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Covalent adaptable networks (CANs) are being developed as future replacements for thermosets as they can retain the high mechanical and chemical robustness inherent to thermosets but also integrate the possibility of reprocessing after material use. Here, covalent adaptable polyimine-based networks were designed with methoxy and allyloxy-substituted divanillin as a core component together with long flexible aliphatic fatty acid-based amines and a short rigid chain triamine, yielding CANs with a high renewable content. The designed series of CANs with reversible imine functionality allowed for fast stress relaxation and tailorability of the thermomechanical properties, as a result of the ratio between long flexible and short rigid amines, with tensile strength (σ b ) ranging 1.07-18.7 MPa and glass transition temperatures ranging 16-61 °C. The CANs were subsequently successfully reprocessed up to three times without determinantal structure alterations and retained mechanical performance. The CANs were also successfully chemically recycled under acidic conditions, where the starting divanillin monomer was recovered and utilized for the synthesis of a recycled CAN with similar thermal and mechanical properties. This promising class of thermosets bearing sustainable dynamic functionalities opens a window of opportunity for the progressive replacement of fossil-based thermosets.

Enzymatic reduction of diphenylmethanimine derivatives has rarely been reported owing to their steric hindrance. Herein, imine reductase (IRED) from Nocardia cyriacigeorgica rationally engineered with an efficient strategy of focused rational iterative site-specific mutagenesis (FRISM) was selected for the reduction of a series of N -cyclopropylmethyl-1-aryl-1-phenylmethylimines. Two highly enantioselective IRED variants were identified, providing various bulky amine products with moderate to high yields and high ee values (up to >99%). This work provided an effective method to construct these important pharmaceutical intermediates.

We report the dual-catalytic enantioselective allylic alkylation of 2-(pyridylmethyl)amine-derived ketimines with allylic carbonates. The reaction proceeds under mild reaction conditions to generate α-amino heteroaryl benzylamine stereocenters in good yield and enantioselectivity. Enantioselectivity is achieved through the use of a copper catalyst modified with chiral bisphosphine ligand (2 S ,4 S )-bis(diphenylphosphino)pentane.

Herein, we describe a one-pot aminoalkylation of styrene derivatives with boronic acids (BAs) and boronic acid pinacol esters as radical precursors for the synthesis of complex secondary amines in moderate to high yields through a mild and easily accessible organophotoredox-catalytic four-component reaction. Additionally, we report for the first time in a photoredox process the activation of alkyl boronic acid derivatives by imines, which play a dual role in the reaction as both substrate and Lewis base activator. The protocol applicability was greatly enhanced by its successful adaptation to photoflow reactors.

In recent years, the development of environmentally benign molecular construction methods has been of great importance, and especially, resource recycling, high atomic efficiency, and low environmental impact are in high demand. From this point of view, attention has also been focused on the development of one-pot synthesis of pharmaceuticals and functional molecules. Imines are excellent synthetic intermediates of these useful molecules, and the environmentally friendly oxidative synthesis of imines from amines has been energetically developed using oxygen (or air), which is abundantly available on the Earth, as an oxidant. This review focuses on the latest innovative and green oxidation systems of amines to imines under atmospheric oxygen, and their application to one-pot/eco-friendly and sustainable synthesis of pharmaceuticals and functional molecules. In particular, catalytic systems that activate molecular oxygen are categorized and described in detail as transition metal catalytic systems, photoirradiated catalytic systems, and organocatalytic systems.

A three-component reductive coupling reaction of aldehydes, amines and cyanopyridines under electrochemical conditions has been developed. The in situ generated imine and cyanopyridine simultaneously undergo single-electron reduction at the cathode, and afford diarylmethylamines through radical coupling without the participation of reducing agents. The one-pot electrolysis method can modularly obtain various secondary and tertiary amines and exhibits broad functional group compatibility. Mechanistic experiments verify the pivotal reduction step from imine to α-amino radical and reveal the key role of benzoic acid in reducing the reduction potential of imine and cyanopyridine.

A reagent-controlled highly stereoselective reaction between (S)-difluoromethyl phenyl sulfoximine 1 and imines is reported, and this synthetic method provides a variety of enantiomerically enriched α-difluoromethyl amines. The main pros of this approach include high efficiency, high stereoselectivity, and a broad substrate scope, which is probably achieved through a non-chelating transition state.

Functionalized alicyclic amines are important building blocks for the synthesis of bioactive natural compounds and drugs. Existing methods of functionalization are typically limited to the synthesis of protected amines or the use of highly basic organometallic reagents that can compromise functional group tolerance. Here, we report a novel approach that enables the transformation of O -benzoyl hydroxylamines into α-functionalized cyclic secondary amines by means of a copper-catalyzed regio-, stereo-, and chemoselective coupling with allenes and bis(pinacolato)diboron. A key feature of the present transformation is the use of a catalytic Lewis base additive which inhibits the competing C-N bond forming reaction between the catalytically generated boron-substituted allylcopper intermediate with the O -benzoyl hydroxylamine, thus enabling in situ transformation of the latter into an alicyclic imine which undergoes selective C-C bond formation with the allylcopper species.

Herein, we report a transition metal-free, operationally simple, general method for straightforward syntheses of 2-substituted benzoxazoles from readily available cyclohexanones and aliphatic primary amines by an imine α-oxygenation-initiated cascade reaction sequence. The key to achieving high selectivity and excellent functional-group tolerance is the use of TEMPO as a mild oxidant that selectively oxidizes the reaction intermediates through its multiple reactivity modes, thus facilitating the individual steps to proceed in succession. More than 70 substrate combinations are disclosed, demonstrating the reliability of this protocol to synthesize structurally diverse products, including marketed drugs, drug candidate, and natural products that are unattainable by the existing methods., (© 2022 Wiley-VCH GmbH.)

Ionic (2 e - ) nucleophilic addition of allylmetal regents to imines dominates the synthesis of homo-allyl amine; however, single electron (1 e - ) mediated imine allylation with feedstocks butadiene as an alternative allyl source remains unexplored. In this work, we report a conceptually different radical-radical cross-coupling strategy for the synthesis of a homoallyl amine between an α-amino alkyl radical and a transient allylic radical. This metal-free method provided a novel approach for the synthesis of homoallylic amines (>80 examples) from readily available materials with excellent regioselectivity and exceptional broad functional group compatibility., (© 2022 Wiley-VCH GmbH.)

A number of imines, including 12 new compounds, previously not reported in the literature, derived from variously fluorinated benzaldehydes and different anilines or chiral benzylamines were synthesized by a solvent-free mechanochemical method, which was based on the manual grinding of equimolar amounts of the substrates at the room temperature. In a very short reaction time of only 15 min, the method produced the expected products with good-to-excellent yields. The yields were comparable or significantly higher than those reported in the literature for the imines synthesized by other methods. Importantly, the conditions used for the reactions with aniline derivatives also resulted in the high yields of imines obtained from chiral benzylamines, and can be extended to the synthesis with other similar amines. Structures of all imines were confirmed by NMR spectroscopy: 1 H, 13 C and 19 F. For four compounds, X-ray structures were also obtained. The synthetic approach presented in this paper contributes to the prevention of environmental pollution and can be easily extended for larger-scale syntheses. The mechanochemical solvent-free method provides a convenient strategy particularly useful for the preparation of fluorinated imines being versatile intermediates or starting material in the synthesis of drugs and other fine chemicals.

Pd nanospecies supported on porous g-C3N4 nanosheets were prepared for efficient reductive amination reactions. The structures of the catalysts were characterized via FTIR, XRD, XPS, SEM, TEM, and TG analysis, and the mechanisms were investigated using in situ ATR−FTIR spectroscopic analysis complemented by theoretical calculation. It transpired that the valence state of the Pd is not the dominating factor; rather, the hydroxyl group of the Pd(OH)2 cluster is crucial. Thus, by passing protons between different molecules, the hydroxyl group facilitates both the generation of the imine intermediate and the reduction of the C=N unit. As a result, the sterically hindered amines can be obtained at high selectivity (>90%) at room temperature.

The synthesis of unnatural, tertiary amino acids is a challenging task. While decarboxylation-radical addition has been an important strategy for their formation, the use of alkyl radicals from C(sp 3 )-H bonds has not been fully explored. Herein, we report a photocatalytic protocol for the synthesis of unnatural α-amino esters employing abundant alkanes and imines retaining full atom economy. When this method is applied, several amino acid derivatives are synthesized in moderate to good yields.

The development of two divergent and complementary Lewis acid catalyzed additions of bicyclobutanes to imines is described. Microscale high-throughput experimentation was integral to the discovery and optimization of both reactions. N-arylimines undergo formal (3+2) cycloaddition with bicyclobutanes to yield azabicyclo[2.1.1]hexanes in a single step; in contrast, N-alkylimines undergo an addition/elimination sequence to generate cyclobutenyl methanamine products with high diastereoselectivity. These new products contain a variety of synthetic handles for further elaboration, including many functional groups relevant to pharmaceutical synthesis. The divergent reactivity observed is attributed to differences in basicity and nucleophilicity of the nitrogen atom in a common carbocation intermediate, leading to either nucleophilic attack (N-aryl) or E1 elimination (N-alkyl)., (© 2022 Wiley-VCH GmbH.)

Flow reaction methods have been developed to selectively synthesize tertiary, secondary, and primary amines depending on heterogeneous platinum-group metal species under catalytic hydrogenation conditions using nitriles as starting materials. A 10 % Pd/C-packed catalyst cartridge affords symmetrically substituted tertiary amines in good to excellent yields. A 10 % Rh/C-packed catalyst cartridge enables the divergent synthesis of secondary and primary amines, with either cyclohexane or acetic acid as a solvent, respectively. Reaction parameters, such as the metal catalyst, solvent, and reaction temperature, and continuous-flow conditions, such as flow direction and second support of the catalyst in a catalyst cartridge, are quite important for controlling the reaction between the hydrogenation of nitriles and nucleophilic attack of in situ-generated amines to imine intermediates. A wide variety of aliphatic and aromatic nitriles could be highly selectively transformed into the corresponding tertiary, secondary, and primary amines by simply changing the metal species of the catalyst or flow parameters. Furthermore, the selective continuous-flow methodologies are applied over at least 72 h to afford three different types of amines in 80-99 % yield without decrease in catalytic activities., (© 2021 Wiley-VCH GmbH.)

The development of efficient synthetic methods for accessing enantioenriched α-chiral amines is of great importance in the disciplines of medicinal and synthetic organic chemistry. Enantioselective Rh-catalyzed 1,2-addition reactions to activated imine derivatives are regarded as useful protocols for forming α-chiral amines. This personal account outlines our efforts to develop chiral bicyclo[2.2.1]heptadiene ligands for Rh-catalyzed asymmetric additions of various organoboron reagents to a wide range of imine derivatives. Transformations of the thus-obtained adducts into known natural products or molecules of pharmaceutical importance serve to confirm their synthetic usefulness., (© 2021 The Chemical Society of Japan & Wiley-VCH GmbH.)

Although dynamic reactions of imines have been extensively studied, the dynamic behaviors manipulated by chirality remain nearly unexplored. In this work, enantioselective amine exchange reactions were demonstrated as a first example via the reaction of enantiomeric chiral amines such as natural amino acids with a series of innovative axially chiral 1,1'-binaphthyl-2,2'-diamine (BNDA)-based imines that were prepared from the condensation reactions between BNDA and salicylaldehyde (SA) or its derivatives. This enantioselective dynamic behavior can be directly indicated by the degree of the fluorescence response of the R -configuration of imines to the d-enantiomer of chiral amine, because the released BNDA can serve as the fluorescence signal output when the amine exchange reaction occurs, which is far higher than the response to its l-enantiomer under identical experimental conditions. For the S -configuration of chiral imines, the fluorescence response is the opposite. The enantioselective exchange reaction can be tuned by altering the electron-withdrawing or electron-donating capability of the substituent at position 4 or 5 of the SA part of chiral imines. Not only o -OH groups in SA-based imines but also protic solvents used as reaction media were found to be important to the dynamic behavior at high rates.

The mechanisms for the three- and four-component variants of the Castagnoli-Cushman reaction (CCR) have been investigated. A series of crossover experiments were conducted to probe the structure and reactivity of known amide-acid intermediates for the three- and four-component variants of the CCR (3CR and 4CR, respectively). Control experiments paired with in situ reaction monitoring with infrared spectroscopy for the 4CR align with a mechanism in which amide-acids derived from maleic anhydride can reversibly form free amine and cyclic anhydride. Although this equilibrium is unfavorable, the aldehyde present can trap the primary amine through imine formation and react with the enol form of the anhydride through a Mannich-like mechanism. This detailed mechanistic investigation coupled with additional crossover experiments supports an analogous mechanism for the 3CR and has led to the elucidation of new 3CR conditions with homophthalic anhydride, amines, and aldehydes for the formation of dihydroisoquinolones in good yields and excellent diastereoselectivity. This work represents the culmination of more than a decade of mechanistic speculation for the 3- and 4CR, enabling the design of new multicomponent reactions that exploit this novel mechanism.

N -(Aryloxy)imines, readily accessible by condensation/tautomerization of (pseudo)benzylic primary amines and 2,6-di- tert -butyl-1,4-benzoquinone, undergo efficient allylation to afford a wide range of homoallylic primary amines following hydrolytic workup. Deprotonation of N -(aryloxy)imines generates a delocalized 2-azaallyl anion-type nucleophile that engages in dearomative C-C bond-forming reactions with allylpalladium(II) electrophiles generated from allylic tert -butyl carbonates. This reactivity umpolung enables the formal α-allylation of (pseudo)benzylic primary amines. Mechanistic studies reveal that the apparent regioselectivity of the desired bond-forming event is a convergent process that is initiated by unselective allylation of N -(aryloxy)imines to give several regioisomeric species, which subsequently rearrange via stepwise [1,3]- or concerted [3,3]-sigmatropic shifts, ultimately converging to provide the desired regioisomer of the amine products.

Aminomethylhydroxymethylfuran derivatives are well known compounds which are used in the pharmaceutical industry. Reductive amination of 5-hydroxymethylfurfural (HMF) derived from available non-edible lignocellulosic biomass is an attractive method for the synthesis of this class of compounds. In the present study, the synthesis of N-substituted 5-(hydroxymethyl)-2-furfuryl amines and 5-(acetoxymethyl)-2-furfuryl amines was performed by two-step process, which includes the condensation of furanic aldehydes (HMF and 5-acetoxymethylfurfural) with primary amines in methanol on the first step and the reduction of obtained imines with hydrogen in a flow reactor over CuAlO x catalyst derived from layered double hydroxide on the second step. This process does not require isolation and purification of intermediate imines and can be used to synthesize a number of aminomethylhydroxymethylfurans in good to excellent yield.

The use of dynamic covalent reactions (DCRs) is gaining popularity for the construction of self-assembling architectures. We have recently introduced DCRs that exchange alcohols and aldehydes to create hemiaminal ethers within tri(2-picolyl)amine (TPA) ligands, all of which are templated by Zn(II). To expand the scope of this assembly, aromatic imines derived from pyridine-2-carboxyaldehyde were explored as dynamic covalent receptors for di(2-picolyl)amine in the presence of Zn(II) to create TPA ligands that contain aminal linkages. This represents another metal-templated in situ multicomponent assembly. The stability of the assembly was successfully modulated through substituent effects, and the equilibrium constants from imines to aminals were correlated by a linear free energy relationship (LFER) with σ(+) values. Dynamic component exchange was investigated as a means of probing multiple equilibriums quantitatively in the system. Further, the mechanism was analyzed with a qualitative kinetics study. NMR spectra reveal the different extents of two competing pathways for assembly depending upon whether the aromatic amine has electron-withdrawing or electron-donating groups on the ring. Finally, mass spectral evidence supports the presence and differing extents of dominance of the two pathways as a function of the substituents., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A highly efficient, simple, and versatile transition-metal-free metal-organic framework catalytic system is proposed for the oxidative coupling of amines to imines. The catalytic protocol features high activities and selectivities to target products; compatibility with a variety of substrates, including aliphatic amines and secondary amines; and the possibility to efficiently and selectively promote amine cross-coupling reactions. A high stability and recyclability of the catalyst is also observed under the investigated conditions. Insights into the reaction mechanism indicate the formation of a superoxide species able to efficiently promote oxidative couplings., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Asymmetric hydrogenation of imines leads directly to chiral amines, one of the most important structural units in chemical products, from pharmaceuticals to materials. However, highly effective catalysts are rare. This article reveals that combining an achiral pentamethylcyclopentadienyl (Cp*)-iridium complex with a chiral phosphoric acid affords a catalyst that allows for highly enantioselective hydrogenation of imines derived from aryl ketones, as well as those derived from aliphatic ones, with ee values varying from 81 to 98 %. A range of achiral iridium complexes containing diamine ligands were examined, for which the ligands were shown to have a profound effect on the reaction rate, enantioselectivity and catalyst deactivation. The chiral phosphoric acid is no less important, inducing enantioselection in the hydrogenation. The induction occurs, however, at the expense of the reaction rate., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A variety of N-alkyl-α,α-dichloroaldimines were vinylated by terminal acetylenes in the presence of Lewis acids such as In(OTf)3 or BF3 ⋅OEt2 and hexafluoroisopropanol (HFIP) as an additive. The reaction proceeds at ambient temperature and leads to geometrically pure allylic β,β-dichloroamines. This approach is complementary to previously reported transition-metal-catalyzed vinyl-transfer methods, which are not applicable to aliphatic imines and are restricted to imines that contain an electron-withdrawing nitrogen substituent. In the present approach, terminal alkynes were used as a source of the vinyl residue, and the N-alkyl moiety of the imine acts as a sacrificial hydrogen donor. The additional advantage of this methodology is the fact that no external toxic or hazardous reducing agents or molecular hydrogen has to be used. This new methodology nicely combines a C(sp(2) )C(sp) bond formation, hydride transfer, and an unusual cleavage of an unactivated CN bond, thereby giving rise to functionalized primary allylic amines. A detailed experimental study supported by DFT calculations of the mechanism has been done., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new and efficient method for the preparation of highly enantiomerically enriched α-aryl 2- or 3-indolyl-methanamines by rhodium-catalyzed asymmetric arylation of N-sulfonyl indolylimines with arylboronic acids using chiral bicyclo[3.3.0] diene was developed.

The first Rh(I)-catalyzed addition of alkenylboron reagents to imines is described. The Rh(I)-catalyzed addition of potassium alkenyltrifluoroborate salts to both aromatic and aliphatic N-tert-butanesulfinyl aldimines proceeds in good yields (up to 97%) and with very high diastereoselectivities (95:5 to >99:1). This new method enables the general and efficient asymmetric synthesis of the important class of alpha-branched allylic amines from readily available and stable starting materials.

1. The synthesis of methyl 5-iodopyridine-2-carboximidate and its reaction with amino groups of model compounds and performic acid-oxidized insulin are described. The reagent was designed to introduce heavy atoms into specific sites in proteins. 2. Specific reaction with the amino groups of oxidized insulin can be achieved under reasonably mild conditions giving rise to the corresponding N-monosubstituted amidines. 3. The extent of reaction of this reagent with protein amino groups can be readily determined by difference spectroscopy. Modification of lysine residues inhibits tryptic cleavage at such residues, and this can be of assistance in establishing the site of modification in the primary structure. 4. Evidence is presented to show that methyl 5-iodopyridine-2-carboximidate can react specifically, at pH5.0, with the aromatic amino group of 3-amino-l-tyrosine; the final product of this reaction is a 2-arylbenzoxazole. 5. The use of this reagent as a general method for preparing heavy-atom isomorphous derivatives of proteins is discussed.

Herein, the Cu‐UiO‐66 catalyst was developed for acceptorless dehydrogenative coupling (ADC) between alcohols and amines to produce imines. The Cu‐UiO‐66 catalyst was synthesized by installing Cu2+ onto Zr‐oxo clusters in UiO‐66, and the catalyst efficiently catalyzes the ADC reaction under mild and environmentally friendly conditions with excellent selectivity. Mechanistic studies reveal that the O2⋅− radicals and porosity of formed in Cu‐UiO‐66 participate cooperatively during the catalytic cycle. Meanwhile, the only by‐product of the system is environmentally benign water. Cycling tests and hot filtration tests showed that the Cu‐UiO‐66 catalyst exhibited excellent stability and catalytic activity during the reaction. Importantly, the Cu‐UiO‐66 catalyst might provide a promising strategy for the ADC reaction between alcohols and amines to produce imines. [ABSTRACT FROM AUTHOR]

Nanoparticles made of porous coordination polymers, known as metal‐organic frameworks (MOFs), are becoming increasingly popular in nanomaterials research, especially in catalytic applications. With their intricate architectures, MOFs make it possible to incorporate metal nodes, encapsulate substrates, and use functional linkers, all of which contribute to synergistic engineering. A Ni‐based metal‐organic framework sample was prepared by the solvothermal method with NiCl2.6H2O as a precursor of Ni metal and terephthalic (H2BDC) acid as a linker. The as‐synthesized NiBDC was verified by X‐ray diffraction (XRD), Fourier‐transform infrared spectroscopy (FT‐IR), scanning electron microscopy (SEM), scanning electron microscopy with energy dispersive X‐ray spectroscopy (SEM‐EDX), transmission electron microscopy (TEM), and N2 adsorption/desorption isotherms. Based on these findings, we applied the as‐synthesized NiBDC to the oxidative coupling reaction of benzylamine. The results revealed that with NiBDC as a heterogeneous catalyst, the oxidative coupling reaction of benzylamine achieved a performance of 92%. Furthermore, the catalyst maintains good stability after four catalytic cycles, with an efficiency of approximately 82%. [ABSTRACT FROM AUTHOR]

The catalytic activity of a Ru complex 1, bearing a fused π‐conjugated imidazo[1,2–a][1,8]naphthyridine‐based mesoionic carbene (MIC) ligand, is examined for the oxidation of primary amines. Complex 1 affords nitrile or imine depending on the nature of the terminal oxidants and solvents used in the reactions. Primary amines are converted to nitriles using NaIO4 in EtOAc/H2O mixture, whereas imines are obtained under O2 balloon pressure in toluene. A variety of nitriles and imines are accessed with high yields and selectivity. A set of control experiments, reaction profiles, and kinetic studies are undertaken to disclose the mechanistic details for nitrile and imine formation. The catalytic reactions illustrate a subtle dependency on the choice of oxidants and solvents in the oxidation of primary amines. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Although it offers a direct route to access synthetically valuable α‐chiral primary amines, asymmetric transfer hydrogenation of NH imines has been rarely studied, due in large part to the inaccessibility and instability of NH imines. Herein, we report a Rh‐catalyzed asymmetric transfer hydrogenation of a kind of novel and stable NH imines which are prepared via condensation of easily available sulfonylated 2'‐aminoacetophenones with NH3 in methanol. With this method, enantioenriched chiral 2‐(1‐aminoalkyl)anilines, which are privileged pharmacore groups, have been synthesized with good functional group compatibility, and with up to 99% ee. A gram‐scale reaction using 0.2 mol% of catalyst has been successfully performed to highlight the practicality. Furthermore, the products can be derivatized into enantiopure bioactive molecules as well as chiral tridentate ligands for metal catalysis. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Herein, we report rhodium catalyzed N‐arylation via addition of arylboronic acids to electron‐deficient α‐iminoesters which can be prepared in high efficiency by using easily accessible β‐carbonyl esters. The reaction is highly regiospecific to achieve the N‐aryl addition efficiently with up to 99% yield under mild conditions. The corresponding product can be further efficiently converted into indoles and a series of other important building blocks. [ABSTRACT FROM AUTHOR]