Selective Amination Research Articles

Copper-catalysed chemoselective C-OH bond activation of N-benzoyl cytosine: facile access to 2-(dimethylamino)pyrimidine.

A novel method for the direct amination of N-benzoyl cytosine has been developed, giving access to 2-(dimethylamino)pyrimidine derivatives. A copper(II) catalyst and tert-butyl hydroperoxide easily promote the selective amination process that proceeds via C-OH bond activation. This practical approach can utilize different formamide molecules, N,N-dimethylformamide and N,N-diethylformamide, as efficient amino (-NMe2, -NEt2) sources. Moreover, the facile nature of the procedure, its broad tolerance of aliphatic and aromatic substrates, the high yields and ease of separation of the products, and the fact that it can be conducted under aerobic conditions are all notable advantages of the present protocol.

Iridium-catalyzed selective amination of B(4)-H for the synthesis of o-carborane-fused indolines.

An iridium-catalyzed selective amination of B(4)-H via dehydrogenative cross-coupling of B-H/N-H bonds for the synthesis of o-carborane-fused indolines has been developed for the first time. Various types of unprecedented o-carborane-fused indolines have been synthesized, which would be potential candidates for applications in drug discovery, pharmaceutical chemistry and functional materials. This work offers a valuable reference for the designing and synthesis of o-carborane-fused heterocycles.

Polarization Reorientation of Carbon Nitride Induced by Local Bridge Donor for Boosting Photocatalytic H2 Evolution Integrated with Selective Amines Oxidation

Polarization Reorientation of Carbon Nitride Induced by Local Bridge Donor for Boosting Photocatalytic H2 Evolution Integrated with Selective Amines Oxidation

Deracemization of Racemic Amine Using ω-Transaminase and a Nickel-Based Nanocatalyst

Chiral amines are key building blocks for the development of numerous bioactive compounds. In this study, we developed a concurrent chemoenzymatic cascade approach using ω-transaminase for the isomeric configuration inversion of a racemic amine mixture. One isomer was transaminated using ω-transaminase, generating coproduct ketones and an additional chiral substance. Then, the mixture underwent selective reductive amination of a ketone using a specially designed compatible nickel-based nanocatalyst, which transformed coproduct ketone to racemic amines while leaving the opposite enantiomer unchanged. The combination of the two steps in one reaction system functions as an overall isomeric configuration inversion system. Moreover, the desired chiral amines with an additional chiral substance were formed. The procedure consumed NH3 and generated H2O as the sole byproduct.

Uniformly microporous diatomite supported Ni0/2+ catalyzed controllable selective reductive amination of benzaldehydes to primary amines, secondary imines and secondary amines

The controllable highly selective reductive amination of carbonyl compound to primary amines, secondary imines and secondary amines is one of the challenging problems in organic synthesis. However, there are still many problems, such as difficulty in selective regulation, cumbersome and costly preparation of catalysts, and insufficient green solvents. In this work, commercial diatomite, activated carbon, Al2O3, TiO2 and CeO2 were employed to support nickel through a simple impregnation method. With H2O as the green solvent, Ni/diatomite-400 can achieve controllable selective reductive amination of benzaldehyde to benzylamine, N-benzylidenebenzylamine and dibenzylamine only by regulating H2 pressure and ammonia concentration. Accompanying spectroscopic characterizations and detailed mechanistic experiments illustrate that the synergistic effect of the appropriate proportion of Ni0/Ni2+ is the key to the successful modulation of selectivity, and this catalytic reaction mechanism was proposed. Moreover, the unique uniformly microporous structure of diatomite may facilitate the mass transfer and diffusion process of reactants, intermediates and products, leading to high catalytic efficiency. In addition, the catalyst also has excellent reuse performance and substrate universality. This work provides a new economical and efficient way for the reductive amination of carbonyl compounds in industry.

Merging Gold(I) Catalysis with Amine Transaminases in Cascade Catalysis: Chemoenzymatic Transformation of Propargylic Alcohols into Enantioenriched Allylic Amines

AbstractThe compatibility between gold(I) catalysts and amine transaminases has been explored to transform racemic propargylic alcohols into enantioenriched allylic amines in a straightforward and selective manner. The synthetic approach consists of a gold(I)‐catalysed Meyer‐Schuster rearrangement of a series of 2‐arylpent‐3‐yn‐2‐ols and a subsequent stereoselective enzyme‐catalysed transamination of the resulting α,β‐unsaturated prochiral ketones. The design of cascade processes involving sequential or concurrent approaches has been studied in our search for ideal reaction conditions to produce the desired amines. Thus, the N‐heterocyclic carbene complex [1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene]‐[bis(trifluoromethanesulfonyl)‐imide]gold(I) ([Au(IPr)(NTf2)] (A) in aqueous medium was found to be an ideal catalyst, while selective, made‐in‐house and commercial amine transaminases permitted the asymmetric synthesis of both (E)‐4‐arylpent‐3‐en‐2‐amine enantiomers in good isolated yields (53–84%) and excellent stereoselectivities (97 to >99% enantiomeric excess).magnified image

Zinc Trifluoromethanesulfonate-Catalyzed para-Selective Amination of Free Anilines and Free Phenols with Quinoneimides.

An efficient zinc-catalyzed amination of free anilines and free phenols with quinoneimides has been disclosed, which proceeds smoothly under simple and mild conditions. The para-selective amination is accomplished on the anilines and phenols via a 1,6-addition pathway, leading to C-N bond formation. The developed protocol offers a promising approach not only for the construction of structurally diverse p-phenylenediamine compounds with excellent yields but also for the synthesis of the para-amination of free phenol derivatives with good to excellent yields. This protocol also extends the application of the quinoneimide-involved 1,6-addition reaction.

Optimal Polyethyleneimine Molecular Weight and Arrangement for Modification of γ-Cyclodextrin Metal Organic Frameworks (γ-CD-MOFs) for Post-Combustion CO2 Capture

Modified γ-cyclodextrin metal organic frameworks (γ-CD-MOFs) are a promising eco-friendly sorbents for post-combustion CO2 capture. Polyethyleneimine (PEI) has been widely used for modifying MOFs to enhance their CO2 sorption capacity and selectivity through the introduction of CO2 selective amine groups. The main objective of this study was to determine the optimal PEI molecular weight and arrangement (linear or branched) to enhance γ-CD-MOF’s CO2 sorption capacity. γ-CD-MOFs were impregnated with linear as well as branched PEI with molecular weights of 600, 1200 or 10,000. The CO2 sorption capacity of the PEI-impregnated γ-CD-MOFs was determined using a quartz crystal microbalance assembly at CO2 partial pressures from 0.35–1.0 atm. Impregnation with 600 g/mole branched PEI achieved the highest CO2 sorption capacity of 0.9 mmole/g CO2 at 1 atm, followed by the linear PEI (0.12 mmol/g). Modification with the other branched PEI molecular weights did not achieve detectable CO2 sorption, likely because of pore blockage with the relatively larger PEI molecular weights, as demonstrated by molecular docking simulations. Furthermore, the control γ-CD-MOFs did not sorb CO2, likely because of the lower attraction forces between CO2 and the large pore volume of the unmodified MOFs.

Development Design of Amine Sweetening Unit Plant of Natural Gas

Abstract: In addition to reduced equipment sizes, lower circulation rates, and greater overall amine concentration, selective amines have become more popular for gas sweetening. Selective amines absorb H2S from CO2 through thermodynamic or kinetic processes. Selective amine mixtures may enable a small quantity of CO2 to remain in the treated gas. Plant capacity margins for selective amine units are frequently small. Increasing the acid gas concentration or throughput might result in sweet gas that does not fulfill CO2 specifications. Increasing the amine concentration, employing combinations of amines, and altering the lean amine temperature were explored since adding new equipment may be costly. Compared to increasing reboiler or pumping capacity, these factors need little or no extra capital.

Highly Dispersed and Stable Hydrotalcite-Derived NiCu/MgAlO Alloy Catalyst for Efficient Amination of Cyclohexanol to Cyclohexylamine in the Vapor Phase

Developing a mild and efficient method for highly selective amination of alcohols to amines as important versatile compounds is very interesting in the organic synthesis field. In this work, we have developed a simple and efficient approach for high-yield preparation of cyclohexylamine from the vapor-phase catalytic amination of cyclohexanol with ammonia under atmospheric pressure. The results indicated that the hydrotalcite-derived NiCu/MgAlO alloy catalyst exhibited excellent catalytic performance and stability, and 98% cyclohexanol conversion with 95% selectivity toward cyclohexylamine had still been maintained after running for over 300 h at 170 °C. The super high activity and stability of the NiCu/MgAlO catalyst are attributed to the active Ni–Cu alloy nanoparticles with high dispersion and uniform particle size (about 4 nm). DFT calculation results indicated the Ni site of the NiCu alloy (111) facet as the main catalytic active site. The energy profiles for the potential comparative free energy of cyclohexanol to cyclohexylamine on the NiCu alloy (111) facet were calculated. This approach employing a highly dispersed and stable Ni–Cu bimetallic alloy catalyst for efficient amination of cyclohexanol to cyclohexylamine in the vapor phase is promising and has potential industrial application prospects. Especially, the designed Ni–Cu alloy catalyst can also be applied in the amination of other alcohols with ammonia to prepare the corresponding organic amines.

Iridium-Catalyzed Selective B(4)-H Amination of o-Carboranes with Anthranils.

We report here a catalytic selective cage B4-H amination of o-carboranes employing an Ir(III) complex as a catalyst and anthranils as aminating agents, leading to a large class of B4-aminated o-carboranes with very high yields and a broad substrate scope under mild conditions without any oxidants. In these reactions, the carboxyl group serves as a traceless directing unit to determine the site selectivity and degree of substitution.

Silver Catalyzed Site-Selective C(sp3)-H Bond Amination of Secondary over Primary C(sp3)-H Bonds.

Sulfamates are widespread in numerous pharmacologically active molecules. In this paper, Silver/Bathophenanthroline catalyzed the intramolecular selective amination of primary C(sp3)−H bonds and secondary C(sp3)−H bonds of sulfamate esters, to produce cyclic sulfamates in good yields and with a high site-selectivity. DFT calculations revealed that the interaction between sulfamates and L10 makes the molecule more firmly attached to the catalyst, benefiting the catalysis reaction. The in vitro anticancer activity of the final products was evaluated in MCF-7 breast cancer cells.

Efficient light-driven reductive amination of furfural to furfurylamine over ruthenium-cluster catalyst

Selective reductive amination of carbonyl compounds with high activity is very essential for the chemical and pharmaceutical industry, but scarcely successful paradigm was reported via efficient photocatalytic reactions. Herein, the ultrasmall Ru nanoclusters (∼0.9 nm) were successfully fabricated over P25 support with positive charged Ruδ+ species at the interface. A new route was developed to achieve the furfural (FAL) to furfurylamine (FAM) by coupling the light-driven reductive amination and hydrogen transfer of ethanol over this type catalyst. Strikingly, the photocatalytic activity and selectivity are strongly dependent on the particle size and electronic structure of Ruthenium. The Ruδ+ species at the interface promote the formation of active imine intermediates; moreover, the Ru nanoclusters facilitate the separation efficiency of electrons and holes as well as accelerate the further hydrogenation of imine intermediates to product primary amines. In contrast Ru particles in larger nanometer size facilitate the formation of the furfuryl alcohol and excessive hydrogenation products. In addition, the coupling byproducts can be effectively inhibited via the construction of sub-nanocluster. This study offers a new path to produce the primary amines from biomass-derived carbonyl compounds over hybrid semiconductor/metal-clusters photocatalyst via light-driven tandem catalytic process.

Palladium-catalysed selective oxidative amination of olefins with Lewis basic amines.

Amines are prominent in natural products, pharmaceutical agents and agrochemicals. Moreover, they are synthetically valuable building blocks for the construction of complex organic molecules and functional materials. However, amines, especially aliphatic and aromatic amines with free N-H bonds, tend to coordinate with transition metals and deactivate the catalyst, posing a tremendous challenge to applying Lewis basic amines in the amination of olefins. Here we present an example of oxidative amination of simple olefins with various Lewis basic amines. The combination of a palladium catalyst, 2,6-dimethyl-1,4-benzoquinone and a phosphorous ligand leads to the efficient synthesis of alkyl and aryl allylamines. A series of allylamines were obtained with good yields and excellent regio- and stereoselectivities. Intramolecular amination to synthesize tetrahydropyrrole and piperidine derivatives was also realized. Mechanistic investigations reveal that the reaction undergoes allylic C(sp3)-H activation and subsequent functionalization.

Density Functional Theory Study on the Selective Reductive Amination of Aldehydes and Ketones over Their Reductions to Alcohols Using Sodium Triacetoxyborohydride.

Reductive amination is one of the most important methods to synthesize amines, having a wide application in the pharmaceutical, fine chemicals, and materials industries. In general, the reaction begins with dehydration between a carbonyl compound and an amine compound, forming an imine, which is then reduced to an alkylated amine product. Sodium triacetoxyborohydride (STAB) is a popular choice for the reducing agent as it shows selectivity for imines over aldehydes and ketones, which is particularly important in direct reductive amination where the imine and carbonyl compounds are present concurrently. Here, we analyze the reaction pathways of acid-catalyzed direct reductive amination in 1,2-dichloroethane (DCE) with acetaldehyde and methylamine. We find that the transition states for the formation and subsequent reduction of Z-methylethylideneimine (resultant aldimine from acetaldehyde and methylamine) have lower energies than the reduction of acetaldehyde. Transition state structures for the hydride transfers are organized by the Lewis-acidic sodium ion. Additionally, reduction reactions with formaldehyde and acetone and their imine derivatives (with methylamine) are investigated, and again, the hydride transfer to the resultant aldimine or ketimine is lower in energy than that of their parent carbonyl compound.

Site-Selective Functionalization of C(sp3) Vicinal Boronic Esters

Selective functionalization of the C–B bond in 1,2-bis(boronate) esters has emerged as a powerful tool to prepare 1,2-difunctionalized compounds with stereocontrol. Selective Suzuki cross-coupling, oxidation, amination, and homologation reactions serve as platforms to prepare a wide variety of compounds from a common intermediate. The exquisite selectivity offered and their easy preparation from feedstock material using a myriad of catalytic transformations make them attractive building blocks for the preparation of complex molecules. In this Perspective, we summarize the examples of selective C–B bond functionalization of vicinal bis(boronates), attending to the nature of the C–B bond functionalization.

Cyclic Hypervalent Iodine-Induced Oxidative Phenol and Aniline Couplings with Phenothiazines

C-H/N-H bond functionalization for direct intermolecular aryl C-N couplings is a useful synthetic process. In this study, we achieved metal-free cross-dehydrogenative coupling of phenols and anilines with phenothiazines using hypervalent iodine reagents. This method affords selective amination products under mild conditions. Electron-rich phenols and anilines could be employed, affording moderate-to-high yields of N-arylphenothiazines. Aniline amination proceeded efficiently at 20 °C, a previously unreported phenomenon.

Photocatalytic transfer of nitrenes toward selective intermolecular aminations

In this issue of Chem Catalysis , Koenigs and co-workers provide a strong foundation for future developments in nitrene chemistry by performing extensive substrate-scope and mechanistic experiments for the direct intermolecular amination of allenes, a hitherto underdeveloped field. In this issue of Chem Catalysis , Koenigs and co-workers provide a strong foundation for future developments in nitrene chemistry by performing extensive substrate-scope and mechanistic experiments for the direct intermolecular amination of allenes, a hitherto underdeveloped field.

Transition Metal-Catalyzed Regioselective Direct C-H Amidation: Interplay between Inner- and Outer-Sphere Pathways for Nitrene Cross-Coupling Reactions.

Catalytic C-N bond cross-coupling reactions have been a subject of fundamental importance in synthetic organic and medicinal chemistry because amides and amines are ubiquitous motifs in natural products, functional materials, and pharmaceuticals. Since the pioneering works of Breslow and Mansuy on the metalloporphyrin-catalyzed direct hydrocarbon amidation using sulfonyliminoiodinane reagents, substantial development has been achieved toward practical and selective amination protocols. Notably, Du Bois's group developed the dirhodium(II,II) carboxylate catalytic system for direct C(sp3)-H amidations via Rh-sulfonyl nitrene intermediates. Yet, this protocol suffers from competitive alkene aziridination and is limited to electron-rich tertiary and ethereal C-H bonds; analogous direct amidation of arenes remained ineffective.This Account discusses our early effort to explore cyclopalladated complexes for ortho-selective C(aryl)-H amidations. While Buchwald-Hartwig amination cannot be directly applied to arenes, effective amidation of the 2-arylpyridines occurred when an external oxidant such as K2S2O8 was employed. Preliminary studies suggested that the amidation may proceed through reactive Pd-nitrene intermediates. Aiming to develop more diversified amidation protocols, we employed nosyloxycarbamates as nitrene precursors for the Pd-catalyzed ortho-amidation of N-pivalanilides. Likewise, we developed the ortho-selective amidation of benzoic acids to produce anthranilic acids, which are versatile precursors for many medicinally valuable heterocycles. In an attempt to expand the C(aryl)-N coupling reactions to amines, we studied the d6 piano-stool Cp*Rh(III) systems [Cp* = pentamethylcyclopentadienyl]. Our work established a sound reaction platform based on the electrophilic aminating reagents including N-chloroamines, hydroxyamides, and N-carboxyhydrazides for effective C(aryl)-N bond formation in aryl-metal complexes.Building upon the metal-nitrene reaction platform, we moved forward to examine γ-lactam synthesis by intramolecular carbonyl nitrene C(sp3)-H insertion. Noted that carbonyl nitrenes are prone to undergo Curtius-type rearrangement to form isocyanate; we found that the π-basic Ru(II) center effectively decomposes dioxazolones to afford the carbonyl nitrene for regioselective γ-C(sp3)-H insertion. With chiral diphenylethylenediamines (dpen) as ligands bearing electron-withdrawing arylsulfonyl substituents, the [(p-cymene)Ru(dpen)] complex catalyzed the decomposition of the dioxazolones to afford chiral γ-lactams by formal carbonyl nitrene C(sp3)-H insertion. Enantioselective nitrene insertion to allylic and propargylic C(sp3)-H bonds was also achieved with remarkable tolerance to the C═C and C≡C bonds. Notably, the selectivity of the [(p-cymene)Ru] system switched to C(aryl)-H bonds to give dihydroquinolinones when l-proline was employed as ligand. Recently, we aimed to address the regiocontrolled amidation of unactivated methylene C-H bonds using NiH catalyst. While tertiary and benzyl C-H bonds can be differentiated by their bond dissociation energies and steric properties, methylene groups making up the hydrocarbon skeleton display similar electronic and steric properties. In this context, we exploited the five-membered nickelacycle formation to terminate the NiH-mediated chain-walk isomerization, and the nickelacycle reacted with dioxazolones to furnish the C(sp3)-N bond at the γ-methylene position.This Account summarizes our contribution to the development of C-N bond cross-coupling reactions via C-H activation. By exploiting the inner-sphere and outer-sphere reaction pathways, we successfully developed regioselective protocols that target C(sp3)-H and C(aryl)-H bonds. The mechanistic underpinning of the selectivity of different C-H bonds and related studies on the affiliated catalytic systems will be discussed.

Fluorescence turn on amine detection in a cationic covalent organic framework

Ionic covalent organic frameworks (iCOFs) are new examples of porous materials and have shown great potential for various applications. When functionalized with suitable emission sites, guest uptake via the ionic moieties of iCOFs can cause a significant change in luminescence, making them excellent candidates for chemosensors. In here, we present a luminescence sensor in the form of an ionic covalent organic framework (TGH+•PD) composed of guanidinium and phenanthroline moieties for the detection of ammonia and primary aliphatic amines. TGH+•PD exhibits strong emission enhancement in the presence of selective primary amines due to the suppression of intramolecular charge transfer (ICT) with an ultra-low detection limit of 1.2 × 10‒7 M for ammonia. The presence of ionic moieties makes TGH+•PD highly dispersible in water, while deprotonation of the guanidinium moiety by amines restricts its ICT process and signals their presence by enhanced fluorescence emission. The presence of ordered pore walls introduces size selectivity among analyte molecules, and the iCOF has been successfully used to monitor meat products that release biogenic amine vapors upon decomposition due to improper storage.