Ligand-Enabled Oxidative Fluorination of Gold(I) and Light-Induced Aryl-F Coupling at Gold(III).

MeDalphos Au(I) complexes featuring aryl, alkynyl, and alkyl groups readily react with electrophilic fluorinating reagents such as N-fluorobenzenesulfonimide and Selectfluor. The ensuing [(MeDalphos)Au(R)F]+ complexes have been isolated and characterized by multinuclear NMR spectroscopy as well as X-ray diffraction. They adopt a square-planar contra-thermodynamic structure, with F trans to N. DFT/IBO calculations show that the N lone pair of MeDalphos assists and directs the transfer of F+ to gold. The [(MeDalphos)Au(Ar)F]+ (Ar = Mes, 2,6-F2Ph) complexes smoothly engage in C-C cross-coupling with PhCCSiMe3 and Me3SiCN, providing direct evidence for the oxidative fluorination/transmetalation/reductive elimination sequence proposed for F+-promoted gold-catalyzed transformations. Moreover, direct reductive elimination to forge a C-F bond at Au(III) was explored and substantiated. Thermal means proved unsuccessful, leading mostly to decomposition, but irradiation with UV-visible light enabled efficient promotion of aryl-F coupling (up to 90% yield). The light-induced reductive elimination proceeds under mild conditions; it works even with the electron-deprived 2,6-difluorophenyl group, and it is not limited to the contra-thermodynamic form of the aryl Au(III) fluoride complexes.

Expedient Synthesis of Thermally Stable Acyclic Amino(haloaryl)carbenes: Experimental and Theoretical Evidence of "Push-Pull" Stabilized Carbenes.

A library of novel structurally related singlet carbenes, namely, acyclic amino(haloaryl)carbenes, was designed by a high-yielding two-step procedure, and their chemical stability explored both experimentally and theoretically. Thanks to a careful selection of both the amino and the aryl substitution pattern, these carbenes exhibit a wide range of stability and reactivity, spanning from rapid self-dimerization for carbenes featuring ortho-F substituents to very high chemical stability as bare carbenes, up to 60 °C for several hours for compounds carrying ortho-Br substituents. Their structure was determined through NMR and X-ray diffraction studies, and their reactivity evaluated in benchmark reactions, highlighting the ambiphilic character of this novel class of singlet carbenes. In contrast with previously reported aryl substituents incorporating o-CF3 and t-Bu groups, which were considered "spectator", the high chemical stability of some of these carbenes relates to the stabilization of the σ-orbital of the carbene center by the π-accepting haloaryl substituent through delocalization. Kinetic protection of the carbene center is also provided by the ortho-halogen atoms, as demonstrated computationally. This push-pull stabilization effect makes acyclic amino(haloaryl) carbenes among the most ambiphilic stable carbenes reported to date, holding promise for a variety of applications.

Electrophilic Fluorination of Silyl Dienol Ethers: a General and Selective Access to γ-Fluoro Enals.

We describe the direct synthesis of γ-fluoro enals from the corresponding silyl dienol ethers. This simple process operates under mild conditions and is compatible with a wide range of functionalities. The high γ regioselectivity of this protocol was rationalized by means of theoretical calculations.

Lewis Acid-Assisted C(sp3)-C(sp3) Reductive Elimination at Gold.

The phosphine-borane iPr2P(o-C6H4)BFxyl2 (Fxyl = 3,5-(F3C)2C6H3) 1-Fxyl was found to promote the reductive elimination of ethane from [AuMe2(µ-Cl)]2. Nuclear magnetic resonance monitoring revealed the intermediate formation of the (1-Fxyl)AuMe2Cl complex. Density functional theory calculations identified a zwitterionic path as the lowest energy profile, with an overall activation barrier more than 10 kcal/mol lower than without borane assistance. The Lewis acid moiety first abstracts the chloride to generate a zwitterionic Au(III) complex, which then readily undergoes C(sp3)-C(sp3) coupling. The chloride is finally transferred back from boron to gold. The electronic features of this Lewis-assisted reductive elimination at gold have been deciphered by intrinsic bond orbital analyses. Sufficient Lewis acidity of boron is required for the ambiphilic ligand to trigger the C(sp3)-C(sp3) coupling, as shown by complementary studies with two other phosphine-boranes, and the addition of chlorides slows down the reductive elimination of ethane.

Synthesis of Allenes by Hydroalkylation of 1,3-Enynes with Ketones Enabled by Cooperative Catalysis.

A method for the synthesis of allenes by the addition of ketones to 1,3-enynes by cooperative Pd(0)Senphos/B(C6F5)3/NR3 catalysis is described. A wide range of aryl- and aliphatic ketones undergo addition to various 1,3-enynes in high yields at room temperature. Mechanistic investigations revealed a rate-determining outer-sphere proton transfer mechanism, which was corroborated by DFT calculations.

Base-Triggered Oxidative Addition to Gold.

The coordination of secondary phosphine oxides (SPO) was shown to efficiently promote the activation of C(sp2 )-I bonds by gold, as long as a base is added (NEt3 , K2 CO3 ). These transformations stand as a new type of chelation-assisted oxidative addition to gold. The role of the base and the influence of the electronic properties of the P-ligand were analyzed computationally. Accordingly, the oxidative addition was found to be dominated by Au→(Ar-I) backdonation. In this case, gold behaves similarly to palladium, suggesting that the inverse electron flow reported previously (with prevailing (Ar-I)→Au donation, resulting in faster reactions of electron-enriched substrates) is a specific feature of electron-deficient cationic gold(I) complexes. The reaction gives straightforward access to (P=O,C)-cyclometallated Au(III) complexes. The possibility to chemically derivatize the SPO moiety at Au(III) was substantiated by protonation and silylation reactions.

Mechanism of Pd/Senphos-Catalyzed trans-Hydroboration of 1,3-Enynes: Experimental and Computational Evidence in Support of the Unusual Outer-Sphere Oxidative Addition Pathway.

The reaction mechanism of the Pd/Senphos-catalyzed trans-hydroboration reaction of 1,3-enynes was investigated using various experimental techniques, including deuterium and double crossover labeling experiments, X-ray crystallographic characterization of model reaction intermediates, and reaction progress kinetic analysis. Our experimental data are in support of an unusual outer-sphere oxidative addition mechanism where the catecholborane serves as a suitable electrophile to activate the Pd0-bound 1,3-enyne substrate to form a Pd-η3-π-allyl species, which has been determined to be the likely resting state of the catalytic cycle. Double crossover labeling of the catecholborane points toward a second role played by the borane as a hydride delivery shuttle. Density functional theory calculations reveal that the rate-limiting transition state of the reaction is the hydride abstraction by the catecholborane shuttle, which is consistent with the experimentally determined rate law: rate = k[enyne]0[borane]1[catalyst]1. The computed activation free energy ΔG‡ = 17.7 kcal/mol and KIE (kH/kD = 1.3) are also in line with experimental observations. Overall, this work experimentally establishes Lewis acids such as catecholborane as viable electrophilic activators to engage in an outer-sphere oxidative addition reaction and points toward this underutilized mechanism as a general approach to activate unsaturated substrates.

The aromatic Claisen rearrangement of a 1,2-azaborine.

The first aromatic Claisen rearrangement of a 1,2-azaborine is described along with a quantitative kinetic comparison of the reaction of the azaborine with its direct all-carbon analogue. The azaborine A rearranged in a clean, regioselective fashion and reacted faster than the all-carbon substrate B at all temperatures from 140-180 °C. Activation free energies were extracted from observed first-order rate constants (A: ΔG‡298K = 32.7 kcal mol-1; B: ΔG‡298K = 34.8 kcal mol-1) corresponding to a twenty fold faster rate for A at observed reaction temperatures. DFT calculations show that the rearrangement proceeds via a concerted six-membered transition state and that the electronic structure of the BN and CC rings is mostly responsible for the observed regioselectivity and relative reactivity.

σ-Cyclopropyl to π-Allyl Rearrangement at AuIII.

The possibility for AuIII σ-cyclopropyl complexes to undergo ring-opening and give π-allyl complexes was interrogated. The transformation was first evidenced within (P,C)-cyclometalated complexes, it occurs within hours at -50 °C. It was then generalized to other ancillary ligands. With (N,C)-cyclometalated complexes, the rearrangement occurs at room temperature while it proceeds already at -80 °C with a dicationic (P,N)-chelated complex. Density Functional Theory (DFT) calculations shed light on the mechanism of the transformation, a disrotatory electrocyclic ring-opening. Intrinsic Bond Orbital (IBO) analysis along the reaction profile shows the cleavage of the distal σ(CC) bond to give a π-bonded allyl moiety. Careful inspection of the structure and bonding of cationic σ-cyclopropyl complexes support the possible existence of C-C agostic interactions at AuIII .

Regio- and Stereoselective Hydroelementation of SF5 -Alkynes and Further Functionalizations.

Herein is described a fully regio- and stereoselective hydroelementation reaction of SF5 -alkynes with N, O and S-nucleophiles and further functionalization of the corresponding Z-(hetero)vinyl-SF5 intermediates, a suitable platform to access α-SF5 ketones and esters, ß-SF5 amines and alcohols under mild reaction conditions. Experimental and computational comparative studies between SF5 - and CF3 -alkynes have been performed to highlight and explain the difference of reactivity and selectivity observed between these two fluorinated motifs.

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.

Mechanistic Insights about the Ligand-Enabled Oxy-arylation/vinylation of Alkenes via Au(I)/Au(III) Catalysis.

The mechanism of oxy-arylation/vinylation of alkenes catalyzed by the (MeDalphos)AuCl complex was comprehensively investigated by DFT. (P,N)Au(Ph)2+ and (P,N)Au(vinyl)2+ are key intermediates accounting for the activation of the alkenols and for their cyclization by outer-sphere nucleophilic attack of oxygen. The 5-exo and 6-endo paths have been computed and compared, reproducing the peculiar regioselectivity difference observed experimentally between 4-penten-1-ol, (E) and (Z)-4-hexen-1-ols. Examining the way the alkenol coordinates to gold (more η2 or η1 ) can offer, in some cases, a simple way to predict the favored path of cyclization.

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.

Gold(I) α-Trifluoromethyl Carbenes: Synthesis, Characterization and Reactivity Studies.

Aryl trifluoromethyl diazomethanes 2-R (R=Ph, OMe, CF3 ) are readily decomposed by the (o-carboranyl)diphosphine gold(I) complex 1. The resulting α-CF3 substituted carbene complexes 3-R have been characterized by multi-nuclear NMR spectroscopy as well as X-ray crystallography (for 3-Ph). The bonding situation was thoroughly assessed by computational means, showing stabilization of the electrophilic carbene center by π-donation from the aryl substituent and backdonation from Au, as enhanced by the chelating P^P ligand. Reactivity studies under stoichiometric and catalytic conditions substantiate typical carbene-type behavior for 3-Ph.

Metal-Free Phosphorus-Directed Borylation of C(sp2 )-H Bonds.

Spectacular progress has recently been achieved in transition metal-catalyzed C-H borylation of phosphines as well as directed electrophilic C-H borylation. As shown here, P-directed electrophilic borylation provides a new, straightforward, and efficient access to phosphine-boranes. It operates under metal-free conditions and leverages simple, readily available substrates. It is applicable to a broad range of backbones (naphthyl, biphenyl, N-phenylpyrrole, binaphthyl, benzyl, naphthylmethyl) and gives facile access to various substitution patterns at boron (by varying the boron electrophile or post-derivatizing the borane moiety). NMR monitoring supports the involvement of P-stabilized borenium cations as key intermediates. DFT calculations reveal the existence and stabilizing effect of π-arene/boron interactions in the (biphenyl)(i-Pr)2 P→BBr2 + species.

Nucleophilic Addition to π-Allyl Gold(III) Complexes: Evidence for Direct and Undirect Paths.

π-Allyl complexes play a prominent role in organometallic chemistry and have attracted considerable attention, in particular the π-allyl Pd(II) complexes which are key intermediates in the Tsuji-Trost allylic substitution reaction. Despite the huge interest in π-complexes of gold, π-allyl Au(III) complexes were only authenticated very recently. Herein, we report the reactivity of (P,C)-cyclometalated Au(III) π-allyl complexes toward ß-diketo enolates. Behind an apparently trivial outcome, i.e. the formation of the corresponding allylation products, meticulous NMR studies combined with DFT calculations revealed a complex and rich mechanistic picture. Nucleophilic attack can occur at the central and terminal positions of the π-allyl as well as the metal itself. All paths are observed and are actually competitive, whereas addition to the terminal positions largely prevails for Pd(II). Auracyclobutanes and π-alkene Au(I) complexes were authenticated spectroscopically and crystallographically, and Au(III) σ-allyl complexes were unambiguously characterized by multinuclear NMR spectroscopy. Nucleophilic additions to the central position of the π-allyl and to gold are reversible. Over time, the auracyclobutanes and the Au(III) σ-allyl complexes evolve into the π-alkene Au(I) complexes and release the C-allylation products. The relevance of auracyclobutanes in gold-mediated cyclopropanation was demonstrated by inducing C-C coupling with iodine. The molecular orbitals of the π-allyl Au(III) complexes were analyzed in-depth, and the reaction profiles for the addition of ß-diketo enolates were thoroughly studied by DFT. Special attention was devoted to the regioselectivity of the nucleophilic attack, but C-C coupling to give the allylation products was also considered to give a complete picture of the reaction progress.

C-Boron Enolates Enable Palladium Catalyzed Carboboration of Internal 1,3-Enynes.

A new family of carbon-bound boron enolates, generated by a kinetically controlled halogen exchange between chlorocatecholborane and silylketene acetals, is described. These C-boron enolates are demonstrated to activate 1,3-enyne substrates in the presence of a Pd0 /Senphos ligand complex, resulting in the first examples of a carboboration reaction of an alkyne with enolate-equivalent nucleophiles. Highly substituted dienyl boron building blocks are produced in excellent site-, regio-, and diastereoselectivity by the described catalytic cis-carboboration reaction.

Fluorosilane Activation by Pd/Ni→Si-F→Lewis Acid Interaction: An Entry to Catalytic Sila-Negishi Coupling.

A new mode of bond activation involving M→Z interactions is disclosed. Coordination to transition metals as σ-acceptor ligands was found to enable the activation of fluorosilanes, opening the way to the first transition-metal-catalyzed Si-F bond activation. Using phosphines as directing groups, sila-Negishi couplings were developed by combining Pd and Ni complexes with external Lewis acids such as MgBr2. Several key catalytic intermediates have been authenticated spectroscopically and crystallographically. Combined with DFT calculations, all data support cooperative activation of the fluorosilane via Pd/Ni→Si-F→Lewis acid interaction with conversion of the Z-type fluorosilane ligand into an X-type silyl moiety.

Gold(III) π-Allyl Complexes.

Gold(III) π-complexes have been authenticated recently with alkenes, alkynes, and arenes. The key importance of PdII π-allyl complexes in organometallic chemistry (Tsuji-Trost reaction) prompted us to explore gold(III) π-allyl complexes, which have remained elusive so far. The (P,C)AuIII (allyl) and (methallyl) complexes 3 and 3' were readily prepared and isolated as thermally and air-stable solids. Spectroscopic and crystallographic analyses combined with detailed DFT calculations support tight quasi-symmetric η3 -coordination of the allyl moiety. The π-allyl gold(III) complexes are activated towards nucleophilic additions, as substantiated with ß-diketo enolates.

Divergent Synthesis of 1,2-Benzo[ e]thiazine and Benzo[ d]thiazole Analogues Containing a S-Trifluoromethyl Sulfoximine Group: Preparation and New Properties of the Adachi Reagent.

We report here the preparation of unprecedented analogues of 1,2-benzothiazine and benzoisothiazole incorporating the S-trifluoromethyl sulfoximine group in their core. Using a stable precursor to start, cyclization occurs via a catalytic controlled process. The choice of the catalyst is crucial for selectivity toward the five- or the six-membered ring. Interestingly, one of the benzothiazines can be converted on a gram scale into the trifluoromethylating Adachi reagent. We also disclose the first use of this reagent as a source of radical CF3 under photoredox catalysis. DFT calculations were performed to clarify the cyclization mechanism.