Amine Reagents Research Articles

Depolymerization of Waste Polycarbonates to Value-Added Products.

Additive free aminolysis method developed for the depolymerization/upcycling of polycarbonates. We report here chemical recycling of polycarbonate under ambient conditions to get its monomer bisphenol A, monoaminocarbamate and biscarbamates in 1 : 2 : 1 ratio respectively. By employing the secondary amine as the aminating reagent, facilitates the depolymerization to work under additive/catalyst free conditions. The developed method deals with depolymerization of waste polycarbonates and works even with late-stage amine derivatives such as amoxapine and desloratadine which are drugs molecules known to treat neurotic disorders and allergies respectively. The reaction can be scaled up and works with similar efficacy which depicts the efficiency of the depolymerization of wasteend-of-life polycarbonate plastic waste. The biscarbamate and bisphenol-A was further subjected for the post functionalization to obtain amides and phenol in good yields.

Cu-Catalyzed Asymmetric Synthesis of γ-Amino Alcohols Featuring Tertiary Carbon Stereocenters.

Alkyne-functionalized oxetanes are presented as versatile substrates that in combination with amine reagents can be transformed into structurally diverse, chiral γ-amino alcohols featuring a tetrasubstituted tertiary stereocenter under Cu catalysis. Control experiments demonstrate the privileged nature of these oxetane precursors in terms of yield and asymmetric induction levels in the developed protocol, and postsynthetic modifications offer an easy way to access more advanced synthons.

One‐Pot Biocatalytic Conversion of Chemically Inert Hydrocarbons into Chiral Amino Acids through Internal Cofactor and H2O2 Recycling

Chemically inert hydrocarbons are the primary feedstocks used in the petrochemical industry and can be converted into more intricate and valuable chemicals. However, two major challenges impede this conversion process: selective activation of C‐H bonds in hydrocarbons and systematic functionalization required to synthesize complex structures. To address these issues, we developed a multi‐enzyme cascade conversion system based on internal cofactor and H2O2 recycling to achieve the one‐pot deep conversion from heptane to chiral (S)‐2‐aminoheptanoic acid under mild conditions. First, a hydrogen‐borrowing‐cycle‐based NADH regeneration method and H2O2in situ generation and consumption strategy were applied to realize selective C‐H bond oxyfunctionalization, converting heptane into 2‐hydroxyheptanoic acid. Integrating subsequent reductive amination driven by the second hydrogen‐borrowing cycle, (S)‐2‐aminoheptanoic acid was finally accumulated at 4.57 mM with eep > 99%. Hexane, octane, 2‐methylheptane, and butylbenzene were also successfully converted into the corresponding chiral amino acids with eep > 99%. Overall, the conversion system employed internal cofactor and H2O2 recycling, with O2 as the oxidant and ammonium as the amination reagent to fulfill the enzymatic conversion from chemically inert hydrocarbons into chiral amino acids under environmentally friendly conditions, which is a highly challenging transformation in traditional organic synthesis.

One-Pot Biocatalytic Conversion of Chemically Inert Hydrocarbons into Chiral Amino Acids through Internal Cofactor and H2O2 Recycling.

Chemically inert hydrocarbons are the primary feedstocks used in the petrochemical industry and can be converted into more intricate and valuable chemicals. However, two major challenges impede this conversion process: selective activation of C-H bonds in hydrocarbons and systematic functionalization required to synthesize complex structures. To address these issues, we developed a multi-enzyme cascade conversion system based on internal cofactor and H2O2 recycling to achieve the one-pot deep conversion from heptane to chiral (S)-2-aminoheptanoic acid under mild conditions. First, a hydrogen-borrowing-cycle-based NADH regeneration method and H2O2in situ generation and consumption strategy were applied to realize selective C-H bond oxyfunctionalization, converting heptane into 2-hydroxyheptanoic acid. Integrating subsequent reductive amination driven by the second hydrogen-borrowing cycle, (S)-2-aminoheptanoic acid was finally accumulated at 4.57 mM with eep > 99%. Hexane, octane, 2-methylheptane, and butylbenzene were also successfully converted into the corresponding chiral amino acids with eep > 99%. Overall, the conversion system employed internal cofactor and H2O2 recycling, with O2 as the oxidant and ammonium as the amination reagent to fulfill the enzymatic conversion from chemically inert hydrocarbons into chiral amino acids under environmentally friendly conditions, which is a highly challenging transformation in traditional organic synthesis.

Ex Situ Gaseous Reagent for Multicomponent Amine Bioconjugation.

We report a minimalist gaseous sulfonyl-chloride-derived reagent for multicomponent bioconjugation with amine, phenol, or aniline reagents to afford urea or carbamate products. With the utilization of a gas-phase reagent for a reaction mediated by metal ions, a variety of biologically relevant molecules, such as saccharide, poly(ethylene glycol), fluorophore, and affinity tag, can be efficiently cross-linked to the N terminus or lysine side-chain amines on natural polypeptides or proteins.

Novel Amination Reagent for Preparing 2° Amines

Novel Amination Reagent for Preparing 2° Amines

Decarboxylative stereoretentive C–N coupling by harnessing aminating reagent

In recent decades, strategies involving transition-metal catalyzed carbon-carbon or carbon-heteroatom bond coupling have emerged as potent synthetic tools for constructing intricate molecular architectures. Among these, decarboxylative carbon-nitrogen bond formation using abundant carboxylic acids or their derivatives has garnered notable attention for accessing alkyl- or arylamines, one of key pharmacophores. While several decarboxylative amination methods have been developed, the involvement of a common carboradical intermediate currently poses challenges in achieving stereospecific transformation toward chiral alkylamines. Herein, we present a base-mediated, stereoretentive decarboxylative amidation by harnessing 1,4,2-dioxazol-5-one as a reactive and robust amidating reagent under transition-metal-free ambient conditions, encompassing all types of primary, secondary and tertiary carboxylic acids, thereby providing access to the important pharmacophore, α-chiral amines. This method exhibits high functional group tolerance, convenient scalability, and ease of applicability for 15N-isotope labeling, thus accentuating its synthetic utilities. Experimental and computational mechanistic investigations reveal a sequence of elementary steps: i) nucleophilic addition of carboxylate to dioxazolone, ii) rearrangement to form a dicarbonyl N-hydroxy intermediate, iii) conversion to hydroxamate, followed by a Lossen-type rearrangement, and finally, iv) reaction of the in situ generated isocyanate with carboxylate leading to C–N bond formation in a stereoretentive manner.

Stereoselective Amine-omics Using Heavy Atom Isotope Labeled l-and d-Marfey's Reagents.

Biological amines and amino acids play essential roles in many biochemical processes. The chemical complexity of biological samples is challenging, and the selective identification and quantification of amines and amino acid stereoisomers would be very useful for amine-focused "amino-omics" studies. Many amines and amino acids are chiral, and their stereoisomers cannot be resolved on achiral media without chiral derivatization. In prior studies, we demonstrated the use of Marfey's reagent─a chiral derivatization reagent for amines and phenolic OH groups─for the LC-MS/MS resolution and quantification of amines and amino acid stereoisomers. In this study, a heavy atom isotope labeled Marfey's reagent approach for the stereoselective detection and quantification of amines and amino acids was developed. Heavy (13C2) l-Marfey's (Hl-Mar) and heavy (2H3) d-Marfey's (Hd-Mar) were synthesized from 13C2-l-Ala and 2H3-d-Ala, respectively. Both light and heavy Marfey's reagents were used to derivatize standard amine mixtures, which were analyzed by LC-QToF-HRMS. Aligned peak lists were comparatively analyzed by light vs heavy Mar mass differences to identify mono-, di-, and tri-Marfey's adducts and then by the retention time difference between l- and d-Mar derivatives to identify stereoisomers. This approach was then applied to identify achiral and chiral amine and amino acid components in a methicillin-resistant Staphylococcus aureus (MRSA) extract. This approach shows high analytical selectivity and reproducibility.

Pd(II)-Catalyzed 1,2-Oxyarylation of Alkenes with O-Acylhydroxylamines as the Oxygen Source.

O-Acylhydroxylamine has been widely employed as an electrophilic amination reagent in transition-metal-catalyzed C-N coupling reactions, but its use as an electrophilic oxygen source has not been disclosed. Here, we report a Pd-catalyzed 1,2-oxyarylation of alkenes with O-acylhydroxylamines as an oxidant and an oxygen source for the first time. With simple amide as the monodentate directing group, this method features a broad substrate scope, good functional group tolerance, and mild conditions.

Gold-catalyzed intermolecular amination of allyl azides with ynamides: efficient construction of 3-azabicyclo[3.1.0] scaffold

Gold-catalyzed amination reactions based on azides via α-imino gold carbene intermediates have attracted extensive attention in the past decades because this methodology leads to the facile and efficient construction of synthetically useful N-containing molecules, especially valuable N-heterocycles. However, successful examples of intermolecular generation of α-imino gold carbenes by using azides as amination reagents are rarely explored probably due to the weak nucleophilicity of azides. Herein, we disclose an efficient gold-catalyzed intermolecular aminative cyclopropanation of ynamides with the allyl azides, enabling flexible synthesis of a wide range of valuable 3-azabicyclo[3.1.0]hex-2-ene derivatives in good to excellent yields with excellent diastereoselectivities. Importantly, this protocol represents the first use of allyl azide as an efficient amination reagent in gold-catalyzed alkyne amination reactions.

Synthesis and in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes activity of aldehyde and Schiff base substituted cobalt (II), copper (II), and zinc (II) phthalocyanines

In this work, a series of aldehyde‐substituted phthalocyanine compounds (1, 3, and 5) were prepared by the cyclotetramerization of the 4‐(5‐(diethylamino)‐2‐formylphenoxy) phthalonitrile (a) and the corresponding metal salts. Schiff base‐substituted phthalocyanines (2, 4, and 6) were derived from an aldehyde‐substituted phthalocyanine (1, 3, and 5) via the reaction of aldehyde‐substituted phthalocyanines with an amine reagent. The compounds that were obtained were characterized using FT‐IR, 1H {13C} NMR, UV–Vis, and MS spectra (a and 1–6). The inhibitory qualities of synthesized aldehyde and Schiff base‐substituted complexes against the enzymes butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) were assessed. The majority of phthalocyanines exhibited strong enzyme‐inhibiting properties. Out of the six produced phthalocyanines, 3 and 4 displayed the most intriguing profiles as submicromolar selective AChE inhibitors (IC50 = 0.060 μM), whereas 1 demonstrated the most potent BChE inhibitor (IC50 = 0.024 μM). The aggregation studies of CoPcs, CuPcs, and ZnPcs (1–6) were also carried out in this work.

Aminative Suzuki-Miyaura coupling.

The Suzuki-Miyaura and Buchwald-Hartwig coupling reactions are widely used to form carbon-carbon (C-C) and carbon-nitrogen (C-N) bonds, respectively. We report the incorporation of a formal nitrene insertion process into the Suzuki-Miyaura reaction, altering the products from C-C-linked biaryls to C-N-C-linked diaryl amines and thereby joining the Suzuki-Miyaura and Buchwald-Hartwig coupling pathways to the same starting-material classes. A combination of a bulky ancillary phosphine ligand on palladium and a commercially available amination reagent enables efficient reactivity across aryl halides and pseudohalides, boronic acids and esters, and many functional groups and heterocycles. Mechanistic insights reveal flexibility on the order of bond-forming events, suggesting potential for expansion of the aminative cross-coupling concept to encompass diverse nucleophiles and electrophiles as well as four-component variants.

Ring‐Opening Amino Esterification of Cyclic Ketones to Access Distal Amino Acid Derivatives

AbstractThis study developed a method of synthesizing distal amino acid derivatives by the ring‐opening reaction of cyclic ketones, following the amino esterification functionalization of both terminals. To achieve this goal, we performed the ring‐opening reaction of cyclic ketones with an aminating reagent and alcohol under metal‐ and photocatalysis‐free conditions in a single step. The method directly afforded distal amino acid derivatives bearing C4−C6, C8, and C12 carbon main chains, such as γ, δ, and ϵ‐amino esters. The obtained amino esters were simply transformed into amino acids by hydrolysis.

Electrochemical Ni‐Catalyzed Decarboxylative C(sp3)−N Cross‐Electrophile Coupling

AbstractA new electrochemical transformation is presented that enables chemists to couple simple alkyl carboxylic acid derivatives with an electrophilic amine reagent to construct C(sp3)−N bond. The success of this reaction hinges on the merging of cooperative electrochemical reduction with nickel catalysis. The chemistry exhibits a high degree of practicality, showcasing its wide applicability with 1°, 2°, 3° carboxylic acids and remarkable compatibility with diverse functional groups, even in the realm of late‐stage functionalization. Furthermore, extensive mechanistic studies have unveiled the engagement of alkyl radicals and iminyl radicals; and elucidated the multifaceted roles played by iPr2O, Ni catalyst, and electricity.

Electrochemical Ni-Catalyzed Decarboxylative C(sp3 )-N Cross-Electrophile Coupling.

A new electrochemical transformation is presented that enables chemists to couple simple alkyl carboxylic acid derivatives with an electrophilic amine reagent to construct C(sp3 )-N bond. The success of this reaction hinges on the merging of cooperative electrochemical reduction with nickel catalysis. The chemistry exhibits a high degree of practicality, showcasing its wide applicability with 1°, 2°, 3° carboxylic acids and remarkable compatibility with diverse functional groups, even in the realm of late-stage functionalization. Furthermore, extensive mechanistic studies have unveiled the engagement of alkyl radicals and iminyl radicals; and elucidated the multifaceted roles played by i Pr2 O, Ni catalyst, and electricity.

Atroposelective Synthesis of 2‐Arylindoles via Chiral Phosphoric Acid‐Catalyzed Direct Amination of Indoles†

Comprehensive SummaryIndole‐based atropisomers are a very important class of axially chiral compounds. However, the atroposelective synthesis of axially chiral 2‐arylindole remains largely unexplored. In this study, we report the successful synthesis of atropisomeric 2‐arylindoles using direct amination of indoles with p‐quinonediimines in the presence of chiral phosphoric acid as a catalyst. Quinonediimine acts as an aminating reagent through formal polarity inversion of imine. The malonate group on the 2‐aryl of 2‐indoles was found to be essential for high enantioselectivity of the products. This could be due to the additional interaction between the ester group and the catalyst, as well as the intramolecular hydrogen bonding. Our findings provide a new strategy for the asymmetric construction of 2‐arylindole atropisomers.

Photoredox-catalyzed unsymmetrical diamination of alkenes for access to vicinal diamines.

A photoredox-catalyzed unsymmetrical diamination of alkenes by using N-aminopyridinium salts and nitriles as the amination reagents has been developed. Various vicinal diamines were obtained in moderate to excellent yields under mild reaction conditions. Furthermore, this protocol could be applied in the late-stage modification of pharmaceuticals and natural products. Preliminary mechanistic studies suggested that this methodology may undergo a radical pathway followed by a Ritter-type reaction.

Photoexcitation of (diarylmethylene)amino benziodoxolones for alkylamination of styrene derivatives with carboxylic acids.

The alkylamination of alkenes using pristine carboxylic acids was achieved by the photoexcitation of (diarylmethylene)amino benziodoxolones (DABXs), which serve as both an oxidant and an aminating reagent (an iminyl radical precursor). The developed method is a simple photochemical reaction without the need for external photosensitizers and shows a broad substrate scope for aliphatic carboxylic acids leading to the formation of primary, secondary, and tertiary alkyl radicals, thus enabling the facile synthesis of various structurally complex amines. Mechanistic investigations including transient absorption spectroscopy measurements using a laser flash photolysis (LFP) method disclosed the unique photochemical reactivity of DABXs, which undergoes homolysis of their I-N bonds to give an iminyl radical and ortho-iodobenzoyloxy radical, the latter of which participates in the single-electron oxidation of carboxylates.

γ-Lactam synthesis from cyclobutanone via transoximation and the Beckmann rearrangement.

This manuscript describes the synthesis of γ-lactam from the nitrogen insertion reaction of cyclobutanones using an oxime as an aminating reagent with a catalytic amount of Brønsted acid. This method was employed with a more stable oxime reagent, which is a precursor analog of hydroxylamine derivatives with explosive properties. The reaction was tolerated by various substituted cyclobutanones and less strained five- or six-membered ketones. The obtained γ-lactam products could be transformed into γ-aminobutyric acid derivatives via ring-opening hydrolysis. The reaction mechanism is discussed from the perspective of the isotope effect, etc.

Synthesis of BODIPY FL-tethered ridaifen-B, RID-B-BODIPY, and its localization in cancer cells.

We synthesized ridaifen-B boron dipyrromethene (RID-B-BODIPY) using 2-methyl-6-nitro benzoic anhydride (MNBA)-mediated dehydration condensation reaction between amino alkyl-tethered RID and BODIPY FL. Comparative experiments between dicyclohexylcarbodiimide (DCC) and MNBA for their coupling reactions demonstrated that MNBA is an effective condensation reagent for amines and BODIPY FL. A cell staining study with RID-B-BODIPY showed intracellular localization of BODIPY FL fluorescence, attributed to the RID-B structure, indicating the successful development of a tool for analyzing intracellular molecular behavior efficiently.