Multicomponent Synthesis of α-Branched Amines via a Zinc-Mediated Carbonyl Alkylative Amination Reaction

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9045 - 9062

Published: March 15, 2024

Methods for the synthesis of α-branched alkylamines are important due to their ubiquity in biologically active molecules. Despite development many methods amine preparation, C(sp3)-rich nitrogen-containing compounds continue pose challenges synthesis. While carbonyl reductive amination (CRA) between ketones and is cornerstone method alkylamine synthesis, it sometimes limited by sterically demanding condensation step dialkyl amines more restricted availability compared aldehydes. We recently reported a "higher-order" variant this transformation, alkylative (CAA), which utilized halogen atom transfer (XAT)-mediated radical mechanism, enabling streamlined complex alkylamines. efficacy visible-light-driven approach, displayed scalability issues, competitive was problem certain substrate classes, limiting applicability. Here, we report change reaction regime that expands CAA platform through realization an extremely broad zinc-mediated reaction. This new strategy enabled elimination CRA, simplified purification, improved scope. Furthermore, harnessed carboxylic acid derivatives as alkyl donors facilitated α-trialkyl tertiary amines, cannot be accessed via CRA. Zn-mediated can carried out at variety scales, from 10 μmol setup microtiter plates high-throughput experimentation, gram-scale medicinally-relevant compounds. believe transformation enables robust, efficient, economical access provides viable alternative current benchmark methods.

Language: Английский

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Enable biomass-derived alcohols mediated alkylation and transfer hydrogenation

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 15, 2024

A single-atom catalyst with generally regarded inert Zn–N4 motifs derived from ZIF-8 is unexpectedly efficient for the activation of alcohols, enabling alcohol-mediated alkylation and transfer hydrogenation. C-alkylation nitriles, ketones, N-heterocycles, amides, keto acids, esters, N-alkylation amines amides all go smoothly developed method. Taking α-alkylation nitriles alcohols as an example, starts (1) nitrogen-doped carbon support catalyzed dehydrogenation into aldehydes, which further condensed to give vinyl followed by (2) hydrogenation C=C bonds in on sites. The experimental results DFT calculations reveal that Lewis acidic Zn-N4 sites promote step activating alcohols. This first example highly catalysts various organic transformations biomass-derived alkylating reagents hydrogen donors. Using carbonyl compounds or synthesis α-alkylated appealing a sustainability perspective. Here, acting acid effectively activates thus promoting reactions using both

Language: Английский

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Manganese‐Catalyzed Mono‐N‐Methylation of Aliphatic Primary Amines without the Requirement of External High‐Hydrogen Pressure

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(13)

Published: Feb. 1, 2024

Abstract The synthesis of mono‐ N ‐methylated aliphatic primary amines has traditionally been challenging, requiring noble metal catalysts and high‐pressure H 2 for achieving satisfactory yields selectivity. Herein, we developed an approach the selective coupling methanol amines, without hydrogen, using a manganese‐based catalyst. Remarkably, up to 98 % with broad substrate scope were achieved at low catalyst loadings. Notably, due weak base‐catalyzed alcoholysis formamide intermediates, our novel protocol not only obviates addition but also prevents side secondary ‐methylation, supported by control experiments density functional theory calculations.

Language: Английский

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A Guide for Mono‐Selective N‐Methylation, N‐Ethylation, and N‐n‐Propylation of Primary Amines, Amides, and Sulfonamides and Their Applicability in Late‐Stage Modification

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(26)

Published: Feb. 14, 2024

Abstract This review provides a comprehensive overview of mono‐alkylation methodologies targeting crucial nitrogen moieties – amines, amides, and sulfonamides found in organic building blocks pharmaceuticals. Emphasizing the intersection chemical precision with drug discovery, central challenge addressed is achieving one‐pot mono‐selective short‐chain N‐alkylations (methylations, ethylations, n ‐propylations), preventing undesired overalkylation. Additionally, sustainable, safe, benign alternatives to traditional alkylating agents, including alcohols, carbon dioxide, carboxylic acids, nitriles, alkyl phosphates, quaternary ammonium salts, carbonates, are explored. review, categorized by nature agent, aids researchers selecting suitable methods for N‐alkylation.

Language: Английский

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Strategies and Methods for the Synthesis of 2‐Pyrazolines: Recent Developments (2012–2022)

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(12), P. 1934 - 1969

Published: May 22, 2023

Abstract 2‐Pyrazolines are important five‐membered heterocycles, containing two adjacent nitrogen atoms. They can incorporate various functional groups and possess unique biological properties. Moreover, they have been used as useful building blocks. In recent years, the field of 2‐pyrazoline synthesis has experienced enormous progress. Novel strategies developed, many studies reporting improvements or adaptations existing protocols published, giving access to new functionalizations, unexplored structures, and/or enantioselective synthesis. This review summarizes progress made in synthetic methodologies during period from 2012 2022. The functionalization challenges capabilities, scopes limitations reactions, substitution patterns, mechanisms where appropriate, will be discussed.

Language: Английский

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Ruthenium Complexes with NNN-Pincer Ligands for N-Methylation of Amines Using Methanol

Inorganic Chemistry, Journal Year: 2024, Volume and Issue: 63(25), P. 11821 - 11831

Published: June 7, 2024

A series of ruthenium complexes (Ru1–Ru4) bearing new NNN-pincer ligands were synthesized in 58–78% yields. All the are air and moisture stable characterized by IR, NMR, high-resolution mass spectra (HRMS). In addition, structures Ru1–Ru3 confirmed X-ray crystallographic analysis. These Ru(II) exhibited high catalytic efficiency broad functional group tolerance N-methylation reaction amines using CH3OH as both C1 source solvent. Experimental results indicated that electronic effect substituents on considerably affects reactivity which Ru3 an electron-donating OMe showed highest activity. Deuterium labeling control experiments suggested dehydrogenation methanol to generate hydride species was rate-determining step reaction. Furthermore, this protocol also provided a ready approach versatile trideuterated N-methylamines under mild conditions CD3OD deuterated methylating agent.

Language: Английский

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Highly Efficient Base Catalyzed N‐alkylation of Amines with Alcohols and β‐Alkylation of Secondary Alcohols with Primary Alcohols

ChemCatChem, Journal Year: 2023, Volume and Issue: 15(20)

Published: Aug. 8, 2023

Abstract Borrowing hydrogen (BH) reactions are very useful for the sustainable synthesis of C−C and C−N bonds. They generally operate with transition metal‐based catalysts along stoichiometric/catalytic amounts added base. Here we report that two catalytic transformations, carried out BH methodology, i. e. N ‐alkylation amines alcohols β‐alkylation secondary primary alcohols, can be performed effectively just base under air without using any catalyst. The mechanism is proposed to based on oxidation alcohol aldehyde followed by condensation an unsaturated intermediate which undergoes transfer hydrogenation product.

Language: Английский

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TEMPO/PhI(OAc)₂ promotes the α-aminophosphinoylation of alcohols with amines and H-phosphine oxides in aqueous medium

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(19), P. 3860 - 3865

Published: Jan. 1, 2024

The aminophosphinoylation of alcohols with amines and H-phosphine oxides provides an efficient mild approach to access various α-aminoalkylphosphine in good yields tolerance functional groups using H 2 O as a clean solvent.

Language: Английский

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Recent Developments of Transition‐Metal‐Catalyzed Cross‐Coupling of Nitriles and Alcohols

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(32)

Published: Aug. 22, 2024

Abstract Cross‐coupling of nitriles and alcohols offers an environmentally friendly atom‐economical method for the synthesis various valuable compounds. These compounds include α ‐alkylated ‐olefinated nitriles, primary amines, imines, N ‐alkylation amides, ‐heterocycles, δ ‐hydroxynitriles, olefins, etc . Herein, we have reviewed recent developments (from 2013–date) transition‐metal‐catalyzed cross‐coupling alcohols. A number transition metal complexes such as noble metals Ru Ir, well base Mn, Fe, Co, Ni are presented. Moreover, different product types, reaction conditions mechanisms discussed to understand catalyst development.

Language: Английский

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A general and expedient amination of alcohols catalysed by a single-site (NN)Co(ii)-bidentate complex under solventless conditions

Catalysis Science & Technology, Journal Year: 2023, Volume and Issue: 14(1), P. 98 - 109

Published: Nov. 22, 2023

Here we designed and synthesized a NN–Co II bidentate complex efficiently used it for general expedient amination of alcohols under benign, solventless conditions.

Language: Английский

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