Imine Insertion Research Articles

Theoretical investigation of the nickel-catalyzed Mizoroki-Heck/Amination reaction towards the synthesis of biologically active Indolo[2,1-a] isoquinolines derivatives

Density functional theory (DFT) was employed to computationally investigate the nickel-catalyzed Mizoroki-Heck/amination cascade reaction of o-dihaloarenes with cyclic imines. The computational results reveal that this reaction proceeds via the generation of a sterically bulky N-heterocylcic carbene ligand-coordinated Ni(0) active catalyst, which triggers the Ni(0)-Ni(II)-Ni(0) catalytic cycle. Furthermore, during the cyclic imine insertion, the formation of hydrogen bond (NH…Cl) plays a pivotal role in facilitating the reaction. Additionally, theoretical analysis elucidates the origin of high regioselectivity and provides valuable insights for experiments and theoretical research in the future.

An alternative non-redox Ni(I) pathway in hydroaminomethylation: A theoretical perspective

Herein, we report a theoretical investigation on the nickel-catalyzed hydroaminomethylation reaction of alkyne with imine. In this work, an alternative Ni(I) mechanism, without a redox reaction, was proposed by DFT calculations. The mechanism based on these calculations is favorable compared with the previously proposed redox Ni(0)-Ni(II) pathway. A Ni(I)-amino complex is considered to be the active species, which can be obtained from hydrogen transfer between an imine-coordinated Ni(0) complex and an amine. A Meerwein-Ponndorf type hydride transfer takes place between an amino group and a coordinated alkyne. Then an imine insertion affords Ni(I)-allylamino. Proton transfer with the approaching imine yields the hydroaminomethylation product and regenerates the Ni(I)-amino active species. Throughout the catalytic cycle, the oxidative state of Ni remains at +1. Furthermore, AIM analysis shows that the dissociation of the amine ligand to provide a vacancy would lead to a higher free-energy barrier for the Ni(0)-Ni(II) pathway.

LiAlH4‐catalyzed Imine Hydrogenation with Dihydrogen: New DFT Mechanistic Insights

AbstractRecently, it was found that the widely used stoichiometric reducing reagent LiAlH4 can also be used as a useful catalyst for imine hydrogenation with H2 under relatively mild conditions. In this work, extensive state‐of‐the‐art DFT calculations are conducted to explore the detailed catalytic mechanism. In sharp contrast to the recent proposal involving heterolytic H2‐activation over Al−N amide bonds after multiple imine insertion, our new mechanism highlights the dual role of the Lewis‐acidic lithium cation in frustrated‐Lewis‐pair‐like activation of both imine substrate and H2 when combined with the aluminum‐bound hydride and amide ligands, respectively. Ionic Li−N amide bonds are about 13 kcal/mol more reactive than Al−N amide bonds for H2 activation, thus providing a useful structural feature for rational design of active hydrogenation catalysts.

Insights into LiAlH4 Catalyzed Imine Hydrogenation.

Commercial LiAlH4 can be used in catalytic quantities in the hydrogenation of imines to amines with H2. Combined experimental and theoretical investigations give deeper insight in the mechanism and identifies the most likely catalytic cycle. Activity is lost when Li in LiAlH4 is exchanged for Na or K. Exchanging Al for B or Ga also led to dramatically reduced activities. This indicates a heterobimetallic mechanism in which cooperation between Li and Al is crucial. Potential intermediates on the catalytic pathway have been isolated from reactions of MAlH4 (M=Li, Na, K) and different imines. Depending on the imine, double, triple or quadruple imine insertion has been observed. Prolonged reaction of LiAlH4 with PhC(H)=NtBu led to a side‐reaction and gave the double insertion product LiAlH2[N]2 ([N]=N(tBu)CH2Ph) which at higher temperature reacts further by ortho‐metallation of the Ph ring. A DFT study led to a number of conclusions. The most likely catalyst for hydrogenation of PhC(H)=NtBu with LiAlH4 is LiAlH2[N]2. Insertion of a third imine via a heterobimetallic transition state has a barrier of +23.2 kcal mol−1 (ΔH). The rate‐determining step is hydrogenolysis of LiAlH[N]3 with H2 with a barrier of +29.2 kcal mol−1. In agreement with experiment, replacing Li for Na (or K) and Al for B (or Ga) led to higher calculated barriers. Also, the AlH4 − anion showed very high barriers. Calculations support the experimentally observed effects of the imine substituents at C and N: the lowest barriers are calculated for imines with aryl‐substituents at C and alkyl‐substituents at N.

Formal Insertion of Imines (or Nitrogen Heteroarenes) and Arynes into the C–Cl Bond of Carbon Tetrachloride

The formal insertion of double and triple bonds into the C-Cl bond of carbon tetrachloride has enabled the full utilization of carbon tetrachloride in chemical synthesis. A range of unactivated imines and electron-deficient nitrogen heteroarenes served as effective sources of C=N bonds to react with arynes and carbon tetrachloride to afford functionalized anilines whose core structures are present in some valuable arthropodicides. Control experiments and DFT calculations suggest the involvement of a trichloromethyl anion intermediate.

Nonchelated Phosphoniomethylidene Complexes of Scandium and Lutetium.

The first phosphoniomethylidene complexes of scandium and lutetium, [LLn(CHPPh3)X] (L = [MeC(NDIPP)CHC(NDIPP)Me]-; Ln = Sc, X = Me, I, TfO; Ln = Lu, X = CH2SiMe3), have been synthesized and fully characterized. DFT calculations clearly demonstrate the presence of an allylic Ln, C, P π-type interaction in these complexes. X-ray diffraction indicates that the scandium iodide complex has the shortest Sc-C bond length to date (2.044(5) Å). These phosphoniomethylidene complexes readily convert into the ylide complexes, and the reactivity is affected by both X- anion and Ln3+ ion. The reaction of lutetium complex with imine shows a rapid insertion of imine into the Lu-C(alkylidene) bond. DFT calculations indicate that, although the bonding situation seems similar to that of the scandium analog, the strong negative charge at the alkylidene carbon is not sufficiently screened by one hydrogen in the lutetium complex because of a more ionic bonding, and therefore, the reactivity of the lutetium complex is much higher.

Mechanism, Regio-, and Diastereoselectivity of Rh(III)-Catalyzed Cyclization Reactions of N-Arylnitrones with Alkynes: A Density Functional Theory Study.

Nitrones have been used for rhodium-catalyzed cyclization C-H bond activation and O atom transfer of arylnitrones with alkynes by Chang et al. ( J. Am. Chem. Soc. 2015 , 137 , 4908 - 4911 ). Density functional theory method has been used to study the mechanism, regio-, and diastereoselectivity of type reactions. The results elucidated that the reaction pathway for Rh(III)-catalyzed cyclization of N-arylnitrones with alkyne contains a C-H bond activation, an alkyne insertion into Rh-C bond, a reductive elimination to form a Rh(I) complex, an oxidative addition leading to N-O cleavage, an imine insertion into the Rh-C bond, and the final protonolysis to regenerate the products and the active catalyst. The regioselectivity of this reaction with asymmetric alkyne is controlled by the electronic effect in alkyne insertion type instead of steric effects. The distortion-interaction analysis is also used to explain the regioselectivity. The diastereoselectivity is controlled by the imine insertion step. In this step, the sterically less hindered transition state is favored, leading to stereoselective product formation.

ChemInform Abstract: Insertion of Imines into Vinylcyclopropanes Catalyzed by Nucleophilic Iron Complexes: A Formal [3 + 2]‐Cycloaddition Strategy for the Synthesis of Substituted Pyrrolidine Derivatives.

Pyrrols are substructures in various biological active molecules. A straightforward iron-catalyzed synthesis of pyrrols via insertion of an imine into a vinylcyclopropane is presented. The corresponding pyrrols are obtained in moderate to good yields. Scope and limitations will be discussed.

Insertion of Imines into Vinylcyclopropanes Catalyzed by Nucleophilic Iron Complexes: A Formal [3+2]-Cycloaddition Strategy for the Synthesis of Substituted Pyrrolidine Derivatives

Pyrrols are substructures in various biological active molecules. A straightforward iron-catalyzed synthesis of pyrrols via insertion of an imine into a vinylcyclopropane is presented. The corresponding pyrrols are obtained in moderate to good yields. Scope and limitations will be discussed.

Ruthenium(II)/N-heterocyclic carbene catalyzed [3+2] carbocyclization with aromatic N-H ketimines and internal alkynes.

Convenient and highly efficient: Indenamines were synthesized using the title reaction, which occurs at ambient temperature, in the absence of oxidants or other metal salts, and in nonpolar solvents. A proposed mechanism involves imine-directed activation of an aromatic CH bond, alkyne insertion, and carbocyclization by intramolecular imine insertion into Ru–alkenyl linkages.

Comparison of Imine to Olefin Insertion Reactions: Generation of Five- and Six-Membered Lactams via a Nickel-Mediated CO, Olefin, CO, Imine Insertion Cascade

Cationic nickel complexes of the form L2Ni(CH3)(RN═C(H)R)+ (L2 = bidentate nitrogen donor) have been probed for their ability to mediate olefin and imine migratory insertion reactions. While these complexes do not undergo alkene insertion into the nickel−methyl bond, the use of olefin-tethered imines CH2═CH(CH2)nN═C(R)aryl (n = 1−3; R = H, methyl, phenyl) and the addition of CO initiates competitive olefin and imine insertion into the in situ generated nickel−acyl complex. The insertion selectivity shows clear steric and electronic influences and suggests that strong imine coordination can allow it to compete with the more rapid insertion of alkenes. This reactivity has been employed to develop a CO/alkene/CO/imine insertion cascade to synthesize five- and six-membered-ring lactams.

Synthesis of neutral nickel–methyl complexes with monodentate imines and their sequential insertion of carbon monoxide and imine

Neutral nickel–imine complexes of the form (N^O)Ni(R)(R 1N C(H)R 2) (N^O = salicylaldiminato; R = CH 3, Ph; R 1 = alkyl; R 2 = aryl) can be prepared by the reaction of (tmeda)Ni(CH 3) 2, imine and the corresponding salicylaldiminato ligand. The addition of carbon monoxide to these complexes lead to the in situ generation of the corresponding nickel–acyl complexes. With N-methyl or N-benzyl substituted imines, these complexes reductively eliminate the phenolic and acyl ligands to generate esters. However, the less sterically encumbered 3,4-dihydroisoquinoline can couple with the nickel–acyl ligand to form 1,2-diamides in high yield. In situ 1H NMR analysis suggests this reaction occurs via insertion of imine into the nickel-acyl bond to form a nickel-bound amide complex. [Display omitted]

Palladium Iminoacyl Imine Complexes: Strategies toward Imine Insertion

The syntheses and characterization of a number of palladium complexes containing imine and/or iminoacyl groups are reported. Our strategies toward the insertion of imines into palladium iminoacyl complexes are outlined. The imine complexes [Pd(Me)(L2){N(R′)═C(H)Ph}]X (where L2 = dppe, dppp, dppf; R′ = Ph, Me, Bz; and X = BF4 or OTf) were prepared and fully characterized. [Pd(Me)(dppe){N(Ph)═C(H)Ph}]BF4 (1) and [Pd(Me)(dppp){N(Ph)═C(H)Ph}]OTf (4) were structurally characterized by X-ray crystallography. The iminoacyl-imine complexes [Pd{C(Me)═NXyl} (L2){N═C(Me)OCH2CH2}]BF4 (L2 = dppe, 12; dppp, 13) were prepared. The bis-imine complex [Pd(dppe){N═C(Me)OCH2CH2}2][BF4]2 (14) resulting from disproportionation of 12 was also prepared and structurally characterized. Protonation of the iminoacyl fragment provided iminoacyl imine complex [Pd{C(CH3)═N(H)Xyl}(dppe){N(Bz)═CPhH}][BF4]2 (17), which was sufficiently stable to be structurally characterized, providing some insight into the coordination of these fragments to palladium.

Neutral N−O Chelated Palladium(II) Complexes: Syntheses, Characterization, and Reactivity

A series of neutral salicylaldiminato Pd(II) complexes, Pd(Me)(Ph-CHN-R‘)[3-tBu-2-(O)C6H3-CHN-2,6-di-iPr-C6H3] (R = CH3, n-Pr, tert-Bu, Ph, benzyl) (3a−3e) and Pd(Me)[2-(CHN-t-Bu)-Py][3-tBu-2-(O)C6H3-CHN-2,6-di-iPr-C6H3] (4), have been synthesized and characterized. The structures of complexes 3a, 3c−3e, and 4 have been confirmed by X-ray analysis. NMR studies utilizing 3c indicate that the insertion of CO into the Pd−Me bond occurs through a five-coordinate intermediate. The acyl compounds in turn undergo imine insertion. The neutral complexes 3a−3e show moderate catalytic activity for the polymerization of methyl acrylate at ambient temperature. However, a radical rather than vinyl insertion mechanism appears to be operative.

Carboamination: Additions of Imine C=N Bonds Across Alkynes Catalyzed by Imidozirconium Complexes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Insertion reactions of hydridonitrosyltetrakis(trimethylphosphine) tungsten(0)

[W(H)(NO)(PMe3)4] (1) was prepared by the reaction of [W(Cl)(NO)(PMe3)4] with NaBH4 in the presence of PMe3. The insertion of acetophenone, benzophenone and acetone into the W-H bond of 1 afforded the corresponding alkoxide complexes [W(NO)(PMe3)4(OCHR1R2)](R1 = R2 = Me (2); R1 = Me, R2 = Ph (3); R1 = R2 = Ph (4)), which were however thermally unstable. Insertion of CO2 into the W-H bond of yields the formato-O complex trans-W(NO)(OCHO)(PMe3)4 (5). Reaction of trans-W(NO)(H)(PMe3)4 with CO led to the formation of mer-W(CO)(NO)(H)(PMe3)3 (6) and not the formyl complex W(NO)(CHO)(PMe3)4. Insertion of Fe(CO)(5), Re2(CO)10 and Mn2(CO)10 into trans-W(NO)(H)(PMe3)4 resulted in the formation of trans-W(NO)(PMe3)4(mu-OCH)Fe(CO)4 (7), trans-W(NO)(PMe3)4(mu-OCH)Re2(CO)9 (8) and trans-W(NO)(PMe3)4(mu-OCH)Mn2(CO)9 (9). For Re2(CO)10, an equilibrium was established and the thermodynamic data of the equilibrium reaction have been determined by a variable-temperature NMR experiments (K(298K)= 104 L mol(-1), DeltaH=-37 kJ mol(-1), DeltaS =-86 J K(-1) mol(-1)). Both compounds 7 and 8 were separated in analytically pure form. Complex 9 decomposed slowly into some yet unidentified compounds at room temperature. Insertion of imines into the W-H bond of 1 was also additionally studied. For the reactions of the imines PhCH=NPh, Ph(Me)C=NPh, C6H5CH=NCH2C6H5, and (C6H5)2C=NH with only decomposition products were observed. However, the insertion of C10H7N=CHC6H5 into the W-H bond of led to loss of one PMe3 ligand and at the same time a strong agostic interaction (C17-H...W), which was followed by an oxidative addition of the C-H bond to the tungsten center giving the complex [W(NO)(H)(PMe3)3(C10H6NCH2Ph)] (10). The structures of compounds 1, 4, 7, 8 and 10 were studied by single-crystal X-ray diffraction.

Imine insertion into a late metal-carbon bond to form a stable amido complex.

An arylrhodium(I) complex containing a labile dative ligand was prepared, and its reactivity toward aryl imines was investigated. The arylrhodium(I) complex (DPPE)Rh(C5H5N)(p-tol), 2, was isolated in 65% yield from [(DPPE)Rh(mu-Cl)]2, pyridine, and p-tolyllithium. Reaction of 2 with the aldimine (p-tol)CH=N(C6H4-p-CO2Me) (3a-Tol) gave the Rh amide insertion product 4 in 88% isolated yield. The solid-state structure of 4 was determined by single-crystal X-ray diffraction. The reaction of 2 with the electron-neutral and electron-rich aldimines (Ph)CH=NPh (3b) and (p-tol)CH=N(C6H4-p-OMe) (3c) also appeared to involve insertion, but the amido complexes formed from these insertions were not stable. Thus, reaction of 2 with 3b, followed by addition of Et3NHCl, gave the amine and ketimine products (Ph)(p-tol)CH-NHPh, 5, and (p-tol)(Ph)C=N(Ph), 6, in 25% and 50% yields. Several lines of data indicate that these products are formed by a sequence of transformations involving insertion of imine to give a Rh amide intermediate, beta-hydrogen elimination, cyclometalation to form a bound imine and H2, and protonolysis of the metallacycle upon addition of Et3NHCl. Consistent with this proposal, the proposed metallacycle containing the ortho-metalated ketimine ligand (p-tol)2C=N(C6H4-p-OMe) was isolated and characterized by single-crystal X-ray diffraction.

Addition of a phosphinidene complex to C=N bonds: P-ylides, azaphosphiridines, and 1,3-dipolar cycloadditions.

The terminal phosphinidene complex PhPW(CO)5 adds to the imine bond of PhHC=N-Ph to give 3-membered ring azaphosphiridines, which undergo ring-expansion with an additional imine to yield a set of four isomeric five-membered ring diazaphospholanes. Treatment with the diimines PhHC=N-(CH2)n-N=CHPh (n=2,3,4) results instead-in all three cases-in only a single isomer of the (CH2)n bridged diazaphospholane. For n=2 or 3, this aminal group is easily hydrolyzed to afford new 6- and 7-membered ring heterocycles. No intermediate azaphosphiridine complex is observed during the addition reaction to the diimines. B3LYP/6-31G* calculations on an unsubstituted, uncomplexed system suggest that the initially formed P,N-ylide of the H2C=N-(CH)2-N=CH2 diimine both kinetically and thermodynamically favors an intramolecular 1,3-dipolar cycloaddition over an imine insertion into the CPN ring of an intermediate azaphosphiridine. Single-crystal X-ray structures for the (CH2)2-bridged azaphospholane complex and the HCl adduct of the 7-membered hydrolysis product are presented.

Insertion of Imines and Carbon Monoxide into Manganese−Alkyl Bonds: Synthesis and Structure of a Manganese−α-Amino Acid Derivative

Two new routes have been developed to generate manganese-chelated amides from imine and carbon monoxide building blocks. The reaction of (CO)5MnR (R = CH3, Ph) with (p-tolyl)(R1)NR2 (R1 = H, tBu; R2 = alkyl, H) results in the generation of the cyclometalated imine complexes (CO)4Mn[η2-4-CH3-2-(C(R1)NR2)-C6H3] in 50−84% isolated yield. However, when the reaction of (p-tolyl)(H)CNCH3 with (CO)5MnCH3 is performed in the presence of AlCl3, the product of sequential carbon monoxide and imine insertion is generated in 35% yield: (CO)4Mn[η2-C(H)(p-tolyl)N(CH3)COCH3]. The addition of PPh3 to the latter complex results in replacement of a carbonyl ligand and formation of the isolable fac-(CO)3(PPh3)Mn[η2-C(H)(p-tolyl)N(CH3)COCH3]. In an alternative route to metal-bound amides, the oxidative addition of the N-acyl iminium salt (p-tolyl(H)CN(CH3)COPh+Cl- to (CO)5Mn-Na+ has been found to lead to the generation of the product of subsequent CO insertion, (CO)4Mn[η2-COC(H)(p-tolyl)N(CH3)COPh]. The latter represents the first example of a acyl-bound transition-metal-chelated α-amino acid complex and has been characterized by X-ray crystallography. Preliminary reactivity studies demonstrate that (CO)4Mn[η2-COC(H)(p-tolyl)N(CH3)COPh] reacts with PPh3 to generate the unchelated cis-(CO)4(PPh3)Mn[COC(H)(p-tolyl)N(CH3)COPh], while reaction with NaBH4 leads to the liberation of the amide (p-tolyl)CH2N(CH3)COPh, rather than the amino acid residue.

Insertion of Imine into Palladium−Methyl and Palladium−Acyl Bonds. A Density Functional Study

The insertion mechanism of imine into the Pd−methyl and Pd−acyl bonds with a phosphane or a nitrogen-based ligand coordinated to the Pd atom has been studied with density functional theory. In agreement with the experimental findings, σ coordination of the imine is preferred. Imine insertion into the Pd−methyl bond presents high energy barriers (>40 kcal mol-1) independently of the Pd-ligand used. On the contrary, insertion into the Pd−acyl bond is more facile, with energy barriers close to 20 kcal mol-1. A geometrical and energetic analysis of the transition states suggests that the formation of the very strong amide linkage constitutes the added driving force for the imine insertion into the Pd−acyl bond.