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The synthesis and catalytic activity of novel phosphine palladium PEPPSI and dimer complexes bearing RuPhos, SPhos and XPhos phosphines is reported.

We report a combined experimental and mechanistic study on the Buchwald-Hartwig amination and C-S/S-H metathesis of aryl sulfides by selective activation of C-S bonds mediated by well-defined, air-and moisture-stable Pd(II)-NHC precatalysts, [Pd(NHC)(mu-Cl)Cl]2. This class of Pd(II)-NHC precatalysts displays excellent activity in the cross coupling of aryl sulfides. Most crucially, we unravel the unified mechanism for activation of C-S bonds in the C-N cross-coupling and C-S metathesis manifolds, where the inert C-S bond serves as a precursor to valuable amine or thioether products.

A simple and efficient method for the oxidative coupling of terminal alkynes is reported for the first time, making use of imidazol(in)ium aurates as pre-catalysts. This approach displays high functional group tolerance and leads to a broad range of 1,3-diyne compounds in moderate to excellent yields using low catalyst loading and is performed in air under mild and sustainable conditions.

A simple synthetic pathway to new families of Au–NHC amido complexes under mild reaction conditions is described. Their in vitro anticancer activity was investigated on three human cell lines, showing comparable or even better results than cisplatin.

We present the use of gold sensitizers [Au(SIPr)(Cbz)] (PhotAu 1) and [Au(IPr)(Cbz)] (PhotAu 2) as attractive alternatives to state-of-the-art iridium-based systems. These novel photocatalysts are deployed in [2 + 2] cycloadditions of diallyl ethers and N-tosylamides. The reactions proceed in short reaction times and in environmentally friendly solvents. [Au(SIPr)Cbz] and [Au(IPr)(Cbz)] have higher triplet energy (E-T) values (66.6 and 66.3 kcal mol(-1), respectively) compared to commonly used iridium photosensitizers. These E-T values permit the use of these gold complexes as sensitizers enabling energy transfer catalysis involving unprotected indole derivatives, a substrate class previously inaccessible with state-of-the-art Ir photocatalysts. The photosynthesis of unprotected tetracyclic spiroindolines via intramolecular [2 + 2] cycloaddition using our simple mononuclear gold sensitizer is readily achieved. Mechanistic studies support the involvement of triplet-triplet energy transfer (TTEnT) for both [2 + 2] photocycloadditions.

A synthetic route making use of a weak inorganic base has been developed to easily access [M(diketonato)(NHC)] complexes.

The synthetic access to monomeric copper-alkynyl and copper-thiolato complexes of the type [(NHC)Cu(R)] (R = alkynyl or thiolato) using a weak base approach is reported. All reported reactions proceed under mild conditions in air and in environmentally acceptable solvents. The novel complexes are fully characterized and single crystal X-ray analyses unambiguously establish the atom connectivity in these mononuclear complexes. The importance of the supporting NHC ligand steric properties in stabilizing mononuclear complexes is discussed.

Green and sustainable access to chiral and achiral gold-IBiox complexes is reported. The gold complexes were synthesized using a simple, air-tolerant, weak base protocol carried out in a green solvent. Their catalytic activity was examined in the hydroamination of alkynes. The steric protection afforded the gold center by these ligands was quantified using the %; V; bur; model and compared with the most commonly encountered NHCs.

An operationally simple, user and eco-friendly synthetic protocol for the synthesis of [Rh(acac)(CO)(NHC)] complexes is described. Insights into the mechanism are provided using operando spectroscopy. The spectroscopic fingerprints of these complexes are correlated to NHCs reported electron-donating descriptor values, highlighting a new strategy to evaluate carbenes' electronic properties. An assessment of these complexes in catalytic applications is also reported, showing promising results in the catalytic hydrogenation of aromatic ketones.

The use of weak and inexpensive bases has recently opened promising perspectives towards the simpler and more sustainable synthesis of Au(I)-aryl complexes with valuable applications in catalysis, medicinal chemistry, and materials science. In recent years, continuous manufacturing has shown to be a reliable partner in establishing sustainable and controlled process scalability. Herein, the first continuous flow synthesis of a range of Au(I)-aryl starting from widely available boronic acids and various [Au(NHC)Cl] (NHC=N-heterocyclic carbene) complexes in unprecedentedly short reaction times and high yields is reported. Successful synthesis of previously non- or poorly accessible complexes exposed fascinating reactivity patterns. Via a gram-scale synthesis, convenient process scalability of the developed protocol was showcased.

Silver N-heterocyclic carbenes (Ag–NHCs) exhibit good biocompatibility and have found a wide range of applications in medicine and coordination chemistry. However, due to the strong σ donor nature of NHC, its coordination with silver can weaken the Lewis acidity of Ag(I), leading to slow development of Ag-NHCs in the field of catalysis. Here, we systematically review the application of Ag-NHCs as catalysts in organic synthesis and clearly elaborate the reasons for the slow development of Ag-NHCs in the field of catalysis along with future development opportunities for such complexes as catalysts.

Polarized alkynes such as ynol ethers and ynamides have attracted much attention due to their inherent unique reactivity. Herein, we report Au(I)-catalyzed hydroalkoxylation/Claisen rearrangement cascade reactions of aryl ynol ethers and ynamides with allylic alcohols. At the first stage (hydroalkoxylation) of this cascade reaction, attack of allylic alcohols to aryl ynol ethers or ynamides occurs at the α-position of the polarized alkynes in a completely regioselective manner. Claisen rearrangement of the resulting adducts subsequently takes place to give γ,δ-unsaturated esters or amides, respectively. The [Au(IPr)NTf2] catalyst is most effective for this reaction, and the reaction proceeds under mild conditions (in the case of aryl ynol ether: in THF, 60 °C; in the case of ynamides: in toluene, 80 °C) in an atom-economical way.

This review considers phosphine and N-heterocyclic carbene complexes of gold(I) that are used as (pre)catalysts for a range of reactions in organic synthesis. These are divided according to the structure of the ligand, with the narrative focusing on studies that offer a quantitative comparison between the ligands and readily available or widely used existing systems.

The development of asymmetric carbene transfer reactions using N-sulfonylhydrazones as the diazo surrogate is a long-term issue in organic synthesis since N-sulfonylhydrazones commonly require high...

Gold catalysis has witnessed immense evolution in recent years, yet it still requires the use of activators to render the common [AuCl(L)] complexes catalytically active. Herein, the H-bonding donor properties of hexafluoroisopropanol (HFIP) are utilized for Au-Cl bond activation and the ancillary ligand and counteranion effects on cycloisomerization reactions are showcased in HFIP as solvent.

N-Heterocyclic carbenes (NHCs) are nowadays ubiquitous in organometallic chemistry and catalysis. Recently, a synthetic method which makes use of weak bases and desirable solvents has emerged as a simple, widely applicable and cost-effective pathway to well defined M-NHC complexes. Herein, recent studies devoted to the weak base approach are examined in detail, in order to showcase the simplicity, scope and variations of the method with regards to the azolium salts, bases and the metal sources, as well as the reaction conditions used. Mechanistic investigations are presented, illustrating the formation of intermediates which are air and moisture stable, prior to the metallation step. Finally, the importance, limitations and future prospects of the weak base route are discussed.

A simple and efficient synthetic route to [RuCl2(NHC)(p-cymene)] and [Ru(CO3)(NHC)(p-cymene)] complexes making use of a weak base, under aerobic conditions, is reported. This method enables access to a series of NHC-ruthenium compounds with moderate to good yields under mild conditions. The Ru pre-catalysts were successfully used in olefin oxidation catalysis at low catalyst loading and reach complete conversion in short times.

Fluoroalkyl 1,2,3-triazoles have great potential as medicinal chemistry building blocks. However, only a few synthetic routes to these compounds are currently available. Herein, we report on a novel method to access 5-fluoroalkyl 1,2,3-triazoles from easily prepared bench-stable perfluoroalkyl N-mesylhydrazone (PFHZ-Ms), a reagent that can transform amines to 5 fluoroalkyl 1,2,3-triazoles via defluorinative [4 + 1] annulation. The simple reaction protocol can be applied to a variety of amines containing a range of functional groups, delivering 1,2,3-triazoles in good to excellent yield. The utility of this method was demonstrated in the late-stage modification of bioactive molecules.

The cross-coupling of aryl esters has emerged as a powerful platform for the functionalization of otherwise inert acyl C–O bonds in chemical synthesis and catalysis. Herein, we report a combined experimental and computational study on the acyl Suzuki–Miyaura cross-coupling of aryl esters mediated by well-defined, air- and moisture-stable Pd(II)–NHC precatalysts [Pd(NHC)(μ-Cl)Cl]2. We present a comprehensive evaluation of [Pd(NHC)(μ-Cl)Cl]2 precatalysts and compare them with the present state-of-the-art [(Pd(NHC)allyl] precatalysts bearing allyl-type throw-away ligands. Most importantly, the study reveals [Pd(NHC)(μ-Cl)Cl]2 as the most reactive precatalysts discovered to date in this reactivity manifold. The unique synthetic utility of this unconventional O–C(O) cross-coupling is highlighted in the late-stage functionalization of pharmaceuticals and sequential chemoselective cross-coupling, providing access to valuable ketone products by a catalytic mechanism involving Pd insertion into the aryl ester bond. Furthermore, we present a comprehensive study of the catalytic cycle by DFT methods. Considering the clear advantages of [Pd(NHC)(μ-Cl)Cl]2 precatalysts on several levels, including facile one-pot synthesis, superior atom-economic profile to all other Pd(II)–NHC catalysts, and versatile reactivity, these should be considered as the ‘first-choice’ catalysts for all routine applications in ester O–C(O) bond activation.

A novel, efficient and facile protocol for the synthesis of a series of [Ru(NHC)(CO3)(p-cymene)] complexes is reported. This family of Ru-NHC complexes was obtained from imidazol(in)ium tetrafluoroborate or imidazolium hydrogen carbonate salts in moderate to excellent yields, employing sustainable weak base. The ruthenium complexes were successfully utilized in the transfer hydrogenation of ketones as highly active multifunctional catalysts.

N-heterocyclic carbenes (NHCs) are a widely used class of ligands that have enabled an exciting variety of organometallic chemistry and catalysis. As researchers design and customize these ligands for specific applications, various design concepts have emerged. This review covers several of these design concepts and their impact on and promise for organometallic chemistry and catalysis. These concepts are bulky ligands that remain flexible for substrate binding and reactivity, ring-expanded NHCs with different steric and electronic properties, NHCs appended to supramolecular assemblies that control the microenvironment around the metal center; and NHCs with pendant labile functional groups.

Amides are among the most important and ubiquitous functional groups in organic chemistry and process development. In this Practical Synthetic Procedure, a protocol for the Suzuki–Miyaura cross-coupling of amides by selective N–C(O) bond activation catalyzed by commercially available, air- and moisture-stable palladium/N-heterocyclic carbene (NHC) complexes is described. The procedure described involves [Pd(IPr)(cin)Cl] [IPr = 2,6-(diisopropylphenyl)imidazol-2-ylidene, cin = cinnamyl] at 0.10 mol% at room temperature and is performed on decagram scale. Furthermore, a procedure for the synthesis of amide starting materials is accomplished via selective N-tert-butoxycarbonylation, which is the preferred method over N-acylation. The present protocol carries advantages of operational simplicity, commercial availability of catalysts, and excellent conversions at low catalyst loadings. The method is generally useful for activation of N–C(O) amide bonds in a broad spectrum of amide precursors. The protocol should facilitate the implementation of amide cross-coupling reactions.

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

The modularity and ease of synthesis of carbene-metal-amide (CMA) complexes based on the coinage metals (Au, Ag, Cu) and N-heterocyclic carbenes (NHCs) as ancillary ligands pave the way for the expansion of their applications beyond photochemistry and catalysis. Herein, we further improve the synthesis of such compounds by circumventing the use of toxic organic solvents which were previously required for their purification, and we expand their scope to include complexes incorporating carbolines as the amido fragments. The novel complexes are screened both in vitro and ex vivo, against several cancer cell lines and high-grade serous ovarian cancer (HGSOC) tumoroids, respectively. Excellent cytotoxicity values are obtained for most complexes, while the structural variety of the CMA library screened thus far, provides promising leads for future developments. Variations of all three components (NHC, metal, amido ligand), enable the establishment of trends regarding cytotoxicity and selectivity towards cancerous over normal cells.

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 were obtained. Cyclic voltammetry was carried out to characterize the oxidation and reduction potentials of these [E(NHC)] species; selenoureas were found to be easier to oxidize 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 moiety. The reactivity of these chalcogenoureas with different halogenating reagents (Br2, SO2Cl2, I2) was then investigated, and products were characterized 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.

To explore the mechanism of silver and rhodium catalysis and reveal the origin of the chemo- and enantioselectivity of the reaction, density functional theory calculations were performed on the first silver-catalyzed highly enantioselective carbene transfer reaction. The calculation results reveal that when silver is used as a catalyst, due to the participation of the phosphate anion in the transition state, the enhanced nucleophilicity of the α-diazoacetamide unit promotes smooth dearomatization before generation of the silver carbene. Because the generated rhodium carbene has stronger electrophilicity, typical carbene reactions (C-H insertion and the Büchner reaction) are favored. In addition, in the process of silver catalyzed dearomatization, the formation of an R-type transition state is determined by the small torsion energy and strong interaction energy.

We have investigated the reactions of chalcogenoureas derived from

Transition metal complexes bearing N-heterocyclic carbene ligands (NHCs) have gained a place of crucial importance in numerous areas of research such as medicinal chemistry, material sciences, and homogeneous/heterogeneous catalysis. In the present review, an updated overview of the main synthetic routes used for the preparation of this broad class of compounds along with their main applications are reported. Particular attention will be paid to the synthesis of late transition metal-NHC complexes using weak bases, eco-friendly solvents, and mild operating conditions. This simple synthetic approach, also known as the 'weak base route', represents a recent development with yet unrealized potential.