Reductive Elimination Reactions Research Articles

Rebuttal to the article Pathological crystal structures.

A section in the Acta Crystallographica Section C article by Raymond & Girolami [Acta Cryst. (2023), C79, 445-455] stated that the product of the reaction of [(Cp*Rh)2(μ-OH)3]+ (Cp* is 1,2,3,4,5-pentamethylcyclopentadiene) with 1-methylthymine (1-MT) at pH 10 and 60 °C, to synthesize the anionic component [RhI(η1-N3-1-MT)2]-, was not an RhI complex, but rather an AgI complex, due to the use of silver triflate (AgOTf) to remove Cl- from [Cp*RhCl2]2 to synthesize [Cp*Rh(H2O)3](OTf)2, a water-soluble crystalline complex. We will clearly show that this premise, as stated, is invalid, while the authors have simply avoided several important facts, including that Cp*OH, a reductive elimination product, at pH 10 and 60 °C, was unequivocally identified, thus leading to the RhI anionic component [RhI(η1-N3-1-MT)2]-. More importantly, AgOH, from the reaction of NaOH at pH 10 with any potentially remaining AgOTf, after the AgCl was filtered off, would be insoluble in water. Furthermore, a control experiment with the inorganic complex Rh(OH)3, reacting with 1-methylthymine at pH 10, provided no product, and this bodes well for a similar fate with AgOTf and 1-methylthymine, i.e. at pH 10, AgOTf would again be converted to the water-insoluble AgOH; therefore, no reaction would occur! Finally, a 1H NMR spectroscopy experiment was carried out with synthesized and crystallized [Cp*Rh(H2O)3](OTf)2 in D2O at various pD values; at pD 8.65 no reaction took place, while at pD 13.6, and at 60 °C for 2 h, a reductive elimination reaction caused the precipitation of Cp*OH. The subsequent 1H NMR spectrum clearly demonstrated, in the absence of any AgI complexes, that the solution structure and the X-ray crystals in D2O were similar. A postulated mechanism for this novel anionic component structure, as published previously [Smith et al. (2014). Organometallics, 33, 2389-2404], will be presented, along with the experimental data, to insure the credibility of our results. We will also answer the comments in the response of Drs Raymond and Girolami to this rebuttal.

Trajectory-Based Time-Resolved Mechanism for Benzene Reductive Elimination from Cyclopentadienyl Mo/W Phenyl Hydride Complexes.

Calculated potential energy structures and landscapes are very often used to define the sequence of reaction steps in an organometallic reaction mechanism and interpret kinetic isotope effect (KIE) measurements. Underlying most of this structure-to-mechanism translation is the use of statistical rate theories without consideration of atomic/molecular motion. Here we report direct dynamics simulations for an organometallic benzene reductive elimination reaction, where nonstatistical intermediates and dynamic-controlled pathways were identified. Specifically, we report single spin state as well as mixed spin state quasiclassical direct dynamics trajectories in the gas phase and explicit solvent for benzene reductive elimination from Mo and W bridged cyclopentadienyl phenyl hydride complexes ([Me2Si(C5Me4)2]M(H)(Ph), M = Mo and W). Different from the energy landscape mechanistic sequence, the dynamics trajectories revealed that after the benzene C-H bond forming transition state (often called reductive coupling), σ-coordination and π-coordination intermediates are either skipped or circumvented and that there is a direct pathway to forming a spin flipped solvent caged intermediate, which occurs in just a few hundred femtoseconds. Classical molecular dynamics simulations were then used to estimate the lifetime of the caged intermediate, which is between 200 and 400 picoseconds. This indicates that when the η2-π-coordination intermediate is formed, it occurs only after the first formation of the solvent-caged intermediate. This dynamic mechanism intriguingly suggests the possibility that the solvent-caged intermediate rather than a coordination intermediate is responsible (or partially responsible) for the inverse KIE value experimentally measured for W. Additionally, this dynamic mechanism prompted us to calculate the kH/kD KIE value for the C-H bonding forming transition states of Mo and W. Surprisingly, Mo gave a normal value, while W gave an inverse value, albeit small, due to a much later transition state position.

Exploring the energetics of Suzuki cross-coupling reaction: A computational study of palladium and nickel catalysts

The present study employed density-functional theory (DFT) calculations to investigate the Suzuki-Miyaura Cross-Coupling reaction using single atom catalysis (SAC) via palladium or nickel. The reaction barriers for chloride bond cleavage in phenyl chloride were found to be 34.68 kJ/mol and 24.24 kJ/mol for palladium and nickel catalysts, respectively. During the transmetalation process, the energy barrier for boronic acid release from phenyl trihydroxyboronate using SAC via palladium and SAC via nickel was calculated to be 74.17 kJ/mol and 65.22 kJ/mol, respectively. The results indicated that in the oxidative addition and transmetalation reactions, the SAC via nickel outperforms the SAC via palladium, while the SAC via palladium excels in the reductive elimination reaction. These findings suggest the effectiveness of a SAC via nickel as a substitute for SAC via palladium in the synthesis of biphenyls in the Suzuki-Miyaura cross-coupling reaction.

Mechanistic study on the reductive elimination of (aryl)(fluoroaryl)palladium complexes: a key step in regiospecific dehydrogenative cross-coupling.

Cross-dehydrogenative coupling (CDC) reactions have attracted attention as short-step synthetic methods for C-C bond formation. Recently, we have developed CDC reactions between naphthalene and fluorobenzene. Rather than exhibiting general regioselectivity, this reaction proceeds selectively at the β-position of naphthalene. In this study, investigation using model complexes as reaction intermediates revealed that the origin of the unique selectivity is the exclusive occurrence of reductive elimination at the β-position. Detailed studies on the reductive elimination showed that the steric hindrance of the naphthyl group and the electron-withdrawing properties of fluorobenzene determine the position at which the reductive elimination reaction proceeds. These results show that the selectivity of the C-H functionalisation of polycyclic aromatic hydrocarbons (PAHs) is determined not by the C-H cleavage step, but by the subsequent reductive elimination step. The regioselective CDC reaction was adaptable to various PAHs but was less selective for pyrene with extended π-conjugation. In fluorobenzene substrates, the F atoms at the two ortho positions of the C-H moiety are necessary for high selectivity. The substrate ranges are in good agreement with the proposed mechanism, in which the reductive elimination step determines the regioselectivity.

A Simple Protocol for the C−N Cross‐Coupling of Aryl Chlorides with Amines Applying Ni/NHC Catalysis

AbstractAn efficient protocol for the C−N cross‐coupling of aryl chlorides with (hetero)aryl‐ and alkyl amines under nickel catalysis has been developed. The main advantage of the protocol is the use of a self‐activated Ni/NHC catalytic system generated in situ from readily available bench‐stable air‐tolerant precursors: NiCl2Py2, IPr ⋅ HCl, and sodium tert‐butoxide. A mass spectrometry mechanistic study of the reaction system revealed the dynamics of competitive processes of Ni/NHC active species formation and degradation involving NHC reductive elimination reactions and tert‐butoxide base. Optimization of the NiCl2Py2/IPr ⋅ HCl/tBuONa ratio and the reaction temperature allowed efficient catalysis to be achieved. The developed simple protocol represents an alternative for methods relying on the use of air‐sensitive and unstable Ni(cod)2 or expensive well‐defined Ni/NHC precatalysts.

Reductive Elimination Reactions in Gold(III) Complexes Leading to C(sp3)-X (X = C, N, P, O, Halogen) Bond Formation: Inner-Sphere vs SN2 Pathways.

The reactions leading to the formation of C-heteroatom bonds in the coordination sphere of Au(III) complexes are uncommon, and their mechanisms are not well known. This work reports on the synthesis and reductive elimination reactions of a series of Au(III) methyl complexes containing different Au-heteroatom bonds. Complexes [Au(CF3)(Me)(X)(PR3)] (R = Ph, X = OTf, OClO3, ONO2, OC(O)CF3, F, Cl, Br; R = Cy, X = Me, OTf, Br) were obtained by the reaction of trans-[Au(CF3)(Me)2(PR3)] (R = Ph, Cy) with HX. The cationic complex cis-[Au(CF3)(Me)(PPh3)2]OTf was obtained by the reaction of [Au(CF3)(Me)(OTf)(PPh3)] with PPh3. Heating these complexes led to the reductive elimination of MeX (X = Me, Ph3P+, OTf, OClO3, ONO2, OC(O)CF3, F, Cl, Br). Mechanistic studies indicate that these reductive elimination reactions occur either through (a) the formation of tricoordinate intermediates by phosphine dissociation, followed by reductive elimination of MeX, or (b) the attack of weakly coordinating anionic (TfO- or ClO4-) or neutral nucleophiles (PPh3 or NEt3) to the Au-bound methyl carbon. The obtained results show for the first time that the nucleophilic substitution should be considered as a likely reductive elimination pathway in Au(III) alkyl complexes.

How does multi-reference computation change the catalysis chemistry? DFT and CASPT2 studies of the Cu-catalysed coupling reactions between aryl iodides and β-diketones.

The molecular mechanism of a Cu-catalysed coupling reaction was theoretically studied using density functional theory (DFT) and the complete active space self-consistent field method followed by the second-order perturbation theory (CASSCF/CASPT2) to investigate the effects of the strong electron correlation of the Cu centre on the reaction profile. Both DFT and CASSCF/CASPT2 calculations showed that the catalytic cycle proceeds via an oxidative addition (OA) reaction, followed by a reductive elimination (RE) reaction, where OA is the rate-determining step. Although the DFT-calculated activation energies of the OA and RE steps are highly dependent on the choice of functionals, the CASSCF/CASPT2 results are less affected by the choice of DFT-optimised geometries. Therefore, with a careful assessment based on the CASSCF/CASPT2 single-point energy evaluation, an optimal choice of the DFT geometry is of good qualitative use for energetics at the CASPT2 level of theory. Based on the changes in the electron populations of the 3d orbitals during the OA and RE steps, the characteristic features of the DFT-calculated electronic structure were qualitatively consistent with those calculated using the CASSCF method. Further electronic structure analysis by the natural orbital occupancy of the CASSCF wavefunction showed that the ground state is almost single-reference in this system and the strong electron correlation effect of the Cu centre can be dealt with using the MP2 or CCSD method, too. However, the slightly smaller occupation numbers of the 3dπ orbital in the course of reactions suggested that the electron correlation effect of the Cu(III) centre appears through the interaction between the 3dπ orbital and the C-I antibonding σ* orbital in the OA step, and between the 3dπ orbital and the Cu-C antibonding σ* orbital in the RE step.

Evidence for C−F Bond Formation through Formal Reductive Elimination from Tellurium(VI)

AbstractThe fundamental challenge of C−F bond formation by reductive elimination has been met by compounds of select transition metals and fewer main group elements. The work detailed herein expands the list of main group elements known to be capable of reductively eliminating a C−F bond to include tellurium. Surprising and novel modes of both sp2 and sp3 C−F bond formation were observed alongside formation of TeIV cations during two separate attempts to synthesize/characterize fluorinated organotellurium(VI) cations in superacidic media (SbF5/SO2ClF). Following detailed low‐temperature NMR experiments, the mechanisms of the two unique reductive elimination reactions were probed and investigated using density functional theory (DFT) calculations. Ultimately, we found that an “indirect” reductive elimination pathway is likely operative whereby Sb plays a key role in fluoride abstraction and C−F bond formation, as opposed to unimolecular reductive elimination from a discrete TeVI cation.

Evidence for C-F Bond Formation through Formal Reductive Elimination from Tellurium(VI).

The fundamental challenge of C-F bond formation by reductive elimination has been met by compounds of select transition metals and fewer main group elements. The work detailed herein expands the list of main group elements known to be capable of reductively eliminating a C-F bond to include tellurium. Surprising and novel modes of both sp2 and sp3 C-F bond formation were observed alongside formation of TeIV cations during two separate attempts to synthesize/characterize fluorinated organotellurium(VI) cations in superacidic media (SbF5 /SO2 ClF). Following detailed low-temperature NMR experiments, the mechanisms of the two unique reductive elimination reactions were probed and investigated using density functional theory (DFT) calculations. Ultimately, we found that an "indirect" reductive elimination pathway is likely operative whereby Sb plays a key role in fluoride abstraction and C-F bond formation, as opposed to unimolecular reductive elimination from a discrete TeVI cation.

Easy Csp2–Csp2 reductive elimination from organoplatinum complexes by electrophilic fluorinating reagents

Electrophilic fluorination of bisaryl-platinum(II) complexes at RT leads to an exceptionally fast Ar–Ar instead of Ar–F reductive elimination. By reacting bisphosphine bisaryl-platinum(II) complex with NFSI, the biaryl product was formed with >90% yield within <30 minutes at RT. Moreover, by experimental and computational studies, the influence of ancillary ligands on the Ar–Ar reductive elimination reaction was investigated by changing their steric and electronic effects. The stability of some platinum fluoride complexes in the presence of water was also investigated.

C-Cl Oxidative Addition and C-C Reductive Elimination Reactions in the Context of the Rhodium-Promoted Direct Arylation.

A cycle of stoichiometric elemental reactions defining the direct arylation promoted by a redox-pair Rh(I)–Rh(III) is reported. Starting from the rhodium(I)-aryl complex RhPh{κ3-P,O,P-[xant(PiPr2)2]} (xant(PiPr2)2 = 9,9-dimethyl-4,5-bis(diisopropylphosphino)xanthene), the reactions include C–Cl oxidative addition of organic chlorides, halide abstraction from the resulting six-coordinate rhodium(III) derivatives, C–C reductive coupling between the initial aryl ligand and the added organic group, oxidative addition of a C–H bond of a new arene, and deprotonation of the generated hydride-rhodium(III)-aryl species to form a new rhodium(I)-aryl derivative. In this context, the kinetics of the oxidative additions of 2-chloropyridine, chlorobenzene, benzyl chloride, and dichloromethane to RhPh{κ3-P,O,P-[xant(PiPr2)2]} and the C–C reductive eliminations of biphenyl and benzylbenzene from [RhPh2{κ3-P,O,P-[xant(PiPr2)2]}]BF4 and [RhPh(CH2Ph){κ3-P,O,P-[xant(PiPr2)2]}]BF4, respectively, have been studied. The oxidative additions generally involve the cis addition of the C–Cl bond of the organic chloride to the rhodium(I) complex, being kinetically controlled by the C–Cl bond dissociation energy; the weakest C–Cl bond is faster added. The C–C reductive elimination is kinetically governed by the dissociation energy of the formed bond. The C(sp3)–C(sp2) coupling to give benzylbenzene is faster than the C(sp2)–C(sp2) bond formation to afford biphenyl. In spite of that a most demanding orientation requirement is needed for the C(sp3)–C(sp2) coupling than for the C(sp2)–C(sp2) bond formation, the energetic effort for the pregeneration of the C(sp3)–C(sp2) bond is lower. As a result, the weakest C–C bond is formed faster.

Asymmetrically Difunctionalized 1,1′‐Ferrocenyl Metalloligands and Their Transition Metal Complexes

AbstractThe synthesis and full characterization of novel 1,1′‐difunctionalized ferrocene metalloligands is described. While one cyclopentadienyl ring has been functionalized with 2,2′‐bipyridine for secondary coordination, the second Cp ring has been decorated with different aryl moieties containing electron withdrawing groups such as 4‐(CF3)C6H4 (2A) 3,5‐(CF3)2C6H3 (2B) or 4‐(NO2)C6H4 (2C). The newly developed metalloligands were reacted with [Pd(cod)Cl2] (3A–C), CuCl2 (4A–C) and trans‐[(PPh3)2Ni(Mes)Br] (5A,B) to obtain the corresponding square‐planar and dimeric square‐pyramidal complexes. The electrochemical behaviour of the ligands and complexes was investigated with the aid of cyclic voltammetry and compared with the corresponding monofunctionalized derivatives. The influence of the implemented functional groups on the nickel complexes was then confirmed for the reductive elimination reaction of an aryl ether induced by oxidation of the corresponding methoxides (6A,B,D). The experimental findings are supported by quantum chemical calculations.

Palladacycle-Catalyzed Regioselective Heck Reaction Using Diaryliodonium Triflates and Aryl Iodides

We describe a P-containing palladacycle-catalyzed regioselective Heck reaction of 2,3-dihydrofuran with diaryliodonium salts and aryl iodides to afford 2-aryl-2,5-dihydrofurans and 2-aryl-2,3-dihydrofurans, respectively, in good yields. Mechanistic studies revealed that the oxidative addition of diaryliodonium salts to palladacycles to form Pd(IV) species showed high chemoselectivity and that electron-rich aryl moieties were preferentially transferred to the Heck product. DFT calculations indicated that the regioselectivity-determining step is the reductive elimination reaction rather than the isomerization and reinsertion of Pd(IV)-hydride intermediates into the double bond.

Oxidative Addition of a Hypervalent Iodine Compound to Cycloplatinated(II) Complexes for the C-O Bond Construction: Effect of Cyclometalated Ligands.

The complex [PtMe(Obpy)(OAc)2(H2O)], 2a, Obpy = 2,2'-bipyridine N-oxide, is prepared through the reaction of [PtMe(Obpy)(SMe2)], 1a, by 1 equiv of PhI(OAc)2 via an oxidative addition (OA) reaction. Pt(IV) complex 2a attends the process of C-O bond reductive elimination (RE) reaction to form methyl acetate and corresponding Pt(II) complex [Pt(Obpy)(OAc)(H2O)], 3a. The kinetic of OA and RE reactions are investigated by means of different spectroscopies. The obtained results show that the reaction rates of OA step of 1a are faster than its analogous complex [PtMe(ppy)(SMe2)], 1b, ppy = 2-phenylpyridine. The density functional theory (DFT) calculations signify that the OA reaction initiated by a nucleophilic attack of the platinum(II) central atom of 1b on the iodine(III) atom while it had commenced by a nucleophilic substitution reaction of coordinated SMe2 in 1a with a carbonyl oxygen atom of PhI(OAc)2. Our calculation revealed that the key step for 1a is an acetate transfer from the I(III) to Pt(II) through a formation of square pyramidal iodonium complex. This can be attributed to the more electron-withdrawing character of Obpy ligand than to ppy which reduces the nucleophilicity of Pt atom in 1a. Furthermore, 2a with electron-withdrawing Obpy ligand prone to C-O bond formation faster than complex [PtMe(ppy)(OAc)2(H2O)], 2b, with an electron-rich ppy ligand which conforms to the anticipation that REs occur faster on electron-poor metal centers.

Reductive Cytochrome P450 Reactions and Their Potential Role in Bioremediation.

Cytochrome P450 enzymes, or P450s, are haem monooxygenases renowned for their ability to insert one atom from molecular oxygen into an exceptionally broad range of substrates while reducing the other atom to water. However, some substrates including many organohalide and nitro compounds present little or no opportunity for oxidation. Under hypoxic conditions P450s can perform reductive reactions, contributing electrons to drive reductive elimination reactions. P450s can catalyse dehalogenation and denitration of a range of environmentally persistent pollutants including halogenated hydrocarbons and nitroamine explosives. P450-mediated reductive dehalogenations were first discovered in the context of human pharmacology but have since been observed in a variety of organisms. Additionally, P450-mediated reductive denitration of synthetic explosives has been discovered in bacteria that inhabit contaminated soils. This review will examine the distribution of P450-mediated reductive dehalogenations and denitrations in nature and discuss synthetic biology approaches to developing P450-based reagents for bioremediation.

Thermal ranges and figures of merit for gold-containing precursors for atomic layer deposition

This is a survey of known gold-containing chemical vapor deposition (CVD) and atomic layer deposition (ALD) precursors with a focus on collecting their volatilization and decomposition data. These data were applied to a figure of merit (σ) developed to easily assess the thermal characteristics (“volatilization temperature” and the onset of decomposition]) important in the initial assessment of molecules as potential ALD precursors. Of the 46 compounds that were identified, 23 had sufficient thermal data reported in the literature to determine a σ value. The two known gold ALD precursors (15, σ = 104 and 22, σ = 44) were both shown to be in a cluster of excellent precursors. They were each the best in their families of precursors, measured by their σ and their onset of volatility. It was also found that many potentially excellent gold ALD precursors had gold in the +3 oxidation state. Some gold(I) compounds were identified as having good figures of merit (28, σ = 78, 29, σ = 32, 36, σ = 31), but 28 and 29 were found to undergo a reductive elimination reaction at growing gold surfaces, which is a common CVD deposition route for gold(I) compounds. β-diketonates and β-ketoiminates of gold were the most encouraging family of compounds, with σ values of greater than 50. This family contained the precursor with the highest figure of merit (9, σ = 212). These compounds are difficult to make in high yield, but an alternate synthetic route that was identified during this survey might serve to make this class of gold compound competitive as a precursor.

Force-modulated reductive elimination from platinum(ii) diaryl complexes.

Coupled mechanical forces are known to drive a range of covalent chemical reactions, but the effect of mechanical force applied to a spectator ligand on transition metal reactivity is relatively unexplored. Here we quantify the rate of C(sp2)–C(sp2) reductive elimination from platinum(ii) diaryl complexes containing macrocyclic bis(phosphine) ligands as a function of mechanical force applied to these ligands. DFT computations reveal complex dependence of mechanochemical kinetics on the structure of the force-transducing ligand. We validated experimentally the computational finding for the most sensitive of the ligand designs, based on MeOBiphep, by coupling it to a macrocyclic force probe ligand. Consistent with the computations, compressive forces decreased the rate of reductive elimination whereas extension forces increased the rate relative to the strain-free MeOBiphep complex with a 3.4-fold change in rate over a ∼290 pN range of restoring forces. The calculated natural bite angle of the free macrocyclic ligand changes with force, but 31P NMR analysis and calculations strongly suggest no significant force-induced perturbation of ground state geometry within the first coordination sphere of the (P–P)PtAr2 complexes. Rather, the force/rate behavior observed across this range of forces is attributed to the coupling of force to the elongation of the O⋯O distance in the transition state for reductive elimination. The results suggest opportunities to experimentally map geometry changes associated with reactions in transition metal complexes and potential strategies for force-modulated catalysis.

Reversible Reductive Elimination in Aluminum(II) Dihydrides

AbstractOxidative addition and reductive elimination are defining reactions of transition‐metal organometallic chemistry. In main‐group chemistry, oxidative addition is now well‐established but reductive elimination reactions are not yet general in the same way. Herein, we report dihydrodialanes supported by amidophosphine ligands. The ligand serves as a stereochemical reporter for reversible reductive elimination/oxidative addition chemistry involving AlIand AlIIIintermediates.

Reversible Reductive Elimination in Aluminum(II) Dihydrides.

Oxidative addition and reductive elimination are defining reactions of transition‐metal organometallic chemistry. In main‐group chemistry, oxidative addition is now well‐established but reductive elimination reactions are not yet general in the same way. Herein, we report dihydrodialanes supported by amidophosphine ligands. The ligand serves as a stereochemical reporter for reversible reductive elimination/oxidative addition chemistry involving AlI and AlIII intermediates.

Aryl C(sp2)-X Coupling (X = C, N, O, Cl) and Facile Control of N-Mono- and N,N-Diarylation of Primary Alkylamines at a Pt(IV) Center.

We present the first example of an unprecedented and fast aryl C(sp2)–X reductive elimination from a series of isolated Pt(IV) aryl complexes (Ar = p-FC6H4) LPtIVF(py)(Ar)X (X = CN, Cl, 4-OC6H4NO2) and LPtIVF2(Ar)(HX) (X = NHAlk; Alk = n-Bu, PhCH2, cyclo-C6H11, t-Bu, cyclopropylmethyl) bearing a bulky bidentate 2-[bis(adamant-1-yl)phosphino]phenoxide ligand (L). The C(sp2)–X reductive elimination reactions of all isolated Pt(IV) complexes follow first-order kinetics and were modeled using density functional theory (DFT) calculations. When a difluoro complex LPtIVF2(Ar)(py) is treated with TMS–X (TMS = trimethylsilyl; X= NMe2, SPh, OPh, CCPh) it also gives the corresponding products of the Ar–X coupling but without observable LPtIVF(py)(Ar)X intermediates. Remarkably, the LPtIVF2(Ar)(HX) complexes with alkylamine ligands (HX = NH2Alk) form selectively either mono- (ArNHAlk) or diarylated (Ar2NAlk) products in the presence or absence of an added Et3N, respectively. This method allows for a one-pot preparation of diarylalkylamine bearing different aryl groups. These findings were also applied in unprecedented mono- and di-N-arylation of amino acid derivatives (lysine and tryptophan) under very mild conditions.