Homogeneous hydrogenation of electron‐deficient alkenes by iridium complexes

The catalytic homogeneous hydrogenation of electron‐deficient alkenes (nucleophilic hydrogenation) was achieved in the presence of iridium complexes and a base as co‐catalyst. Contrary to hydrogenation of electron‐rich alkenes, which is inactivated by bases, the hydrogenation of the electron‐deficient alkenes turned out to be base activated. Here, we present a more thorough study on the capacities but also limitations of this new reaction mechanism using screenings of the reaction conditions as well as different Ir complexes and substrates. The formation of a catalytically active Ir complex is proposed. The active complex usually attacks a soft electron‐deficient atom, if more than one possibility exists (as shown by density functional theory computations). Additionally, first examples of enantiomeric enrichments in the presence of chiral Ir complexes are presented. The high catalyst load needed and the moderate yields show that the active complex is very unstable under conditions of nucleophilic hydrogenation and is quickly deactivated, which has to be addressed in further studies. Copyright © 2011 John Wiley & Sons, Ltd.     

Mechanistic Investigation of Molybdate‐Catalysed Transfer Hydrodeoxygenation

The molybdate‐catalysed transfer hydrodeoxygenation (HDO) of benzyl alcohol to toluene driven by oxidation of the solvent isopropyl alcohol to acetone has been investigated by using a combination of experimental and computational methods. A Hammett study that compared the relative rates for the transfer HDO of five para‐substituted benzylic alcohols was carried out. Density‐functional theory (DFT) calculations suggest a transition state with significant loss of aromaticity contributes to the lack of linearity observed in the Hammett study. The transfer HDO could also be carried out in neat PhCH₂OH at 175 °C. Under these conditions, PhCH₂OH underwent disproportionation to yield benzaldehyde, toluene, and significant amounts of bibenzyl. Isotopic‐labelling experiments (using PhCH₂OD and PhCD₂OH) showed that incorporation of deuterium into the resultant toluene originated from the α position of benzyl alcohol, which is in line with the mechanism suggested by the DFT study.     

Computational Mechanistic Elucidation of the Intramolecular Aminoalkene Hydroamination Catalysed by Iminoanilide Alkaline‐Earth Compounds

A comprehensive computational exploration of plausible alternative mechanistic pathways for the intramolecular hydroamination (HA) of aminoalkenes by a recently reported class of kinetically stabilised iminoanilide alkaline‐earth silylamido compounds [{N^N}Ae{N(SiMe₃)₂} ? (thf)_n] ({N^N}=iminoanilide; Ae=Ca, Sr, Ba) is presented. On the one hand, a proton‐assisted concerted N?C/C?H bond‐forming pathway to afford the cycloamine in a single step can be invoked and on the other hand, a stepwise σ‐insertive pathway that involves a fast, reversible migratory olefin 1,2‐insertion step linked to a less rapid, irreversible metal?C azacycle tether σ‐bond aminolysis. Notably, these alternative mechanistic avenues are equally consistent with reported key experimental features. The present study, which employs a thoroughly benchmarked and reliable DFT methodology, supports the prevailing mechanism to be a stepwise σ‐insertive pathway that sees an initial conversion of the {N^N}Ae silylamido into the catalytically competent {N^N}Ae amidoalkene compound and involves thereafter facile and reversible insertive N?C bond‐forming ring closure, linked to irreversible intramolecular Ae?C tether σ‐bond aminolysis at the transient {N^N}Ae alkyl intermediate. Turnover‐limiting protonolysis accounts for the substantial primary kinetic isotope effect observed; its DFT‐derived barrier satisfactorily matches the empirically determined Eyring parameter and predicts the decrease in rate observed across the series Ca>Sr>Ba correctly. Non‐competitive kinetic demands militate against the operation of the concerted proton‐assisted pathway, which describes N?C bond‐forming ring closure triggered by concomitant amino proton delivery at the C?C linkage evolving through a multi‐centre TS structure. Valuable insights into the catalytic structure–activity relationships are unveiled by a detailed comparison of [{N^N}Ae(NHR)] catalysts. Moreover, the intriguingly opposite trends in reactivity observed in intramolecular (Ca>Sr>Ba) and intermolecular (Ca<Sr<Ba) HA catalysis for the studied family of iminoanilide alkaline‐earth amido catalysts are rationalised.     

On the Mechanism of the Digold(I)–Hydroxide‐Catalysed Hydrophenoxylation of Alkynes

Herein, we present a detailed investigation of the mechanistic aspects of the dual gold‐catalysed hydrophenoxylation of alkynes by both experimental and computational methods. The dissociation of [{Au(NHC)}₂(μ‐OH)][BF₄] is essential to enter the catalytic cycle, and this step is favoured by the presence of bulky, non‐coordinating counter ions. Moreover, in silico studies confirmed that phenol does not only act as a reactant, but also as a co‐catalyst, lowering the energy barriers of several transition states. A gem‐diaurated species might form during the reaction, but this lies deep within a potential energy well, and is likely to be an “off‐cycle” rather than an “in‐cycle” intermediate.     

Chemodivergent Metathesis of Dienynes Catalyzed by Ruthenium–Indenylidene Complexes: An Experimental and Computational Study

A study on the enyne metathesis reaction leading to the formation cyclic compounds using ruthenium–indenylidene complexes is presented. Several 1,11‐dien‐6‐ynes have been subjected to ruthenium metathesis cyclization by using ruthenium–indenylidene complexes bearing various phosphine and N‐heterocyclic carbene (NHC) ligands. Interestingly, for some substrates chemodivergent metathesis occurs and is a function of the catalyst employed. This led us to investigate the competing “ene‐then‐yne” or “yne‐then‐ene” reaction pathways apparently at play in these systems using both experimental observations and DFT calculations. Experimental and computational studies were found in good agreement and permit to conclude that for phosphine‐containing catalysts, the “ene‐then‐yne” pathway is exclusively adopted. On the other hand, for catalysts bearing NHC ligands, both pathways are possible.     

Hydrogenation and Transfer Hydrogenation Promoted by Tethered Ru−S Complexes: From Cooperative Dihydrogen Activation to Hydride Abstraction/Proton Release from Dihydrogen Surrogates

Hydrogenation and transfer hydrogenation of imines with cyclohexa‐1,4‐dienes, as well as with a representative Hantzsch ester dihydrogen surrogate, are reported. Both processes are catalyzed by tethered Ru?S complexes but differ in the activation mode of the dihydrogen source: cooperative activation of the H?H bond at the Ru?S bond leads to the corresponding Ru?H complex and protonation of the sulfur atom, whereas the same cationic Ru?S catalyst abstracts a hydride from a donor‐substituted cyclohexa‐1,4‐diene to form the neutral Ru?H complex and a low‐energy Wheland intermediate. A sequence of proton and hydride transfers on the imine substrate then yields an amine. The reaction pathways are analyzed computationally, and the established mechanistic pictures are in agreement with the experimental observations.     

Computational Kinetics of Cobalt‐Catalyzed Alkene Hydroformylation

Density functional theory, coupled‐cluster theory, and transition state theory are used to build a computational model of the kinetics of phosphine‐free cobalt‐catalyzed hydroformylation and hydrogenation of alkenes. The model provides very good agreement with experiment, and enables the factors that determine the selectivity and rate of catalysis to be determined. The turnover rate is mainly determined by the alkene coordination step.     

Ligand‐Controlled Regiodivergent Pathways of Rhodium(III)‐Catalyzed Dihydroisoquinolone Synthesis: Experimental and Computational Studies of Different Cyclopentadienyl Ligands

Rh^III‐catalyzed directed C?H functionalizations of arylhydroxamates have become a valuable synthetic tool. To date, the regioselectivity of the insertion of the unsaturated acceptor into the common cyclometalated intermediate was dependent solely on intrinsic substrate control. Herein, we report two different catalytic systems that allow the selective formation of regioisomeric 3‐aryl dihydroisoquinolones and previously inaccessible 4‐aryl dihydroisoquinolones under full catalyst control. The differences in the catalysts are computationally examined using density functional theory and transition state theory of different possible pathways to elucidate key contributing factors leading to the regioisomeric products. The stabilities of the initially formed rhodium complex styrene adducts, as well as activation barrier differences for the migratory insertion, were identified as key contributing factors for the regiodivergent pathways.     

A Computational Study of the Olefin Epoxidation Mechanism Catalyzed by Cyclopentadienyloxidomolybdenum(VI) Complexes

A DFT analysis of the epoxidation of C₂H₄ by H₂O₂ and MeOOH (as models of tert‐butylhydroperoxide, TBHP) catalyzed by [Cp*MoO₂Cl] ( 1 ) in CHCl₃ and by [Cp*MoO₂(H₂O)]⁺ in water is presented (Cp*=pentamethylcyclopentadienyl). The calculations were performed both in the gas phase and in solution with the use of the conductor‐like polarizable continuum model (CPCM). A low‐energy pathway has been identified, which starts with the activation of ROOH (R=H or Me) to form a hydro/alkylperoxido derivative, [Cp*MoO(OH)(OOR)Cl] or [Cp*MoO(OH)(OOR)]⁺ with barriers of 24.9 (26.5) and 28.7 (29.2) kcal mol^?1 for H₂O₂ (MeOOH), respectively, in solution. The latter barrier, however, is reduced to only 1.0 (1.6) kcal mol^?1 when one additional water molecule is explicitly included in the calculations. The hydro/alkylperoxido ligand in these intermediates is η²‐coordinated, with a significant interaction between the Mo center and the O^β atom. The subsequent step is a nucleophilic attack of the ethylene molecule on the activated O^α atom, requiring 13.9 (17.8) and 16.1 (17.7) kcal mol^?1 in solution, respectively. The corresponding transformation, catalyzed by the peroxido complex [Cp*MoO(O₂)Cl] in CHCl₃, requires higher barriers for both steps (ROOH activation: 34.3 (35.2) kcal mol^?1; O atom transfer: 28.5 (30.3) kcal mol^?1), which is attributed to both greater steric crowding and to the greater electron density on the metal atom.     

Neutral Nickel Ethylene Oligo‐ and Polymerization Catalysts: Towards Computational Catalyst Prediction and Design

DFT calculations have been used to elucidate the chain termination mechanisms for neutral nickel ethylene oligo‐ and polymerization catalysts and to rationalize the kind of oligomers and polymers produced by each catalyst. The catalysts studied are the (κ²‐O,O)‐coordinated (1,1,1,5,5,5‐hexafluoro‐2,4‐acetylacetonato)nickel catalyst I , the (κ²‐P,O)‐coordinated SHOP‐type nickel catalyst II , the (κ²‐N,O)‐coordinated anilinotropone and salicylaldiminato nickel catalysts III and IV , respectively, and the (κ²‐P,N)‐coordinated phosphinosulfonamide nickel catalyst V . Numerous termination pathways involving β‐H elimination and β‐H transfer steps have been investigated, and the most probable routes identified. Despite the complexity and multitude of the possible termination pathways, the information most critical to chain termination is contained in only few transition states. In addition, by consideration of the propagation pathway, we have been able to estimate chain lengths and discriminate between oligo‐ and polymerization catalysts. In agreement with experiment, we found the Gibbs free energy difference between the overall barrier for the most facile propagation and termination pathways to be close to 0 kcal mol^?1 for the ethylene oligomerization catalysts I and V , whereas values of at least 7 kcal mol^?1 in favor of propagation were determined for the polymerization catalysts III and IV . Because of the shared intermediates between the termination and branching pathways, we have been able to identify the preferred cis/trans regiochemistry of β‐H elimination and show that a pronounced difference in σ donation of the two bridgehead atoms of the bidentate ligand can suppress hydride formation and thus branching. The degree of rationalization obtained here from a handful of key intermediates and transition states is promising for the use of computational methods in the screening and prediction of new catalysts of the title class.     

Iron Borohydride Pincer Complexes for the Efficient Hydrogenation of Ketones under Mild,Base‐Free Conditions: Synthesis and Mechanistic Insight

The new, structurally characterized hydrido carbonyl tetrahydridoborate iron pincer complex [(iPr‐PNP)Fe(H)(CO)(η¹‐BH₄)] ( 1 ) catalyzes the base‐free hydrogenation of ketones to their corresponding alcohols employing only 4.1 atm hydrogen pressure. Turnover numbers up to 1980 at complete conversion of ketone were reached with this system. Treatment of 1 with aniline (as a BH₃ scavenger) resulted in a mixture of trans‐[(iPr‐PNP)Fe(H)₂(CO)] ( 4 a ) and cis‐[(iPr‐PNP)Fe(H)₂(CO)] ( 4 b ). The dihydrido complexes 4 a and 4 b do not react with acetophenone or benzaldehyde, indicating that these complexes are not intermediates in the catalytic reduction of ketones. NMR studies indicate that the tetrahydridoborate ligand in 1 dissociates prior to ketone reduction. DFT calculations show that the mechanism of the iron‐catalyzed hydrogenation of ketones involves alcohol‐assisted aromatization of the dearomatized complex [(iPr‐PNP*)Fe(H)(CO)] ( 7 ) to initially give the Fe⁰ complex [(iPr‐PNP)Fe(CO)] ( 21 ) and subsequently [(iPr‐PNP)Fe(CO)(EtOH)] ( 38 ). Concerted coordination of acetophenone and dual hydrogen‐atom transfer from the PNP arm and the coordinated ethanol to, respectively, the carbonyl carbon and oxygen atoms, leads to the dearomatized complex [(iPr‐PNP*)Fe(CO)(EtO)(MeCH(OH)Ph)] ( 32 ). The catalyst is regenerated by release of 1‐phenylethanol, followed by dihydrogen coordination and proton transfer to the coordinated ethoxide ligand.     

DFT Methods to Study the Reaction Mechanism of Iridium‐Catalyzed Hydrogenation of Olefins: Which Functional Should be Chosen?

To enable the selection of more accurate computational methods for the future theoretical exploration of the reaction mechanism of Ir‐catalyzed olefin hydrogenation, we compared high‐level ab initio coupled cluster and DFT calculations with a simplified model of Pfaltz's Ir/P,N‐type catalyst for all four previously proposed Ir^I/Ir^III and Ir^III/Ir^V mechanisms. Through the systematic assessment of the DFT performances, the DFT empirical dispersion correction (DFT‐D3) is found to be indispensable for improving the accuracy of relative energies between the Ir^I/Ir^III and Ir^III/Ir^V mechanisms. After including the DFT‐D3 correction, the three best performing density functionals (DFs) are B2‐PLYP, BP86, and TPSSh. In these recommended DFs, the computationally more expensive double‐hybrid functional B2‐PLYP‐D3 has a balanced and outstanding performance for calculations of the reaction barriers, reaction energies, and energy gaps between different mechanisms, whereas the less costly BP86‐D3 and TPSSh‐D3 methods have outstanding, but relatively less uniform performances.     

Understanding Electrogenerated Chemiluminescence Efficiency in Blue‐Shifted Iridium(III)‐Complexes: An Experimental and Theoretical Study

Compared to tris(2‐phenylpyridine)iridium(III) ([Ir(ppy)₃]), iridium(III) complexes containing difluorophenylpyridine (df‐ppy) and/or an ancillary triazolylpyridine ligand [3‐phenyl‐1,2,4‐triazol‐5‐ylpyridinato (ptp) or 1‐benzyl‐1,2,3‐triazol‐4‐ylpyridine (ptb)] exhibit considerable hypsochromic shifts (ca. 25–60 nm), due to the significant stabilising effect of these ligands on the HOMO energy, whilst having relatively little effect on the LUMO. Despite their lower photoluminescence quantum yields compared with [Ir(ppy)₃] and [Ir(df‐ppy)₃], the iridium(III) complexes containing triazolylpyridine ligands gave greater electrogenerated chemiluminescence (ECL) intensities (using tri‐n‐propylamine (TPA) as a co‐reactant), which can in part be ascribed to the more energetically favourable reactions of the oxidised complex (M⁺) with both TPA and its neutral radical oxidation product. The calculated iridium(III) complex LUMO energies were shown to be a good predictor of the corresponding M⁺ LUMO energies, and both HOMO and LUMO levels are related to ECL efficiency. The theoretical and experimental data together show that the best strategy for the design of efficient new blue‐shifted electrochemiluminophores is to aim to stabilise the HOMO, while only moderately stabilising the LUMO, thereby increasing the energy gap but ensuring favourable thermodynamics and kinetics for the ECL reaction. Of the iridium(III) complexes examined, [Ir(df‐ppy)₂(ptb)]⁺ was most attractive as a blue‐emitter for ECL detection, featuring a large hypsochromic shift (λ_max=454 and 484 nm), superior co‐reactant ECL intensity than the archetypal homoleptic green and blue emitters: [Ir(ppy)₃] and [Ir(df‐ppy)₃] (by over 16‐fold and threefold, respectively), and greater solubility in polar solvents.     

Theoretical Study on the Mechanism of Ni‐Catalyzed Alkyl–Alkyl Suzuki Cross‐Coupling

Ni‐catalyzed cross‐coupling of unactivated secondary alkyl halides with alkylboranes provides an efficient way to construct alkyl–alkyl bonds. The mechanism of this reaction with the Ni/ L1 ( L1 =trans‐N,N′‐dimethyl‐1,2‐cyclohexanediamine) system was examined for the first time by using theoretical calculations. The feasible mechanism was found to involve a Ni^I–Ni^III catalytic cycle with three main steps: transmetalation of [Ni^I( L1 )X] (X=Cl, Br) with 9‐borabicyclo[3.3.1]nonane (9‐BBN)R₁ to produce [Ni^I( L1 )(R₁)], oxidative addition of R₂X with [Ni^I( L1 )(R₁)] to produce [Ni^III( L1 )(R₁)(R₂)X] through a radical pathway, and C? C reductive elimination to generate the product and [Ni^I( L1 )X]. The transmetalation step is rate‐determining for both primary and secondary alkyl bromides. KOiBu decreases the activation barrier of the transmetalation step by forming a potassium alkyl boronate salt with alkyl borane. Tertiary alkyl halides are not reactive because the activation barrier of reductive elimination is too high (+34.7 kcal mol^?1). On the other hand, the cross‐coupling of alkyl chlorides can be catalyzed by Ni/ L2 ( L2 =trans‐N,N′‐dimethyl‐1,2‐diphenylethane‐1,2‐diamine) because the activation barrier of transmetalation with L2 is lower than that with L1 . Importantly, the Ni⁰–Ni^II catalytic cycle is not favored in the present systems because reductive elimination from both singlet and triplet [Ni^II( L1 )(R₁)(R₂)] is very difficult.     

Metal–Ligand Cooperation in Catalytic Intramolecular Hydroamination: A Computational Study of Iridium–Pyrazolato Cooperative Activation of Aminoalkenes

The present study comprehensively explores diverse mechanistic pathways for intramolecular hydroamination of prototype 2,2‐dimethyl‐4‐penten‐1‐amine by Cp*Ir chloropyrazole ( 1 ; Cp*=pentamethylcyclopentadienyl) in the presence of KOtBu base with the aid of density functional theory (DFT) calculations. The most accessible mechanistic pathway for catalytic turnover commences from Cp*Ir pyrazolato (Pz) substrate adduct 2 ?S, representing the catalytically competent compound and proceeds via initial electrophilic activation of the olefin C?C bond by the metal centre. It entails 1) facile and reversible anti nucleophilic amine attack on the iridium–olefin linkage; 2) Ir? C bond protonolysis via stepwise transfer of the ammonium N? H proton at the zwitterionic [Cp*IrPz–alkyl] intermediate onto the metal that is linked to turnover‐limiting, reductive, cycloamine elimination commencing from a high‐energy, metastable [Cp*IrPz–hydrido–alkyl] species; and 3) subsequent facile cycloamine liberation to regenerate the active catalyst species. The amine–iridium bound 2 a ?S likely corresponds to the catalyst resting state and the catalytic reaction is expected to proceed with a significant primary kinetic isotope. This study unveils the vital role of a supportive hydrogen‐bonded network involving suitably aligned β‐basic pyrazolato and cycloamido moieties together with an external amine molecule in facilitating metal protonation and reductive elimination. Cooperative hydrogen bonding thus appears pivotal for effective catalysis. The mechanistic scenario is consonant with catalyst performance data and furthermore accounts for the variation in performance for [Cp*IrPz] compounds featuring a β‐ or γ‐basic pyrazolato unit. As far as the route that involves amine N? H bond activation is concerned, a thus far undocumented pathway for concerted amidoalkene → cycloamine conversion through olefin protonation by the pyrazole N? H concurrent with N? C ring closure is disclosed as a favourable scenario. Although not practicable in the present system, this pathway describes a novel mechanistic variant in late transition metal–ligand bifunctional hydroamination catalysis that can perhaps be viable for tailored catalyst designs. The insights revealed herein concerning the operative mechanism and the structure–reactivity relationships will likely govern the rational design of late transition metal–ligand bifunctional catalysts and facilitate further conceptual advances in the area.     

NH3 Synthesis in the N2/H2 Reaction System using Cooperative Molecular Tungsten/Rhodium Catalysis in Ionic Hydrogenation: A DFT Study

The ionic hydrogenation of N₂ with H₂ to give NH₃ is investigated by means of density functional theory (DFT) computations using a cooperatively acting catalyst system. In this system, N₂ binds to a neutral tungsten pincer complex of the type [(PNP)W(N₂)₃] (PNP=pincer ligand) and is reduced to NH₃. The protons and hydride centers necessary for the reduction are delivered by heterolytic cleavage of H₂ between the N₂–tungsten complex and the cationic rhodium complex [Cp*Rh{2‐(2‐pyridyl)phenyl}(CH₃CN)]⁺. Successive transfer of protons and hydrides to the bound N₂, as well as all N_xH_y units that occur during the reaction, enable the computation of closed catalytic cycles in the gas and in the solvent phase. By optimizing the pincer ligands of the tungsten complex, energy spans as low as 39.3 kcal mol^?1 could be obtained, which is unprecedented in molecular catalysis for the N₂/H₂ reaction system.     

New mechanistic insights into the iridium-phosphanooxazoline-catalyzed hydrogenation of unfunctionalized olefins: a DFT and kinetic study

The reaction mechanism of the iridium-phosphanooxazoline-catalyzed hydrogenation of unfunctionalized olefins has been studied by means of density functional theory calculations (B3LYP) and kinetic experiments. The calculations suggest that the reaction involves an unexpected Ir(III)-Ir(V) catalytic cycle facilitated by coordination of a second equivalent of dihydrogen. Thus, in the rate-determining migratory insertion of the substrate alkene into an iridium-hydride bond, simultaneous oxidative addition of the bound dihydrogen occurs. The kinetic data shows that the reaction is first order with respect to hydrogen pressure. This is interpreted in terms of an endergonic coordination of this second equivalent of dihydrogen, although a rate-determining step, in which coordinated solvent is replaced by dihydrogen, could not be ruled out. Furthermore, the reaction was found to be zeroth order with respect to the alkene concentration. This correlates well with the calculated exothermicity of substrate coordination, and the catalyst is thus believed to coordinate an alkene in the resting state. On the basis of the proposed catalytic cycle, calculations were performed on a full-sized system with 88 atoms to assess the appropriateness of the model calculations. These calculations were also used to explain the enantioselectivity exerted by the catalyst.     

Mechanism of the Asymmetric Hydrogenation of Exocyclic α,β‐Unsaturated Carbonyl Compounds with an Iridium/BiphPhox Catalyst: NMR and DFT Studies

The mechanism of the asymmetric hydrogenation of exocyclic α,β‐unsaturated carbonyl compounds with the (aS)‐Ir/iPr‐BiphPhox catalyst was studied by NMR experiments and DFT computational analyses. Computed optical yields of the asymmetric hydrogenation proceeding by an iridium(I)/iridium(III) mechanism involving a transition state stabilized through two intramolecular hydrogen bonds are in good accordance with the experimental ee values.