Photoinduced NiH Catalysis with Trialkylamines for the Stereodivergent Transfer Semi-Hydrogenation of Alkynes.

We report a selectivity-switchable nickel hydride-catalyzed methodology that enables the stereocontrolled semi-reduction of internal alkynes to E- or Z-alkenes under very mild conditions. The proposed transfer semi-hydrogenation process involves the use of a dual nickel/photoredox catalytic system and triethylamine, not only as a sacrificial reductant, but also as a source of hydrogen atoms. Mechanistic studies revealed a pathway involving photo-induced generation of nickel hydride, syn-hydronickelation of alkyne, and alkenylnickel isomerization as key steps. Remarkably, mechanistic experiments indicate that the control of the stereoselectivity is not ensuing from a post-reduction alkene photoisomerization under our conditions. Instead, we demonstrate that the stereoselectivity of the reaction is dependent on the rate of a final protonolysis step which can be tuned by adjusting the pKa of an alcohol additive.

Mechanism of Alkyne Hydroarylation Catalyzed by (P,C)-Cyclometalated Au(III) Complexes.

Over the last 5-10 years, gold(III) catalysis has developed rapidly. It often shows complementary if not unique features compared to gold(I) catalysis. While recent work has enabled major synthetic progress in terms of scope and efficiency, very little is yet known about the mechanism of Au(III)-catalyzed transformations and the relevant key intermediates have rarely been authenticated. Here, we report a detailed experimental/computational mechanistic study of the recently reported intermolecular hydroarylation of alkynes catalyzed by (P,C)-cyclometalated Au(III) complexes. The cationic (P,C)Au(OAcF)+ complex (OAcF = OCOCF3) was authenticated by mass spectrometry (MS) in the gas phase and multi-nuclear NMR spectroscopy in solution at low temperatures. According to density functional theory (DFT) calculations, the OAcF moiety is κ2-coordinated to gold in the ground state, but the corresponding κ1-forms featuring a vacant coordination site sit only slightly higher in energy. Side-on coordination of the alkyne to Au(III) then promotes nucleophilic addition of the arene. The energy profiles for the reaction between trimethoxybenzene (TMB) and diphenylacetylene (DPA) were computed by DFT. The activation barrier is significantly lower for the outer-sphere pathway than for the alternative inner-sphere mechanism involving C-H activation of the arene followed by migratory insertion. The π-complex of DPA was characterized by MS. An unprecedented σ-arene Au(III) complex with TMB was also authenticated both in the gas phase and in solution. The cationic complexes [(P,C)Au(OAcF)]+ and [(P,C)Au(OAcF)(σ-TMB)]+ stand as active species and off-cycle resting state during catalysis, respectively. This study provides a rational basis for the further development of Au(III) catalysis based on π-activation.

Evidence for genuine hydrogen bonding in gold(I) complexes.

The ability of gold to act as proton acceptor and participate in hydrogen bonding remains an open question. Here, we report the synthesis and characterization of cationic gold(I) complexes featuring ditopic phosphine-ammonium (P,NH+) ligands. In addition to the presence of short Au∙∙∙H contacts in the solid state, the presence of Au∙∙∙H-N hydrogen bonds was inferred by NMR and IR spectroscopies. The bonding situation was extensively analyzed computationally. All features were consistent with the presence of three-center four-electron attractive interactions combining electrostatic and orbital components. The role of relativistic effects was examined, and the analysis is extended to other recently described gold(I) complexes.

From Academia to the Market - Air-stable Ni(ii)/Josiphos Catalysts.

The design, synthesis, commercialization and application of air-stable Ni(II)/Josiphos complexes has been realized in a collaboration between Solvias and ICBMS (University Lyon 1). The Ni-complexes are utilized as versatile precatalysts for diverse cross-coupling reactions. Apart from being active in established C-C and C-N couplings at low catalyst loadings, the novel Ni-precatalysts enabled the development of the challenging monoarylation of ammonia, ammonia surrogates and even alkylammonium chlorides with aryl carbamates. Finally, the α-arylation of acetone with aryl chlorides, carbamates and pivalates was demonstrated using the Ni(II)/Josiphos precatalysts.

Gold(I)/Gold(III) Catalysis that Merges Oxidative Addition and π-Alkene Activation.

Heteroarylation of alkenes with aryl iodides was efficiently achieved with a (MeDalphos)AuCl complex through AuI /AuIII catalysis. The possibility to combine oxidative addition of aryl iodides and π-activation of alkenes at gold is demonstrated for the first time. The reaction is robust and general (>30 examples including internal alkenes, 5-, 6-, and 7-membered rings). It is regioselective and leads exclusively to trans addition products. The (P,N) gold complex is most efficient with electron-rich aryl substrates, which are troublesome with alternative photoredox/oxidative approaches. In addition, it provides a very unusual switch in regioselectivity from 5-exo to 6-endo cyclization between the Z and E isomers of internal alkenols.

Nickel-Catalyzed Mono-Selective α-Arylation of Acetone with Aryl Chlorides and Phenol Derivatives.

The challenging nickel-catalyzed mono-α-arylation of acetone with aryl chlorides, pivalates, and carbamates has been achieved for the first time. A nickel/Josiphos-based catalytic system is shown to feature unique catalytic behavior, allowing the highly selective formation of the desired mono-α-arylated acetone. The developed methodology was applied to a variety of (hetero)aryl chlorides including biologically relevant derivatives. The methodology has been extended to the unprecedented coupling of acetone with phenol derivatives. Mechanistic studies allowed the isolation and characterization of key Ni0 and NiII catalytic intermediates. The Josiphos ligand is shown to play a key role in the stabilization of NiII intermediates to allow a Ni0 /NiII catalytic pathway. Mechanistic understanding was then leveraged to improve the protocol using an air-stable NiII pre-catalyst.

Formation of a peri-Bridged Phosphonio-Naphthalene by Cu-Mediated Phosphine-Aryl Coupling.

The peri-iodo naphthyl phosphine 1 reacts with CuI to give the peri-bridged phosphonio-naphthalene 2, which has been fully characterized (multi-nuclear NMR, MS, XRD). The outcome of the reaction differs markedly from that observed with gold. A two-step pathway involving P-assisted C-I oxidative addition to copper, followed by P-C reductive elimination is shown to be energetically feasible by DFT calculations.

(P,C) Cyclometalated Gold(III) Complexes: Highly Active Catalysts for the Hydroarylation of Alkynes.

The first catalytic application of well-defined (P,C) cyclometalated gold(III) complexes is reported. The bench-stable bis(trifluoroacetyl) complexes 2 a,b perform very well in the intermolecular hydroarylation of alkynes. The reaction is broad in scope, it proceeds within few hours at 25 °C at catalytic loadings of 0.1-5 mol %. The electron-rich arene adds across the C≡C bond with complete regio- and stereo-selectivity. The significance of well-defined gold(III) complexes and ligand design are highlighted in a powerful but challenging catalytic transformation.

Isolation of a Reactive Tricoordinate α-Oxo Gold Carbene Complex.

The [(P,P)Au=C(Ph)CO2 Et]+ complex 3 [where (P,P) is an o-carboranyl diphosphine ligand] was prepared by diazo decomposition at -40 °C. It is the first α-oxo gold carbene complex to be characterized. Its crystallographic structure was determined and DFT calculations have been performed, unraveling the key influence of the chelating (P,P) ligand. The gold center is tricoordinate and the electrophilicity of the carbene center is decreased. Complex 3 mimics transient α-oxo gold carbenes in a series of catalytic transformations, and provides support for the critical role of electrophilicity in the chemoselectivity of phenol functionalization (O-H vs. C-H insertion).

A Nucleophilic Gold(III) Carbene Complex.

The first AuIII carbene complex was prepared by reacting a geminal dianion with a (P,C) cyclometalated AuIII precursor. Its structure and bonding situation have been thoroughly investigated by experimental and computational means. The presence of a high-energy highest occupied molecular orbital (HOMO) centered at the carbene center suggests nucleophilic character for the AuIII carbene complex. This unprecedented feature was confirmed by reactions with two electrophiles (PhNCS and CS2 ), resulting in two types of C=C coupling reactions.

ß-Hydride Elimination at Low-Coordinate Gold(III) Centers.

This Article reports the first comprehensive study of ß-hydride elimination at gold(III). The stability/fate of gold(III) alkyl species have been investigated experimentally and computationally. A series of well-defined cationic cyclometalated gold(III) alkyl complexes [(P,C)gold(III)(R)][NTf2] [(P,C) = 8-diisopropylphosphino-naphthyl; R = Me, nPr, nBu] have been synthesized and spectroscopically characterized. While the cationic gold(III) methyl derivative 3c is stable for days at room temperature, the gold(III) n-propyl and n-butyl complexes 3a,b readily undergo ß-hydride elimination at low temperature to generate propylene and 2-butenes, respectively. The formation of internal olefins from the gold(III) n-butyl complex 3b shows that olefin isomerization takes place after ß-hydride elimination. Computational studies indicate that this isomerization proceeds through a chain-walking mechanism involving a highly reactive gold(III) hydride intermediate and a sequence of ß-hydride elimination/reinsertion into the Au-H bond. The reaction of the cationic gold(III) methyl complex 3c with ethylene was also explored. According to (1)H and (13)C NMR spectroscopy, a mixture of propylene, 1-butene, and 2-butenes is formed. DFT calculations provide detailed mechanistic insights and support the occurrence of migratory insertion of ethylene, ß-hydride elimination, and olefin exchange at gold(III).

Experimental and Theoretical Evidence for an Agostic Interaction in a Gold(III) Complex.

The first agostic interaction in a gold complex is described. The presence of a bonding C-H⋅⋅⋅Au interaction in a cationic "tricoordinate" gold(III) complex was suggested by DFT calculations and was subsequently confirmed by NMR spectroscopy at low temperature. The agostic interaction was analyzed computationally using NBO and QTAIM analyses (NBO=natural bond orbital; QTAIM=quantum theory of atoms in molecules).

Reactivity of Gold Complexes towards Elementary Organometallic Reactions.

For a while, the reactivity of gold complexes was largely dominated by their Lewis acid behavior. In contrast to the other transition metals, the elementary steps of organometallic chemistry-oxidative addition, reductive elimination, transmetallation, migratory insertion-have scarcely been studied in the case of gold or even remained unprecedented until recently. However, within the last few years, the ability of gold complexes to undergo these fundamental reactions has been unambiguously demonstrated, and the reactivity of gold complexes was shown to extend well beyond π-activation. In this Review, the main achievements described in this area are presented in a historical context. Particular emphasis is set on mechanistic studies and structure determination of key intermediates. The electronic and structural parameters delineating the reactivity of gold complexes are discussed, as well as the remaining challenges.

Cationic gold(III) alkyl complexes: generation, trapping, and insertion of norbornene.

Migratory insertion of alkenes into gold-carbon bonds, a fundamental yet unprecedented organometallic transformation, has been investigated from a discrete (P,C) cyclometalated gold(III) dimethyl complex. Methide abstraction by B(C6F5)3 is shown to generate a highly reactive cationic Au(III) complex that evolves spontaneously by C6F5 transfer from boron. In the presence of norbornene, migratory insertion into the Au-C bond proceeds readily. The resulting norbornyl complex is efficiently trapped with pyridines or chloride to give stable four-coordinate adducts.

Oxidative addition of carbon-carbon bonds to gold.

The oxidative addition of strained CC bonds (biphenylene, benzocyclobutenone) to DPCb (diphosphino-carborane) gold(I) complexes is reported. The resulting cationic organogold(III) complexes have been isolated and fully characterized. Experimental conditions can be adjusted to obtain selectively acyl gold(III) complexes resulting from oxidative addition of either the C(aryl)C(O) or C(alkyl)C(O) bond of benzocyclobutenone. DFT calculations provide mechanistic insight into this unprecedented transformation.

Activation of aryl halides at gold(I): practical synthesis of (P,C) cyclometalated gold(III) complexes.

Taking advantage of phosphine chelation, direct evidence for oxidative addition of Csp(2)-X bonds (X = I, Br) to a single gold atom is reported. NMR studies and DFT calculations provide insight into this unprecedented transformation, which gives straightforward access to stable (P,C) cyclometalated gold(III) complexes.

Mechanisms of syn-insertion of alkynes and allenes into gold-silicon bonds: a comprehensive experimental/theoretical study.

A detailed mechanistic study is reported for the syn-insertion of alkynes and allenes in the Au-Si bonds of complexes (R3P)Au-SiR'Ph2 (R = Ph, Me and R' = t-Bu, Ph). Kinetic experiments indicate that (i) the reaction is first-order in alkyne and gold silyl complex and (ii) it requires a rather low enthalpy of activation and a relatively large negative entropy of activation [ΔH(‡) = 13.7 (±1.6) kcal·mol(-1) and ΔS(‡) = -32.0 (±5.0) cal·mol(-1)·K(-1) for the reaction of (Ph3P)Au-Si(t-Bu)Ph2 with methyl propiolate], in line with a bimolecular associative transformation. The different mechanistic pathways have been explored by DFT calculations. Accordingly, the reaction is found to proceed via a two-step inner-sphere mechanism: (i) first, the alkyne coordinates to the gold silyl complex to form a π-complex; (ii) the subsequent migratory insertion step is rate determining and occurs in a concerted manner. Provided dispersion effects are taken into account (B97D functional), the enthalpy of activation estimated theoretically [ΔH(‡) = 11.5 kcal·mol(-1)] is in good agreement with that measured experimentally. The influence of the π substrate (methyl propiolate, dimethyl acetylene dicarboxylate, phenyl acetylene, ethyl 2,3-butadienoate) has been analyzed theoretically, and the regioselectivity of the insertion has been rationalized. In particular, the unexpected selectivity observed experimentally with the allene is shown to result from the insertion of the terminal nonactivated C═C double bond into the Au-Si bond of (Ph3P)Au-SiPh3, followed by an original isomerization (Au/Si exchange process). This study provides unambiguous evidence for coordination-insertion at gold and thereby strongly supports the possible occurrence of inner-sphere mechanisms during the functionalization of alkynes and allenes.

Facile oxidative addition of aryl iodides to gold(I) by ligand design: bending turns on reactivity.

Thanks to rational ligand design, the first gold(I) complexes to undergo oxidative addition of aryl iodides were discovered. The reaction proceeds under mild conditions and is general. The ensuing aryl gold(III) complexes have been characterized by spectroscopic and crystallographic means. DFT calculations indicate that the bending induced by the diphosphine ligand plays a key role in this process.

Direct evidence for intermolecular oxidative addition of σ(Si-Si) bonds to gold.

Oxidative addition plays a major role in transition-metal catalysis, but this elementary step remains very elusive in gold chemistry. It is now revealed that in the presence of GaCl3, phosphine gold chlorides promote the oxidative addition of disilanes at low temperature. The ensuing bis(silyl) gold(III) complexes were characterized by quantitative (31)P and (29)Si NMR spectroscopy. Their structures (distorted Y shape) and the reaction profile of σ(Si-Si) bond activation were analyzed by DFT calculations. These results provide evidence for the intermolecular oxidative addition of σ(Si-Si) bonds to gold and open promising perspectives for the development of new gold-catalyzed redox transformations.

Enhanced π-backdonation from gold(I): isolation of original carbonyl and carbene complexes.

The specific electronic properties of bent o-carborane diphosphine gold(I) fragments were exploited to obtain the first classical carbonyl complex of gold [(DPCb)AuCO](+) (ν(CO)=2143 cm(-1) ) and the diphenylcarbene complex [(DPCb)Au(CPh2 )](+) , which is stabilized by the gold fragment rather than the carbene substituents. These two complexes were characterized by spectroscopic and crystallographic means. The [(DPCb)Au](+) fragment plays a major role in their stability, as substantiated by DFT calculations. The bending induced by the diphosphine ligand substantially enhances π-backdonation and thereby allows the isolation of carbonyl and carbene complexes featuring significant π-bond character.