Contemporary Approaches for Amide Bond Formation

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(24), P. 4359 - 4391

Published: Nov. 7, 2023

Abstract Amide bond construction has garnered significant interest in recent decades due to amides being one of the most prevalent functional groups among bioactive molecules. Out thirty‐seven new drugs approved by FDA 2022, eleven are small molecules containing at least amide bond. Additionally, there nineteen large as drugs, some which have peptide structures, and therefore, also bear bonds. In years, multiple teams embraced challenge developing more efficient methods for formation. This dedication led numerous publications appearing monthly prestigious journals, showcasing advancements this field. The primary goal review is present viable strategies constructing It crucial differentiate between formation synthesis; hence, focus on describing specific forming C(O)−N particular, concentrates developed within last six years. There a particular emphasis approaches that consider thought process when selecting starting materials groups. approach ensures coverage all common chemical transformations yield

Language: Английский

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Switchable Radical Carbonylation by Philicity Regulation

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(32), P. 14923 - 14935

Published: Aug. 8, 2022

Carbonylation reactions involving CO as readily available C1 synthons have become one of the most important tools for construction carbonyl compounds from feedstock chemicals. Despite numerous catalytic methods carbonylation proceeding via ionic or radical pathways, an inherent limitation to these is need control switchable single and double carbonylative formation value-added products same simple starting materials. Here, we describe a new strategy that exploits photoredox catalysis regulate philicity amine coupling partners drive reactions. In carbonylation, amines were first transformed into nitrogen cations by single-electron transfer-oxidation coupled with form carbamoyl radicals, which further underwent cross-coupling incipient cyanoalkyl acyl radicals afford products. Upon addition stoichiometric 4-dimethylaminopyridine (DMAP), DMAP competitively traps initially formed relatively stabilized acyl-DMAP salts engaged in subsequent substitution nucleophilic produce The reaction proceeded smoothly excellent selectivity presence various nucleophiles at room temperature, generating valuable amides α-ketoamides versatile controlled fashion. Combined experimental computational studies provided mechanistic insights possible pathways.

Language: Английский

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Photoredox-Catalyzed and Copper(II) Salt-Assisted Radical Addition/Hydroxylation Reaction of Alkenes, Sulfur Ylides, and Water

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(6), P. 3279 - 3285

Published: Feb. 25, 2022

A visible light-driven photoredox-catalyzed and copper(II)-assisted three-component radical addition/hydroxylation reaction of alkenes, sulfur ylides, water is reported. This process shows broad substrate scope high functional group tolerance, with respect to both readily available ylides providing high-yielding practical access valuable γ-hydroxy carbonyl compounds. Key the success controlled generation α-carbonyl carbon radicals from via sulfonium salts by a visible-light-driven proton-coupled electron transfer (PCET) strategy in mixture 2,2,2-trifluoroethanol/CH2Cl2. Addition Cu(TFA)2·H2O helps accelerate radical-cation crossover improve efficiency. Mechanistic studies suggest that hydroxy moiety products stems water. study also builds up platform for further investigation into synthetic chemistry ylides.

Language: Английский

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Visible-light-induced dehydrogenative amidation of aldehydes enabled by iron salts

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(19), P. 2771 - 2774

Published: Jan. 1, 2023

A direct dehydrogenative amidation reaction of aldehydes and amines under a visible light mediated ligand-to-metal charge transfer (LMCT) process was described. In this protocol, aldehyde substrates were activated by photoinduced hydrogen atom abstraction (HAA), generating acyl chloride intermediates followed nucleophilic addition amines. The synthetic method furnishes good functional group tolerance broad substrate scope toward both aliphatic aromatic components.

Language: Английский

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Photoinduced carbamoylation reactions: unlocking new reactivities towards amide synthesis

Chemical Communications, Journal Year: 2022, Volume and Issue: 58(60), P. 8322 - 8339

Published: Jan. 1, 2022

In this review, we summarize the latest advances for amide moiety installation through photoinduced carbamoylation protocols.

Language: Английский

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An Efficient Light‐Mediated Protocol for the Direct Amide Bond Formation via a Novel Carboxylic Acid Photoactivation Mode by Pyridine‐CBr₄

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(35)

Published: April 4, 2023

The direct amide bond formation between a carboxylic acid and an amine still constitutes challenging reaction for both academia industry. We demonstrate herein that several pairs of amines (halogen acceptors) organohalogen sources may be used the photochemical amidation under either UVA or sunlight irradiation. Our studies led to identification pyridine-CBr4 as efficient agent perform synthesis LED 370 nm irradiation, avoiding super-stoichiometric quantities. An extended substrate scope was demonstrated, showing widely amino carboxyl protecting groups are compatible with this protocol, while number industrially interesting products bioactive compounds were synthesized. Direct infusion-high resolution mass spectrometry suggest unprecedented type activation mode upon involving generation symmetric anhydride, active ester pyridine N-oxide mixed anhydride hypobromous acid.

Language: Английский

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Minisci‐Type Carbamoylation of Azauracils with Oxamic Acids

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 27(7)

Published: Jan. 19, 2024

Abstract A Minisci‐type carbamoylation of azauracils was developed to afford 6‐carbamoyl in yields up 94 %. In this transformation, oxamic acids were employed as the carbamoyl radical sources under metal‐free conditions. It features high atom economy, good functional group compatibility and convenient operation.

Language: Английский

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Synthesis of non-equivalent diamides and amido-esters via Pd-catalysed carbonylation

Nature Synthesis, Journal Year: 2023, Volume and Issue: 3(2), P. 202 - 213

Published: Oct. 5, 2023

Abstract Given the widespread use of amides in chemistry and biology, development methods for their synthesis remains important. Although construction amide bonds has principle been known since Wöhler’s urea synthesis, direct atom-efficient preparation amides, especially with multiple amido groups, continues to be difficult. To address this challenge, we developed an efficient access heterobifunctional compounds through linking amines as well alcohols specific molecular pincers presence advanced carbonylation catalysts. In detail, describe non-symmetrical diamides amido-esters from available propargylic acetates using selective palladium-catalysed diamino- amino-alkoxy carbonylations. Mechanistic studies control experiments reveal a cascade process allenoic allylic amine dienamide crucial intermediates. The generality protocol is showcased by highly >100 molecules including many pharmaceutically relevant products.

Language: Английский

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Visible‐Light‐Mediated Amide Synthesis in Deep Eutectic Solvents

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 366(4), P. 870 - 876

Published: July 22, 2023

Abstract In the present study, for first time environmentally friendly deep eutectic solvents (DESs) are used as reaction media to perform an efficient, simple and straightforward photocatalytic amide synthesis at room temperature using thioacids amines. This method features mild conditions, a broad substrate scope, high yields (≤99%) under ambient conditions with air moisture tolerance. Moreover, applied operationally tolerate presence of several different functional group substituents on amine counterpart. Finally, developed approach allows recycling medium catalyst least three consecutive cycles without significant decrease in yield.

Language: Английский

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Decarboxylative Nickel- and Photoredox-Catalyzed Aminocarbonylation of (Hetero)Aryl Bromides

Organic Letters, Journal Year: 2023, Volume and Issue: 26(14), P. 2768 - 2772

Published: Oct. 5, 2023

An efficient methodology for the photoredox- and nickel-catalyzed aminocarbonylation of (hetero)aryl bromides was developed. The utilization readily available oxamic acids, application a broadly used organic photoredox catalyst (4CzIPN), mild reaction conditions make this transformation an appealing alternative to classical amidation procedures. generation carbamoyl radicals supported by trapping reactions with hydrogen atom transfer in presence D2O, yielding deuterated formamide. generality deuteration protocol confirmed various acids.

Language: Английский

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