Reversible Oxidative Addition Research Articles

Reversible Oxidative Addition of Nonactivated C-H Bonds to Structurally Constrained Phosphenium Ions.

A series of structurally constrained phosphenium ions based on pyridinylmethylamidophenolate scaffolds are shown to undergo P(III)/P(V) oxidative addition with C-H bonds of alkynes, alkenes, and arenes. Nonactivated substrates such as benzene, toluene, and deactivated chlorobenzene are phosphorylated in quantitative yields. Computational and spectroscopic studies suggest a low-barrier isomerization from a bent to a T-shaped isomer that initiates a phosphorus-ligand-cooperative pathway and subsequent ring-chain tautomerism. Remarkably, C-H bond activations occur reversibly, allowing for reductive elimination back to P(III) at elevated temperatures or the exchange with other substrates.

Reversible Oxidative Addition of Zinc Hydride at a Gallium(I)-Centre: Labile Mono- and Bis(hydridogallyl)zinc Complexes.

In the presence of TMEDA (N,N,N',N'-tetramethylethylenediamine), partially deaggregated zinc dihydride as hydrocarbon suspensions react with the gallium(I) compound [(BDI)Ga] (I, BDI={HC(C(CH3 )N(2,6-iPr2 -C6 H3 ))2 }- ) by formal oxidative addition of a Zn-H bond to the gallium(I) centre. Dissociation of the labile TMEDA ligand in the resulting complex [(BDI)Ga(H)-(H)Zn(tmeda)] (1) facilitates insertion of a second equiv. of I into the remaining Zn-H to form a thermally sensitive trinuclear species [{(BDI)Ga(H)}2 Zn] (2). Compound 1 exchanges with polymeric zinc dideuteride [ZnD2 ]n in the presence of TMEDA, and with compounds I and 2 via sequential and reversible ligand dissociation and gallium(I) insertion. Spectroscopic and computational studies demonstrate the reversibility of oxidative addition of each Zn-H bond to the gallium(I) centres.

Realizing 1,1-Dehydration of Secondary Alcohols to Carbenes: Pyrrolidin-2-ols as a Source of Cyclic (Alkyl)(Amino)Carbenes.

Herein we report secondary pyrrolidin‐2‐ols as a source of cyclic (alkyl)(amino)carbenes (CAAC) for the synthesis of CAAC‐CuI‐complexes and cyclic thiones when reacted with CuI‐salts and elemental sulfur, respectively, under reductive elimination of water from the carbon(IV)‐center. This result demonstrates a convenient and facile access to CAAC‐based CuI‐salts, which are well known catalysts for different organic transformations. It further establishes secondary alcohols to be a viable source of carbenes—realizing after 185 years Dumas’ dream who tried to prepare the parent carbene (CH2) by 1,1‐dehydration of methanol. Addressed is also the reactivity of water towards CAACs, which proceeds through an oxidative addition of the O−H bond to the carbon(II)‐center. This emphasizes the ability of carbon‐compounds to mimic the reactivity of transition‐metal complexes: reversible oxidative addition and reductive elimination of the O−H bond to/from the C(II)/C(IV)‐centre.

Realizing 1,1‐Dehydration of Secondary Alcohols to Carbenes: Pyrrolidin‐2‐ols as a Source of Cyclic (Alkyl)(Amino)Carbenes

AbstractHerein we report secondary pyrrolidin‐2‐ols as a source of cyclic (alkyl)(amino)carbenes (CAAC) for the synthesis of CAAC‐CuI‐complexes and cyclic thiones when reacted with CuI‐salts and elemental sulfur, respectively, under reductive elimination of water from the carbon(IV)‐center. This result demonstrates a convenient and facile access to CAAC‐based CuI‐salts, which are well known catalysts for different organic transformations. It further establishes secondary alcohols to be a viable source of carbenes—realizing after 185 years Dumas’ dream who tried to preparetheparent carbene (CH2) by 1,1‐dehydration of methanol. Addressed is also the reactivity of water towards CAACs, which proceeds through an oxidative addition of the O−H bond to the carbon(II)‐center. This emphasizes the ability of carbon‐compounds to mimic the reactivity of transition‐metal complexes: reversible oxidative addition and reductive elimination of the O−H bond to/from the C(II)/C(IV)‐centre.

Fast reversible oxidative addition of demanding aryl chlorides to Pd under real conditions of catalysis in the Mizoroki-Heck reaction: The kinetic proof

• Quasi-equilibrium character of the oxidative addition of ArCl to Pd was demonstrated. • Quasi-equilibrated oxidative addition cannot be therefore the RDS. • Low reactivity of ArCl is caused by another reason not related to oxidative addition. The retarded oxidative addition of aryl chlorides to palladium is commonly believed to be the main obstacle for their successful conversion in cross-coupling reactions. However, this point has been fairly challenged in several papers, including those published recently, by providing experimental data obtained under both model and real catalytic conditions. Here, we provide proof of the fast and reversible character of the oxidative addition elementary step with aryl chlorides in the catalytic cycle of the Mizoroki-Heck reaction. The results have been obtained by the original kinetic approach using the differential selectivity of the competing Mizoroki-Heck reaction with two aryl chlorides. The kinetic data obtained in the real phosphine-free catalytic system unambiguously disproved the rate-determining character of the oxidative addition of aryl chloride as the key factor for lowering the catalytic activity when using aryl chlorides instead of aryl iodides and aryl bromides in the Mizoroki-Heck reaction.

Reversible CO2 activation by a N-phosphinoamidinato digermyne.

The N-phosphinoamidinato digermynes [LG̈e-G̈eL] (L = tBu2PNC(Ph)NAr, 4: Ar = 2,6-iPr2C6H3, 5: Ar = Ph) underwent reversible CO2 activation to form [LG̈eOC(O)G̈eL] (6: Ar = 2,6-iPr2C6H3, 7: Ar = Ph). Compound 7 was further reacted with diphenylacetylene and hexafluorobenzene, which proceeded through compound 5 in the first step, to form CO2, [LG̈eC(Ph) = C(Ph) G̈eL] (8), [LG̈eF] (9) and [LG̈eC6F5] (10), respectively.

Experimental and Computational Studies towards Chemoselective C−F over C−Cl Functionalisation: Reversible Oxidative Addition is the Key

AbstractCatalytic cross‐coupling is a valuable tool for forming new carbon‐carbon and carbon‐heteroatom bonds, allowing access to a variety of structurally diverse compounds. However, for this methodology to reach its full potential, precise control over all competing cross‐coupling sites in poly‐functionalised building blocks is required. Carbon‐fluorine bonds are one of the most stable bonds in organic chemistry, with oxidative addition at C−F being much more difficult than at other C‐halide bonds. As such, the development of methods to chemoselectively functionalise the C−F position in poly‐halogenated arenes would be very challenging if selectivity was to be induced at the oxidative addition step. However, metal‐halide complexes exhibit different trends in reactivity to the parent haloarenes, with metal‐fluoride complexes known to be very reactive towards transmetalation. In this current work we sought to exploit the divergent reactivity of Ni−Cl and Ni−F intermediates to develop a chemoselective C−F functionalisation protocol, where selectivity is controlled by the transmetalation step. Our experimental studies highlight that such an approach is feasible, with a number of nickel catalysts shown to facilitate Hiyama cross‐coupling of 1‐fluoronapthalene under base free conditions, while no cross‐coupling with 1‐chloronapthalene occurred. Computational and experimental studies revealed the importance of reversible C−Cl oxidative addition for the development of selective C−F functionalisation, with ligand effects on the potential for reversibility also presented.

Oxidative Addition of Water, Alcohols, and Amines in Palladium Catalysis.

The homolytic cleavage of O−H and N−H or weak C−H bonds is a key elementary step in redox catalysis, but is thought to be unfeasible for palladium. In stark contrast, reported here is the room temperature and reversible oxidative addition of water, isopropanol, hexafluoroisopropanol, phenol, and aniline to a palladium(0) complex with a cyclic (alkyl)(amino)carbene (CAAC) and a labile pyridino ligand, as is also the case in popular N‐heterocyclic carbene (NHC) palladium(II) precatalysts. The oxidative addition of protic solvents or adventitious water switches the chemoselectivity in catalysis with alkynes through activation of the terminal C−H bond. Most salient, the homolytic activation of alcohols and amines allows atom‐efficient, additive‐free cross‐coupling and transfer hydrogenation under mild reaction conditions with usually unreactive, yet desirable reagents, including esters and bis(pinacolato)diboron.

Oxidative Addition of Water, Alcohols, and Amines in Palladium Catalysis

AbstractThe homolytic cleavage of O−H and N−H or weak C−H bonds is a key elementary step in redox catalysis, but is thought to be unfeasible for palladium. In stark contrast, reported here is the room temperature and reversible oxidative addition of water, isopropanol, hexafluoroisopropanol, phenol, and aniline to a palladium(0) complex with a cyclic (alkyl)(amino)carbene (CAAC) and a labile pyridino ligand, as is also the case in popular N‐heterocyclic carbene (NHC) palladium(II) precatalysts. The oxidative addition of protic solvents or adventitious water switches the chemoselectivity in catalysis with alkynes through activation of the terminal C−H bond. Most salient, the homolytic activation of alcohols and amines allows atom‐efficient, additive‐free cross‐coupling and transfer hydrogenation under mild reaction conditions with usually unreactive, yet desirable reagents, including esters and bis(pinacolato)diboron.

Mechanism of Palladium‐Catalyzed Spiroannulation of Naphthols with Alkynes: A Density Functional Theory Study

AbstractPd‐catalyzed spiroannulation of bromophenylnaphthalenols with acetylenes to achieve asymmetric dearomatization is a powerful way to construct chiral spiro‐compounds. DFT calculations with the M06 functional have been performed to reveal the mechanism and enantioselectivity of this reaction. After reversible oxidative addition of aryl bromide to Pd(0), acetylene insertion into the Pd−C(aryl) bond is considered to be the rate‐ and enantioselectivity determining step. Subsequent deprotonation and reductive elimination then give the spiroannulation product. The overlay and noncovalent interaction analysis of the critical transition states were used to reveal the origin of the enantioselectivity for this reaction. We found that the axial chirality of the naphthol moiety affects the relative free energies of the corresponding transition states, whereas the enantioselectivity is controlled by the steric repulsion between the naphthol moiety and the ligand.

Oxidative Addition of Alkenyl and Alkynyl Iodides to a AuI Complex

AbstractThe first isolated examples of intermolecular oxidative addition of alkenyl and alkynyl iodides to AuI are reported. Using a 5,5′‐difluoro‐2,2′‐bipyridyl ligated complex, oxidative addition of geometrically defined alkenyl iodides occurs readily, reversibly and stereospecifically to give alkenyl‐AuIII complexes. Conversely, reversible alkynyl iodide oxidative addition generates bimetallic complexes containing both AuIII and AuI centers. Stoichiometric studies show that both new initiation modes can form the basis for the development of C−C bond forming cross‐couplings.

Oxidative Addition of Alkenyl and Alkynyl Iodides to a AuI Complex.

The first isolated examples of intermolecular oxidative addition of alkenyl and alkynyl iodides to AuI are reported. Using a 5,5'-difluoro-2,2'-bipyridyl ligated complex, oxidative addition of geometrically defined alkenyl iodides occurs readily, reversibly and stereospecifically to give alkenyl-AuIII complexes. Conversely, reversible alkynyl iodide oxidative addition generates bimetallic complexes containing both AuIII and AuI centers. Stoichiometric studies show that both new initiation modes can form the basis for the development of C-C bond forming cross-couplings.

Reversible oxidative-addition and reductive-elimination of thiophene from a titanium complex and its thermally-induced hydrodesulphurization chemistry.

The masked Ti(ii) synthon (Ketguan)(η6-ImDippN)Ti (1) oxidatively adds across thiophene to give ring-opened (Ketguan)(ImDippN)Ti[κ2-S(CH)3CH] (2). Complex 2 is photosensitive, and upon exposure to light, reductively eliminates thiophene to regenerate 1 - a rare example of early-metal mediated oxidative-addition/reductive-elimination chemistry. DFT calculations indicate strong titanium π-backdonation to the thiophene π*-orbitals leads to the observed thiophene ring opening across titanium, while a proposed photoinduced LMCT promotes the reverse thiophene elimination from 2. Finally, pressurizing solutions of 2 with H2 (150 psi) at 80 °C leads to the hydrodesulphurization of thiophene to give the Ti(iv) sulphide (Ketguan)(ImDippN)Ti(S) (3) and butane.

The emergence of Pd-mediated reversible oxidative addition in cross coupling, carbohalogenation and carbonylation reactions

Exploiting the reversibility of chemical processes is a long-standing tactic of organic chemists, and permeates most areas of the discipline. The notion that oxidative addition of Pd(0) to Ar–X bonds can be considered an irreversible process has been challenged, periodically, over the last 30 years. Recent examples of methodologies that harness the reversibility of oxidative addition reactions in catalytic processes have enabled access to challenging carbocyclic and heterocyclic scaffolds. This Perspective seeks to describe the development of these processes from the early proof-of-principle findings, and highlight key challenges that remain in this avenue of research. In particular, we draw attention to significant deficiencies that remain in the choice of suitable ligands and additives for these transformations. We conclude by describing how the concept of reversible oxidative addition has recently been exploited in the development of novel carbonylation reactions. While the oxidative addition of Pd to carbon–halide bonds is often regarded as being essentially irreversible, this is sometimes not the case. This Perspective looks at the conditions leading to reductive elimination of Pd from carbon–halide bonds, and the synthetic opportunities that this offers are discussed.

Highly-chemoselective step-down reduction of carboxylic acids to aromatic hydrocarbons via palladium catalysis.

Aryl carboxylic acids are among the most abundant substrates in chemical synthesis and represent a perfect example of a traceless directing group that is central to many processes in the preparation of pharmaceuticals, natural products and polymers. Herein, we describe a highly selective method for the direct step-down reduction of carboxylic acids to arenes, proceeding via well-defined Pd(0)/(ii) catalytic cycle. The method shows a remarkably broad substrate scope, enabling to direct the classical acyl reduction towards selective decarbonylation by a redox-neutral mechanism. The utility of this reaction is highlighted in the direct defunctionalization of pharmaceuticals and natural products, and further emphasized in a range of traceless processes using removable carboxylic acids under mild, redox-neutral conditions orthogonal to protodecarboxylation. Extensive DFT computations were conducted to demonstrate preferred selectivity for the reversible oxidative addition and indicated that a versatile hydrogen atom transfer (HAT) pathway is operable.

The Road Travelled: After Main‐Group Elements as Transition Metals

AbstractSince the latter quarter of the twentieth century, main group chemistry has undergone significant advances. Power's timely review in 2010 highlighted the inherent differences between the lighter and heavier main group elements, and that the heavier analogues resemble transition metals as shown by their reactivity towards small molecules. In this concept article, we present an overview of the last 10 years since Power's seminal review, and the progress made for catalytic application. This examines the use of low oxidation state and/or low coordinate group 13 and 14 complexes towards small molecule activation (oxidative addition step in a redox based cycle) and how ligand design plays a crucial role in influencing subsequent reactivity. The challenge in these redox based catalytic cycles still centres on the main group complexes’ ability to undergo reductive elimination, however considerable progress in this field has been reported via reversible oxidative addition reactions. Within the last 5 years the first examples of well‐defined low valent main group catalysts have begun to emerge, representing a bright future ahead for main group chemistry.

Evidence for single metal two electron oxidative addition and reductive elimination at uranium

Reversible single-metal two-electron oxidative addition and reductive elimination are common fundamental reactions for transition metals that underpin major catalytic transformations. However, these reactions have never been observed together in the f-block because these metals exhibit irreversible one- or multi-electron oxidation or reduction reactions. Here we report that azobenzene oxidises sterically and electronically unsaturated uranium(III) complexes to afford a uranium(V)-imido complex in a reaction that satisfies all criteria of a single-metal two-electron oxidative addition. Thermolysis of this complex promotes extrusion of azobenzene, where H-/D-isotopic labelling finds no isotopomer cross-over and the non-reactivity of a nitrene-trap suggests that nitrenes are not generated and thus a reductive elimination has occurred. Though not optimally balanced in this case, this work presents evidence that classical d-block redox chemistry can be performed reversibly by f-block metals, and that uranium can thus mimic elementary transition metal reactivity, which may lead to the discovery of new f-block catalysis.

Reversible Oxidative Addition at Carbon.

The reactivity of N-heterocyclic carbenes (NHCs) and cyclic alkyl amino carbenes (cAACs) with arylboronate esters is reported. The reaction with NHCs leads to the reversible formation of thermally stable Lewis acid/base adducts Ar-B(OR)2 ⋅NHC (Add1-Add6). Addition of cAACMe to the catecholboronate esters 4-R-C6 H4 -Bcat (R=Me, OMe) also afforded the adducts 4-R-C6 H4 Bcat⋅cAACMe (Add7, R=Me and Add8, R=OMe), which react further at room temperature to give the cAACMe ring-expanded products RER1 and RER2. The boronate esters Ar-B(OR)2 of pinacol, neopentylglycol, and ethyleneglycol react with cAAC at RT via reversible B-C oxidative addition to the carbene carbon atom to afford cAACMe (B{OR}2 )(Ar) (BCA1-BCA6). NMR studies of cAACMe (Bneop)(4-Me-C6 H4 ) (BCA4) demonstrate the reversible nature of this oxidative addition process.

Dynamic, Reversible Oxidative Addition of Highly Polar Bonds to a Transition Metal.

The combination of Pt0 complexes and indium trihalides leads to compounds that form equilibria in solution between their In-X oxidative addition (OA) products (PtII indyl complexes) and their metal-only Lewis pair (MOLP) isomers (LnPt→InX3). The position of the equilibria can be altered reversibly by changing the solvent, while the equilibria can be reversibly and irreversibly driven toward the MOLP products by addition of further donor ligands. The results mark the first observation of an equilibrium between MOLP and OA isomers, as well as the most polar bond ever observed to undergo reversible oxidative addition to a metal complex. In addition, we present the first structural characterization of MOLP and oxidative addition isomers of the same compound. The relative energies of the MOLP and OA isomers were calculated by DFT methods, and the possibility of solvent-mediated isomerization is discussed.

C–H Activation Induced by Oxidative Addition of N–O Bonds in Oxime Esters: Formation of Rhodacycles and Cycloaddition with Alkynes

The reaction of oxime esters with a rhodium(I) precursor to form five-membered rhodacycles via N–O bond cleavage followed by C–H bond activation has been investigated by isolating these complexes. Kinetic studies on the formation of rhodacycles show that the reversible oxidative addition of the N–O bond in the oxime ester to RhCl(PPh3)3 occurs at room temperature. The E-isomer of the oxime ester was found to undergo rhodacycle formation faster than the Z-isomer, which suggests that the geometry of the oxime esters reflects the geometry of intermediates during C–H activation. The rhodacycle reacted with an alkyne to construct an isoquinoline ring in both stoichiometric and catalytic conditions, despite its basic stability in air, in moisture, and even during heating, which demonstrates the potential of the rhodacycle as an intermediate for further catalytic transformation of oxime esters.