Subsequent Migratory Insertion Research Articles

A Dual Cobalt-Photoredox Catalytic Approach for Asymmetric Dearomatization of Indoles with Aryl Amides via C-H Activation.

In this study, we unveil a novel method for the asymmetric dearomatization of indoles under cobalt/photoredox catalysis. By strategically activating C-H bonds of amides and subsequent migratory insertion of π-bonds present in indole as reactive partner, we achieve syn-selective tetrahydro-5H-indolo[2,3-c]isoquinolin-5-one derivatives with excellent yields and enantiomeric excesses of up to >99 %. The developed method operates without a metal oxidant, relying solely on oxygen as the oxidant and employing an organic dye as a photocatalyst under irradiation. Control experiments and stoichiometric studies elucidate the reversible nature of the enantiodetermining C-H activation step, albeit not being rate-determining. This study not only expands the horizon of cobalt-catalyzed asymmetric C-H bond functionalization, but also showcases the potential synergy between cobalt and photoredox catalysis in enabling asymmetric synthesis of complex molecules.

A Dual Cobalt‐Photoredox Catalytic Approach for Asymmetric Dearomatization of Indoles with Aryl Amides via C‐H Activation

In this study, we unveil a novel method for the asymmetric dearomatization of indoles under cobalt/photoredox catalysis. By strategically activating C‐H bonds of amides and subsequent migratory insertion of p‐bonds present in indole as reactive partner, we achieve syn‐selective tetrahydro‐5H‐indolo[2,3‐c]isoquinolin‐5‐one derivatives with excellent yields and enantiomeric excesses of up to >99%. The developed method operates without a metal oxidant, relying solely on oxygen as the oxidant and employing an organic dye as a photocatalyst under irradiation. Control experiments and stoichiometric studies elucidate the reversible nature of the enantiodetermining C‐H activation step, albeit not being rate‐determining. This study not only expands the horizon of cobalt‐catalyzed asymmetric C‐H bond functionalization, but also showcases the potential synergy between cobalt and photoredox catalysis in enabling asymmetric synthesis of complex molecules.

Mechanism and Origins of Regio- and Stereoselective Alkylboration of Endocyclic Olefins Enabled by Nickel Catalysis.

The Ni-catalyzed alkylboration of endocyclic olefins is a stereo- and regioselective approach for the synthesis of boron-containing compounds. We report a detailed density functional theory (DFT) study to elucidate the mechanism and origins of the stereo-, chemo-, and regioselectivity of alkylboration of endocyclic olefins enabled by nickel catalysis. The alkylboration proceeds via the migratory insertion of alkenes, β-H elimination of the Ni(II) complex, subsequent migratory insertion leading to a new Ni(II) complex, combined with an alkyl radical, and reductive eliminations. The electronic effects of the endocyclic olefins synergistically control the regioselectivity toward the C1- and C2-position boration. In C1-position boration, a more electron-deficient carbon atom tends to combine with an electron-rich -Bpin group and leads to C1-position boration products. The stereoselectivity is influenced by the solvent effect, and the interaction between the substrate and Ni-catalyzed groups, the low-polarity solvent 1,4-dioxane, and a favorable steric hindrance effect result in the cis-alkylboration product. Chemoselectivity toward 1,3-alkylboration results from the steric hindrance effects of the -Bpin group.

Migratory insertion of isocyanide into a ketenyl-tungsten bond as key step in cyclization reactions.

Treatment of the side-on tungsten alkyne complex of ethinylethyl ether [Tp*W(CO)2(η2-C,C′-HCCOCH2CH3)]+ {Tp* = hydridotris(3,4,5-trimethylpyrazolyl)borate} (2a) with n-Bu4NI afforded the end-on ketenyl complex [Tp*W(CO)2(κ1-HCCO)] (4a). This formal 16 ve complex bearing the prototype of a ketenyl ligand is surprisingly stable and converts only under activation by UV light or heat to form a dinuclear complex [Tp*2W2(CO)4(μ-CCH2)] (6). The ketenyl ligand in complex 4a underwent a metal template controlled cyclization reaction upon addition of isocyanides. The oxametallacycles [Tp*W(CO)2{κ2-C,O-C(NHXy)C(H)C(Nu)O}] {Nu = OMe (7), OEt (8), N(i-Pr)2 (9), OH (10), O1/2 (11)} were formed by coordination of Xy-NC (Xy = 2,6-dimethylphenyl) at 4a and subsequent migratory insertion (MI) into the W-ketenyl bond. The resulting intermediate is susceptible to addition reactions with protic nucleophiles. Compounds 2a-PF6, 4a/b, and 7–11 were fully characterized including XRD analysis. The cyclization mechanism has been confirmed both experimentally and by DFT calculations. In cyclic voltammetry, complexes 7–9 are characterized by a reversible W(ii)/W(iii) redox process. The dinuclear complex 11 however shows two separated redox events. Based on cyclic voltammetry measurements with different conducting electrolytes and IR spectroelectrochemical (SEC) measurements the W(ii)/W(iii) mixed valent complex 11+ is assigned to class II in terms of the Robin-Day classification.

Pd-Catalyzed Asymmetric Acyl-Carbamoylation of an Alkene to Construct an α-Quaternary Chiral Cycloketone.

Herein, we report the palladium-catalyzed asymmetric acyl-carbamoylation of an alkene by employing thioesters as the acyl electrophiles and t-BuNC as the carbamoyl reagent, affording an α-quaternary chiral cycloketone in synthetically useful yields with excellent enantioselectivity. The reaction proceeded via asymmetric 1,2-migratory insertions of acyl-Pd into alkenes and subsequent migratory insertion of isocyanides into C(sp3)-PdII. The product could be diversified to some valuable skeletons with retention of enantiopurity, demonstrating the synthetic utility of this protocol.

Palladium(0)‐Catalyzed Si—Si Bond Insertion by the Terminal Nitrogen of Diazo Compounds

AbstractThe palladium(0)‐catalyzed nitrogen insertion into cyclic Si—Si bonds has been realized by using N‐tosylhydrazones/diazo compounds as the nitrogen source. The palladium(II) nitrene formation and subsequent migratory insertion process are proposed as the key steps for this reaction.

Electronic Control on Linear versus Branched Alkylation of 2-/3-Aroylbenzofurans with Acrylates: Combined DFT and Synthetic Studies.

Investigations on the factors that govern unusual branched alkylation of 2-aroylbenzofurans with acrylates by Ru-catalyzed carbonyl-directed C-H activation has been carried out by calculating the kinetics associated with the two key steps-the coordination of the acrylate with the intermediate ruthenacycle and the subsequent migratory insertion reaction-studied with the help of DFT calculations. Eight possible orientations for each mode of alkylation have been considered for the calculations. From these calculations, it has been understood that there is a synergistic operation of the steric and electronic effects favoring the branched alkylation. Further DFT investigations on the alkylation of the isomeric 3-aroylbenzofurans indicated a preference for the linear alkylation and this has been verified experimentally. Overall, the observed/calculated complementary selectivity in the alkylation of 2-/3-aroylbenzofurans with acrylates reveals that the substrate-dependent charge distribution of the Ru-C bond in the intermediate ruthenacycle is an important determining factor and thus the current work opens up a new domain of substrate design for controlling regioselectivity.

ChemInform Abstract: Pd(0)‐Catalyzed Cross‐Coupling of Allyl Halides with α‐Diazocarbonyl Compounds or N‐Mesylhydrazones: Synthesis of 1,3‐Diene Compounds.

With palladium catalysis, allyl bromides or chlorides react with α-diazocarbonyl compounds or N-mesylhydrazones to afford 1,3-diene derivatives. The reaction represents a novel and efficient method for the synthesis of 1,3-butadiene derivatives. Mechanistically, the reaction is proposed to follow a pathway involving the formation of a π-allylic palladium carbene complex and subsequent migratory insertion.

How Does an Earth-Abundant Copper-Based Catalyst Achieve Anti-Markovnikov Hydrobromination of Alkynes? A DFT Mechanistic Study

The first catalytic hydrohalogenation of alkynes was recently achieved using a copper(I) N-heterocyclic carbene (NHC) complex, and the reaction was found to be syn and anti-Markovnikov selective. The present work is a density functional theory (DFT) computational study (B3LYP and M06) on the detailed mechanism of this remarkable catalytic reaction. The reaction begins with a phenoxide additive turning over the precatalyst (NHC)CuCl into (NHC)Cu(OAr), which subsequently transmetalates with the hydride source Ph2SiH2 to deliver the copper(I) hydride complex (NHC)CuH. (NHC)CuH undertakes hydrocupration of the substrate RC≡CH via alkyne coordination and subsequent migratory insertion into the Cu–H bond, forming (E)-(NHC)Cu(CH═CHR). The migratory insertion step determines the syn selectivity because it occurs by a concerted pathway, and it also determines the anti-Markovnikov regioselectivity that arises from the charge distributions across the Cu–H and C≡C bonds. The brominating agent (BrCl2C)2 uses the bromo...

Ruthenium(II)-catalyzed cross-dehydrogenative C–H alkenylations by triazole assistance

Ruthenium(II) carboxylate complexes allowed for efficient cross-dehydrogenative alkenylations of N-aryl-1,2,3-triazoles. The twofold C–H functionalizations occurred with excellent chemo-, regio-, site- and diastereoselectivities, and ample substrate scope. The versatile ruthenium(II) catalyst proved tolerant of moisture, air, and various electrophilic functional groups. Mechanistic studies were in good agreement with an initial C–H metalation by a cationic ruthenium(II) carboxylate, along with a subsequent migratory insertion of the olefin.

Copper(I)‐Catalyzed Alkylation of Polyfluoroarenes through Direct CH Bond Functionalization

AbstractThe copper(I)‐catalyzed alkylation of electron‐deficient polyfluoroarenes with N‐tosylhydrazones and diazo compounds has been developed. This reaction uses readily available starting materials and is operationally simple, thus representing a practical method for the construction of C(sp2)C(sp3) bonds with polyfluoroarenes through direct CH bond functionalization. Mechanistically, copper(I) carbene formation and subsequent migratory insertion are proposed as the key steps in the reaction pathway.

Copper(I)-catalyzed alkylation of polyfluoroarenes through Direct C-H bond functionalization.

The copper(I)-catalyzed alkylation of electron-deficient polyfluoroarenes with N-tosylhydrazones and diazo compounds has been developed. This reaction uses readily available starting materials and is operationally simple, thus representing a practical method for the construction of C(sp(2) )-C(sp(3) ) bonds with polyfluoroarenes through direct C-H bond functionalization. Mechanistically, copper(I) carbene formation and subsequent migratory insertion are proposed as the key steps in the reaction pathway.

Mechanisms of syn-insertion of alkynes and allenes into gold-silicon bonds: a comprehensive experimental/theoretical study.

A detailed mechanistic study is reported for the syn-insertion of alkynes and allenes in the Au-Si bonds of complexes (R3P)Au-SiR'Ph2 (R = Ph, Me and R' = t-Bu, Ph). Kinetic experiments indicate that (i) the reaction is first-order in alkyne and gold silyl complex and (ii) it requires a rather low enthalpy of activation and a relatively large negative entropy of activation [ΔH(‡) = 13.7 (±1.6) kcal·mol(-1) and ΔS(‡) = -32.0 (±5.0) cal·mol(-1)·K(-1) for the reaction of (Ph3P)Au-Si(t-Bu)Ph2 with methyl propiolate], in line with a bimolecular associative transformation. The different mechanistic pathways have been explored by DFT calculations. Accordingly, the reaction is found to proceed via a two-step inner-sphere mechanism: (i) first, the alkyne coordinates to the gold silyl complex to form a π-complex; (ii) the subsequent migratory insertion step is rate determining and occurs in a concerted manner. Provided dispersion effects are taken into account (B97D functional), the enthalpy of activation estimated theoretically [ΔH(‡) = 11.5 kcal·mol(-1)] is in good agreement with that measured experimentally. The influence of the π substrate (methyl propiolate, dimethyl acetylene dicarboxylate, phenyl acetylene, ethyl 2,3-butadienoate) has been analyzed theoretically, and the regioselectivity of the insertion has been rationalized. In particular, the unexpected selectivity observed experimentally with the allene is shown to result from the insertion of the terminal nonactivated C═C double bond into the Au-Si bond of (Ph3P)Au-SiPh3, followed by an original isomerization (Au/Si exchange process). This study provides unambiguous evidence for coordination-insertion at gold and thereby strongly supports the possible occurrence of inner-sphere mechanisms during the functionalization of alkynes and allenes.

Mechanistic Study of Rhodium/xantphos-Catalyzed Methanol Carbonylation

Rhodium/iodide catalysts modified with the xantphos ligand are active for the homogeneous carbonylation of methanol to acetic acid using either pure CO or CO/H2. Residues from catalytic reactions contain a Rh(III) acetyl complex, [Rh(xantphos)(COMe)I2] (1), which was isolated and crystallographically characterized. The xantphos ligand in 1 adopts a “pincer” κ3-P,O,P coordination mode with the xanthene oxygen donor trans to the acetyl ligand. The same product was also synthesized under mild conditions from [Rh(CO)2I]2. Iodide abstraction from 1 in the presence of donor ligands (L = MeCN, CO) gives the cationic acetyl species [Rh(xantphos)(COMe)I(L)]+, whereas in CH2Cl2 migratory CO deinsertion gives [Rh(xantphos)(Me)I(CO)]+ (4), which reacts with H2 to liberate methane, as observed in catalytic reactions using syngas. A number of Rh(I) xantphos complexes have been synthesized and characterized. Oxidative addition of methyl iodide to the cation [Rh(xantphos)(CO)]+ is very slow but can be catalyzed by addition of an iodide salt, via a mechanism involving neutral [Rh(xantphos)(CO)I] (6). IR spectroscopic data and DFT calculations for 6 suggest the existence in solution of conformers with different Rh–O distances. Kinetic data and activation parameters are reported for the reaction of 6 with MeI, which proceeds by methylation of the Rh center and subsequent migratory insertion to give 1. The enhancement of nucleophilicity arising from a Rh- - -O interaction is supported by DFT calculations for the SN2 transition state. A mechanism for catalytic methanol carbonylation based on the observed stoichiometric reaction steps is proposed. A survey of ligand conformations in xantphos complexes reveals a correlation between P–M–P bite angle and M–O distance and division into two broad categories with bite angle <120° (cis) or >143° (trans).

Ni-catalyzed, ZnCl(2)-assisted domino coupling of enones, alkynes, and alkenes.

A Ni(0)/ZnCl(2) system effectively promotes the coupling of enones and alkene-tethered alkynes. In the reaction with 1,6-enynes, the oxidative cyclization of Ni(0) species on enones across the alkyne part followed by ZnCl(2)-promoted cleavage generates alkenylnickel intermediates. Subsequent migratory insertion of the tethered alkene occurs with 5-exo-cyclization. When the resulting sigma-alkylnickel intermediates have beta-hydrogen atoms, the reaction terminates by beta-hydrogen elimination to provide cyclopentane derivatives. On the other hand, a sigma-alkylnickel intermediate that does not have beta-hydrogen atoms undergoes the insertion of a second alkene unit to cause a domino effect via a three-fold C-C bond formation process with and without the cleavage of one C-C bond.

Polyene Cyclization by a Double Intramolecular Heck Reaction. A DFT Study

A density functional theory (DFT) model study has been carried out on the cyclization of aryl polyene triflate catalyzed by a Pd(II)-BINAP complex in a Heck type reaction. In the model study, the catalyst was represented by Pd(PH2(CH)4PH2), whereas the aryl polyene triflate substrate was simplified by replacing the dimethoxy naphthalene fragment with hydrogens. Formally, this cyclization reaction consists of an intramolecular Heck reaction with two olefin insertions, also known as a double or cascade Heck reaction. The postulated cationic pathway for aryl triflate substrates has been explored as the reaction mechanism. The study has mainly focused on the two migratory insertion steps, where the identity of the final reaction products is decided. At both steps two distinct insertions may occur: exo, or 1,2-insertion, and endo, or 2,1-insertion. The computation of the possible intermediates and transition states demonstrated that the first insertion is exo-selective, with an energy barrier of only 4.1 kcal/mol, while the second insertion is endo-selective, involving a much higher energy barrier of 22.8 kcal/mol. The calculated subsequent preference for exo and endo selectivity is in good agreement with qualitative experimental observation. According to our results, the main factor controlling the exo/endo selectivity, at both the thermodynamic and the kinetic levels, is the relative stability of the cyclic system resulting from the migratory insertion. Furthermore, a furan ring present in the substrate can play an important role by forming a stable and inert π-complex that is able to suppress subsequent migratory insertion steps. On the other hand, taking into account the solvent effects using a continuum model, we found that the exo/endo selectivity of the first insertion step is solvent-dependent. As the polarity of the solvent increases, the relative stability of the endo intermediate also increases, in good agreement with the available experimental data. The β-elimination steps affording the final reaction products were also investigated. The results show that the β-elimination on the endo intermediates is thermodynamically favored over the β-elimination on the exo intermediates. On the other hand, the results for the β-elimination on the endo intermediates show that this reaction is highly reversible.

Heavy-atom kinetic isotope effects, cocatalysts, and the propagation transition state for polymerization of 1-hexene using the rac-(C(2)H(4)(1-indenyl)(2))ZrMe(2) catalyst precursor.

Using 13C NMR techniques, the 12C/13C kinetic isotope effects (KIEs) for the polymerization of 1-hexene catalyzed by rac-(C2H4(1-indenyl)2)ZrMe2 in the presence of four different cocatalysts (tris(pentfluorophenyl)borane, tris(pentafluorophenyl)alane, anilinium tetrakis(pentafluorophenyl)borate, and methylalumoxane) have been determined. All cocatalysts yield similar KIEs within experimental uncertainty, with values of 1.009(1) and 1.017(2) at C1 and C2, respectively. Ab initio DFT computational modeling of the polymerization KIE indicates that alkene binding to the catalyst must be reversible, with the majority of the KIE developing in the subsequent migratory insertion reaction.

Intrinsic Aptitude of Cationic Methyl- and Ethylpalladium To Associate Ethylene and To Further Undergo Subsequent Migratory Insertion. A Theoretical Study

Density Functional Theory (DFT) calculations at the B3LYP level and PCI-80 calculations have been carried out for the following reaction sequence: (a) association of ethylene to cationic (σ-alkyl)palladium(II) complexes, forming a π-ethylene σ-alkyl intermediate, (b) subsequent migratory insertion, and (c) β-hydride elimination of the insertion product. Ethylene coordinates strongly to the “naked” complexes PdCH3+ and PdC2H5+ (43.9 kcal/mol and 36.0 kcal/mol respectively). Nitrogen ligands modify association exothermicity (or conversely dissociation endothermicity): Pd(NH3)2CH3+ (27.3 kcal/mol), Pd(NH3)2C2H5+ (14.9 kcal/mol) and Pd(CHNH)2CH3+ (29.8 kcal/mol), where (CHNH)2 is chelating diimine. Substantial agostic interaction between metal and β-hydrogens and differences in charge on palladium account for the differences. The migratory insertion step is endothermic for naked 12-electron (π-ethylene)(σ-alkyl)palladium complexes and exothermic for 16-electron complexes with two nitrogen ligands. Calculate...

Heterobinuclear Alkyl Complexes of Rhodium and Iridium. Migratory Insertion or Ir-to-Rh Migration of a Methyl Group in Reactions with Small Molecules

The reaction of [RhIr(CO)3(dppm)2] (dppm = Ph2PCH2PPh2) with methyl triflate yields [RhIr(CH3)(CO)3(dppm)2][CF3SO3] (2), having the methyl group and two terminal carbonyls on Ir and one carbonyl on Rh. An Ir → Rh dative bond is proposed, giving Rh+ a 16e square-planar configuration. Reaction of 2 with hydrogen at ambient temperature yields [RhIrH(CO)2(μ-H)2(dppm)2]+ and methane. At 0 °C the intermediate [RhIrH(CH3)(CO)2(μ-H)(dppm)2][CF3SO3] is observed which under H2 yields the trihydride species and CH4 upon warming. Protonation of 2 with HCl and CF3SO3H yields [RhIr(CH3)(CO)2(μ-H)(μ-Cl)(dppm)2]+ and [RhIr(CH3)(CO)2(μ-H)(μ-CO)(dppm)2]+2, respectively. The reaction of 2 with CO resulted in decomposition to several unidentified products. Reaction of 2 with CNtBu yields the iminoacyl product [RhIr(CO)2(μ-tBuNCMe)(dppm)2]+ via migratory insertion. Two intermediates in the formation of the iminoacyl species were identified at low temperature yielding some information about the subsequent migratory insertion. ...