Bond Reductive Elimination Research Articles

Practical synthesis of anti-β-hydroxy-α-amino acids by Pd(II) -catalyzed sequential C(sp(3) )-H functionalization.

An improved and practical procedure for the stereoselective synthesis of anti-β-hydroxy-α-amino acids (anti-βhAAs), by palladium-catalyzed sequential C(sp(3) )-H functionalization directed by 8-aminoquinoline auxiliary, is described. followed by a previously established monoarylation and/or alkylation of the β-methyl C(sp(3) )-H of alanine derivative, β-acetoxylation of both alkylic and benzylic methylene C(sp(3) )-H bonds affords various anti-β-hydroxy-α-amino acid derivatives. As an example, the synthesis of β-mercapto-α-amino acids, which are highly important to the extension of native chemical ligation chemistry beyond cysteine, is described. The synthetic potential of this protocol is further demonstrated by the synthesis of diverse β-branched α-amino acids. The observed diastereoselectivities are strongly influenced by electronic effects of aromatic AAs and steric effects of the linear side-chain AAs, which could be explained by the competition of intramolecular C-OAc bond reductive elimination from Pd(IV) intermediates vs. intermolecular attack by an external nucleophile (AcO(-) ) in an SN 2-type process.

Understanding the Mechanisms of Unusually Fast HH, CH, and CC Bond Reductive Eliminations from Gold(III) Complexes

Carbon-carbon bond reductive elimination from gold(III) complexes are known to be very slow and require high temperatures. Recently, Toste and co-workers have demonstrated extremely rapid CC reductive elimination from cis-[AuPPh3 (4-F-C6 H4 )2 Cl] even at low temperatures. We have performed DFT calculations to understand the mechanistic pathway for these novel reductive elimination reactions. Direct dynamics calculations inclusive of quantum mechanical tunneling showed significant contribution of heavy-atom tunneling (>25 %) at the experimental reaction temperatures. In the absence of any competing side reactions, such as phosphine exchange/dissociation, the complex cis-[Au(PPh3 )2 (4-F-C6 H4 )2 ](+) was shown to undergo ultrafast reductive elimination. Calculations also revealed very facile, concerted mechanisms for HH, CH, and CC bond reductive elimination from a range of neutral and cationic gold(III) centers, except for the coupling of sp(3) carbon atoms. Metal-carbon bond strengths in the transition states that originate from attractive orbital interactions control the feasibility of a concerted reductive elimination mechanism. Calculations for the formation of methane from complex cis-[AuPPh3 (H)CH3 ](+) predict that at -52 °C, about 82 % of the reaction occurs by hydrogen-atom tunneling. Tunneling leads to subtle effects on the reaction rates, such as large primary kinetic isotope effects (KIE) and a strong violation of the rule of the geometric mean of the primary and secondary KIEs.

Selective CH Bond Functionalization of 2‐(2‐Thienyl)pyridine by a Rhodium N‐Heterocyclic Carbene Catalyst

Abstract[Rh(μ‐Cl)(H)2(IPr)]2 (IPr=1,3‐bis‐(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) catalyzes the selective functionalization of 2‐(2‐thienyl)pyridine efficiently with a range of alkenes and internal alkynes. A catalytic cycle is proposed on the basis of the identification of key reaction intermediates and the study of their reactivity by NMR spectroscopy. Theoretical calculations at the DFT level support that the reaction proceeds by initial κ1N coordination of 2‐(2‐thienyl)pyridine followed by the loss of H2 to afford the active catalyst. Subsequently, cyclometalation of 2‐(2‐thienyl)pyridine, coordination of the unsaturated substrate (alkyne or alkene) at the vacant position trans to the hydride, and reductive elimination of the thiophene moiety occur. Finally, cyclometalation of the thiophene moiety renders the hydride cis to the unsaturated substrate, which leads to migratory insertion into the RhH bond and subsequent reductive elimination of the functionalized product.

Exploring Bis(cyclometalated) Ruthenium(II) Complexes as Active Catalyst Precursors: Room-Temperature Alkene-Alkyne Coupling for 1,3-Diene Synthesis

Described is the development of a new class of bis(cyclometalated) ruthenium(II) catalyst precursors for CC coupling reactions between alkene and alkyne substrates. The complex [(cod)Ru(3-methallyl)2] reacts with benzophenone imine or benzophenone in a 1:2 ratio to form bis(cyclometalated) ruthenium(II) complexes (1). The imine-ligated complex 1 a promoted room-temperature coupling between acrylic esters and amides with internal alkynes to form 1,3-diene products. A proposed catalytic cycle involves CC bond formation by oxidative cyclization, β-hydride elimination, and CH bond reductive elimination. This RuII/RuIV pathway is consistent with the observed catalytic reactivity of 1 a for mild tail-to-tail methyl acrylate dimerization and for cyclobutene formation by [2+2] norbornene/alkyne cycloaddition.

Exploring bis(cyclometalated) ruthenium(II) complexes as active catalyst precursors: room-temperature alkene-alkyne coupling for 1,3-diene synthesis.

Described is the development of a new class of bis(cyclometalated) ruthenium(II) catalyst precursors for C-C coupling reactions between alkene and alkyne substrates. The complex [(cod)Ru(3-methallyl)2] reacts with benzophenone imine or benzophenone in a 1:2 ratio to form bis(cyclometalated) ruthenium(II) complexes (1). The imine-ligated complex 1 a promoted room-temperature coupling between acrylic esters and amides with internal alkynes to form 1,3-diene products. A proposed catalytic cycle involves C-C bond formation by oxidative cyclization, β-hydride elimination, and C-H bond reductive elimination. This Ru(II)/Ru(IV) pathway is consistent with the observed catalytic reactivity of 1 a for mild tail-to-tail methyl acrylate dimerization and for cyclobutene formation by [2+2] norbornene/alkyne cycloaddition.

Photoinitiated oxidative addition of CF3I to gold(I) and facile aryl-CF3 reductive elimination.

Herein we report the mechanism of oxidative addition of CF3I to Au(I), and remarkably fast Caryl–CF3 bond reductive elimination from Au(III) cations. CF3I undergoes a fast, formal oxidative addition to R3PAuR′ (R = Cy, R′ = 3,5-F2-C6H4, 4-F-C6H4, C6H5, 4-Me-C6H4, 4-MeO-C6H4, Me; R = Ph, R′ = 4-F-C6H4, 4-Me-C6H4). When R′ = aryl, complexes of the type R3PAu(aryl)(CF3)I can be isolated and characterized. Mechanistic studies suggest that near-ultraviolet light (λmax = 313 nm) photoinitiates a radical chain reaction by exciting CF3I. Complexes supported by PPh3 undergo reversible phosphine dissociation at 110 °C to generate a three-coordinate intermediate that undergoes slow reductive elimination. These processes are quantitative and heavily favor Caryl–I reductive elimination over Caryl–CF3 reductive elimination. Silver-mediated halide abstraction from all complexes of the type R3PAu(aryl)(CF3)I results in quantitative formation of Ar–CF3 in less than 1 min at temperatures as low as −10 °C.

Addendum: Exceptionally fast carbon–carbon bond reductive elimination from gold(III)

Addendum: Exceptionally fast carbon–carbon bond reductive elimination from gold(III)

Theoretical investigation on the regioselectivity of Ni(COD)2-catalyzed [2 + 2 + 2] cycloaddition of unsymmetric diynes and CO2

Reaction mechanisms of the Ni(COD)2-catalyzed [2 + 2 + 2] cycloaddition of unsymmetric diynes and CO2 have been theoretically studied by using the density functional theory calculations. Three major steps are included, oxidative coupling of CO2 with Et-substituted CC bond, the second CC bond insertion and reductive elimination of the product from the Ni center, in which the CC bond insertion was found to be rate-determinant. The steric arrangement of the N,P-bidentate ligand was demonstrated to be influential on reaction barriers. Based on the mechanistic study, the regioselectivity of the catalytic reaction was elucidated. In addition, we also explained why the mechanisms involving oxidative coupling of both the CC bonds are unavailable.

Pd‐catalyzed bicyclization of 2‐alkynylhalobenzenes and propargylic alcohols for the formation of indeno[1,2]furans: a DFT study

The mechanism of palladium‐catalyzed bicyclization of 2‐alkynylhalobenzenes and propargylic alcohols for the formation of indeno[1,2]furans has been studied computationally with the aid of density functional theory (DFT). Full free energy profiles are computed for different reaction equations between different reaction substrates. The calculation results showed that the catalytic cycle is found to contain six steps, oxidative addition, ligand substitution, first C ≡ C triple bond insertion, rearrangement, second C ≡ C triple bond insertion and reductive elimination, with the reductive elimination being the rate‐determining step for the different reaction equations (1), (2) and (3). Our calculations are consistent with experimental observations. Copyright © 2014 John Wiley & Sons, Ltd.

Exceptionally fast carbon–carbon bond reductive elimination from gold(III)

Reductive elimination of carbon-carbon (C-C) bonds occurs in numerous metal-catalyzed reactions. This process is well documented for a variety of transition metal complexes. However, C-C bond reductive elimination from a limited number of Au(III) complexes has been shown to be a slow and prohibitive process, generally requiring elevated temperature. Herein, we show that oxidation of a series of mono- and bimetallic Au(I) aryl complexes at low temperature generates observable Au(III) and Au(II) intermediates. We also show that aryl-aryl bond reductive elimination from these oxidized species is not only among the fastest observed for any transition metal, but is also mechanistically distinct from previously studied alkyl-alkyl and aryl-alkyl reductive eliminations from Au(III).

Double Role of the Hydroxy Group of Phosphoryl in Palladium(II)-Catalyzed ortho-Olefination: A Combined Experimental and Theoretical Investigation

Density functional theory calculations have been carried out on Pd-catalyzed phosphoryl-directed ortho-olefination to probe the origin of the significant reactivity difference between methyl hydrogen benzylphosphonates and dimethyl benzylphosphonates. The overall catalytic cycle is found to include four basic steps: C-H bond activation, transmetalation, reductive elimination, and recycling of catalyst, each of which is constituted from different steps. Our calculations reveal that the hydroxy group of phosphoryl plays a crucial role almost in all steps, which can not only stabilize the intermediates and transition states by intramolecular hydrogen bonds but also act as a proton donor so that the η(1)-CH3COO(-) ligand could be protonated to form a neutral acetic acid for easy removal. These findings explain why only the methyl hydrogen benzylphosphonates and methyl hydrogen phenylphosphates were found to be suitable reaction partners. Our mechanistic findings are further supported by theoretical prediction of Pd-catalyzed ortho-olefination using methyl hydrogen phenylphosphonate, which is verified by experimental observations that the desired product was formed in a moderate yield.

The quest for stable σ-methane complexes: computational and experimental studies

A series of cationic late transition metal pincer complexes with tridentate, neutral pincer ligands and their corresponding metal methyl complexes have been investigated by density functional theory (DFT). The key calculated quantities of interest for each metal–ligand pair were the energy of the metal methyl hydride relative to the metal σ-methane complex and the methane dissociation enthalpy and free energy. A few promising pincer ligand frameworks emerged as candidates for the syntheses of σ-methane complexes with enhanced thermal stability. The calculational predictions have been tested experimentally, and new iridium and rhodium complexes of a tridentate pincer ligand, 2,6-bis(di-tert-butylphosphinito)-3,5-diphenylpyrazine (N-PONOP) have been prepared as well as a cationic palladium methyl complex with 2,6-bis(di-tert-butylphosphinito)pyridine (PONOP) and subjected to several protonation experiments. Protonation of the (N-PONOP)Ir methyl complex yielded the corresponding five-coordinate iridium(III) methyl hydride cation. Kinetic studies of the C–H bond coupling and reductive elimination have been carried out. Line broadening NMR spectroscopic techniques have been established a barrier of 7.9(1) kcal mol−1 for H–Calkyl bond coupling in the iridium(III) methyl hydride (−100 °C). A protonation of the iridium pincer complexes at the uncoordinated pyrazine-N atom was not achieved.

Rhodium and Iridium Amido Complexes Supported by Silyl Pincer Ligation: Ammonia N−H Bond Activation by a [PSiP]Ir Complex

Ir silyl pincer complexes insert into the N-H bonds of anilines and ammonia under mild conditions to form isolable [Cy-PSiP]Ir(H)(NHR) complexes that are resistant to N-H bond reductive elimination at room temperature, even in the presence of arenes, alkenes, and phosphines.

Investigations of Iridium-Mediated Reversible C−H Bond Cleavage: Characterization of a 16-Electron Iridium(III) Methyl Hydride Complex

New iridium complexes of a tridentate pincer ligand, 2,6-bis(di-tert-butylphosphinito)pyridine (PONOP), have been prepared and used in the study of hydrocarbon C-H bond activation. Intermolecular oxidative addition of a benzene C-H bond was directly observed with [(PONOP)Ir(I)(cyclooctene)][PF(6)] at ambient temperature, resulting in a cationic five-coordinate iridium(III) phenyl hydride product. Protonation of the (PONOP)Ir(I) methyl complex yielded the corresponding iridium(III) methyl hydride cation, a rare five-coordinate, 16-valence electron transition metal alkyl hydride species which was characterized by X-ray diffraction. Kinetic studies of C-H bond coupling and reductive elimination reactions from the five-coordinate complexes have been carried out. Exchange NMR spectroscopy measurements established a barrier of 17.8(4) kcal/mol (22 degrees C) for H-C(aryl) bond coupling in the iridium(III) phenyl hydride cation and of 9.3(4) kcal/mol (-105 degrees C) for the analogous H-C(alkyl) coupling in the iridium(III) methyl hydride cation. The origin of the higher barrier of H-C(aryl) relative to H-C(alkyl) bond coupling is proposed to be influenced by a hindered rotation about the Ir-C(aryl) bond, a result of the sterically demanding PONOP ligand.

Kinetic and Equilibrium Deuterium Isotope Effects for C—H Bond Reductive Elimination and Oxidative Addition Reactions Involving the ansa‐Tungstenocene Methyl—Hydride Complex [Me2Si(C5Me4)2]W(Me)H

AbstractFor Abstract see ChemInform Abstract in Full Text.

Normal and inverse primary kinetic deuterium isotope effects for C-H bond reductive elimination and oxidative addition reactions of molybdenocene and tungstenocene complexes: evidence for benzene sigma-complex intermediates.

The overall reductive elimination of RH from the ansa-molybdenocene and -tungstenocene complexes [Me(2)Si(C(5)Me(4))(2)]Mo(Ph)H and [Me(2)Si(C(5)Me(4))(2)]W(R)H (R = Me, Ph) is characterized by an inverse primary kinetic isotope effect (KIE) for the tungsten system but a normal KIE for the molybdenum system. Oxidative addition of PhH to [[Me(2)Si(C(5)Me(4))(2)]M] also differs for the two systems, with the molybdenum system exhibiting a substantial intermolecular KIE, while no effect is observed for the tungsten system. These differences in KIEs indicate a significant difference in the reactivity of the hydrocarbon adducts [Me(2)Si(C(5)Me(4))(2)]M(RH) for the molybdenum and tungsten systems. Specifically, oxidative cleavage of [Me(2)Si(C(5)Me(4))(2)]M(RH) is favored over RH dissociation for the tungsten system, whereas RH dissociation is favored for the molybdenum system. A kinetics analysis of the interconversion of [Me(2)Si(C(5)Me(4))(2)]W(CH(3))D and [Me(2)Si(C(5)Me(4))(2)]W(CH(2)D)H, accompanied by elimination of methane, provides evidence that the reductive coupling step in this system is characterized by a normal KIE. This observation demonstrates that the inverse KIE for overall reductive elimination is a result of an inverse equilibrium isotope effect (EIE) and is not a result of an inverse KIE for a single step. A previous report of an inverse kinetic isotope effect of 0.76 for C-H reductive coupling in the [Tp]Pt(CH(3))H(2) system is shown to be erroneous. Finally, a computational study provides evidence that the reductive coupling of [Me(2)Si(C(5)Me(4))(2)]W(Ph)H proceeds via the initial formation of a benzene sigma-complex, rather than an eta(2)-pi-benzene complex.

The Methylene-Transfer Reaction: Synthetic and Mechanistic Aspects of a Unique C−C Coupling and C−C Bond Activation Sequence

Oxidative addition of aryl iodides ArI (Ar = (a) C6H5, (b) C6H4CF3, (c) C6H3(CF3)2, (d) C6H4CH3, (e) C6H4OCH3), to the PCP-type complex Rh(PPh3)[CH2C6H(CH3)2(CH2PPh2)2] (1), yields the complexes Rh(Ar)[CH2C6H(CH3)2(CH2PPh2)2](I) (2a−e). Compounds 2a−e undergo intramolecular methylene transfer from the bis-chelating ligand to the incoming aryl under mild conditions (room temperature) giving Rh(CH2Ar)[C6H(CH3)2(CH2PPh2)2](I) (3a−e). The methylene transfer, which is a unique sequence of sp2−sp3 C−C bond reductive elimination and sp2−sp3 C−C bond activation, was investigated kinetically (reaction 2a → 3a), yielding the activation parameters ΔH⧧ = 17 ± 3 kcal/mol, ΔS⧧ = −23 ± 4 eu. The rate-determining step of this reaction is the C−C reductive elimination rather than the C−C activation step. X-ray structural analysis of 2a and 3b demonstrates that the Rh atom is located in the center of a square pyramid with the aryl (2a) and the benzyl (3b) trans to the vacant coordination site. Reaction of the complex Rh(CH...

The Mechanism of Silicon−Hydrogen and Carbon−Hydrogen Bond Activation by Iridium(III): Production of a Silylene Complex and the First Direct Observation of Ir(III)/Ir(V) C−H Bond Oxidative Addition and Reductive Elimination

The complexes Cp*(PMe{sub 3})Ir(Me)OTf (Me = CH{sub 3}, OTf = OSO{sub 2}CF{sub 3}) (1) and Cp*(PMe{sub 3})Ir(Me)(CH{sub 2}Cl{sub 2})[BAr{sub f}] (BAr{sub f}{sup {minus}} = [(3,5-(CF{sub 3}){sub 2}C{sub 6}H{sub 3}){sub 4}B]{sup {minus}}) (2), which contain iridium in oxidation state +3, were recently shown to undergo C-H activation reactions with alkanes under mild thermal conditions. The authors report a series of observations, including the first conversion of Ir(III) precursors to an isolable, structurally characterized Ir(V) aryl-hydride and a spectroscopically observable Ir(V) alkyl-hydride, that lends convincing experimental support to the Ir(III) {r{underscore}arrow} Ir(V) {r{underscore}arrow} Ir(III) mechanism. The complex Cp*(PMe{sub 3})Ir(Me)OTf (1) reacts rapidly with alkanes (H-CR{sub 3}) to produce 1 equiv of methane (CH{sub 4}) and rearranged products derived from Cp*(PMe{sub 3})Ir(CR{sub 3})OTf, which form as a consequence of the {beta}-hydride elimination pathway. When 1 is added to silanes (H-SiR{sub 3}, R = Me, Ph), products of a structural rearrangement type unobserved in C-H activation reactions are isolated along with 1 equiv of methane. These products, Cp*(PMe{sub 3})Ir(SiR{sub 2}OTf)(R), are presumably derived from a 1,2-migration in Cp*(PMe{sub 3})Ir(SiR{sub 3})OTf, wherein one of the groups initially bound to silicon migrates to iridium (eq 1).

Electrophilic Platinum Complexes: Methyl Transfer Reactions and Catalytic Reductive Elimination of Ethane from a Tetramethylplatinum(IV) Complex

Methyl ligand transfer reactions occur easily between tetramethylplatinum(IV) complexes [PtMe4(LL)] [LL = 4,4‘-di-tert-butyl-2,2‘-bipyridine (bu2bpy) (1), N,N,N‘,N‘-tetramethylethylenediamine (tmeda) (2), bis(2,6-diisopropylphenyl)-1,4-diaza-1,3-butadiene (Ar2NN) (3), 1,2-bis(diphenylphosphino)ethane (dppe) (4)] and electrophilic platinum complexes fac-[PtMe3(SO3CF3)(LL)] [LL = bu2bpy (6a), tmeda (7a), Ar2NN (8a)] or [PtMe(SO3CF3)(dppe)] (10a). It is proposed that the complexes 6a, 7a, 8a, or 10a undergo initial dissociation of the triflate ligand to give an electrophilic platinum cation which attacks one of the mutually trans methylplatinum ligands of [PtMe4(LL)]. The reaction of [PtMe4(LL)] [LL = bu2bpy (1), tmeda (2), Ar2NN (3)] with fac-[PtMe3(SO3CF3)(L‘L‘)] [L‘L‘ = bu2bpy (6a), tmeda (7a), Ar2NN (8a)] gives an equilibrium mixture between the reactants and fac-[PtMe3(SO3CF3)(LL)] and [PtMe4(L‘L‘)], in which [PtMe4(LL)] is favored in the same order as the π-accepting properties of the LL ligand (Ar2NN ≫ bu2bpy > tmeda). The reaction of [PtMe4(dppe)] (4) with 6a, 7a, 8a, or 10a results in rapid room-temperature catalytic, C−C bond reductive elimination to give C2H6 and [PtMe2(dppe)] (5). It is proposed that the actual reductive elimination step occurs from the five-coordinate species [PtMe3(dppe)]+, formed by methyl ligand transfer from 4 to the electrophilic platinum complex (6a, 7a, 8a or 10a). The triflato complexes 6a−10a are in rapid equilibrium with the cationic aqua complexes fac-[PtMe3(OH2)(LL)]SO3CF3 [LL = bu2bpy (6b), tmeda (7b), Ar2NN (8b), dppe (9b)] and [PtMe(OH2)(dppe)]SO3CF3 (10b), respectively, thus confirming lability of the triflate ligands.

Molecular Rearrangements of a Low-Valent Niobium Amide: Ligand C−H Bond Oxidative Addition and Reductive Elimination

Reaction of the dinuclear and divalent (TMEDA)2Nb2Cl5Li(TMEDA) with Ph2NK led to the formation of three different compounds. The first complex contains no amide ligands. It is a mixed-valence dinuc...