Organolanthanide-mediated intramolecular hydroamination/cyclization of conjugated aminodienes: a computational exploration of diverse mechanistic pathways for the regioselective generation of functionalized azacycles supported by a lanthanocene-based catalyst complex

The complete catalytic reaction course for the organolanthanide-mediated intramolecular hydroamination/cyclization (IHC) of (4E,6)-heptadien-1-amine by a prototypical achiral Cp*(2)LaCH(TMS)(2) precatalyst is critically scrutinized by employing a gradient-corrected DFT method. The condensed free-energy profile for the overall reaction, comprised of thermodynamic and kinetic aspects of individual elementary steps, is presented. A computationally verified, revised mechanistic scenario has been proposed, which is consistent with the empirical rate law, accounts for crucial experimental observations, and provides a first understanding of the origin of the measured negative DeltaS(++). It involves rapid substrate association/dissociation equilibria and facile intramolecular diene insertion, linked to turnover-limiting protonolysis of the eta(3)-butenyl-Ln functionality, with the amine-amidodiene-Ln adduct complex representing the catalyst's resting state. The thermodynamic and kinetic factors that determine the high regio- and stereoselectivity of the mechanistically diverse IHC of aminodienes have been elucidated. These achievements allow a deeper understanding and a consistent rationalization of the experimental results for aminodiene IHC and furthermore enhance the insights into general mechanistic aspects of the organolanthanide-mediated cycloamination.     

Intramolecular hydroamination/cyclisation of aminoallenes mediated by a cationic zirconocene catalyst: a computational mechanistic study

The complete sequence of steps of a tentative catalytic cycle for intramolecular hydroamination/cyclisation (IHC) of 4,5-hexadien-1-ylamine (1) by a prototypical cationic [Cp(2)ZrCH(3)](+) zirconocene precatalyst (2) has been examined by employing a gradient-corrected DFT method. The predicted smooth overall reaction energy profile is consistent with the available experimental data, thereby providing further confidence in the proposed mechanism. Following activation of the precatalyst by protonolytic cleavage of the Zr-Me bond, the catalytically active amidoallene-Zr complex undergoes addition of an allenic C[double bond, length as m-dash]C linkage across the Zr-N sigma-bond. The alternative exo- and endocyclic pathways show similar probabilities for the sterically less encumbered reactants {1 + 2} investigated herein. However, steric factors are expected to exert control on the regioselectivity of ring closure. On the other hand, the metathesis-type transition states for subsequent protonolysis are indicated to be less sensitive to steric demands. Formation of the six-membered azacycle-Zr intermediate through intramolecular C[double bond, length as m-dash]C insertion into the Zr-N sigma-bond is predicted to be turnover limiting. The factors that govern the regioselectivity of the aminoallene IHC have been elucidated.     

Intramolecular hydroamination/cyclisation of aminoallenes mediated by a neutral zirconocene catalyst: a computational mechanistic study

The complete catalytic cycle for the intramolecular hydroamination/cyclisation (IHC) of 4,5-hexadien-1-ylamine (1) by a prototypical [ZrCp(2)Me(2)] precatalyst (2) has been scrutinized by employing a reliable DFT method. The present study conducted by means of a detailed computational characterisation of structural and energetic aspects of alternative pathways for all of the relevant elementary steps complements the mechanistic insights revealed from experimental results. The operative mechanism entails an initial transformation of precatalyst 2 into the thermodynamically prevalent, but dormant, bis(amido)-Zr compound in the presence of aminoallene 1. This complex undergoes a reversible, rate-determining alpha-elimination of 1 to form the imidoallene-Zr complex. The substrate-free form, which contains a chelating imidoallene functionality, is the catalytically active species and is rapidly transformed into azazirconacyclobutane intermediates through a [2+2] cycloaddition reaction. This highly facile process does not proceed regioselectively because the alternative pathways for the formation of five- and six-membered azacycles have comparable probabilities. Degradation of cyclobutane intermediates by following the most feasible pathway occurs through protonolysis of the metallacycle moiety and subsequent proton transfer from the Zr-NHR moiety onto the azacycle. The five-membered allylamine is generated through protonation at carbon atom C(6) followed by alpha-hydrogen elimination, whereas protonolysis of the cyclobutane moiety at the Zr-N bond followed by proton transfer onto carbon atom C(5) is the dominant route for the six-membered product. Of the two consecutive proton transfer steps, the second one determines the overall kinetics of the entire protonation sequence. This process is predicted to be substantially slower than the cycloaddition reaction. The factors that regulate the composition of the cycloamine products have been elucidated.     

Mechanistic investigation of organolanthanide-mediated hydroamination of aminoallenes: a comprehensive computational assessment of various routes for allene activation

The present mechanistic study comprehensively explores alternative scenarios for activation of the amine-linked allene C=C linkage toward nucleophilic amido attack in the intramolecular hydroamination of a prototypical 1,3-disubstituted aminoallene by a well-characterised samarocene-amido catalyst. Firstly, the non-insertive mechanism by Scott featuring C-N ring closure with concomitant amino proton delivery onto the allene unit has been explored and its key features have been defined. This scenario has been compared and contrasted with the classical stepwise Ln-N σ-bond insertive mechanism that involves rapid substrate association/dissociation equilibria for the Ln-amido-substrate resting state and also for Ln-azacycle intermediates, facile and reversible exocyclic ring closure through migratory allene insertion into the Ln-N amido σ-bond, linked to turnover-limiting Ln-C azacycle aminolysis. The Ln-N σ-bond insertive mechanism prevails for the studied intramolecular hydroamination of 4,5-heptadien-1-ylamine 1 by [Cp*(2)Sm-CH(TMS)(2)] starting material 2. The following aspects are in support of this mechanism: 1) the derived rate law is consistent with the observed empirical rate law; 2) the assessed effective barrier for turnover-limiting aminolysis does agree reasonably well with empirically determined Eyring parameters; 3) the ring-tether double bond selectivity is consistently elucidated. On the other hand, this study reveals that the non-insertive mechanism, which features a prohibitively large barrier, is unachievable. Spatial demands around the lanthanide centre effect the two mechanisms differently. A sufficiently accessible lanthanide is a crucial requirement of the Ln-N σ-bond insertive mechanism and enhanced encumbrance renders the cyclisation step less accessible kinetically. This contrasts with the non-insertive mechanism, where greater lanthanide protection has a rather modest influence. The present study indicates that the non-insertive mechanism would prevail if the lanthanide centre were to be protected effectively against C=C bond approach, whilst ensuring a high polarity of the Ln-N σ-bond together with a sufficiently acidic amino proton.     

Mechanistic Exploration of Intramolecular Aminodiene Hydroamination/Cyclisation Mediated by Constrained Geometry Organoactinide Complexes: A DFT Study

The present computational mechanistic study explores comprehensively the organoactinide‐mediated intramolecular hydroamination/cyclisation (IHC) of aminodienes by employing a reliable DFT method. All the steps of a plausible catalytic reaction course have been scrutinised for the IHC of (4E,6)‐heptadienylamine 1 t by [(CGC)Th(NMe₂)₂] precatalyst 2 (CGC=[Me₂Si(η⁵‐Me₄C₅)(tBuN)]^2?). For each of the relevant elementary steps the most accessible pathway has been identified from a multitude of mechanistic possibilities. The operative mechanism involves rapid substrate association/dissociation equilibria for the 3 t ‐S resting state and also for azacyclic intermediates 4 a , 4 s , easily accessible and reversible exocyclic ring closure, supposedly facile isomerisation of the azacycle’s butenyl tether prior to turnover‐limiting protonolysis. The following aspects are in support of this scenario: 1) the derived rate law is consistent with the experimentally obtained empirical rate law; 2) the accessed barrier for turnover‐limiting protonolysis does agree remarkably well with observed performance data; 3) the ring‐tether double‐bond selectivity is consistently elucidated, which led to predict the product distribution correctly. This study provides a computationally substantiated rationale for observed activity and selectivity data. Steric demands at the CGC framework appear to be an efficient means for modulating both performance and ring‐tether double‐bond selectivity. The careful comparison of (CGC)4f‐element and (CGC)5f‐element catalysts revealed that aminodiene IHC mediated by organoactinides and organolanthanides proceeds through a similar mechanistic scenario. However, cyclisation and protonolysis steps, in particular, feature a markedly different reactivity pattern for the two catalyst classes, owing to enhanced bond covalency of early actinides when compared to lanthanides.     

Is an M?N σ‐Bond Insertion Route a Viable Alternative to the MN [2+2] Cycloaddition Route in Intramolecular Aminoallene Hydroamination/Cyclisation Catalysed by Neutral Zirconium Bis(amido) Complexes? A Computational Mechanistic Study

This study examines alternative reaction channels for intramolecular hydroamination/cyclisation (IHC) of primary 4,5-hexadien-1-ylamine aminoallene (1) by a neutral [Cp(2)ZrMe(2)] zirconocene precatalyst (2) by using the density functional theory (DFT) method. The first channel proceeds through a [Cp(2)Zr(NHR)(2)] complex as the reactive species and relevant steps including the insertion of an allenic C=C linkage into the Zr--NHR sigma-bond and ensuing protonolysis. This is contrasted to the [2+2] cycloaddition mechanism involving a [Cp(2)Zr=NR] transient species. The salient features of the rival mechanisms are disclosed. The cycloaddition route entails the first transformation of the dormant [Cp(2)Zr(NHR)(2)] complex 3 B into the transient [Cp(2)Zr=NR] intermediate 3 A', which is turnover limiting. This route features a highly facile ring closure together with a substantially slower protonolysis (k(cycloadd)>k(protonolysis)) and can display inhibition by high substrate concentration. In contrast, protonolysis is the more facile step for the channel proceeding through the [Cp(2)Zr(NHR)(2)] complex as the catalytically active species. Here, C=C insertion into the Zr--C sigma-bond of 3 B, which represents the catalyst resting state, is turnover limiting and substrate concentration is unlikely to influence the rate. The regulation of the selectivity is elucidated for the two channels. DFT predicts that five-ring allylamine and six-ring imine are generated upon traversing the cycloaddition route, thereby comparing favourably with experiment, whereas the cycloimine should be formed solely along the sigma-bond insertion route. The mechanistic analysis is indicative of an operating [2+2] cycloaddition mechanism. The Zr--NHR sigma-bond insertion route, although appearing not to be employed for the reactants studied herein, is clearly suggested as being viable for hydroamination by charge neutral organozirconium compounds.     

Mechanistic elucidation of the yttrium(III)-catalysed intramolecular aminoalkene hydroamination: DFT favours a stepwise σ-insertive mechanism

A comprehensive computational mechanistic study regarding intramolecular hydroamination (HA) of aminoalkenes mediated by a recently reported class of highly active cyclopentadienyl-bis(oxazolinyl)borate {Cpo}Y(III) alkyl compounds is presented. Two distinct mechanistic pathways of catalytic HA mediated by rare earth and alkaline earth compounds have emerged over the years, describing amidoalkene → cycloamine conversion proceeding through a stepwise σ-insertive mechanism or a concerted non-insertive N-C/C-H bond forming pathway. Notably, both mechanisms account equally for reported distinct process features. Non-competitive kinetic demands revealed for the concerted amino proton transfer associated with N-C ring closure, which commences from a {Cpo(M)}Y(NHR)·(NH(2)R) substrate adduct and evolves through a six-centre TS structure, militates against a proton-triggered non-insertive pathway to promote HA for the rare earth catalyst at hand. A stepwise σ-insertive pathway, featuring rapid and reversible olefin insertion into the Y-N amido σ-bond, linked to a less facile and irreversible intramolecular Y-C azacycle tether aminolysis, is found to prevail energetically. The assessed effective barrier for turnover-limiting aminolysis matches the empirically determined Eyring parameter well and the computationally estimated primary KIE is close to the observed values. A recent computational study revealed a similar scenario for an analogous tris(oxazolinyl)borate {To(M)}Mg system. Valuable insights into the catalytic structure-reactivity relationships have been unveiled by a comparison of {Cpo(M)}Y(NHR)- and {To(M)}Mg(NHR)-catalysed hydroaminations.     

Origin of diastereoselectivity in the organolanthanide-mediated intramolecular hydroamination/cyclisation of aminodienes: a computational exploration of constrained geometry CGC-Ln catalysts

The regulation of ring-substituent diastereoselectivity in the intramolecular hydroamination/cyclisation (IHC) of alpha-substituted aminodienes by constrained geometry CGC-lanthanide catalysts (CGC=[Me(2)Si(eta(5)-Me(4)C(5))(tBuN)](2-)) has been elucidated by means of a reliable DFT method. The first survey of relevant elementary steps for the 1-methyl-(4E,6)-heptadienylamine substrate (1) and the [{Me(2)Si(eta(5)-Me(4)C(5))(tBuN)}Sm{N(TMS)(2)}] starting material (2) identified the following general mechanistic aspects of Ln-catalysed aminodiene IHC. The substrate-adduct 3-S of the active CGC-Ln-amidodiene compound represents the catalyst's resting state, but the substrate-free form 3' with a chelating amidodiene functionality is the direct precursor for cyclisation. This step proceeds with almost complete regioselectivity through exocyclic ring closure by means of a frontal trajectory, giving rise to the CGC-Ln-azacycle intermediate 4. Subsequent protonolysis of 4 is turnover limiting, whilst the ring-substituent diastereoselectivity is dictated by exocyclic ring closure. Unfavourable close interatomic contacts between the substrate's alpha-substituent and the catalyst backbone have been shown to largely govern the trans/cis selectivity. Substituents of sufficient bulk in the alpha-position of the substrate have been identified as being vital for stereochemical induction. The present study has indicated that the diastereoselectivity of ring closure can be considerably modulated. The variation of the lanthanide's ionic radius and introduction of extra steric pressure at the substrate's alpha-position and/or the CGC N centre have been identified as effective handles for tuning the selectivity. The quantification of these factors reported herein represents the first step toward the rational design of improved CGC-Ln catalyst architectures and will thus aid this process.     

Use of group 4 bis(sulfonamido) complexes in the intramolecular hydroamination of alkynes and allenes

Titanium tetrakis(amido) complexes catalyze the intramolecular hydroamination of alkynes and allenes more efficiently than Cp-based species. We report here that electron-withdrawing and sterically demanding bis(sulfonamido) ligands lead to enhanced catalytic activity. Zirconium analogues have also been prepared, and the tosyl-substituted complex 20 has been structurally characterized. As in the titanium series, bis(sulfonamido) zirconium catalysts are more efficient in the intramolecular hydroamination of allenes than bis(cyclopentadienyl) complex Cp(2)ZrMe(2) (23). Furthermore, these compounds transform 1,3-disubstituted aminoallenes with high stereoselectivity to the Z-allylamines and allow the hydroamination of a trisubstituted allene. Titanium bis(sulfonamido) imido complex 27 was synthesized. It converts aminoallene 10 to cylic imine 11 with a rate comparable to that of tetrakis(amide) 15, supporting the hypothesis of a catalytically active titanium imido intermediate.     

Mechanism of enyne metathesis catalyzed by Grubbs ruthenium-carbene complexes: a DFT study

The complete catalytic cycle of the reaction of alkenes and alkynes to dienes by Grubbs ruthenium carbene complexes has been modeled at the B3LYP/LACV3P**+//B3LYP/LACVP level of theory. The core structures of the substrates and the catalyst were used as models, namely, ethene, ethyne, hept-1-en-6-yne, (Me(3)P)(2)Cl(2)Ru=CH(2), and [C(2)H(4)(NMe)(2)C](Me(3)P)Cl(2)Ru=CH(2). Insight into the electronically most preferred mechanistic pathways was gained for both intermolecular as well as for intramolecular enyne metathesis. Alkene metathesis is predicted to proceed fast and reversible, while the insertion of the alkyne substrate is slower, irreversible, and kinetically regioselectivity determining. Ruthenacyclobut-2-ene structures do not exist as local minima in the catalytic cycle. Instead, vinylcarbene complexes are formed directly. The alkyne insertion step and the cycloreversion of 2-vinyl ruthenacyclobutanes feature comparable predicted overall barriers in intermolecular enyne metathesis. For intramolecular enyne metathesis, a noncyclic alkene fragment of the enyne substrate is first incorporated into the Grubbs catalyst by an alkene metathesis reaction. The subsequent insertion of the alkyne fragment then proceeds intramolecularly. Alkene association, cycloaddition, and cycloreversion to the diene product complex close the catalytic cycle. Rate enhancement by an ethene atmosphere (Mori's conditions) originates from a constantly higher overall alkene concentration that is necessary for the rate-limiting [2 + 2] cycloreversion step to the diene product complex.     

Mechanistic investigation of organolanthanide-mediated hydroamination of conjugated aminodienes: a comprehensive computational assessment of various routes for diene activation

The present computational mechanistic study comprehensively explores alternative scenarios for activation of the amine-linked diene C=C linkage toward C-N ring closure in intramolecular hydroamination of a prototypical aminodiene by a well-characterised lanthanocene-amido catalyst. Firstly, the non-insertive mechanism by Scott featuring ring closure with concomitant amino proton delivery onto the diene unit has been explored and key features have been defined. This scenario has been compared with the classical stepwise insertion mechanism that involves rapid substrate association/dissociation equilibria for the 3t-S1 resting state and also for azacycle intermediates 4s, 4a, facile and reversible exocyclic migratory diene insertion into the La-N(amido) σ-bond, linked to turnover-limiting La-C azacycle aminolysis. The Ln-N σ-bond insertive mechanism prevails for the examined intramolecular hydroamination of (4E,6)-heptadienylamine 1t by [Cp*(2)La-CH(TMS)(2)] starting material 2.The following aspects are in support of this mechanism: 1) the derived rate law is consistent with the observed empirical rate law; 2) the assessed effective barrier for turnover-limiting aminolysis does agree remarkably well with empirically determined Eyring parameters; 3) the ring-ether double-bond selectivity is consistently elucidated. This study reveals that the non-insertive mechanism is not achievable for the particular lanthanocene-amido catalyst and furthermore cannot account for the observed product spectrum. Notwithstanding of these findings, the non-insertive mechanism cannot be discarded a priori for intramolecular aminodiene hydroamination. Spatial demands around the lanthanide centre influence the two mechanisms differently. The Ln-N σ-bond insertive mechanism critically relies on a sufficiently accessible lanthanide and enhanced encumbrance renders cyclisation and aminolysis steps less accessible kinetically. It contrasts with the non-insertive mechanism, where greater lanthanide protection has a rather modest influence. The present study indicates that the non-insertive mechanism would prevail if the lanthanide centre were to be protected effectively against C=C bond approach. Notably, a different product spectrum would be expected for aminodiene hydroamination following the insertive or non-insertive route.     

Nickela‐electrocatalyzed Mild C−H Alkylations at Room Temperature

Direct alkylations of carboxylic acid derivatives are challenging and particularly nickel catalysis commonly requires high reaction temperatures and strong bases, translating into limited substrate scope. Herein, nickel‐catalyzed C?H alkylations of unactivated 8‐aminoquinoline amides have been realized under exceedingly mild conditions, namely at room temperature, with a mild base and a user‐friendly electrochemical setup. This electrocatalyzed C?H alkylation displays high functional group tolerance and is applicable to both the primary and secondary alkylation. Based on detailed mechanistic studies, a nickel(II/III/I) catalytic manifold has been proposed.     

Intramolecular hydrophosphination/cyclization of phosphinoalkenes and phosphinoalkynes catalyzed by organolanthanides: scope, selectivity, and mechanism

Organolanthanide complexes of the general type Cp'(2)LnE(TMS)(2) (Cp' = eta(5)-Me(5)C(5); Ln = La, Sm, Y, Lu; E = CH, N; TMS = SiMe(3)) serve as effective precatalysts for the rapid intramolecular hydrophosphination/cyclization of the phosphinoalkenes and phosphinoalkynes RHP(CH(2))(n)()CH=CH(2) (R = Ph, H; n = 3, 4) and H(2)P(CH(2))(n)C triple bond C-Ph (n = 3, 4) to afford the corresponding heterocycles and respectively. Kinetic and mechanistic data for these processes exhibit parallels to, as well as distinct differences from, organolanthanide-mediated intramolecular hydroamination/cyclizations. The turnover-limiting step of the present catalytic cycle is insertion of the carbon-carbon unsaturation into the Ln-P bond, followed by rapid protonolysis of the resulting Ln-C linkage. The rate law is first-order in [catalyst] and zero-order in [substrate] over approximately one half-life, with inhibition by heterocyclic product intruding at higher conversions. The catalyst resting state is likely a lanthanocene phosphine-phosphido complex, and dimeric [Cp'(2)YP(H)Ph](2) was isolated and cystallographically characterized. Lanthanide identity and ancillary ligand structure effects on rate and selectivity vary with substrate unsaturation: larger metal ions and more open ligand systems lead to higher turnover frequencies for phosphinoalkynes, and intermediate-sized metal ions with Cp'(2) ligands lead to maximum turnover frequencies for phosphinoalkenes. Diastereoselectivity patterns also vary with substrate, lanthanide ion, and ancillary ligands. Similarities and differences in hydrophosphination vis-à-vis analogous organolanthanide-mediated hydroamination are enumerated.     

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.     

Organolanthanide-mediated intermolecular hydroamination of 1,3-dienes: mechanistic insights from a computational exploration of diverse mechanistic pathways for the stereoselective hydroamination of 1,3-butadiene with a primary amine supported by an ansa-neodymocene-based catalyst

The complete catalytic reaction course for the organolanthanide-mediated intermolecular hydroamination of 1,3-butadiene and n-propylamine by an archetypical [Me2Si(eta5-Me4C5)2NdCH(SiMe3)2] precatalyst was critically scrutinized by employing a reliable gradient-corrected DFT method. A free-energy profile of the overall reaction is presented that is based on the thorough characterization of all crucial elementary steps for a tentative catalytic cycle. A computationally verified, revised mechanistic scenario is proposed which is consistent with the experimentally derived empirical rate law and accounts for crucial experimental observations. It involves kinetically mobile reactant association/dissociation equilibria and facile, reversible intermolecular diene insertion into the Nd-amido bond, linked to turnover-limiting protonolysis of the eta3-butenyl-Nd functionality. The computationally predicted effective kinetics (Delta(tot) = 11.3 kcal mol(-1), Delta(tot) = -35.7 e.u.) are in reasonably good agreement with experimental data for the thoroughly studied hydroamination of alkynes. The thermodynamic and kinetic factors that determine the almost complete regio- and stereoselectivity of the mechanistically diverse intermolecular 1,3-diene hydroamination have been unraveled. The present computational study complements experiments because it allows, first, a more detailed understanding and a consistent rationalization of the experimental results for the hydroamination of 1,3-dienes and primary amines and, second, enhances the insights into general mechanistic aspects of organolanthanide-mediated intermolecular hydroamination.     

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.     

Mechanistic studies of Wacker-type intramolecular aerobic oxidative amination of alkenes catalyzed by Pd(OAc)2/pyridine

Wacker-type oxidative cyclization reactions have been the subject of extensive research for several decades, but few systematic mechanistic studies of these reactions have been reported. The present study features experimental and DFT computational studies of Pd(OAc)(2)/pyridine-catalyzed intramolecular aerobic oxidative amination of alkenes. The data support a stepwise catalytic mechanism that consists of (1) steady-state formation of a Pd(II)-amidate-alkene chelate with release of 1 equiv of pyridine and AcOH from the catalyst center, (2) alkene insertion into a Pd-N bond, (3) reversible β-hydride elimination, (4) irreversible reductive elimination of AcOH, and (5) aerobic oxidation of palladium(0) to regenerate the active trans-Pd(OAc)(2)(py)(2) catalyst. Evidence is obtained for two energetically viable pathways for the key C-N bond-forming step, featuring a pyridine-ligated and a pyridine-dissociated Pd(II) species. Analysis of natural charges and bond lengths of the alkene-insertion transition state suggest that this reaction is best described as an intramolecular nucleophilic attack of the amidate ligand on the coordinated alkene.     

Group IV Organometallic Compounds Based on Dianionic “Pincer” Ligands: Synthesis,Characterization, and Catalytic Activity in Intramolecular Hydroamination Reactions

Neutral Zr^IV and Hf^IV diamido complexes stabilized by unsymmetrical dianionic N,C,N′ pincer ligands have been prepared through the simplest and convenient direct metal‐induced C_aryl? H bond activation. Simple ligand modification has contributed to highlight the non‐innocent role played by the donor atom set in the control of the cyclometallation kinetics. The as‐prepared bis‐amido catalysts were found to be good candidates for the intramolecular hydroamination/cyclization of primary aminoalkenes. The ability of these compounds to promote such a catalytic transformation efficiently (by providing, in some cases, fast and complete substrate conversion at room temperature) constitutes a remarkable step forward toward catalytic systems that can operate at relatively low catalyst loading and under milder reaction conditions. Kinetic studies and substrate‐scope investigations, in conjunction with preliminary DFT calculations on the real systems, were used to elucidate the effects of the substrate substitution on the catalyst performance and to support the most reliable mechanistic path operative in the hydroamination reaction.     

Rhodium-catalyzed acylation with quinolinyl ketones: carbon-carbon single bond activation as the turnover-limiting step of catalysis

The rhodium-catalyzed intramolecular carboacylation of quinolinyl ketones serves as an ideal subject for the mechanistic study of carbon-carbon bond activation. Combined kinetic and NMR studies of this reaction allowed the identification of the catalytic resting state and determination of the rate law, (12)C/(13)C kinetic isotope effects, and activation parameters. These results have identified the activation of a ketone-arene carbon-carbon single bond as the turnover-limiting step of catalysis and provided quantitative detail into this process.     

Enantioselective Copper(I)/Chiral Phosphoric Acid Catalyzed Intramolecular Amination of Allylic and Benzylic C−H Bonds

Radical-involved enantioselective oxidative C−H bond functionalization by a hydrogen-atom transfer (HAT) process has emerged as a promising method for accessing functionally diverse enantioenriched products, while asymmetric C(sp³)−H bond amination remains a formidable challenge. To address this problem, described herein is a dual Cu^I/chiral phosphoric acid (CPA) catalytic system for radical-involved enantioselective intramolecular C(sp³)−H amination of not only allylic positions but also benzylic positions with broad substrate scope. The use of 4-methoxy-NHPI (NHPI=N-hydroxyphthalimide) as a stable and chemoselective HAT mediator precursor is crucial for the fulfillment of this transformation. Preliminary mechanistic studies indicate that a crucial allylic or benzylic radical intermediate resulting from a HAT process is involved.