Non-metallocene rare earth metal catalysts for the diastereoselective and enantioselective hydroamination of aminoalkenes

In this short review we summarize our work on new cyclopentadienyl-free rare earth metal catalysts for the diastereoselective and enantioselective hydroamination of aminoalkenes. Non-metallocene rare earth metal catalysts based on diamidoamine, biphenolate and binaphtholate ligands are readily available through alkane and amine elimination procedures. Diamidoamine yttrium complexes are efficient catalysts for the highly diastereoselective cyclization of 1-methyl-pent-4-enylamine to yield trans-2,5-dimethyl-pyrroldine with trans to cis ratios of up to 23:1. The X-ray crystal structural analysis of [((2,6-Et₂C₆H₃NCH₂CH₂)₂NMe)Y{N(SiMe₃)₂}] is reported in which yttrium is coordinated in a highly distorted tetrahedral fashion. 3,3′-Di-tert-butyl substituted biphenolate complexes tend to form phenolate-bridged hetero- and homochiral dimers. The low steric demand of the tert-butyl substituents resulted also in low enantioselectivities in hydroamination/cyclization reactions. Binaphtholate complexes with sterically more demanding tris(aryl)silyl substituents were more efficient catalysts; giving enantioselectivities of up to 83% ee. These catalysts could also be applied in kinetic resolution of chiral aminoalkenes giving k_rel values as high as 16. Catalyst activities strongly depend on the reactivity of the leaving group which is protolytically exchanged for the substrate during the initiation step. Complexes with bis(dimethylsilyl)amido ligand initiate rather sluggishly because of the low basicity of this amido ligand and appreciable catalytic activity is only observed at elevated temperatures. Aryl and Alkyl complexes showed significant better rates comparable in magnitude to lanthanocene catalysts.     

Computational Mechanistic Insights on Homogeneous Water Oxidation Versus Catalyst Deactivation: A Case Study with Mononuclear Nickel and Copper Complexes

Water splitting is a potential pathway for hydrogen gas evolution and thereby realization of a carbon-neutral sustainable energy scheme. However, oxidation of water to dioxygen is the major impediment in conversion of solar energy to fuel. Herein, density functional studies are conducted to explore the reactivity conduits of two molecular electro-catalysts consisting of nickel and copper tetra-anionic tetradentate amide ligand complexes of the type [(L1)M^II]²⁻, where L1=o-phenylenebis(oxamidate), and their substitutionally modified analogues. While nickel complexes demonstrate complex borderline chemistry between homogeneous and heterogeneous pathways, showing competition between water oxidation and molecular species degradation, copper complexes display robust and efficient molecular water oxidation behavior. Our analysis predict that this disparity is primarily due to the reversible O−O bond formation in nickel complexes, which provide the platform necessary for a direct attack of OH⁻/H⁺ on the metal and terminally accessible amidate groups of the 2e⁻ oxidized anionic intermediate, [(L1⋅)Ni^III(OH)]¹⁻, respectively. This intermediate streamline ligand deactivation with a comparatively higher driving force for nickel complexes in acidic medium. Contrarily, the copper complexes display radical character on the hydroxyl ligand in the corresponding intermediate, [(L1⋅)Cu^II(OH⋅)]¹⁻, that expedite O−O interaction, leading to predominant homogeneous water oxidation under all conditions.     

Comparison of dppf‐Supported Nickel Precatalysts for the Suzuki–Miyaura Reaction: The Observation and Activity of Nickel(I)

Ni‐based precatalysts for the Suzuki–Miyaura reaction have potential chemical and economic advantages compared to commonly used Pd systems. Here, we compare Ni precatalysts for the Suzuki–Miyaura reaction supported by the dppf ligand in 3 oxidation states, 0, I and II. Surprisingly, at 80 °C they give similar catalytic activity, with all systems generating significant amounts of Ni^I during the reaction. At room temperature a readily accessible bench‐stable Ni^II precatalyst is highly active and can couple synthetically important heterocyclic substrates. Our work conclusively establishes that Ni^I species are relevant in reactions typically proposed to involve exclusively Ni⁰ and Ni^II complexes.     

An easy-to-use, regioselective, and robust bis(amidate) titanium hydroamination precatalyst: mechanistic and synthetic investigations toward the preparation of tetrahydroisoquinolines and benzoquinolizine alkaloids

Amidate-supported titanium amido complexes are efficient and regioselective precatalysts for intermolecular hydroamination of terminal alkynes with primary amines. The synthesis and characterization of the first bis(amidate)-supported titanium-imido complex is reported. Its role as the active catalytic species is suggested in the course of product distribution studies using deuterated substrates. The bis(amidate)-supported precatalysts exhibit good functional-group tolerance, even performing hydroaminations in the presence of ester and amide groups. This functional-group tolerance was exploited in the synthesis of a variety of 1-substituted tetrahydroisoquinoline alkaloids and a one-pot hydroaminative procedure for the high yielding preparation of the benzo[a]quinolizine skeleton.     

Palladium Complexes Based on Ylide-Functionalized Phosphines (YPhos): Broadly Applicable High-Performance Precatalysts for the Amination of Aryl Halides at Room Temperature

Palladium allyl, cinnamyl, and indenyl complexes with the ylide-substituted phosphines Cy₃P⁺−C⁻(R)PCy₂ (with R=Me ( L1 ) or Ph ( L2 )) and Cy₃P⁺−C⁻(Me)PtBu₂ ( L3 ) were prepared and applied as defined precatalysts in C−N coupling reactions. The complexes are highly active in the amination of 4-chlorotoluene with a series of different amines. Higher yields were observed with the precatalysts in comparison to the in situ generated catalysts. Changes in the ligand structures allowed for improved selectivities by shutting down β-hydride elimination or diarylation reactions. Particularly, the complexes based on L2 (joYPhos) revealed to be universal precatalysts for various amines and aryl halides. Full conversions to the desired products are reached mostly within 1 h reaction time at room temperature, thus making L2 to one of the most efficient ligands in C−N coupling reactions. The applicability of the catalysts was demonstrated for aryl chlorides, bromides and iodides together with primary and secondary aryl and alkyl amines, including gram-scale applications also with low catalyst loadings of down to 0.05 mol %. Kinetic studies further demonstrated the outstanding activity of the precatalysts with TOF over 10.000 h⁻¹.     

Optically active, bulky tris(oxazolinyl)borato magnesium and calcium compounds for asymmetric hydroamination/cyclization

The synthesis of the new chiral, pseudo C₃-symmetric, monoanionic ligand tris(4S-tert-butyl-2-oxazolinyl)phenylborate [To^T]⁻ is reported. The steric bulk, tridentate coordination, and anionic charge of [To^T]⁻ are suitable for formation of complexes of the type To^TMX, where one valence is available for reactivity. With this point in mind, we prepared magnesium and calcium To^T complexes that resist redistribution to (To^T)₂M compounds. Both To^TMgMe and To^TCaC(SiHMe₂)₃ contain tridentate To^T-coordination to the metal center, as shown by NMR spectroscopy, infrared spectroscopy, and X-ray crystallography. These compounds are active catalysts for the cyclization of three aminoalkenes to pyrrolidines, and provide non-racemic mixtures of pyrrolidines in enantiomeric excesses up to 36%.     

Asymmetric hydroamination/cyclization catalyzed by group 4 metal complexes with chiral biaryl-based ligands

Group 4 metal complexes based on chiral biaryl ligands are readily prepared by a convenient amine elimination procedure, and they are efficient catalysts for the asymmetric hydroamination/cyclization of aminoalkenes. The biaryl-based ligands are highly modular enabling facile tuning of the catalyst reactivity and selectivity. The corresponding heterocyclic products have been obtained in excellent enantiomeric excesses (up to 93%) using sterically hindered C₂-symmetric titanium and zirconium mesitoylamidate complexes such as [1,1′-(C₁₀H₁₀)₂-2,2′-{NCO(2,4,6-Me₃C₆H₂)}₂]M(NMe₂)₂ (M = Ti, Zr). These results are presented in this short review.     

Heteroleptic Alkyl and Amide Iminoanilide Alkaline Earth and Divalent Rare Earth Complexes for the Catalysis of Hydrophosphination and (Cyclo)Hydroamination Reactions

[{N^N}M(X)(thf)_n] alkyl (X=CH(SiMe₃)₂) and amide (X=N(SiMe₃)₂) complexes of alkaline earths (M=Ca, Sr, Ba) and divalent rare earths (Yb^II and Eu^II) bearing an iminoanilide ligand ({N^N}^?) are presented. Remarkably, these complexes proved to be kinetically stable in solution. X‐ray diffraction studies allowed us to establish size–structure trends. Except for one case of oxidation with [{N^N}Yb^II{N(SiMe₃)₂}(thf)], all these complexes are stable under the catalytic conditions and constitute effective precatalysts for the cyclohydroamination of terminal aminoalkenes and the intermolecular hydroamination and intermolecular hydrophosphination of activated alkenes. Metals with equal sizes across alkaline earth and rare earth families display almost identical apparent catalytic activity and selectivity. Hydrocarbyl complexes are much better catalyst precursors than their amido analogues. In the case of cyclohydroamination, the apparent activity decreases with metal size: Ca>Sr>Ba, and the kinetic rate law agrees with R_CHA=k[precatalyst]¹[aminoalkene]¹. The intermolecular hydroamination and hydrophosphination of styrene are anti‐Markovnikov regiospecific. In both cases, the apparent activity increases with the ionic radius (Ca<Sr<Ba) but the rate laws are different, and obey R_HA=k[styrene]¹[amine]¹[precatalyst]¹ and R_HP=k[styrene]¹[HPPh₂]⁰[precatalyst]¹, respectively. Mechanisms compatible with the rate laws and kinetic isotopic effects are proposed. [{N^N}Ba{N(SiMe₃)₂}(thf)₂] ( 3 ) and [{N^N}Ba{CH(SiMe₃)₂}(thf)₂] ( 10 ) are the first efficient Ba‐based precatalysts for intermolecular hydroamination and hydrophosphination, and display activity values that are above those reported so far. The potential of the precatalysts for C? N and C? P bond formation is detailed and a rare cyclohydroamination–intermolecular hydroamination “domino” sequence is presented.     

Synthesis, structure, and catalytic activity of organolanthanides with chiral biphenyl-based tridentate amidate ligands

Four new chiral organolanthanide amidate complexes have been readily prepared in good yields via silylamine elimination reaction between Ln[N(SiMe₃)₂]₃ (Ln = Sm, Y, Yb) and chiral amidate ligands, (R)-2-(mesitoylamino)-2′-methoxy-6,6′-dimethyl-1,1′-biphenyl (1H) and (R)-2-(mesitoylamino)-2′-dimethylamino-6,6′-dimethyl-1,1′-biphenyl (2H). The steric effect of the ligand coupled with the size effect of the lanthanide ion plays an important role in complex formation. For example, treatment of 1H with half equiv of Sm[N(SiMe₃)₂]₃ gives the C₂-symmetric bis-ligated amidate complex (σOMe:κO:κN-1)₂SmN(SiMe₃)₂ (3) in 75% yield, while reaction of 1H or 2H with half equiv of Ln[N(SiMe₃)₂]₃ (Ln = Y, Yb) affords the C₁-symmetric bis-ligated amidate complexes [(κO:κN-1)(σOMe:κO:κN-1)]LnN(SiMe₃)₂ (Ln = Y (4), Yb (5) and the C₁-symmetric mono-ligated amidate complex (σNMe₂:κO:κN-2)Y[N(SiMe₃)₂]₂ (6), respectively, in good yields. These organolanthanide amidate complexes have been characterized by various spectroscopic techniques, elemental analyses, and X-ray diffraction analyses. They are active catalysts for asymmetric hydroamination/cyclization of aminoalkenes and ring-opening polymerization of rac-lactide, affording cyclic amines in excellent conversions with good ee values and isotactic-rich polylactides, respectively.     

Group 4 Complexes Bearing Pyrrolide Ligand for Intramolecular Alkene Hydroamination and Activation of C≡N Bond

Titanium and zirconium complexes supported by a pyrrolide ligand HL¹ [HL¹ = 2‐cyano‐1H‐pyrrole], Ti₂(L²)₂(NMe₂)₂ ( 1 ) and Zr₃(L²)₃(NMe₂)₆ ( 2 ) [L² = N,N‐dimethyl‐1H‐pyrrol‐2‐carboximidamide, NMe₂‐L¹] were synthesized and characterized. The ligand L² was generated by activation of C≡N bond of HL¹ with HNMe₂. In complex 1 , two Ti^IV atoms are bridged by two nitrogen atoms. There are three characteristic Zr^IV ions in 2 , which are six‐, seven‐ and six‐coordinate, respectively. They were tested as catalysts for the intramolecular hydroamination of aminoalkenes, and the respective N‐heterocycles were afforded in 74–99 % yields. Moreover, the formation of L² ligand indicates that the amination of C≡N bond can be considered as a new and rapid way to synthesize other C–N bonds.     

Ruthenium (II) complexes bearing thioether-appended α-iminopyridine ligands: Arene precursors permit access to κ2-N,N and κ3-N,N,S complexes

Herein we report the preparation of a series of Ru(II) complexes featuring α-iminopyridine ligands bearing thioether functionality (NNS^R, where R = Me, CH₂Ph, Ph). Metallation using [(p-cymene)RuCl]₂ permits access to Ru complexes with a κ²-N,N donor set in which the thioether moiety remains uncoordinated. In the presence of a strong field ligand such as acetonitrile or triphenylphosphine, the p-cymene moiety is displaced, and the ligand adopts a κ³-N,N,S binding mode. These complexes are characterized using a combination of solution and solid state methods, including the crystal structure of [(NNS^Me)Ru (NCMe)₂Cl]Cl. The κ²-N,N-Ru(II) complexes are shown to serve as efficient precatalysts for the oxidation of sec-phenethyl alcohol at modest loadings (alcohol: Ru = 20:1), using a variety of external oxidants and solvents. The complex bearing an S-Ph donor was found to be the most active oxidation catalyst of those surveyed, suggesting that the thioether donor plays an active role in the catalytic cycle.     

Carbocyclic carbene ligands in palladium-catalyzed C-N coupling reactions

Palladium complexes bearing a cycloheptatrienylidene ligand are powerful precatalysts for C-N coupling reactions. Their catalytic performance is directly compared to analogous 2,3-diphenylcyclopropenylidene complexes. The crystal structure of cis-dibromo(cycloheptatrienylidene)(triphenylphosphane)palladium(II) is presented.     

Highly enantioselective hetero-Diels-Alder reaction between trans-1-methoxy-2-methyl-3-trimethylsiloxybuta-1,3-diene and aldehydes catalyzed by (R)-BINOL-Ti(IV) complex

An efficient enantioselective approach to 2,5-disubstituted dihydropyrones was developed. Some easily accessible inexpensive diol ligand metal complexes were employed, and [(R)-BINOL]₂-Ti(OiPr)₄ complex was found to be the most effective catalyst (up to 99% yield and 99% ee in the presence of 5 mol% catalyst) for the hetero-Diels-Alder reaction between trans-1-methoxy-2-methyl-3-trimethylsiloxybuta-1,3-diene (1) and aldehydes. The potential and generality of this catalyst were evaluated by a variety of aldehydes including aromatic, heteroaromatic, α,β-unsaturated and aliphatic aldehydes. Based on the isolated intermediate from the reaction of benzaldehyde being confirmed by ¹H, ¹³C NMR and HRMS data, the mechanism was proposed as a Mukaiyama aldol pathway.     

Yttrium (amidate) complexes for catalytic C-N bond formation. Rapid, room temperature amidation of aldehydes

Yttrium (amidate) precatalysts are highly active for the mild amidation of aldehydes with amines. Reactions occur at room temperature within 5 min in up to 98% isolated yield. These rare-earth systems are effective for this transformation in the absence of supplementary heat, light, base, or oxidants. The reaction proceeds with functionalized amines and/or aldehydes. A comparison of various amidate precatalysts in combination with reaction monitoring suggests that the targeted amide products formed during the reaction promote the formation of alternative catalytically active amidate species in situ.     

Volatile zirconium complexes with sterically hindered β-diketonates: Structure and thermal properties

The structure and thermal properties of a novel zirconium(IV) complex with a methoxy substituted β-diketonate ligand tetrakis-(2-methoxy-2,6,6-trimethylheptane-3,5-dionato)zirconium are described. The complex sublimes without decomposition under low pressure (10^–2 Torr) at 200 °C. The crystal structure of the complex is molecular and is composed of two structural Zr(zis)₄ isomers in a 1:1 ratio. The crystallographic data are as follows: C₈₈H₁₅₂F₂₄O₂₄Zr₂, P-1, a = 12.1350(7) Å, b = 19.7733(10) Å, c = 21.0526(12) Å, α = 83.338(2)°, β = 89.571(2)°, γ = 73.515(2)°, V = 4809.5(5) ų, Z = 2, d = 1.227 g/cm³. The coordination environment of the zirconium atom consists of eight oxygen atoms from four β-diketonate ligands; the coordination polyhedron is a square antiprism. The Zr–O distances are in a range 2.127-2.202 Å. The thermal properties of the complex are studied by TG–DTA. The effect of the crystal structure (molecular packing) on the volatility and thermal properties is compared for the new complex and two other analogous zirconium complexes with β-diketonate ligands containing bulky terminal substituents. The results of the mass spectrometric study of thermal behavior of the complexes on programmed heating of vapor under the conditions similar to those in a hot wall CVD reactor under low pressure, including the decomposition in the presence of oxygen, are discussed.     

Intermolecular hydroamination of oxygen-substituted allenes. New routes for the synthesis of N,O-chelated zirconium and titanium amido complexes

Intermolecular hydroamination of heteroatom-substituted allenes with a bulky arylamine was carried out using a bis(amidate) bis(amido) titanium(IV) complex (1) as a precatalyst. The reaction of 2,6-dimethylaniline with oxygen-substituted allene 2c or 2d in the presence of complex 1 gives the ketimine regioisomer as the exclusive product. Reduction of such ketimine products resulted in the formation of amino ethers that were further employed as proligands for the formation of N,O-chelating five-membered titana- and zirconacycles. Such sterically demanding N,O-chelating ligands result in the high-yielding preparation of mono-ligated products. Solid-state molecular structures of all the complexes revealed distorted trigonal bipyramidal geometry about the metal centers, with a dative bond between the metal and the oxygen donor atom. These new complexes obtained using hydroamination as the key-step in ligand preparation were also shown to be useful cyclohydroamination precatalysts in their own right.     

Metal-ligand bonding in benzeneseleninato complexes of p- and d-block metals

Summary New complexes of lead(II) and zirconium(IV) withmeta-andpara-substituted benzeneseleninic acids are reported and characterized by chemical analyses, spectroscopic methods and conductivity and magnetic measurements. The complexes are of the Pb(XC₆H₄SeO₂)₂ and ZrO(XC₆H₄SeO₂)₂ type; for zirconium(IV), working with a 1:4 metal:ligand stoichiometrical ratio, invariably the oxy derivative was obtained. The i.r. spectral data suggest that the complexes contain RSeO ₂ ^– ligands acting as bidentate in O,O-seleninato complexes, Where possible, a tentative stereochemistry for the complexes is discussed on the basis of the results obtained.     

2-Electron reduction of N2O yields a new ligand binding mode: N-Nitrosoimide

A new mode of bonding of the traditionally weak ligand N₂O to highly reducing transition metal complexes is described based on DFT calculations for a variety of late transition metals. These η¹-NNO can be singly bent (at the central nitrogen) or doubly bent (at both N), and thus involve a triple or double M/N bond, respectively. The ligand is therefore properly termed an N-nitrosoimide, N₂O²⁻.     

Providing Support in Favor of the Existence of a PdII/PdIV Catalytic Cycle in a Heck‐Type Reaction

The complex [Pd(O,N,C‐L)(OAc)], in which L is a monoanionic pincer ligand derived from 2,6‐diacetylpyridine, reacts with 2‐iodobenzoic acid at room temperature to afford the very stable pair of Pd^IV complexes (OC‐6‐54)‐ and (OC‐6‐26)‐[Pd(O,N,C‐L)(O,C‐C₆H₄CO₂‐2)I] (1.5:1 molar ratio, at ?55 °C). These complexes and the Pd^II species [Pd(O,N,C‐L)(OX)] and [Pd(O,N,C‐L′)(NCMe)]ClO₄, (X=MeC(O) or ClO₃, L′=another monoanionic pincer ligand derived from 2,6‐diacetylpyridine), are precatalysts for the arylation of CH₂?CHR (R?CO₂Me, CO₂Et, Ph) using IC₆H₄CO₂H‐2 and AgClO₄. These catalytic reactions have been studied and a tentative mechanism is proposed. The presence of two Pd^IV complexes was detected by ESI(+)‐MS during the catalytic process. All the data obtained strongly support a Pd^II/Pd^IV catalytic cycle.     

A Multi-Technique Investigation of the Complex Formation Equilibria between Bis-Deferiprone Derivatives and Oxidovanadium (IV)

The increasing biomedical interest in high-stability oxidovanadium(IV) complexes with hydroxypyridinone ligands leads us to investigate the complex formation equilibria of V^IVO²⁺ ion with a tetradentate ligand, named KC21, which contains two 3-hydroxy-1,2-dimethylpyridin-4(1H)-one (deferiprone) moieties, and with the simple bidentate ligand that constitutes the basic unit of KC21, for comparison, named L5. These equilibrium studies were conducted with joined potentiometric–spectrophotometric titrations, and the results were substantiated with EPR measurements at variable pH values. This multi-technique study gave evidence of the formation of an extremely stable 1:1 complex between KC21 and oxidovanadium(IV) at a physiological pH, which could find promising pharmacological applications.