Bond Amination Research Articles

Catalytic Reduction of Imines with Silylformates: Formation of Silyl Carbamates through CO2 Insertion.

Silylformates are emerging surrogates of hydrosilanes, able to reduce carbonyl groups in transfer hydrosilylation reactions, with the concomitant release of CO2. In this work, a new reactivity is revealed for silylformates, in the presence of imines. Using ruthenium catalysts, and lithium iodide as a co-catalyst, imines are shown to undergo hydrocarboxysilylation by formal insertion of CO2 to the N-Si bond of silyl amine to yield silyl carbamates in excellent yields.

Visible-Light-Mediated Deaminative Alkylation of Primary Amines with Silacarboxylic Acids via Isonitrile Formation.

The functionalization of the C-N bond of amines is a straightforward strategy for the construction of complex scaffolds or for the late-stage functionalization of pharmaceuticals. Herein, we describe a photoredox-catalyzed strategy for the deaminative alkylation of primary amine-derived isonitriles that provides unnatural amino acid derivatives under mild conditions. The use of silacarboxylic acids as silyl radical precursors enables the generation of carbon-centered radicals that allow the construction of Csp3-Csp3 bonds via a Giese-type addition, avoiding the undesired hydrodeamination product.

TBN-promoted regioselective C–C bond cleavage: a new strategy for the synthesis of unsymmetrically substituted N-aryl oxalamides

The intermolecular regioselective C–C and C–O bond cleavage and amination was accomplished by CuCl2-TBN system under mild reaction conditions for the synthesis of unsymmetrically substituted N-aryl oxalamides.

Iodine-Promoted C-H Bond Amination Reaction for the Synthesis of Fused Tricyclic Heteroarenes.

Fused heterocyclic scaffolds, such as benzimidazoles or larger ring systems containing a benzimidazole fragment, are frequently encountered in pharmaceutical compounds and other biologically active molecules. While there are many examples of N9- and/or C3-substituted 9H-benzo[4,5]imidazo[2,1-c][1,2,4]triazoles, current examples of the regioselective preparation of N1-substituted 1H-benzo[4,5]imidazo[2,1-c][1,2,4]triazoles are limited to N1-aryl substituted compounds, which also contain a C3-substituent. Here, we report an iodine-promoted C-H bond amination reaction that allows the selective preparation of 1H-benzo[4,5]imidazo[2,1-c][1,2,4]triazoles with a variety of aryl and alkyl N1-substituents. Not only do these cyclization reactions allow access to a new substitution pattern on the benzo[4,5]imidazo[2,1-c][1,2,4]triazole scaffold, but they are also tolerant toward a wide range of functional groups, including esters, amides, alcohols, alkynes, and alkenes. Our findings expand the synthetic toolbox for the preparation of nitrogen containing fused heteroarenes.

Investigating proton shuttling and electrochemical mechanisms of amines in integrated CO2 capture and utilization

Carbon capture and utilization (CCU) technologies present a promising solution for converting CO2 emissions into valuable products. Here we show how amines, such as monoethanolamine (MEA) and 2-amino-2-methyl-1-propanol (AMP), influence the electrochemical CO2 reduction process in an integrated CCU system. Using in situ spectroscopic techniques, we identify the key roles of carbamate bond strength, proton shuttling, and amine structure in dictating reaction pathways on copper (Cu) and lead (Pb) electrodes. Our findings demonstrate that on Cu electrodes, surface blockage by ammonium species impedes CO₂ reduction, whereas on Pb electrodes, proton shuttling enhances the production of hydrocarbon products. This study provides additional insights into optimizing CCU systems by tailoring the choice of amines and electrode materials, advancing the selective conversion of CO₂ into valuable chemicals.

Asymmetric Amination of Unstrained C(sp3)-C(sp3) Bonds.

The asymmetric functionalization of unstrained C(sp3)-C(sp3) bonds could be a powerful strategy to stereoselectively reconstruct the backbone of an organic compound, but such reactions are rare. Although allylic substitutions have been used frequently to construct C-C bonds by the cleavage of more reactive C-X bonds (X is usually an O atom of an ester) by transition metals, the reverse process that involves the replacement of a C-C bond with a C-heteroatom bond is rare and generally considered thermodynamically unfavorable. We show that an unstrained, inert allylic C-C σ bond can be converted to a C-N bond stereoselectively via a designed solubility-control strategy, which makes the thermodynamically unfavorable process possible. The C-C bond amination occurs with a range of amine nucleophiles and cleaves multiple classes of alkyl C-C bonds in good yields with high enantioselectivity. A novel resolution strategy is also reported that transforms racemic allylic amines to the corresponding optically active allylic amine by the sequential conversion of a C-N bond to a C-C bond and back to a C-N bond. Mechanistic studies show that formation of the C-N bond is the rate-limiting step and is driven by the low solubility of the salt formed from the cleaved alkyl group in a nonpolar solvent.

Organophotocatalytic Selective Deuteration of Metabolically Labile Heteroatom Adjacent C-H Bonds via H/D Exchange with D2O.

We report a general approach for efficient deuteration of the metabolically labile α-C-H bonds of widespread amides and amines. Temporarily masking the secondary amine group as a carbamate allows an unprecedented photoredox hydrogen atom transfer-promoted α-carbamyl radical formation for efficient H/D exchange with D2O. The mild protocol delivers structurally diverse α-deuterated secondary amines including "privileged" piperidine and piperazine structures highly regioselectively with excellent levels of deuterium incorporation (≤100%). Furthermore, we successfully implemented the strategy for α-deuteration of amides, lactams, and ureas with high regioselectivity and high levels of D incorporation. Finally, the observed efficient deuteration of secondary alcohol moieties in late-stage modification of complex amine-containing pharmaceuticals allows for the development of a viable method for efficient α-deuteration of the important functionality.

Magnetic covalent organic framework as an absorbent coupled with a portable mass spectrometer for rapid detection of malachite green and its metabolite residues

It is important to develop specific adsorbents for malachite green and other fish drug residues. Herein, a simple strategy for synthesizing a novel magnetic covalent organic frameworks (rFe3O4@Py-COF) has been studied, and the materials were used as a magnetic absorbent for solid phase extraction (MSPE) of malachite green (MG) and its metabolite as leucomalachite green (LMG) in fishes. In this study, the mild reduction program of formic acid replacing traditional sodium borohydride as a reducing agent has been adopted to increase the stability of the framework, which can maintain the original high crystallinity and surface area of the reduced COF. The secondary amine bond is expected to be used as the reaction center for further functionalization of COF pore wall. Subsequently, rFe3O4@Py-COF (rmCOF) obtained after reduction was used as MSPE materials to detect MG and LMG by a portable mass spectrometer. After optimizing the conditions, the linearity is good within the range of 1.25∼100 μg/kg (R2≥0.9954), the limits of detection (LODs) are 0.31∼0.44 μg/kg with satisfactory recovery (85.0 %∼106.0 %). These results indicate that the assay is suitable for monitoring MG and LMG in complex aquatic foods, providing protection for food safety.

A thermo-responsive chemically crosslinked long-term-release chitosan hydrogel system increases the efficiency of synergy chemo-immunotherapy in treating brain tumors

Glioblastoma multiforme (GBM) is an aggressive and common brain tumor. The blood-brain barrier prevents several treatments from reaching the tumor. This study proposes a Chemo-Immunotherapy synergy treatment chemically crosslinked hydrogel system that is injected into the tumor to treat GBM. The strategy uses doxorubicin and BMS-1 with a thermo-responsive and chemically crosslinked hydrogel for extended drug release into the affected area. The hydrogels are produced by mixing with Chitosan (Chi), modified Pluronic F-127 (PF-127) with aldehyde end group and doxorubicin and then chemically crosslinking the aldehyde and amine bonds to increase the drug retention time. PF-127-CHO/Chi, which gels at body temperatures and chemically crosslinks between PF-127-CHO and Chitosan, increases the time that the drug remains in the affected area and prevents the hydrogel from swelling and compressing surrounding tissue. The drug is released from the chemically crosslinked hydrogels, prevents tumor progression and increases survival for subjects with GBM tumors. The Synergy Chemo-Immunotherapy also allows more efficient treatment of GBM than chemotherapy. The PF-127-CHO/Chi DOX and BMS-1 group have a tumor that is 43 times smaller than the untreated group. These results show that the proposed chemically crosslinking hydrogel is an efficient intratumoral delivery platform for the treatment of tumors.

Photocatalytic Direct Para‐Selective C−H Amination of Benzyl Alcohols: Selectivity Independent of Side Substituents

AbstractAminoarenes are important molecules for broad applications in nearly all modern industries that involve chemicals. Direct and site‐selective C−H bond amination of arenes provides the most efficient and convenient method to prepare aminoarenes. A main challenge is to selectively install the amino group (or other functional groups) to the distal para‐carbon of arenes (especially multi‐substituted arenes) during the C−H bond functionalization events. Herein, we address this problem by designing a new strategy via a sequential radical dearomatization/radical amination/rearomatization process for para‐selective amination of benzyl alcohols. The para‐selectivity of our reaction is completely independent of the electronic and steric properties of the other substituents of the arene substrates. Aminoarenes with many substituents (up to full substitution) and diverse substitution patterns, including those difficult to synthesize previously, could be readily prepared using our protocols. Further exploration of the current strategy shall lead to other challenging C−H functionalization of arenes.

Photocatalytic Direct Para-Selective C-H Amination of Benzyl Alcohols: Selectivity Independent of Side Substituents.

Aminoarenes are important molecules for broad applications in nearly all modern industries that involve chemicals. Direct and site-selective C-H bond amination of arenes provides the most efficient and convenient method to prepare aminoarenes. A main challenge is to selectively install the amino group (or other functional groups) to the distal para-carbon of arenes (especially multi-substituted arenes) during the C-H bond functionalization events. Herein, we address this problem by designing a new strategy via a sequential radical dearomatization/radical amination/rearomatization process for para-selective amination of benzyl alcohols. The para-selectivity of our reaction is completely independent of the electronic and steric properties of the other substituents of the arene substrates. Aminoarenes with many substituents (up to full substitution) and diverse substitution patterns, including those difficult to synthesize previously, could be readily prepared using our protocols. Further exploration of the current strategy shall lead to other challenging C-H functionalization of arenes.

Photoredox cross-dehydrogenative C(sp2)-C(sp3) coupling of heteroarenes with secondary amines through 1,5-HAT.

The functionalization of α-C(sp3)-H bonds in amines has become a focal point of contemporary research. Here, we report a new approach utilizing photocatalysis α-C(sp3)-H bond functionalization in alicyclic and aliphatic secondary amines facilitated by intramolecular 1,5-hydrogen atom transfer (HAT). This finding unlocks a sustainable method for rapidly constructing complex heterocyclics via cross-dehydrogenative C-C coupling of protected amines and nitrogen-containing heterocycles. This protocol boasts broad applicability to various substrates, exhibits tolerance to numerous functional groups, and supports the late-stage modification of drug molecules.

One step synthesis of nitrogen-rich covalent organic frameworks with flexible secondary amine bonds for efficient iodide capture in aqueous solutions

One step synthesis of nitrogen-rich covalent organic frameworks with flexible secondary amine bonds for efficient iodide capture in aqueous solutions

Transformative potential: Utilizing Teos-modified mugwort for sustainable construction

Exploring innovative materials derived from natural sources holds significant promise in pursuing sustainable construction practices. This study investigates the modification of mugwort (Artemisia dubia Wall.) with TEOS (tetraethyl orthosilicate) and its application as a sustainable reinforcement material in construction applications. It aims to integrate the plant's inherent strength with TEOS-enhanced mechanical properties and assess the feasibility of incorporating TEOS-modified mugwort into a lime-based matrix. The modified mugwort and its lime-based composite characterisation were conducted using FTIR, SEM-EDS, thermogravimetric analysis, compressive strength tests, and nitrogen adsorption analysis. FTIR analysis showcases significant structural enhancements post-modification, corroborated by SEM-EDS findings indicating increased silicon content. Peaks at 2915, 2845, and 1256 cm⁻¹ confirm successful modification with octadecyl amine and Si-C bond integration. Silica-related peaks at 1052, 801, and 456 cm⁻¹ indicate the presence of Si-O-Si structures. SEM analysis observes the presentation of Si as a layer confirming line scan position results, and EDS analysis findings indicate an increased silicon content of 15.16 %. Thermogravimetric analysis of modified samples displayed improved stability at low temperatures and more significant mass loss at high temperatures (72.01 % for modified and 28.91 % for unmodified samples) due to the decomposition of new chemical components. Nitrogen adsorption measurements reveal enhanced porosity in modified mugwort, suggesting diverse applications. The surface area of modified mugwort increased by 85 % compared to unmodified samples. Compressive strength analyses underscore the material's suitability for construction, with modified samples exhibiting denser structures at 8.5 % and higher strength at 13.3 % compared to unmodified samples. Macrostructure analysis further supports this, highlighting enhanced compatibility with binding materials. Overall, modified mugwort emerges as a versatile, eco-friendly reinforcement material with improved mechanical and thermal properties, poised for various applications in sustainable construction.

Oxidative Cross-Dehydrogenative C–H Bond Amination of Imidazo[1,2-a]pyridines in Aqueous Media under Metal-Free Conditions

AbstractThe metal-free direct oxidative cross-dehydrogenative C–H bond amination of imidazopyridines with pyrazole in water as solvent has been developed under K2S2O8-promoted mild conditions. This strategy was applied to variable imidazoheterocycles to give amination products in moderate to good yields. The described protocol also offers scale-up synthesis for the construction of C–N bonds, which makes it suitable for the synthesis of biologically active compounds and pharmaceuticals.

Palladium(0)‐catalyzed Synthesis of Indoles and Carbazoles from o‐ Alkenyl (Alkyl) Anilines via C–H Amination Cyclization

Various indoles and carbazoles were synthesized from o‐alkenyl anilines and o‐aryl anilines by the β‐C(sp2)‐H bond amination cyclization without any oxidants or hydrogen acceptors. Likewise, employing o‐alkyl anilines as substrates, indole products are also obtained by the β‐C(sp3)‐H bond amination cyclization, and dehydrogenation. In this cross‐dehydrogenative coupling, many different functional groups are tolerated, and hydrogen gas is the only by‐product, thereby providing an intrinsically waste‐free approach for the synthesis of indoles and carbazoles.

Rhodium(II)-Catalyzed Alkynyl Carbene Insertion into N-H Bonds.

The first insertion of an alkynyl carbene into N-H bonds under Rh-catalysis is developed. Alkynyl hydrazone carboxylates are used as donor-acceptor carbene precursors and are exquisitely inserted into the N-H bonds of various amines, amides, and 1,2-diamines. A wide variety of 3-alkynyl 3,4-dihydroquinoxalin-2(1H)-ones and densely functionalized α-alkynyl α-amino esters are obtained in good to excellent yields. Further, chemoselective N-H insertion reactions, mechanistic studies, and various synthetic transformations for obtaining valuable heterocycles are demonstrated.

Electron Donor‐Acceptor (EDA) Complex Enabled C−C Cross‐Coupling Reactions of α‐Amino Radicals

AbstractElectron‐donor acceptor (EDA) complex has been an integral part of visible‐light photocatalysis and is different from the traditional photoredox catalysis, which requires an exogenous photocatalyst, typically a colored compound to initiate the photocatalytic cycle. Interestingly, the EDA‐complex photochemistry has found profound use in activating the inert α‐C−H bonds of amines. The strategy relied upon the formation of colored EDA‐complex between the donor (amine) and acceptor (Lewis acid), which upon harvesting light energy perform a SET process to generate radical cation and anion intermediates. The radical cation then loses the activated acidic proton (because of the SET, the acidity of α‐proton increases by lowering the BDE) to form α‐amino radical, which then participates in various C−C coupling cascades. In this review, different conceptual approaches for the generation of α‐amino radicals and their coupling for the C−C bond‐forming reaction under EDA‐complex triggered photocatalysis will be discussed with particular emphasis on the reaction mechanism from 2018 onwards.

Selective cleavage of Csp3–N bonds in aliphatic tertiary amines enabled by difluorocarbene to access esters and thioethers

Presented herein is a series of C–X (X ​= ​O, S) couplings for the synthesis of esters and thioethers via difluorocarbene-promoted selective Csp3–N bond cleavage between tertiary amines and carboxylic acids or thiols. In those reactions, difluorocarbene plays an important role for generating quaternary ammonium salts and thus efficiently activates the Csp3–N bonds in aliphatic tertiary acyclic amines. The developed reaction does not require any transition metal catalyst and features broad substrate scope, good functional group compatibility and ease of execution with more than 70 examples in total.

Preparation of chitosan‐based macromolecular synergistic antioxidants containing hindered phenolic and secondary amine structures and its effects on thermo‐oxidative aging of styrene‐butadiene rubber/silica composites

AbstractIn this study, chitosan (CS)‐based macromolecular synergistic antioxidant CS‐UC‐TDAA containing carbon–carbon double bond, hindered phenol, and aromatic secondary amine was prepared by using CS,10‐undecenoyl chloride (UC), p‐aminobenzoic acid (AA), 3,5‐di‐tert‐butyl‐2‐hydroxybenzaldehyde (TD) via esterification, Schiff base reaction, and acylation reaction. The molecular structure of CS‐UC‐TDAA was characterized by fourier transform infrared, 1H NMR, and elemental analysis. The effects of macromolecular synergistic antioxidant CS‐UC‐TDAA, small molecular antioxidant TDAA, commercial antioxidant 4020, and butylated hydroxytoluene (BHT) on the antiaging properties of styrene‐butadiene rubber (SBR)/SiO2 composites were systematically studied by accelerated thermo‐oxidative aging test, thermogravimetric (TG) analysis, and methanol Soxhlet extraction experiment. The experimental results show that CS‐UC‐TDAA has more outstanding thermo‐oxidative aging resistance, thermal stability, and solvent extraction resistance in SBR/SiO2 composites than TDAA, 4020, and BHT. The macromolecular synergistic antioxidant CS‐UC‐TDAA endows SBR/SiO2 composites with more durable antiaging performance, which is attributed to the synergistic antioxidant effect of its hindered phenol and aromatic secondary amine groups. Additionally, its resistance to migration and extraction is facilitated by the crosslinking of the carbon–carbon double bond with the rubber and its substantial molecular weight.