non-cytotoxic selective antitubercular agents

New (E)-5-[2-(5-nitrofuran-2-yl)vinyl]-1,2,4-oxadiazoles and 5-(5-nitrofuran-2-yl)-1,2,4-oxadiazoles were synthesized via the base-promoted condensation of nitrofuran-containing acyl chlorides with amidoximes. Testing these compounds against Gram-negative E. coli, Gram-positive B. subtilis and S. aureus as well as M. tuberculosis HRv37 strain revealed three compounds being selectively antimycobacterial. None of these compounds displayed any cytotoxicity towards human pancreatic epithelioid carcinoma cell line, PANC-1.     

Donor-Flexible Bis(pyridylidene amide) Ligands for Highly Efficient Ruthenium-Catalyzed Olefin Oxidation

An exceptionally efficient ruthenium-based catalyst for olefin oxidation has been designed by exploiting N,N′-bis(pyridylidene)oxalamide (bisPYA) as a donor-flexible ligand. The dynamic donor ability of the bisPYA ligand, imparted by variable zwitterionic and neutral resonance structure contributions, paired with the redox activity of ruthenium provided catalytic activity for Lemieux–Johnson-type oxidative cleavage of olefins to efficiently prepare ketones and aldehydes. The ruthenium bisPYA complex significantly outperforms state-of-the-art systems and displays extraordinary catalytic activity in this oxidation, reaching turnover frequencies of 650 000 h⁻¹ and turnover numbers of several millions.     

Dual catalytic performance of arene-ruthenium amine complexes for norbornene ring-opening metathesis and methyl methacrylate atom-transfer radical polymerizations

Arene ruthenium(II) complexes bearing the cyclic amines RuCl₂(η⁶-p-cymene)(pyrrolidine)] ( 1 ), [RuCl₂(η⁶-p-cymene)(piperidine)] ( 2 ), and [RuCl₂(η⁶-p-cymene)(peridroazepine)] ( 3 ) were successfully synthesized. Complexes 1 – 3 were fully characterized by means of Fourier transform infrared, UV–visible, and NMR spectroscopy, elemental analysis, cyclic voltammetry, computational methods, and one of the complexes was further studied by single crystal X-ray crystallography. These compounds were evaluated as catalytic precursors for ring-opening metathesis polymerization (ROMP) of norbornene (NBE) and atom-transfer radical polymerization (ATRP) of methyl methacrylate (MMA). NBE polymerization via ROMP was evaluated using complexes 1 – 3 as precatalysts in the presence of ethyl diazoacetate (EDA) under different [NBE]/[EDA]/[Ru] ratios, temperatures (25 and 50°C), and reaction times (5–60 min). The highest yields of polyNBE were obtained with [NBE]/[EDA]/[Ru] = 5000/28/1 for 60 min at 50°C. MMA polymerization via ATRP was conducted using 1 – 3 as catalysts in the presence of ethyl-α-bromoisobutyrate (EBiB) as initiator. The catalytic tests were evaluated as a function of the reaction time using the initial molar ratio of [MMA]/[EBiB]/[Ru] = 1000/2/1 at 95°C. The increase in molecular weight as function of time indicates that complexes 1–3 were able to mediate the MMA polymerization with an acceptable rate and some level of control. Differences in the rate of polymerization were observed in the order 3 > 2 > 1 for the ROMP and ATRP.     

Large-Scale Synthesis of a Niche Olefin Metathesis Catalyst Bearing an Unsymmetrical N-Heterocyclic Carbene (NHC) Ligand and its Application in a Green Pharmaceutical Context

A large-scale synthesis of known Ru olefin metathesis catalyst VII featuring an unsymmetrical N-heterocyclic carbene (NHC) ligand with one 2,5-diisopropylphenyl (DIPP) and one thiophenylmethylene N-substituent is reported. The optimised procedure does not require column chromatography in any step and allows for preparation of up to 0.5 kg batches of the catalyst from simple precursors. The application profile of the obtained catalyst was studied in environmentally friendly dimethyl carbonate (DMC). Although VII exhibited low efficiency in cross-metathesis (CM) with electron-deficient partners, good to excellent results were noted for substrates featuring easy to isomerise C−C double bonds. This includes polyfunctional substrates of medicinal chemistry interest, such as analogues of psychoactive 5F-PB-22 and NM-2201 and two PDE5 inhibitors—Sildenafil and Vardenafil. Finally, a larger scale ring-closing metathesis (RCM) of a Vardenafil derivative was conducted in DMC, allowing for straightforward isolation of the expected product (23 g) in high yield and with low Ru contamination level (7.7 ppm).     

Stereoselective Synthesis of Enamides through Palladium-Catalyzed Oxidative Amidation of Conjugated Olefins with 2-Pyridones

A palladium-catalyzed oxidative amidation of conjugated olefin with 2-pyridone is described. A series of E-Enamides were synthesized in a highly stereocontrolled manner. The reaction also accommodates other cyclic and acyclic amides. Z-Enamides were predominantly prepared for primary amides probably due to the presence of an intramolecular hydrogen bond. Gram-scale synthesis of enamide and the following oxidative annulation with diphenylacetylene demonstrates the synthetic utility of this reaction.     

Synthesis and Catalytic Study of Ruthenium Carbene Catalyst Containing a Zn‐Porphyrin Ligand

A ruthenium carbene complex containing a Zn‐porphyrin ligand has been developed. The complex was characterized by ¹H NMR, IR, HRMS and elemental analysis. The catalytic activity of the ruthenium carbene complex for olefin metathesis reactions was also investigated. The complex exhibited excellent performance for both ring‐closing and cross metathesis reactions at 35°C.     

Surface‐Functionalized Nanoparticles by Olefin Metathesis: A Chemoselective Approach for In Vivo Characterization of Atherosclerosis Plaque

The use of click chemistry reactions for the functionalization of nanoparticles is particularly useful to modify the surface in a well‐defined manner and to enhance the targeting properties, thus facilitating clinical translation. Here it is demonstrated that olefin metathesis can be used for the chemoselective functionalization of iron oxide nanoparticles with three different examples. This approach enables, in one step, the synthesis and functionalization of different water‐stable magnetite‐based particles from oleic acid‐coated counterparts. The surface of the nanoparticles was completely characterized showing how the metathesis approach introduces a large number of hydrophilic molecules on their coating layer. As an example of the possible applications of these new nanocomposites, a focus was taken on atherosclerosis plaques. It is also demonstrated how the in vitro properties of one of the probes, particularly its Ca²⁺‐binding properties, mediate their final in vivo use; that is, the selective accumulation in atherosclerotic plaques. This opens promising new applications to detect possible microcalcifications associated with plaque vulnerability. The accumulation of the new imaging tracers is demonstrated by in vivo magnetic resonance imaging of carotids and aorta in the ApoE^?/? mouse model and the results were confirmed by histology.