Amine Reagents Research Articles

An umpolung-enabled copper-catalysed regioselective hydroamination approach to α-amino acids.

A copper-catalysed regio- and stereoselective hydroamination of acrylates with hydrosilanes and hydroxylamines has been developed to afford the corresponding α-amino acids in good yields. The key to regioselectivity control is the use of hydroxylamine as an umpolung, electrophilic amination reagent. Additionally, a judicious choice of conditions involving the CsOPiv base and DTBM-dppbz ligand of remote steric hindrance enables the otherwise challenging C–N bond formation at the α position to the carbonyl. The point chirality at the β-position is successfully controlled by the Xyl-BINAP or DTBM-SEGPHOS chiral ligand with similarly remote steric bulkiness. The combination with the chiral auxiliary, (−)-8-phenylmenthol, also induces stereoselectivity at the α-position to form the optically active unnatural α-amino acids with two adjacent stereocentres.

5-(Diarylimino)- and 5-(sulfoximido)dibenzothiophenium triflates: syntheses and applications as electrophilic aminating reagents.

The one-pot synthesis of well-defined 5-(diarylimino) and 5-(sulfoximido)dibenzothiophenium triflates, respectively from diarylimines or sulfoximines, is reported and the structures of a series of these compounds are elucidated by X-ray crystallography. In analogy to their hypervalent I(iii) analogues, the iminoyl and sulfoximidoyl groups of these compounds can be selectively transferred to organic substrates. Specifically, the uncatalyzed imination of thiols or sulfinates proceeds with good yields, while under the mild reaction conditions offered by visible light photoredox catalysis, the radical amination of hydrazones or the sulfoximidation of benzylic, allylic and propargylic C-H bonds takes place satisfactorily.

Visible-light induced generation of bifunctional nitrogen-centered radicals: a concise synthetic strategy to construct bicyclo[3.2.1] octane and azepane cores

A photocatalytic tandem cyclization of o-alkenylbenzaldehydes using pyridinium salts as the amination reagent is described. A variety of valuable seven-membered nitrogenous heterocyclic skeletons are prepared in modest to excellent yields in concise one-step. This transformation features mild reaction conditions and exceptional functional group tolerance. In addition, combining control experiments and density functional theory (DFT) calculations on the mechanism can explain the reaction selectivity.

Decarboxylative Amination: Diazirines as Single and Double Electrophilic Nitrogen Transfer Reagents.

The ubiquity of nitrogen-containing small molecules in medicine necessitates the continued search for improved methods for C-N bond formation. Electrophilic amination often requires a disparate toolkit of reagents whose selection depends on the specific structure and functionality of the substrate to be aminated. Further, many of these reagents are challenging to handle, engage in undesired side reactions, and function only within a narrow scope. Here we report the use of diazirines as practical reagents for the decarboxylative amination of simple and complex redox-active esters. The diaziridines thus produced are readily diversifiable to amines, hydrazines, and nitrogen-containing heterocycles in one step. The reaction has also been applied in fluorous phase synthesis with a perfluorinated diazirine.

Study on the foam behavior of amine reagents adsorbed at gas-liquid and gas-liquid-solid interfaces

Study on the foam behavior of amine reagents adsorbed at gas-liquid and gas-liquid-solid interfaces

Theoretical insights into the synthesis reaction mechanism of 1,2,3-triazole based on sakai reaction

Abstract Sakai reaction is an important method to synthetize 1,2,3-triazole by the addition of α, α-dichlorotosylhydrazones and amines. However, the difficulty of introducing the 1,2,3-triazole ring is often affected by the type of amine reagent. More calculation results and detailed mechanisms are used to screen which amine is more suitable for the Sakai reaction. In this study, the DFT calculations were carried out to study the reaction mechanism of Sakai reaction. Depending on the type of amines, two different paths for Sakai reaction were revealed by our calculations. For the triazolamine, an H atom must transfer from the amines to the diazine synchronously when the new C–N bond is formed. The transformation from trans- to cis- is necessary for the intermediate vinyldiazine. For aniline, the amine molecule can combine with trans-vinyldiazine directly without an H transfer due to the formation of a structure that is similar to NH4+ ion.

Visible‐Light Photoredox Catalyzed C−N Coupling of Quinoxaline‐2(1H)‐ones with Azoles without External Photosensitizer

AbstractA visible‐light photoredox catalyzed C−N coupling of quinoxaline‐2(1H)‐ones with azoles in the absence of external photosensitizer has been developed. The protocol employs commercially available pyrazoles and triazoles as amination reagents and shows wide substrate scope, providing the corresponding C3‐position amination products in good yields and high regioselectivity under ambient conditions. Investigations indicate that the starting materials and products can act as photosensitizers avoiding use of additional photocatalyst in an autocatalytic manner. In addition, 1O2 coexists with O2.− from molecular oxygen (3O2) via an energy transfer (ET) and single electron transfer (SET) process during the reaction.

Design and Scalable Synthesis of N‐Alkylhydroxylamine Reagents for the Direct Iron‐Catalyzed Installation of Medicinally Relevant Amines**

AbstractSecondary and tertiary alkylamines are privileged substance classes that are often found in pharmaceuticals and other biologically active small molecules. Herein, we report their direct synthesis from alkenes through an aminative difunctionalization reaction enabled by iron catalysis. A family of ten novel hydroxylamine‐derived aminating reagents were designed for the installation of several medicinally relevant amine groups, such as methylamine, morpholine and piperazine, through the aminochlorination of alkenes. The method has excellent functional group tolerance and a broad scope of alkenes was converted to the corresponding products, including several drug‐like molecules. Besides aminochlorination, the installation of other functionalities through aminoazidation, aminohydroxylation and even intramolecular carboamination reactions, was demonstrated, further highlighting the broad potential of these new reagents for the discovery of novel amination reactions.

Design and Scalable Synthesis of N-Alkylhydroxylamine Reagents for the Direct Iron-Catalyzed Installation of Medicinally Relevant Amines*.

Secondary and tertiary alkylamines are privileged substance classes that are often found in pharmaceuticals and other biologically active small molecules. Herein, we report their direct synthesis from alkenes through an aminative difunctionalization reaction enabled by iron catalysis. A family of ten novel hydroxylamine-derived aminating reagents were designed for the installation of several medicinally relevant amine groups, such as methylamine, morpholine and piperazine, through the aminochlorination of alkenes. The method has excellent functional group tolerance and a broad scope of alkenes was converted to the corresponding products, including several drug-like molecules. Besides aminochlorination, the installation of other functionalities through aminoazidation, aminohydroxylation and even intramolecular carboamination reactions, was demonstrated, further highlighting the broad potential of these new reagents for the discovery of novel amination reactions.

Genetically Encoded Quinone Methides Enabling Rapid, Site-Specific, and Photocontrolled Protein Modification with Amine Reagents.

Site-specific modification of proteins with functional molecules provides powerful tools for researching and engineering proteins. Here we report a new chemical conjugation method which photocages highly reactive but chemically selective moieties, enabling the use of protein-inert amines for selective protein modification. New amino acids FnbY and FmnbY, bearing photocaged quinone methides (QMs), were genetically incorporated into proteins. Upon light activation, they generated highly reactive QM, which rapidly reacted with amine derivatives. This method features a rare combination of desired properties including fast kinetics, small and stable linkage, compatibility with low temperature, photocontrollability, and widely available reagents. Moreover, labeling via FnbY occurs on the β-carbon, affording the shortest linkage to protein backbone which is essential for advanced studies involving orientation and distance. We installed various functionalities onto proteins and attached a spin label as close as possible to the protein backbone, achieving high resolution in double electron-electron paramagnetic resonance distance measurements.

Enantioselective Synthesis of β‐Amino Acid Derivatives Enabled by Ligand‐Controlled Reversal of Hydrocupration Regiochemistry

AbstractA Cu‐catalyzed enantioselective hydroamination of α,β‐unsaturated carbonyl compounds for the synthesis of β‐amino acid derivatives was achieved through ligand‐controlled reversal of the hydrocupration regioselectivity. While the hydrocupration of α,β‐unsaturated carbonyl compounds to form α‐cuprated species has been extensively investigated, we report herein that, in the presence of an appropriate ancillary chiral ligand, the opposite regiochemistry can be observed for cinnamic acid derivatives, leading to the delivery of the copper to the β‐position. This copper can react with an electrophilic aminating reagent, 1,2‐benzisoxazole, to provide enantioenriched β‐amino acid derivatives, which are important building blocks for the synthesis of natural products and bioactive small molecules.

Enantioselective Synthesis of β-Amino Acid Derivatives Enabled by Ligand-Controlled Reversal of Hydrocupration Regiochemistry.

A Cu-catalyzed enantioselective hydroamination of α,β-unsaturated carbonyl compounds for the synthesis of β-amino acid derivatives was achieved through ligand-controlled reversal of the hydrocupration regioselectivity. While the hydrocupration of α,β-unsaturated carbonyl compounds to form α-cuprated species has been extensively investigated, we report herein that, in the presence of an appropriate ancillary chiral ligand, the opposite regiochemistry can be observed for cinnamic acid derivatives, leading to the delivery of the copper to the β-position. This copper can react with an electrophilic aminating reagent, 1,2-benzisoxazole, to provide enantioenriched β-amino acid derivatives, which are important building blocks for the synthesis of natural products and bioactive small molecules.

Boron Difluoride Complex Dyes: Synthesis and Photophysical Properties

Boron difluoride (BF2) complex dyes are relatively non-polar and electrically neutral tending to reduce the perturbation of the conjugate functional characteristics. Consequently, they are frequently the favored choice for biological labeling. Also, their conjugates of low molecular weight structures are more likely to be permeable to live cells than other conjugates of charged chromophores. As a result of their high extinction coefficient, another significant application of boron difluoride complexes is their reactivity and high detection ability to volatile amine reagents accessible for HPLC and electrophoresis. They are more useful than the majority of other dyes with long absorption wavelength. BF2 complex conjugates are extremely valuable reagents for many bio-analytical screening purposes, such as their affinity to quench the fluorescence upon conjugation to certain biopolymers. In this review, we discuss the preparation of boron difluoride carbonyl based-complexes, including O-O double-dentate and N-O double-dentate dyes, as well as shedding light on their photophysical properties.

A reaction-based sensing scheme for volatile organic amine reagents with the chromophoric-fluorogenic dual mode.

In this study, we present the classical Michael's addition reaction-based sensing scheme for volatile organic amine reagents such as ethylenediamine, N, N-dimethylethylenediamine and diethylenetriamine using a near-infrared fluorescent dye TCF1. Obvious spectral changes in the UV-vis absorption and fluorescence spectra of TCF1 were observed upon addition of these amine reagents with an effective catalyst DBU, resulting in significant and fast color changes detectable by the naked-eye. TCF1 showed an efficient response to these amine reagents with a low detection limit, especially for diethylenetriamine. NMR and MS spectral analysis proved that the mechanism of the detection was based on the classical Michael addition, which was also verified by the theoretical calculations. In addition, a portable test paper incorporated with TCF1 had also successfully realized the detection of a low concentration of these amine reagents.

Selectfluor® Radical Dication (TEDA2+.) – A Versatile Species in Modern Synthetic Organic Chemistry

AbstractAbstract: In radical processes involving Selectfluor®, TEDA2+. (N‐(chloromethyl)triethylenediamine) is often generated after an electron or fluorine transfer step. This is a highly reactive species that displays different and unique reactivity when compared to Selectfluor®: It can act as a hydrogen atom transfer (HAT), halogen atom transfer (XAT), or aminating reagent, as well as a powerful single electron oxidant. Despite this versatility, the use of TEDA2+. in synthetic processes remains highly underexplored. This minireview, which covers recent applications of TEDA2+. to promote a wide range of C‐heteroatom and C−C bond formations, aims to highlight the potential of this interesting species in organic chemistry. Particular attention is paid to mechanistic aspects involving how TEDA2+. is generated and the different reactivity patterns that it can display.

CuH-Catalyzed Olefin Functionalization: From Hydroamination to Carbonyl Addition.

In organic synthesis, ligand-modified copper(I) hydride (CuH) complexes have become well-known reagents and catalysts for selective reduction, particularly toward Michael acceptors and carbonyl compounds. Recently, our group and others have found that these hydride complexes undergo migratory insertion (hydrocupration) with relatively unactivated and electronically unpolarized olefins, producing alkylcopper intermediates that can be leveraged to forge a variety of useful bonds. The resulting formal hydrofunctionalization reactions have formed the basis for a resurgence of research in CuH catalysis. This Account chronicles the development of this concept in our research group, highlighting its origin in the context of asymmetric hydroamination, evolution to more general C-X bond-forming reactions, and applications in the addition of olefin-derived nucleophiles to carbonyl derivatives.Hydroamination, the formal insertion of an olefin into the N-H bond of an amine, is a process of significant academic and industrial interest, due to its potential to transform widely available alkenes and alkynes into valuable complex amines. We developed a polarity-reversed strategy for catalytic enantioselective hydroamination relying on the reaction of olefins with CuH to generate chiral organocopper intermediates, which are intercepted by electrophilic amine reagents. By engineering the auxiliary ligand, amine electrophile, and reaction conditions, the scope of this method has since been extended to include many types of olefins, including challenging internal olefins. Further, the scope of amine reagents has been expanded to enable the synthesis of primary, secondary, and tertiary amines as well as amides, N-alkylated heterocycles, and anilines. All of these reactions exhibit high regio- and stereoselectivity and, due to the mild conditions required, excellent tolerance for heterocycles and polar functional groups.Though the generation of alkylcopper species from olefins was originally devised as a means to solve the hydroamination problem, we soon found that these intermediates could react efficiently with an unexpectedly broad range of electrophiles, including alkyl halides, silicon reagents, arylpalladium species, heterocycles, and carbonyl derivatives. The general ability of olefins to function as precursors for nucleophilic intermediates has proved particularly advantageous in carbonyl addition reactions because it overcomes many of the disadvantages associated with traditional organometallic reagents. By removing the need for pregeneration of the nucleophile in a separate operation, CuH-catalyzed addition reactions of olefin-derived nucleophiles feature improved step economy, enhanced functional group tolerance, and the potential for catalyst control over regio- and stereoselectivity. Following this paradigm, feedstock olefins such as allene, butadiene, and styrene have been employed as reagents for asymmetric alkylation of ketones, imines, and aldehydes.

Application of novel functionalized Al2O3/silica by organosiloxane and amine reagents for enhanced oil recovery

The presence of nanoparticles (NPs), as new and efficient materials in enhanced oil recovery (EOR), has been considerably investigated in recent decades. In addition, smart surface modification of NPs is one of the capabilities recently defined in nanotechnology and nanoscience. Therefore, the main aim of this research is the application of new silica nanoparticles containing Al2O3 activators in EOR. Organosiloxane and amines have been used for surface modification and homogenized dispersibility of NPs in water-based as amine/organosiloxane@Al2O3/SiO2 (AOAS) nanocomposites synthesized using co-precipitation–hydrothermal method. These nanocomposites were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray methods (XRD), and dynamic light scattering (DLS). The stability of these nanocomposites was then investigated in different concentrations (100, 500, 1000, 2000 and 5000 ppm). Furthermore, contact angle, surface and interfacial tension have been measured. The results show that the surface modification process can significantly improve wettability and energetic surface activity. The use of AOAS nano-products in the specified concentrations for flooding into a micromodel shows that these nanocomposites can improve the oil efficiency. Besides, the oil recovery factors at 2000 ppm concentration for nanocomposites A, B (sequently were synthesized by impregnation and wet-chemical methods) and commercial nanosilica were found to be 66, 59.5 and 51.2%, respectively. It was observed that the new AOAS nanocomposites are able to improve the oil recovery factor of glass micromodel through the EOR process, compared with commercial silica nanoparticles.

A facile and practical Amination of 4-Fluoronitrobenzene in continuous flow

A highly efficient protocol for the amination of 4-fluoronitrobenzene by using methylamine aqueous solution as the amination reagent was developed. The reaction proceeds smoothly to provide the desired product in high yield and excellent purity within 15 min at 70 °C. The particle size of the product obtained in this approach was less than 100 μm. And the reaction media exhibited excellent reusability after recovering four times.

Multigram-scale Synthesis of Building Block Nitro-imine Derivative by Using Classical Method and Ultrasound Irradiation and Conversion to Imino-alcohol Derivative, Using Camphor as Starting Material

This study describes a simple multigram-scale procedure for the preparation of (E)-N-(1,7,7- trimethylbicyclo[2.2.1]heptan-2-ylidene)nitramide, nitro-imine 2, by using both classical methods and ultrasound irradiation from 1 utilizing Camphor, a natural product, as starting material. This key intermediate 2, a good building block, is useful to prepare various substances such as terpenoids, reagents for large-scale hydroxylation and amination of organic substrates, and derivatives with anticonvulsant, hypoglycemic, anti-inflammatory, antimicrobial and antiviral activities. It can be transformed into a wide range of other derivatives which can then also be employed in inorganic chemistry. In this work, another useful derivative (E)-2-((1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)amino)ethanol 3 has been prepared from nitro-imine 2 on multigram-scale which also allows access to a variety of products of biological interest after suitable chemical transformations.

Rapid synthesis of solid amine composites based on short mesochannel SBA-15 for CO2 capture

Hydrothermal is common process for synthesizing well-ordered mesoporous silica, however, it costs time and energy simultaneously. To improve the efficiency of synthesis process, it is necessary to propose a facile synthesis strategy with less time and energy requirement. In this study, an innovative non-hydrothermal method using NH3∙H2O as catalyst after ripening step is developed to prepare SBA-15 with short mesochannels (SSBA-15) for the first time. The synthesis period of SSBA-15 framework was extremely shortened within 40 min under the optimized conditions (30 min of ripening step and 25% of NH3∙H2O concentration), while obtained material exhibits well-ordered hexagonal pore structure and fine particle morphology of SSBA-15 (pore length of 250 ± 50 nm and mesopore size of 9.8 nm). This method can also be employed to synthesize conventional SBA-15 successfully. Moreover, the application of SSBA-15 as support of solid amine adsorbents on CO2 adsorption and well-fitting of experimental CO2 adsorption data with Avrami and intraparticle diffusion models reveal that the adsorbents combine the advantages of micro-mesoporous structure, short mesochannel and amine reagents (high affinity of CO2), resulting in enhanced molecular diffusion, fast adsorption kinetics and high CO2 adsorption capacity. Notably, the solid amine adsorbents exhibited excellent regeneration ability during ten adsorption-desorption cycles. This work opens up new opportunities in efficient preparation of materials that require hydrothermal process.