RESUMEN
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.
RESUMEN
Palladium salts and complexes were tested separately and in the presence of added ligands as potential sources of aryl radicals in ground-state coupling reactions of aryl halide with arenes under basic conditions (KOtBu). Our recently developed assay for aryl radicals was employed to test for aryl radicals. In this assay, aryl radicals derived from the test substrate, 1-iodo-2,6-dimethylbenzene 7, undergo base-promoted homolytic aromatic substitution (BHAS) with benzene to produce 2,6-dimethylbiphenyl 8 and biphenyl 9 in an approximately 1:4 ratio as well as m-xylene 10. The biphenyl arises from a diagnostic radical transfer reaction with the solvent benzene. Using substrate 7 with a range of Pd sources as potential initiators led to formation of 8, 9, and 10 in varying amounts. However, when any one of a range of diphosphinoferrocenes (e.g., dppf or dippf) or BINAP or the monophosphine, diphenylphosphinoferrocene, was added as a ligand to Pd(OAc)2, the ratio of [2,6-dimethylbiphenyl 8: biphenyl 9] moved decisively to that expected from the BHAS (radical) pathway. Further studies were conducted with dppf. When dppf was added to each of the other Pd sources, the ratio of coupled products was also diverted to that expected for radical BHAS chemistry. Deuterium isotope studies and radical trap experiments provide strong additional support for the involvement of aryl radicals. Accordingly, under these ground-state conditions, palladium sources, in the presence of defined ligands, convert aryl iodides to aryl radicals. A rationale is proposed for these observations.
RESUMEN
Monodentate phosphine-ligated nickel compounds, e.g., [Ni(PPh3)4] are relevant as active catalysts across a broad range of reactions. This report expands upon the coordination chemistry of this family, offering the reactivity of allyl- and vinyl-substituted diphenylphosphine (PPh2R) with [Ni(COD)2] (COD = 1,5-cyclooctadiene). These reactions provide three-coordinate dinickelacycles that are intermolecularly tethered through adjacent {Ni}-olefin interactions. The ring conformation of such cycles has been studied in the solid-state and using theoretical calculations. Here, a difference in reaction outcome is linked to the presence of an allyl vs vinyl group, where the former is observed to undergo rearrangement, bringing about challenges in clean product isolation.
RESUMEN
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 (Br2, SO2Cl2, I2) 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.
RESUMEN
Transmetalation is a key method for the construction of element-element bonds. Here, we disclose the reactivity of [NiII(Ar)(I)(diphosphine)] compounds with arylgold(I) transmetalating agents, which is directly relevant to cross-coupling catalysis. Both aryl-for-iodide and unexpected aryl-for-aryl transmetalation are witnessed. Despite the strong driving force expected for Au-I bond formation, aryl scrambling can occur during transmetalation and may complicate the outcomes of attempted catalytic cross-coupling reactions.
RESUMEN
A nickel/dppf catalyst system was found to successfully achieve the Suzuki-Miyaura cross-coupling reactions of 3- and 4-chloropyridine and of 6-chloroquinoline but not of 2-chloropyridine or of other α-halo-N-heterocycles. Further investigations revealed that chloropyridines undergo rapid oxidative addition to [Ni(COD)(dppf)] but that α-halo-N-heterocycles lead to the formation of stable dimeric nickel species that are catalytically inactive in Suzuki-Miyaura cross-coupling reactions. However, the corresponding Kumada-Tamao-Corriu reactions all proceed readily, which is attributed to more rapid transmetalation of Grignard reagents.
RESUMEN
Oxidative addition represents a critical elementary step in myriad catalytic transformations. Here, the importance of thoughtful ligand design cannot be overstated. In this work, we report the intermolecular activation of iodobenzene (PhI) at a coordinatively saturated 18-electron [Ni0 (diphosphine)2 ] complex bearing a Lewis acidic secondary coordination sphere. Whereas alkyl-substituted diphosphine complexes of Group 10 are known to be unreactive in such reactions, we show that [Ni0 (P2 BCy 4 )2 ] (P2 BCy 4 =1,2-bis(di(3-dicyclohexylboraneyl)-propylphosphino)ethane) is competent for room-temperature PhI cleavage to give [NiII (P2 BCy 4 )(Ph)(I)]. This difference in oxidative addition reactivity has been scrutinized computationally - an outcome that is borne out in ring-opening to provide the reactive precursor - for [Ni0 (P2 BCy 4 )2 ], a "boron-trapped" 16-electron κ1 -diphosphine Ni(0) complex. Moreover, formation of [NiII (P2 BCy 4 )(Ph)(I)] is inherent to the P2 BCy 4 secondary coordination sphere: treatment of the Lewis adduct, [Ni0 (P2 BCy 4 )2 (DMAP)8 ] with PhI provides [NiII (P2 BCy 4 )2 (DMAP)8 (I)]I via iodine-atom abstraction and not a [NiII (Ph)(I)(diphosphine)] compound - an unusual secondary sphere effect. Finally, the reactivity of [Ni0 (P2 BCy 4 )2 ] with 4-iodopyridine was surveyed, which resulted in a pyridyl-borane linked oligomer. The implications of these outcomes are discussed in the context of designing strongly donating, and yet labile diphosphine ligands for use in a critical bond activation step relevant to catalysis.
RESUMEN
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.
RESUMEN
The reactions of dppf-nickel(0) with alkyl halides proceed via three-coordinate nickel(0) intermediates of the form [Ni(dppf)(L)]. The effects of the identity of the added ligand (L) on catalyst speciation and the rates of reactions of [Ni(COD)(dppf)] with alkyl halides have been investigated using kinetic experiments and density functional theory calculations. A series of monodentate ligands have been investigated in attempts to identify trends in reactivity. Sterically bulky and electron-donating ligands are found to decrease the reaction rate. It was found that (i) the halide abstraction step is not always irreversible and the subsequent recombination of a nickel(I) complex with an alkyl halide can have a significant effect on the overall rate of the reaction and (ii) some ligands lead to very stable [Ni(dppf)(L)2] species. The yields of prototypical (dppf)nickel-catalyzed Kumada cross-coupling reactions of alkyl halides are significantly improved by the addition of free ligands, which provides another important variable to consider when optimizing nickel-catalyzed reactions of alkyl halides.
RESUMEN
Readily prepared and bench-stable [Au(CF3 )(NHC)] compounds were synthesized by using new methods, starting from [Au(OH)(NHC)], [Au(Cl)(NHC)] or [Au(L)(NHC)]HF2 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(CF3 )(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.
RESUMEN
The mechanism of the reactions between dppf-Ni0 complexes and alkyl halides has been investigated using kinetic and mechanistic experiments and DFT calculations. The active species is [Ni(κ2-dppf)(κ1-dppf)], which undergoes a halide abstraction reaction with alkyl halides and rapidly captures the alkyl radical that is formed. The rates of the reactions of [Ni(COD)(dppf)] with alkyl halides and the yields of prototypical nickel-catalyzed Kumada cross-coupling reactions of alkyl halides are shown to be significantly improved by the addition of free dppf ligand.
RESUMEN
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.
RESUMEN
The energetically-favorable coordination of aldehydes and ketones - but not esters or amides - to Ni0 during Suzuki-Miyaura reactions can lead either to exquisite selectivity and enhanced reactivity, or to inhibition of the reaction. Aryl halides where the C-X bond is connected to the same π-system as an aldehyde or ketone undergo unexpectedly rapid oxidative addition to [Ni(COD)(dppf)] (1), and are selectively cross-coupled during competition reactions. When aldehydes and ketones are present in the form of exogenous additives, the cross-coupling reaction is inhibited to an extent that depends on the strength of the coordination of the pendant carbonyl group to Ni0. This work advances our understanding of how common functional groups interact with Ni0 catalysts and how these interactions affect workhorse catalytic reactions in academia and industry.
RESUMEN
Honey bee venom has been established to have significant effect in immunotherapy. In the present study, (Z)-11-eicosenol-a major constituent of bee venom, along with its derivations methyl cis-11-eicosenoate and cis-11-eicosenoic acid, were synthesised to investigate their immune stimulatory effect and possible use as vaccine adjuvants. Stimuli that prime and activate the immune system have exerted profound effects on immune cells, particularly macrophages; however, the effectiveness of bee venom constituents as immune stimulants has not yet been established. Here, the abilities of these compounds to act as pro-inflammatory stimuli were assessed, either alone or in combination with lipopolysaccharide (LPS), by examining the secretion of tumour necrosis factor-α (TNF-α) and the cytokines interleukin-1ß (IL-1ß), IL-6 and IL-10 by THP-1 macrophages. The compounds clearly increased the levels of IL-1ß and decreased IL-10, whereas a decrease in IL-6 levels suggested a complex mechanism of action. A more in-depth profile of macrophage behaviour was therefore obtained by comprehensive untargeted metabolic profiling of the cells using liquid chromatography mass spectrometry (LC-MS) to confirm the ability of the eicosanoids to trigger the immune system. The level of 358 polar and 315 non-polar metabolites were changed significantly (p < 0.05) by all treatments. The LPS-stimulated production of most of the inflammatory metabolite biomarkers in glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, purine, pyrimidine and fatty acids metabolism were significantly enhanced by all three compounds, and particularly by methyl cis-11-eicosenoate and cis-11-eicosenoic acid. These findings support the proposed actions of (Z)-11-eicosenol, methyl cis-11-eicosenoate and cis-11-eicosenoic acid as immune system stimulators.
RESUMEN
The reaction of enol esters with SelectFluor is facile and leads to the corresponding α-fluoroketones under mild conditions and, as a result, this route is commonly employed for the synthesis of medicinally important compounds such as fluorinated steroids. However, despite the use of this methodology in synthesis, the mechanism of this reaction and the influence of structure on reactivity are unclear. A rigorous mechanistic study of the fluorination of these substrates is presented, informed primarily by detailed and robust kinetic experiments. The results of this study implicate a polar two-electron process via an oxygen-stabilised carbenium species, rather than a single-electron process involving radical intermediates. The structure-reactivity relationships revealed here will assist synthetic chemists in deploying this type of methodology in the syntheses of α-fluoroketones.
RESUMEN
Computational investigations of the reactions of [Ni(NHC)2] complexes with aryl halides show that the outcomes are governed by the steric impact of the ligand (NHC = N-heterocyclic carbene). Small ligands permit facile oxidative addition, leading to NiII complexes, while larger NHC ligands prevent coordination of the aryl halide and favour the halide abstraction to form NiI.
RESUMEN
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.
RESUMEN
Ligand metathesis of Pd(II) complexes is mechanistically essential for cross-coupling. We present a study of halideâOH anion metathesis of (Ar)PdII complexes using vinylBPin as a bifunctional chemical probe with Pd(II)-dependent cross-coupling pathways. We identify the variables that profoundly impact this event and allow control to be leveraged. This then allows control of cross-coupling pathways via promotion or inhibition of organoboron transmetalation, leading to either Suzuki-Miyaura or Mizoroki-Heck products. We show how this transmetalation switch can be used to synthetic gain in a cascade cross-coupling/Diels-Alder reaction, delivering borylated or non-borylated carbocycles, including steroid-like scaffolds.
RESUMEN
Density functional theory (DFT) calculations have been used to study the oxidative addition of aryl halides to complexes of the type [Ni(PMen Ph(3-n) )4 ], revealing the crucial role of an open-shell singlet transition state for halide abstraction. The formation of NiI versus NiII has been rationalised through the study of three different pathways: (i)â halide abstraction by [Ni(PMen Ph(3-n) )3 ], via an open-shell singlet transition state; (ii)â SN 2-type oxidative addition to [Ni(PMen Ph(3-n) )3 ], followed by phosphine dissociation; and (iii)â oxidative addition to [Ni(PMen Ph(3-n) )2 ]. For the overall reaction between [Ni(PMe3 )4 ], PhCl, and PhI, a microkinetic model was used to show that our results are consistent with the experimentally observed ratios of NiI and NiII when the PEt3 complex is used. Importantly, [Ni(PMen Ph(3-n) )2 ] complexes often have little, if any, role in oxidative addition reactions because they are relatively high in energy. The behaviour of [Ni(PR3 )4 ] complexes in catalysis is therefore likely to differ considerably from those based on diphosphine ligands in which two coordinate Ni0 complexes are the key species undergoing oxidative addition.