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N-Heterocyclic carbene (NHC)-derived selenoureas comprise a fundamentally important class of NHC derivatives, with key applications in coordination chemistry and the determination of NHC electronic properties. Considering the broad reactivity of chalcogen-containing compounds, it is surprising to note that the use of NHC-derived selenoureas as organic synthons remains essentially unexplored. The present contribution introduces a novel, straightforward transformation leading to azines bearing a guanidine moiety, through the reaction of a wide range of NHC-derived selenoureas with commercially available diazo compounds, in the presence of triphenylphosphine. This transformation offers a new approach to such products, having biological, materials chemistry, and organic synthesis applications. The guanidine-bearing azines are obtained in excellent yields, with all manipulations taking place in air. A reaction mechanism is proposed, based on both experimental mechanistic findings and density functional theory (DFT) calculations. A one-pot, multicomponent transesterification reaction between selenoureas, α-diazoesters, alcohols, and triphenylphosphine was also developed, providing highly functionalized azines., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

We disclose a novel series of N-heterocyclic carbene (NHC) gold complexes with varied steric and electronic properties, bearing fluorinated alkoxide anions. Early reactivity studies involving these synthons, lead to the synthesis of various complexes of relevance to gold chemistry and catalysis.

An efficient olefin hydrosilylation protocol utilising Pt(II)-thioether-based pre-catalysts is reported. These simple and readily available complexes exhibit excellent catalytic performance and offer significant advantages over existing alternatives, enabling rapid and high conversions at ppm-level catalyst loadings.

Triazolinediones are known as highly reactive dienophiles that can also act as electrophilic amination reagents towards enolisable C-H bonds (ionic pathway) or weak C-H bonds (free radical pathway). Here, we report that this C-H amination reactivity can be significantly extended and enhanced via gold(i)-catalysis. Under mild conditions, several alkyl-substituted aryls successfully undergo benzylic C-H aminations at room temperature. The remarkable site selectivity that is observed points towards strong electronic activation and deactivation effects, that go beyond a simple weakening of the C-H bond. The observed catalytic C-H aminations do not follow the expected trends for a free radical-type C-H amination and show complementarity to existing methods. Density functional theory (DFT) calculations and distinct experimental trends provide a clear mechanistic rationale for observed selectivity patterns, postulating a novel pathway for triazolinedione-induced aminations via a carbon-to-nitrogen hydride transfer., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Herein, we report the catalytic activity of a series of platinum(II) pre-catalysts, bearing N-heterocyclic carbene (NHC) ligands, in the alkene hydrosilylation reaction. Their structural and electronic properties are fully investigated using X-ray diffraction analysis and nuclear magnetic resonance spectroscopy (NMR). Next, our study presents a structure-activity relationship within this group of pre-catalysts and gives mechanistic insights into the catalyst activation step. An exceptional catalytic performance of one of the complexes is observed, reaching a turnover number (TON) of 970 000 and a turnover frequency (TOF) of 40 417 h -1 at 1 ppm catalyst loading. Finally, an attractive solvent-free and open-to-air alkene hydrosilylation protocol, featuring efficient platinum removal (reduction of residual Pt from 582 ppm to 5.8 ppm), is disclosed., (© 2023 Wiley-VCH GmbH.)

A series of NHC-based selenourea Ag(I) and Au(I) complexes were evaluated for their anticancer potential in vitro, on 2D and 3D human cancer cell systems. All NHC-based selenourea complexes possess an outstanding cytotoxic potency, which was comparable or even better than that of the reference metallodrug auranofin, and were also able to overcome both platinum-based and multi-drug resistances. Intriguingly, their cytotoxic potency did not correlate with solution stability, partition coefficient or cellular uptake. On the other hand, mechanistic studies in cancer cells revealed their ability to strongly and selectively inhibit the redox-regulating enzyme Thioredoxin Reductase (TrxR), being even more effective than auranofin, a well-known TrxR inhibitor, without affecting other redox enzymes such as Glutathione Reductase (GR). The inhibition of TrxR in H157 human cancer cells caused, in turn, the disruption of cellular thiol-redox homeostasis and of mitochondria pathophysiology, ultimately leading to cancer cell death through apoptosis., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

α-Haloketones play an essential role in the synthesis of complex N -, S -, O -heterocycles; of which some exhibit a remarkable biological activity. Research further illustrated that α-bromo-, α-chloro-, and α-iodoketones are key precursors for blockbuster pharmacological compounds. Over the past twenty years, substantial advances have been made in the synthesis of these industrially relevant building blocks. Efforts have focused on rendering the synthetic protocols greener, more effective and versatile. In this survey, we summarised and thoroughly evaluated the progress of the field, established in the past two decades, in terms of generality, efficacy and sustainability.

A sustainable and facile weak-base synthetic route to platinum N-heterocyclic carbene (NHC) complexes is disclosed. The mechanism of this reaction is also elucidated via experimental and computational investigations. This straightforward protocol is then used for the synthesis of novel Pt(II)-NHC complexes and its utility is further explored to access key Pt(0)-NHC precatalysts.

We have investigated the reactions of chalcogenoureas derived from N -heterocyclic carbenes, referred to here as [E(NHC)], with halogens. Depending on the structure of the chalcogenourea and the identity of the halogen, a diverse range of reactivity was observed and a corresponding range of structures was obtained. Cyclic voltammetry was carried out to characterise the oxidation and reduction potentials of these [E(NHC)] species; selenoureas were found to be easier to oxidise than the corresponding thioureas. In some cases, a correlation was found between the oxidation potential of these compounds and the electronic properties of the corresponding NHC. The reactivity of these chalcogenoureas with different halogenating reagents (Br 2 , SO 2 Cl 2 , I 2 ) was then investigated, and products were characterised using NMR spectroscopy and single-crystal X-ray diffraction. X-ray analyses elucidated the solid-state coordination types of the obtained products, showing that a variety of possible adducts can be obtained. In some cases, we were able to extrapolate a structure/activity correlation to explain the observed trends in reactivity and oxidation potentials.

The integration of a membrane separation protocol with the platinum-catalyzed hydrosilylation of olefins is investigated. The catalytic reaction is first optimized in batch where [Pt(IPr*)(dms)Cl 2 ] (IPr*=1,3-bis[2,6-bis(diphenylmethyl)-4-methylphenyl]imidazol-2-ylidene, dms=dimethyl sulfide) demonstrates superior activity compared to the less sterically encumbered [Pt(SIPr)(dms)Cl 2 ] (SIPr=1,3-bis(2,6-diisopropylphenyl)imidazolidine) congener. Filtration conditions are identified in membrane screening experiments. Hydrosilylation of 1-octene catalyzed by [Pt(IPr*)(dms)Cl 2 ] is conducted in continuous mode and the platinum catalyst is separated efficiently over the commercially available Borsig oNF-2 membrane, all under solvent-free conditions. An advantage of this process is that both reaction and separation are coupled in a single step. Moreover, at the end of the process the intact catalyst was recovered in 80 % yield as an off-white solid without any further purification., (© 2021 Wiley-VCH GmbH.)

Readily prepared and bench-stable [Au(CF 3 )(NHC)] compounds were synthesized by using new methods, starting from [Au(OH)(NHC)], [Au(Cl)(NHC)] or [Au(L)(NHC)]HF 2 precursors (NHC=N-heterocyclic carbene). The mechanism of formation of these species was investigated. Consequently, a new and straightforward strategy for the mild and selective cleavage of a single carbon/fluorine bond from [Au(CF 3 )(NHC)] complexes was attempted and found to be reversible in the presence of an additional nucleophilic fluoride source. This straightforward technique has led to the unprecedented spectroscopic observation of a gold(I)-NHC difluorocarbene species., (© 2021 Wiley-VCH GmbH.)

This review is a critical presentation of catalysts based on palladium and ruthenium bearing N-heterocyclic carbene ligands that have enabled a more sustainable approach to catalysis and to catalyst uses. Aspects of sustainability associated with these in terms of catalytic uses or synthetic access are reviewed.

N-heterocyclic carbene gold(I) chloride and hydroxide complexes are regularly used as synthons to access various oxygen-, nitrogen- or carbon-bound gold complexes. They are also widely employed as efficient catalysts in addition reactions of hydroelements to unsaturated bonds and in several rearrangement and decarboxylation protocols. Here we describe the multigram synthesis of the most common mononuclear N-heterocyclic carbene gold(I) chloride complexes bearing the N,N'-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes), N,N'-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) and N,N'-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazol-2-ylidene (IPr*) ligands. Their synthesis is achieved through the straightforward and practical weak base approach in a total time of 4-5 h. This straightforward methodology is conducted under air and possesses considerable advantages over alternative routes, such as the use of a sustainable reaction solvent, minimal amounts of a mild base and commercially available or easily obtained starting materials. Additionally, we describe the synthesis of the mononuclear gold(I) hydroxide complex bearing the IPr ligand, using the state-of-the-art method requiring 24 h. Finally, the improved synthesis of the dinuclear gold(I) hydroxide complex [{Au(IPr)} 2 (μ-OH)][BF 4 ] is described (~3 h). All procedures can be performed by researchers with standard training and lead to high yields (76-99%) of microanalytically pure bench-stable materials.

A general, user-friendly synthetic route to [Pt(NHC)(L)Cl2] and [Pt(NHC)(dvtms)] (L = DMS, Py; DMS = dimethyl sulfide, dvtms = divinyltetramethylsiloxane, Py = pyridine) complexes has been developed. The procedure is applicable to a wide range of ligands and enables facile synthetic access to key Pt(0)- and Pt(ii)-NHC complexes used in hydrosilylation catalysis.

Chalcogen-based urea compounds supported by a wide range of N-heterocyclic carbenes are synthesised and fully characterised. Coordination of selenoureas is further explored with Group 11 transition metals to form new copper, gold and silver complexes. Single crystal X-ray analyses unambiguously establish the solid-state coordination of these complexes and show that the geometry of a complex is highly influenced by a combination of electronic properties - mainly π-accepting ability - and steric hindrance of the ligands, as well as the nature of the metal, affording a variety of coordination behaviours. In this report, we investigate these phenomena using several experimental methods.

The development of more reactive, general, easily accessible, and readily available Pd(II)-NHC precatalysts remains a key challenge in homogeneous catalysis. In this study, we establish air-stable NHC-Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl] 2 , as the most reactive Pd(II)-NHC catalysts developed to date. Most crucially, compared with [Pd(NHC)(allyl)Cl] complexes, replacement of the allyl throw-away ligand with chloride allows for a more facile activation step, while effectively preventing the formation of off-cycle [Pd 2 (μ-allyl)(μ-Cl)(NHC) 2 ] products. The utility is demonstrated via broad compatibility with amide cross-coupling, Suzuki cross-coupling, and the direct, late-stage functionalization of pharmaceuticals. Computational studies provide key insight into the NHC-Pd(II) chloro-dimer activation pathway. A facile synthesis of NHC-Pd(II) chloro-dimers in one-pot from NHC salts is reported. Considering the tremendous utility of Pd-catalyzed cross-coupling reactions and the overwhelming success of [Pd(NHC)(allyl)Cl] precatalysts, we believe that NHC-Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl] 2 , should be considered as go-to precatalysts of choice in cross-coupling processes., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The reaction mechanism leading to the formation of cross-coupling palladium pre-catalysts of the PEPPSI family was investigated. Two intermediates were isolated and proved to be both suitable synthons to the pre-catalysts, with one permitting the design of a novel and greener user-friendly synthetic route. In light of this mechanistic understanding, the traditional one-pot method was shown to be possible using stoichiometric amounts of throw-away ligand, which represents a considerable synthetic improvement over the wasteful "in pyridine" approach.

The discovery of sustainable and scalable synthetic protocols leading to gold-aryl compounds bearing N-heterocyclic carbene (NHC) ligands sparked an investigation of their reactivity and potential utility as organometallic synthons. The use of a mild base and green solvents provide access to these compounds, starting from widely available boronic acids and various [Au(NHC)Cl] complexes, with reactions taking place under air, at room temperature and leading to high yields with unprecedented ease. One compound, (N,N'-bis[2,6-(di-isopropyl)phenyl]imidazol-2-ylidene)(4-methoxyphenyl)gold, ([Au(IPr)(4-MeOC 6 H 4 )]), was synthesized on a multigram scale and used to gauge the reactivity of this class of compounds towards C-H/N-H bonds and with various acids, revealing simple pathways to gold-based species that possess attractive properties as materials, reagents and/or catalysts., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We have been puzzled by the involvement of weak organic and inorganic bases in the synthesis of metal-N-heterocyclic carbene (NHC) complexes. Such bases are insufficiently strong to permit the presumed required deprotonation of the azolium salt (the carbene precursor) prior to metal binding. Experimental and computational studies provide support for a base-assisted concerted process that does not require free NHC formation. The synthetic protocol was found applicable to a number of transition-metal- and main-group-centered NHC compounds and could become the synthetic route of choice to form M-NHC bonds., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The first example of a NHC-based copper azide complex is reported. Its reactivity was investigated with various reagents affording 8 new complexes.

A new class of [Au(NHC)(Bpin)] complexes has been synthesized and their unusual reactivity was investigated using computational and experimental methods. The gold-boryl complexes exhibit unexpected high stability and reactivity.

Gold(i) catalysed regio- and stereoselective intermolecular hydroamination of internal alkynes was developed for the effective synthesis of a series of (Z)-functionalised vinylazoles under solvent free conditions. The catalytic hydrogenation of the resulting enamines leads to substituted saturated azoles in good yields.

The anti-atherogenic (anti-inflammatory) properties of various aurate(I) salts, of the general formula [NHC⋅H][AuCl 2 ] (NHC=N-heterocyclic carbene) were investigated. The aurates were easily synthesized and obtained in analytically pure form. In addition, the biological activity of these compounds against atheromatosis via in vitro inhibition of platelet-activating factor (PAF)-induced platelet aggregation was probed. All complexes were found to possess anti-aggregatory properties in vitro with [IPr*⋅H][AuCl 2 ] (6) being the most potent inhibitor of PAF at micromolar concentration. Based on our findings, we conclude that these simply assembled aurates are a very promising class of PAF inhibitors and anti-inflammatory drugs., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We describe the synthesis and characterisation of a series of new copper and silver complexes with selenourea ligands derived from common and readily-prepared N-heterocyclic carbenes (NHCs). The copper complexes behave somewhat predictably, typically leading to [CuCl(L)] complexes (with two exceptions). The silver complexes display a diverse range of structural motifs, including [AgCl(μ-L)] 2 , [AgCl(L) 2 ], [Ag(L) 2 ] + , [Ag(L) 3 ] + , and [(Ag(L) 2 ) 2 (μ-L)] 2+ species. All new complexes are characterised by multinuclear NMR spectroscopy, and several examples are characterised by X-ray crystallography. This study demonstrates the diversity of coordination behaviour that these selenourea ligands can engage in.

A stable periodic mesoporous organosilica (PMO) with accessible sulfonic acid functionalities is prepared via a one-pot-synthesis and is used as solid support for highly active catalysts, consisting of gold(I)-N-heterocyclic carbene (NHC) complexes. The gold complexes are successfully immobilized on the nanoporous hybrid material via a straightforward acid-base reaction with the corresponding [Au(OH)(NHC)] synthon. This catalyst design strategy results in a boomerang-type catalyst, allowing the active species to detach from the surface to perform the catalysis and then to recombine with the solid after all the starting material is consumed. This boomerang behavior is assessed in the hydration of alkynes. The tested catalysts were found to be active in the latter reaction, and after an acidic work-up, the IPr*-based gold catalyst can be recovered and then reused several times without any loss in efficiency., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The simple synthesis of a family of palladates containing an imidazolium counterion is presented. These "ate" complexes can be easily converted into well-defined palladium-N-heterocyclic carbene (NHC) complexes. The synthetic protocols leading to the "ate" and to the Pd-NHC neutral complexes have been exemplified with various NHC ligands. The palladates prove efficient pre-catalysts enabling Suzuki-Miyaura and Mizoroki-Heck reactions.

A straightforward method for the hydrophenoxylation of internal alkynes, using N-heterocyclic carbene-based copper(i) and gold(i) complexes, is described. The heterobimetallic catalytic system proceeds via dual activation of the substrates to afford the desired vinylether derivatives. This methodology is shown to be highly efficient and tolerates a wide range of substituted phenols and alkynes.

This report presents the recent advances in the use of copper(i)-NHC (NHC = N-heterocyclic carbene) complexes as transmetallating agents enabling the transfer of NHCs to a wide range of transition metals. The synthesis of these carbene transfer reagents is also discussed.

The homopolymerization and copolymerization of styrene and methyl methacrylate, initiated for the first time by the combination of azo-bis-isobutyronitrile (AIBN) with [(SiMes)Ru(PPh 3 )(Ind)Cl 2 ] complex. The reactions were successfully carried out, on a large scale, in presence this complex at 80 °C. It was concluded from the data obtained that the association of AIBN with the ruthenium complex reduces considerably the transfer reactions and leads to the controlled radical polymerization and the well-defined polymers.

Since the discovery and now widespread use of olefin metathesis, the evolution of metathesis catalysts towards air stability has become an area of significant interest. In this fascinating area of study, beginning with early systems making use of high oxidation state early transition metal centers that required strict exclusion of water and air, advances have been made to render catalysts more stable and yet more functional group tolerant. This review summarizes the major developments concerning catalytic systems directed towards water and air tolerance.

The reaction of triisopropyl phosphite with phosphine-based indenylidene pre-catalysts affords "1(st) generation" cis-complexes. These have been used in olefin metathesis reactions. The cis-Ru species exhibit noticeable differences with the trans-Ru parent complexes in terms of structure, thermal stability and reactivity. Experimental data underline the importance of synergistic effects between phosphites and L-type ligands.

Herein we report robust methods for the preparation and full characterisation of a range of Ir(I) and Rh(I) fluoride and bifluoride complexes using N-heterocyclic carbenes (NHCs) as ancillary ligands. The processes that link the fluoride and the bifluoride species are investigated and reports of the first Ir-bifluoride and Ir(I)-NHC and Rh(I)-NHC trifluoromethyl complexes are revealed.

We report the synthesis of nine new N -heterocyclic carbene gold bifluoride complexes starting from the corresponding N -heterocyclic carbene gold hydroxides. A new methodology to access N,N' -bis(2,6-diisopropylphenyl)imidazol-2-ylidene gold(I) fluoride starting from N,N' -bis(2,6-diisopropylphenyl)imidazol-2-ylidene gold(I) hydroxide and readily available potassium bifluoride is also reported. These gold bifluorides were shown to be efficient catalysts in the hydrofluorination of symmetrical and unsymmetrical alkynes, thus affording fluorinated stilbene analogues and fluorovinyl thioethers in good to excellent yields with high stereo- and regioselectivity. The method is exploited further to access a fluorinated combretastatin analogue selectively in two steps starting from commercially available reagents.

We report herein a versatile cooperative dual catalysis reaction based on a Cu(I)/Pd(0) system. Mechanistic investigation shows that every component plays a crucial role in determining the reaction outcome. The reaction is successfully extended to various substrates; such as α,β-unsaturated ketones, malonates and coumarins. The strategy tolerates different substitution patterns and affords good yields for each family of substrates., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This paper describes a tunable and stereoselective dual catalytic system that uses copper and palladium reagents. This cooperative silylcupration and palladium-catalyzed allylation readily affords trisubstituted alkenylsilanes. Fine-tuning the reaction conditions allows selective access to one stereoisomer over the other. This new methodology tolerates different substituents on both coupling partners with high levels of stereoselectivity. The one-pot reaction involving a Cu(I)/Pd(0) cooperative dual catalyst directly addresses the need to develop more time-efficient and less-wasteful synthetic pathways., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Under hypoxia, cancer cells consume glucose and release lactate at a high rate. Lactate was recently documented to be recaptured by oxygenated cancer cells to fuel the TCA cycle and thereby to support tumor growth. Monocarboxylate transporters (MCT) are the main lactate carriers and therefore represent potential therapeutic targets to limit cancer progression. In this study, we have developed and implemented a stepwise in vitro screening procedure on human cancer cells to identify new potent MCT inhibitors. Various 7-substituted carboxycoumarins and quinolinone derivatives were synthesized and pharmacologically evaluated. Most active compounds were obtained using a palladium-catalyzed Buchwald-Hartwig type coupling reaction, which proved to be a quick and efficient method to obtain aminocarboxycoumarin derivatives. Inhibition of lactate flux revealed that the most active compound 19 (IC50 11 nM) was three log orders more active than the CHC reference compound. Comparison with warfarin, a conventional anticoagulant coumarin, further showed that compound 19 did not influence the prothrombin time which, together with a good in vitro ADME profile, supports the potential of this new family of compounds to act as anticancer drugs through inhibition of lactate flux., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Polymer brushes (PBs) have been used as supports for the immobilization of palladium complexes on silicon surfaces. The polymers were grown by surface-initiated atom-transfer radical polymerization (SI-ATRP) and postdecorated with dipyridylamine (dpa) ligands. The pendant dpa units were in turn complexed with [Pd(OAc)(2)] to afford hybrid catalytic surfaces. A series of catalytic samples of various thicknesses (ca. 20-160 nm) and associated palladium loadings (ca. 10-45 nmol  cm(-2)) were obtained by adjusting the SI-ATRP reaction time and characterized by ellipsometry, X-ray reflectivity, X-ray photoelectron spectroscopy, and inductively coupled plasma mass spectrometry (ICP-MS). ICP-MS revealed a near-linear relationship between thickness of the polymer brush and palladium content, which confirmed the robustness of the preparation and postmodification sequence presented herein, rendering possible the creation of functional architectures with predefined catalytic potential. The activities of the catalytic PBs were determined by systematically exploring a full range of substrate-to-catalyst ratios in a model palladium(0)-catalyzed reaction. Quantitative transformations were observed for loadings down to 0.03 mol % and a maximum turnover number (TON) of around 3500 was established for the system. Comparison of the catalytic performances evidenced a singular influence of the thickness on conversions and TONs. The limited recyclability of the hairy catalysts has been attributed to palladium leaching., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

To be or not to bifluoride: Two synthetic pathways to unprecedented N-heterocyclic carbene copper(I) bifluoride complexes have been developed. Catalytic tests demonstrated that copper(I) bifluorides are very efficient catalysts, which do not require any additional activating agent. The first Cu-catalyzed diastereoselective allylation of (R)-N-tert-butanesulfinyl aldimines was also established. The method enables efficient, simple and general synthesis of enantiomerically enriched homoallylic amines at room temperature in high yields., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)