Well-Defined [Pd(NHC)(η-methylnaphthyl)Br] Complexes in Cross-Coupling Reactions.

The development of efficient and easily accessible Pd(II)-NHC (NHC = N-heterocyclic carbene) pre-catalysts is presented. A series of well-defined [Pd(NHC)(α/β-η-MeNAP)Br] (MeNAP = methylnaphthyl) pre-catalysts has been synthesized by reacting [Pd(α/β-η-MeNAP)Br] and various NHC·HCl precursors in the presence of KCO in acetone. The synthesized Pd(II)-NHC derivatives displayed good to excellent catalytic activity, and rapid activation in classical Suzuki-Miyaura, Buchwald-Hartwig, and Miyaura borylation reactions.

Synthesis of Cyclobuta[]acetylindolines via Gold Photocatalysis.

The [2 + 2] cycloaddition reaction constitutes a powerful tool for the construction of cyclobutane-fused scaffolds. A protocol for the intermolecular cycloaddition of 1-acetylindoles was developed where [Au(SIPr)Cbz] has proven indispensable for this purpose, while conventional photocatalysts, such as iridium and organic photosensitizers, have shown limited efficiency. Our findings unlocked the synthesis of cyclobutane-fused indolines, without any required substituent at the C2 or C3 position.

Electrochemical synthesis of palladium N-heterocyclic carbene (NHC) complexes.

A novel electrochemical method for the preparation of Pd-NHC (N-heterocyclic carbene) catalysts has been developed. Unlike previously reported procedures, the present method does not employ soluble sacrificial anodes as a metal source but makes use of well-defined Pd-containing precursors instead. Importantly, oxygen was observed to play a key role acting as an electrogenerated base.

Investigation of the anticancer potential of bis(imino)acenaphthene-N-heterocyclic carbene transition metal complexes revealed TrxR inhibition and triggering of immunogenic cell death (ICD) for allyl palladates.

Immunogenic cell death (ICD) is a regulated form of cell death that activates an immune response through the release of danger-associated molecular patterns (DAMPs), including calreticulin, ATP, and HMGB1. Gold complexes are known to induce ICD, but the ICD-inducing potential of palladium complexes remains largely unexplored. We report the first examples of palladium compounds capable of inducing ICD, specifically allyl palladates bearing bis(imino)acenaphthene-NHC (BIAN-NHC) ligands.

[Cu(NHC)(OR)] (R = C(CF)) complexes for N-H and S-H bond activation and as pre-catalysts in the Chan-Evans-Lam reaction.

The synthesis, isolation, and full characterization of a series of NHC-copper perfluoro-alkoxide complexes are reported. Their exceptional stability resides with the steric hindrance of the nonafluoro--butyl alkoxide moiety, which exhibits a strong electron withdrawing effect. These new Cu(I) complexes are synthons that can permit the activation of acidic N-H and S-H bonds.

A simply accessible organometallic system to gauge electronic properties of N-heterocyclic carbenes.

The intricate σ and π-bonding of N-heterocyclic carbenes (NHCs) to metals and the need to quantify their electronic properties to rationalize reactivity of complexes have resulted in the creation of numerous methodologies to understand the NHC-metal interaction which are, as we now show, flawed. Our search for a unified, easily accessible system to gauge these fundamental properties has resulted in the discovery of two systems that highlight the flaws present in existing systems and provide a more accurate measure of the NHC ligand electronic properties.

Simply accessible platinum(II) complexes enabling alkene hydrosilylation at ppm catalyst loadings.

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.

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The Suzuki-Miyaura cross-coupling of amides by selective N-C acyl bond cleavage represents a powerful tool for constructing biaryl ketones from historically inert amide bonds. These amide bond activation reactions hinge upon efficient oxidative addition of the N-C acyl bond to Pd(0). However, in contrast to the well-researched activation of aryl halides by C(sp)-X oxidative addition, very few studies on the mechanism of C(acyl)-N bond oxidative addition and catalyst effect have been reported.

Gold complexes with remote-substituted amino N-heterocyclic carbenes.

The 4-RN-1,3-Ar-imidazolium salt, R = iPr, Bu, Ar = Mes, Dipp, Mes = mesityl, Dipp = 2,6-bis-diisopropyl-phenyl was metalated by Au at the C2-, C5- and 4-RN positions depending on the reactants and conditions employed; a rare direct rearrangement of a Au aminide to an abnormal imidazol-5-ylidene Au complex was also observed and based on a DFT study it may involve TfO facilitated H transfer.

An air-stable [Cu(NHC)(OR)] (R = C(H)(CF)) complex for C-H, N-H and S-H bond activation.

The synthesis, isolation and full characterisation of a [Cu(IPr)(OC(H)(CF))] (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) complex are reported. This new Cu(I) complex is a versatile synthon and can activate numerous X-H bonds including C-H, N-H and S-H bonds. [Cu(IPr)(OC(H)(CF))] was investigated as a pre-catalyst in several catalytic reactions.

Pt -N-Heterocyclic Carbene Complexes in Solvent-Free Alkene Hydrosilylation.

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.

Correlation of Experimental and Calculated Reaction Enthalpies with Ligand Donor Strengths.

Ylide-functionalized phosphines (YPhos) have recently proven to be strongly donating ligands that enable high catalyst activities in gold(I)-mediated transformations. We now report on a calorimetric study dealing with the [Au(YPhos)Cl] system and assess YPhos-Au bond dissociation enthalpies (BDE). Comparison with other commonly used phosphines confirmed the high binding strengths of the YPhos ligands.

Synthesis, characterization, and reactivity of [Pd(phosphine)(py)Cl] (PEPPSI) and [Pd(phosphine)Cl] complexes.

The synthesis of novel phosphine palladium PEPPSI and dimer complexes bearing RuPhos, SPhos and XPhos phosphines is reported. The crystal structures of XPhos Pd PEPPSI with pyridine, SPhos Pd PEPPSI with 3-chloropyridine as throw-away ligands and the RuPhos palladium dimer were obtained and compared with previously reported congeners. The catalytic activity of these novel complexes was examined a C-N coupling reaction involving 4-chloroanisole and morpholine.

Buchwald-Hartwig Amination and C-S/S-H Metathesis of Aryl Sulfides by Selective C-S Cleavage Mediated by Air- and Moisture-Stable [Pd(NHC)(μ-Cl)Cl] Precatalysts: Unified Mechanism for Activation of Inert C-S Bonds.

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)(μ-Cl)Cl]. 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 Versatile Palladium Synthon: [Pd(NHC)(PhC≡CPh)].

The synthesis and isolation of [Pd(NHC)(PhC≡CPh)] complexes are reported. These new 14-electron Pd(0)-complexes are key synthons leading to known palladium(0) and palladium(II) species, as well as permitting access to unprecedented mixed NHC-phosphite palladium(0) complexes. This motif permits the facile catalytic hydrosilylation of allenes.

Improved synthetic routes to -heterocyclic carbene-metal-diketonato complexes of gold and copper.

In our search for simple synthetic routes to -heterocyclic carbene (NHC)-metal complexes and their derivatives, we herein report an operationally simple, expedient and scalable method to obtain the widely used NHC-metal-diketonates. The reported complexes are synthesized for the first time under mild, aerobic conditions and in excellent yields in a sustainable manner. The protocol is general with regards to the anionic co-ligand and the ancillary carbene ligands.

Energy transfer (EnT) photocatalysis enabled by gold-N-heterocyclic carbene (NHC) complexes.

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 -tosylamides. The reactions proceed in short reaction times and in environmentally friendly solvents.

Synthetic Access to Aromatic α-Haloketones.

α-Haloketones play an essential role in the synthesis of complex -, -, -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.

Synthesis of Carbene-Metal-Amido (CMA) Complexes and Their Use as Precatalysts for the Activator-Free, Gold-Catalyzed Addition of Carboxylic Acids to Alkynes.

A straightforward synthetic protocol leading to carbene-metal-amido (CMA) complexes (metal=Au, Cu) using a mild base and an environmentally desirable solvent (EtOH) has been explored, with a focus on complexes bearing backbone-substituted N-heterocyclic carbene (NHC) ligands, including BIAN-NHCs (BIAN=bis(imino)acenaphthene). The novel CMAs were structurally characterized, and gold-based CMAs bearing diverse NHCs were screened as simple, Brønsted-basic precatalysts. The readily accessible complexes display high catalytic activity in the intermolecular and intramolecular hydrocarboxylation of internal alkynes and alkynoic acids respectively, while the screening reveals the ancillary ligand effect of NHCs in these catalytic systems.

A green route to platinum N-heterocyclic carbene complexes: mechanism and expanded scope.

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 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.

A Green Synthesis of Carbene-Metal-Amides (CMAs) and Carboline-Derived CMAs with Potent in vitro and ex vivo Anticancer Activity.

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.

The effect of cocoa alkalization on the non-volatile and volatile mood-enhancing compounds.

Alkalization is a process to improve color, dispersibility and flavor of cocoa powder but is likely to have a negative effect on the phytochemicals. Hereto, the impact of alkalization degree (none, medium and high) on the potential mood-enhancing compounds corresponding to the four levels of the mood pyramid model (flavanols, methylxanthines, biogenic amines and orosensory properties) was investigated. The phytochemical content, analyzed via UPLC-HRMS, showed reduction of specific potential mood-enhancing compounds upon alkalization, implying a decrease in bitterness and astringency.