Kinetico‐Mechanistic Insights on the Assembling Dynamics of Allyl‐Cornered Metallacycles: The PtNpy Bond is the Keystone

The square‐like homo‐ and heterometallamacrocycles [{Pd(η³‐2‐Me‐C₃H₄)( L ⁿ )₂}₂{M(dppp)}₂](CF₃SO₃)₆ (dppp=1,3‐bis(diphenylphosphino)propane) and [{Pd(η³‐2‐Me‐C₃H₄)( L¹ )₂}₂{M(PPh₃)₂}₂](CF₃SO₃)₆ [py=pyridine, M=Pd, Pt, L ^{n =}4‐PPh₂py ( L¹ ), 4‐C₆F₄PPh₂py ( L² )] containing allyl corners were synthesised by antisymbiotic self‐assembly of the different palladium and platinum metallic corners and the ambidentate N,P ligands. All the synthesised assemblies displayed a complex dynamic behaviour in solution, the rate of which is found to be dependent on the electronic and/or steric nature of the different building blocks. A kinetico‐mechanistic study by NMR line shape analysis of the dynamics of some of these assemblies was undertaken in order to determine the corresponding thermal activation parameters. Both an enhanced thermodynamic stability and slower dynamics were observed for platinum‐pyridine‐containing species when compared with their palladium analogues. Time‐dependent NMR spectroscopy in combination with ESI mass spectrometry was used to study the exchange between the assemblies and their building blocks, as well as that occurring between different metallamacrocycles. Preliminary studies were carried out on the activity of some of the metallamacrocyclic compounds as catalytic precursors in the allylic substitution reaction, and the results compared with that of the monometallic allylic corner [Pd(η³‐2‐Me‐C₃H₄)( L¹ )₂]⁺.     

Mixed‐Metal MIL‐100(Sc,M) (M=Al,Cr, Fe) for Lewis Acid Catalysis and Tandem CC Bond Formation and Alcohol Oxidation

The trivalent metal cations Al³⁺, Cr³⁺, and Fe³⁺ were each introduced, together with Sc³⁺, into MIL‐100(Sc,M) solid solutions (M=Al, Cr, Fe) by direct synthesis. The substitution has been confirmed by powder X‐ray diffraction (PXRD) and solid‐state NMR, UV/Vis, and X‐ray absorption (XAS) spectroscopy. Mixed Sc/Fe MIL‐100 samples were prepared in which part of the Fe is present as α‐Fe₂O₃ nanoparticles within the mesoporous cages of the MOF, as shown by XAS, TGA, and PXRD. The catalytic activity of the mixed‐metal catalysts in Lewis acid catalysed Friedel–Crafts additions increases with the amount of Sc present, with the attenuating effect of the second metal decreasing in the order Al>Fe>Cr. Mixed‐metal Sc,Fe materials give acceptable activity: 40 % Fe incorporation only results in a 20 % decrease in activity over the same reaction time and pure product can still be obtained and filtered off after extended reaction times. Supported α‐Fe₂O₃ nanoparticles were also active Lewis acid species, although less active than Sc³⁺ in trimer sites. The incorporation of Fe³⁺ into MIL‐100(Sc) imparts activity for oxidation catalysis and tandem catalytic processes (Lewis acid+oxidation) that make use of both catalytically active framework Sc³⁺ and Fe³⁺. A procedure for using these mixed‐metal heterogeneous catalysts has been developed for making ketones from (hetero)aromatics and a hemiacetal.     

Redesigning the DNA‐Targeted Chromophore in Platinum–Acridine Anticancer Agents: A Structure–Activity Relationship Study

Platinum–acridine hybrid agents show low‐nanomolar potency in chemoresistant non‐small cell lung cancer (NSCLC), but high systemic toxicity in vivo. To reduce the promiscuous genotoxicity of these agents and improve their pharmacological properties, a modular build–click–screen approach was used to evaluate a small library of twenty hybrid agents containing truncated and extended chromophores of varying basicities. Selected derivatives were resynthesized and tested in five NSCLC cell lines representing large cell, squamous cell, and adenocarcinomas. 7‐Aminobenz[c]acridine was identified as a promising scaffold in a hybrid agent ( P1–B1 ) that maintained submicromolar activity in several of the DNA‐repair proficient and p53‐mutant cancer models, while showing improved tolerability in mice by 32‐fold compared to the parent platinum–acridine ( P1–A1 ). The distribution and DNA/RNA adduct levels produced by the acridine‐ and benz[c]acridine‐based analogues in NCI‐H460 cells (confocal microscopy, ICP‐MS), and their ability to bind G‐quadruplex forming DNA sequences (CD spectroscopy, HR‐ESMS) were studied. P1–B1 emerges as a less genotoxic, more tolerable, and potentially more target‐selective hybrid agent than P1–A1 .     

Iridium(I)‐Catalyzed Regioselective CH Activation and Hydrogen‐Isotope Exchange of Non‐aromatic Unsaturated Functionality

Isotopic labelling is a key technology of increasing importance for the investigation of new C?H activation and functionalization techniques, as well as in the construction of labelled molecules for use within both organic synthesis and drug discovery. Herein, we report for the first time selective iridium‐catalyzed C?H activation and hydrogen‐isotope exchange at the β‐position of unsaturated organic compounds. The use of our highly active [Ir(cod)(IMes)(PPh₃)][PF₆] (cod=1,5‐cyclooctadiene) catalyst, under mild reaction conditions, allows the regioselective β‐activation and labelling of a range of α,β‐unsaturated compounds with differing steric and electronic properties. This new process delivers high levels of isotope incorporation over short reaction times by using low levels of catalyst loading.     

Supramolecular Water Oxidation with Ru–bda‐Based Catalysts

Extremely slow and extremely fast new water oxidation catalysts based on the Ru–bda (bda=2,2′‐bipyridine‐6,6′‐dicarboxylate) systems are reported with turnover frequencies in the range of 1 and 900 cycles s^?1, respectively. Detailed analyses of the main factors involved in the water oxidation reaction have been carried out and are based on a combination of reactivity tests, electrochemical experiments, and DFT calculations. These analyses give a convergent interpretation that generates a solid understanding of the main factors involved in the water oxidation reaction, which in turn allows the design of catalysts with very low energy barriers in all the steps involved in the water oxidation catalytic cycle. We show that for this type of system π‐stacking interactions are the key factors that influence reactivity and by adequately controlling them we can generate exceptionally fast water oxidation catalysts.     

Rollover‐Assisted C(sp2)C(sp3) Bond Formation

Rollover cyclometalation involves bidentate heterocyclic donors, unusually acting as cyclometalated ligands. The resulting products, possessing a free donor atom, react differently from the classical cyclometalated complexes. Taking advantage of a “rollover”/“retro‐rollover” reaction sequence, a succession of oxidative addition and reductive elimination in a series of platinum(II) complexes [Pt(N,C)(Me)(PR₃)] resulted in a rare C(sp²)?C(sp³) bond formation to give the bidentate nitrogen ligands 3‐methyl‐2,2′‐bipyridine, 3,6‐dimethyl‐2,2′‐bipyridine, and 3‐methyl‐2‐(2′‐pyridyl)‐quinoline, which were isolated and characterized. The nature of the phosphane PR₃ is essential to the outcome of the reaction. This route constitutes a new method for the activation and functionalization of C?H bond in the C(3) position of bidentate heterocyclic compounds, a position usually difficult to functionalize.     

Formal Total Synthesis of Kendomycin by Way of Alkyne Metathesis/Gold Catalysis

In an attempt to study the ability of the latest generation of alkyne metathesis catalysts to process sterically hindered substrates, two different routes to the bacterial metabolite kendomycin ( 1 ) were explored. Whereas the cyclization of the overcrowded arylalkyne 39 and related substrates turned out to be impractical or even impossible, ring closure of the slightly relaxed diyne 45 was achieved in excellent yield under notably mild conditions with the aid of the molybdenum alkylidyne 2 endowed with triphenylsilanolate ligands. The resulting cycloalkyne 46 was engaged into a gold‐catalyzed hydroalkoxylation, which led to benzofuran 47 that had already previously served as a late‐stage intermediate en route to 1 .     

Gold‐Catalyzed Diastereoselective Cycloisomerization of Alkylidene‐Cyclopropane‐Bearing 1,6‐Diynes

An unprecedented gold‐catalyzed diastereoselective cycloisomerization of 1,6‐diynes bearing an alkylidene cyclopropane moiety has been developed. This methodology enables rapid access to a variety of 1,2‐trimethylenenorbornanes, which are important building blocks in the preparations of abiotic and sesquiterpene core structures.     

Enhanced π‐Backdonation from Gold(I): Isolation of Original Carbonyl and Carbene Complexes

The specific electronic properties of bent o‐carborane diphosphine gold(I) fragments were exploited to obtain the first classical carbonyl complex of gold [(DPCb)AuCO]⁺ (ν(CO)=2143 cm^?1) and the diphenylcarbene complex [(DPCb)Au(CPh₂)]⁺, which is stabilized by the gold fragment rather than the carbene substituents. These two complexes were characterized by spectroscopic and crystallographic means. The [(DPCb)Au]⁺ fragment plays a major role in their stability, as substantiated by DFT calculations. The bending induced by the diphosphine ligand substantially enhances π‐backdonation and thereby allows the isolation of carbonyl and carbene complexes featuring significant π‐bond character.