Modular Synthesis of Azines Bearing a Guanidine Core from N-Heterocyclic Carbene (NHC)-Derived Selenoureas and Diazo Reagents.

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.

A Hierarchy of Ligands Controls Formation and Reaction of Aryl Radicals in Pd-Catalyzed Ground-State Base-Promoted Coupling Reactions.

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.

Optimizing Catalyst and Reaction Conditions in Gold(I) Catalysis-Ligand Development.

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.

Lewis Acid-Promoted Oxidative Addition at a [Ni0 (diphosphine)2 ] Complex: The Critical Role of a Secondary Coordination Sphere.

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.

Synthesis of Gold(I)-Trifluoromethyl Complexes and their Role in Generating Spectroscopic Evidence for a Gold(I)-Difluorocarbene Species.

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.

The Electrophilic Fluorination of Enol Esters Using SelectFluor: A Polar Two-Electron Process.

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.

Interrogating Pd(II) Anion Metathesis Using a Bifunctional Chemical Probe: A Transmetalation Switch.

Ligand metathesis of Pd(II) complexes is mechanistically essential for cross-coupling. We present a study of halide→OH 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.

Halide Abstraction Competes with Oxidative Addition in the Reactions of Aryl Halides with [Ni(PMen Ph(3-n) )4 ].

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) halide abstraction by [Ni(PMen Ph(3-n) )3 ], via an open-shell singlet transition state; (ii) SN 2-type oxidative addition to [Ni(PMen Ph(3-n) )3 ], followed by phosphine dissociation; and (iii) 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.

The preference for dual-gold(i) catalysis in the hydro(alkoxylation vs. phenoxylation) of alkynes.

Dinuclear gold complexes and their use in catalysis have received significant recent attention, but there are few critical comparisons of mono- versus dual gold-catalysed pathways. Herein we study the hydroalkoxylation and hydrophenoxylation of alkynes using density functional theory calculations, and compare two possible mechanisms that have been proposed previously on the basis of theoretical and experimental studies, which unravel different preferences because of both the nature of the alkyne and alcohol and the non-innocent role of the counter-anion of a dual gold based catalyst. Entropy is found to have a significant effect, rendering the nucleophilic attack of the monoaurated intermediate [Au(L)(η2-alkyne)]+ difficult both kinetically and thermodynamically; this mechanism cannot easily form only the trans-alkene product that is observed experimentally. Instead, a reaction via a dual gold catalysed mechanism presents much lower barriers. In addition, for the sake of direct comparison with recent results by Belanzoni and Zuccaccia, oversimplification of the N-heterocyclic carbene (NHC) ligand in the calculations might decrease the enthalpy barrier and lead to results that are not directly applicable to experiments. Moreover, the alkylic or arylic nature of the alkyne and/or alcohol is also tested.

On the Mechanism of the Digold(I)-Hydroxide-Catalysed Hydrophenoxylation of Alkynes.

Herein, we present a detailed investigation of the mechanistic aspects of the dual gold-catalysed hydrophenoxylation of alkynes by both experimental and computational methods. The dissociation of [{Au(NHC)}2 (µ-OH)][BF4 ] is essential to enter the catalytic cycle, and this step is favoured by the presence of bulky, non-coordinating counter ions. Moreover, in silico studies confirmed that phenol does not only act as a reactant, but also as a co-catalyst, lowering the energy barriers of several transition states. A gem-diaurated species might form during the reaction, but this lies deep within a potential energy well, and is likely to be an "off-cycle" rather than an "in-cycle" intermediate.

Half-sandwich nickel(II) complexes bearing 1,3-di(cycloalkyl)imidazol-2-ylidene ligands.

Two new nickel catalysts have been prepared using a convenient procedure where nickelocene, the NHC·HBF4 salts, and [Et4N]Cl were heated in THF using microwave irradiation. The resulting [NiCl(Cp)(NHC)] complexes are air- and moisture stable in the solid state, and represent two new members of this valuable and practical class of nickel catalysts. The new species were fully characterised using methods including NMR spectroscopy and X-ray crystallography. When tested in model Suzuki-Miyaura cross-coupling reactions, these complexes were found to be active for the cross-coupling of aryl bromides and aryl chlorides.

Iridium(I) hydroxides in catalysis: rearrangement of allylic alcohols to ketones.

The iridium(I) hydroxide complex [Ir(OH)(COD)(I(i)Pr)] has been shown to be a competent catalyst for the rearrangement of allylic alcohols to ketones. Reactions proceed in short reaction times (1-1.5 h) with microwave heating, in the absence of additives.

Quantifying and understanding the electronic properties of N-heterocyclic carbenes.

The use of N-heterocyclic carbenes (NHCs) in chemistry has developed rapidly over the past twenty years. These interesting compounds are predominantly employed in organometallic chemistry as ligands for various metal centres, and as organocatalysts able to mediate an exciting range of reactions. However, the sheer number of NHCs known in the literature can make the appropriate choice of NHC for a given application difficult. A number of metrics have been explored that allow the electronic properties of NHCs to be quantified and compared. In this review, we discuss these various metrics and what they can teach about the electronic properties of NHCs. Data for approximately three hundred NHCs are presented, obtained from a detailed survey of the literature.

Insights into the decomposition of olefin metathesis precatalysts.

The decomposition of a series of benzylidene, methylidene, and 3-phenylindenylidene complexes has been probed in alcohol solution in the presence of base. Tricyclohexylphosphane-containing precatalysts are shown to yield [RuCl(H)(H2)(PCy3)2] in isopropyl alcohol solutions, while 3-phenylindenylidene complexes lead to η(5)-(3-phenyl)indenyl products. The potential-energy surfaces for the formation of the latter species have been probed using density functional theory studies.

Iridium(I) hydroxides: powerful synthons for bond activation.

A family of iridium(I) hydroxides of the form [Ir(cod)(NHC)(OH)] (cod = 1,5-cyclooctadiene, NHC = N-heterocyclic carbene) is reported. Single-crystal X-ray analyses and computational methods were used to explore the structural characteristics and steric properties of these new complexes. The model complex [Ir(cod)(IiPr)(OH)] (IiPr = 1,3-(diisopropyl)imidazol-2-ylidene) undergoes reaction with a wide variety of substrates including boronic acids and silicon compounds. In addition, O-H, N-H and C-H bond activation was achieved with alcohols, carboxylic acids, amines and various sp-, sp(2)- and sp(3)-hybridised carbon centres, giving access to a wide range of new Ir(I) complexes. These studies have allowed us to explore the exciting reactivity of this motif, revealing a versatile and useful synthon capable of activating important chemical bonds under mild (typically room temperature) conditions. No additives were required and, in the case of X-H bond activation, water was the only waste product, rendering this an atom efficient procedure for bond activation. This system has great potential for the construction of new catalytic cycles for organic synthesis and small-molecule activation.

Synthesis and reactivity of new bis(N-heterocyclic carbene) iridium(I) complexes.

New complexes of the type trans-[IrCl(η(2)-COE)(NHC)2] (COE = cis-cyclooctene; NHC = N-heterocyclic carbene) have been prepared in one step from the reaction of ca. 4 equiv of NHC or [AgCl(NHC)] with [IrCl(η(2)-COE)2]2 in benzene. These new complexes have been characterized by techniques including NMR and IR spectroscopy, X-ray crystallography, and elemental analysis. Exposing trans-[IrCl(COE)(I(i)Pr(Me))2] to CO yielded trans-[IrCl(CO)(I(i)Pr(Me))2], which is the only bis(NHC) analogue of Vaska's complex trans-[IrCl(CO)(PPh3)2] known to date. The synthesis of trans-[Ir(CO)(I(i)Pr(Me))2(R)] (R = MeO, PhCC, OSiPh3, O2CPh) complexes has been achieved via deprotonation reactions involving the new hydroxide species trans-[Ir(OH)(CO)(I(i)Pr(Me))2].

Synthesis, characterization and luminescence studies of gold(I)-NHC amide complexes.

A flexible, efficient and straightforward methodology for the synthesis of N-heterocyclic carbene gold(I)-amide complexes is reported. Reaction of the versatile building block [Au(OH)(IPr)] (1) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) with a series of commercially available (hetero)aromatic amines leads to the synthesis of several [Au(NRR')(IPr)] complexes in good yields and with water as the sole byproduct. Interestingly, these complexes present luminescence properties. UV-vis and fluorescence measurements have allowed the identification of their excitation and emission wavelengths (λmax). These studies revealed that by selecting the appropriate amine ligand the emission can be easily tuned to achieve a variety of colors, from violet to green.

Nickel Complexes of Allyl and Vinyldiphenylphosphine.

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.

Reactions of N-heterocyclic carbene-based chalcogenoureas with halogens: a diverse range of outcomes.

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.

Why is RCM favoured over dimerisation? Predicting and estimating thermodynamic effective molarities by solution experiments and electronic structure calculations.

The thermodynamic effective molarities of a series of simple cycloalkenes, synthesised from α,ω-dienes by reaction with Grubbs' second generation precatalyst, have been evaluated. Effective molarities were measured from a series of small scale metathesis reactions and agreed well with empirical predictions derived from the number of rotors and the product ring strain. The use of electronic structure calculations (at the M06-L/6-311G** level of theory) was explored for predicting thermodynamic effective molarities in ring-closing metathesis. However, it was found that it was necessary to apply a correction to DFT-derived free energies to account for the entropic effects of solvation.