Contemporary Approaches for Amide Bond Formation

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(24), С. 4359 - 4391

Опубликована: Ноя. 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

Язык: Английский

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Mechanistic snapshots of rhodium-catalyzed acylnitrene transfer reactions

Science, Год журнала: 2023, Номер 381(6657), С. 525 - 532

Опубликована: Июль 20, 2023

Rhodium (Rh) acylnitrene complexes are widely implicated in catalytic C-H amidation reactions but have eluded isolation and structural characterization. To overcome this challenge, we designed a chromophoric octahedral Rh complex with bidentate dioxazolone ligand, which photoinduced metal-to-ligand charge transfer initiates amidation. X-ray photocrystallographic analysis of the Rh-dioxazolone allowed elucidation targeted Rh-acylnitrenoid provided firm evidence that singlet nitrenoid species is primarily responsible for acylamino reactions. We also monitored crystallo reaction nucleophile situ-generated Rh-acylnitrenoid, crystallographically traceable system to capture mechanistic snapshots transfer.

Язык: Английский

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Thioether-Directed NiH-Catalyzed Remote γ-C(sp³)–H Hydroamidation of Alkenes by 1,4,2-Dioxazol-5-ones

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(37), С. 14962 - 14968

Опубликована: Сен. 8, 2021

A NiH-catalyzed thioether-directed cyclometalation strategy is developed to enable remote methylene C–H bond amidation of unactivated alkenes. Due the preference for five-membered nickelacycle formation, chain-walking isomerization initiated by NiH insertion an alkene can be terminated at γ-methylene site from moiety. By employing 2,9-dibutyl-1,10-phenanthroline (L4) as ligand and dioxazolones reagent, occurs γ-C(sp3)–H bonds afford amide products in up 90% yield (>40 examples) with remarkable regioselectivity (up 24:1 rr).

Язык: Английский

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Endo-Selective Intramolecular Alkyne Hydroamidation Enabled by NiH Catalysis Incorporating Alkenylnickel Isomerization

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(22), С. 10064 - 10074

Опубликована: Май 27, 2022

Intramolecular alkyne hydroamidation represents a straightforward approach for the access to synthetically valuable cyclic enamides. Despite some advances made in this realm, ability attain precise regiocontrol still remains challenging, especially endo cyclization that leads six-membered and larger azacyclic rings. Herein, we report NiH-catalyzed intramolecular of alkynyl dioxazolones allows an excellent selectivity, thus affording range six- eight-membered endocyclic enamides with broad scope. Mechanistic investigations revealed Ni(I) catalysis is operative current system, proceeding via regioselective syn-hydronickelation, alkenylnickel E/Z isomerization, Ni-centered inner-sphere nitrenoid transfer. In particular, key isomerization step, which previously lacked mechanistic understandings, was found take place through η2-vinyl transition state. The synthetic value protocol demonstrated by diastereoselective modifications obtained highly functionalized δ-lactam scaffolds.

Язык: Английский

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On the Origin of Rh-Catalyzed Selective Ring-Opening Amidation of Substituted Cyclopropanols to Access β²-Amino Ketones

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(8), С. 3667 - 3675

Опубликована: Фев. 15, 2022

β2-Amino carbonyls, an α-substituted β-amino scaffold, hold a prominent place in the development of new pharmaceuticals and peptidomimetics. Herein, we report highly efficient Rh-catalyzed ring-opening amidation substituted cyclopropanols, which turned out to serve as linchpin for selective synthesis β2-amino ketones outcompete formation β3-isomers. Instead generally accepted rationale consider steric factors β2-selectivity, orbital interaction was elucidated play more critical role amidative cyclopropanols generate key Rh–C intermediate. Subsequent inner-sphere acylnitrene transfer achieved excellent efficiency (TON > 5000) by using readily accessible dioxazolones amino source afford with broad applicability.

Язык: Английский

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Transition Metal-Catalyzed Regioselective Direct C–H Amidation: Interplay between Inner- and Outer-Sphere Pathways for Nitrene Cross-Coupling Reactions

Accounts of Chemical Research, Год журнала: 2022, Номер 55(15), С. 2123 - 2137

Опубликована: Июль 19, 2022

ConspectusCatalytic C–N bond cross-coupling reactions have been a subject of fundamental importance in synthetic organic and medicinal chemistry because amides amines are ubiquitous motifs natural products, functional materials, pharmaceuticals. Since the pioneering works Breslow Mansuy on metalloporphyrin-catalyzed direct hydrocarbon amidation using sulfonyliminoiodinane reagents, substantial development has achieved toward practical selective amination protocols. Notably, Du Bois's group developed dirhodium(II,II) carboxylate catalytic system for C(sp3)–H amidations via Rh-sulfonyl nitrene intermediates. Yet, this protocol suffers from competitive alkene aziridination is limited to electron-rich tertiary ethereal C–H bonds; analogous arenes remained ineffective.This Account discusses our early effort explore cyclopalladated complexes ortho-selective C(aryl)–H amidations. While Buchwald–Hartwig cannot be directly applied arenes, effective 2-arylpyridines occurred when an external oxidant such as K2S2O8 was employed. Preliminary studies suggested that may proceed through reactive Pd-nitrene Aiming develop more diversified protocols, we employed nosyloxycarbamates precursors Pd-catalyzed ortho-amidation N-pivalanilides. Likewise, benzoic acids produce anthranilic acids, which versatile many medicinally valuable heterocycles. In attempt expand C(aryl)–N coupling amines, studied d6 piano-stool Cp*Rh(III) systems [Cp* = pentamethylcyclopentadienyl]. Our work established sound reaction platform based electrophilic aminating reagents including N-chloroamines, hydroxyamides, N-carboxyhydrazides formation aryl–metal complexes.Building upon metal-nitrene platform, moved forward examine γ-lactam synthesis by intramolecular carbonyl insertion. Noted nitrenes prone undergo Curtius-type rearrangement form isocyanate; found π-basic Ru(II) center effectively decomposes dioxazolones afford regioselective γ-C(sp3)–H With chiral diphenylethylenediamines (dpen) ligands bearing electron-withdrawing arylsulfonyl substituents, [(p-cymene)Ru(dpen)] complex catalyzed decomposition γ-lactams formal Enantioselective insertion allylic propargylic bonds also with remarkable tolerance C═C C≡C bonds. selectivity [(p-cymene)Ru] switched give dihydroquinolinones l-proline ligand. Recently, aimed address regiocontrolled unactivated methylene NiH catalyst. benzyl can differentiated their dissociation energies steric properties, groups making up skeleton display similar electronic properties. context, exploited five-membered nickelacycle terminate NiH-mediated chain-walk isomerization, reacted furnish C(sp3)–N at γ-methylene position.This summarizes contribution activation. By exploiting inner-sphere outer-sphere pathways, successfully protocols target The mechanistic underpinning different related affiliated will discussed.

Язык: Английский

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Iron-Catalyzed Intermolecular Amination of Benzylic C(sp³)–H Bonds

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(48), С. 21858 - 21866

Опубликована: Ноя. 23, 2022

A catalytic system for intermolecular benzylic C(sp3)-H amination is developed utilizing 1,2,3,4-tetrazole as a nitrene precursor via iron catalysis. This method enables direct installation of 2-aminopyridine into the and heterobenzylic position. The selectively aminates 2° bond over 3° 1° bonds. Experimental studies reveal that undergoes formation radical intermediate. study reports discovery new 2-pyridine substituted benzylamine synthesis using inexpensive, biocompatible base metal catalysis should have wide application in context medicinal chemistry drug discovery.

Язык: Английский

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Iron- and Ruthenium-Catalyzed C–N Bond Formation Reactions. Reactive Metal Imido/Nitrene Intermediates

ACS Catalysis, Год журнала: 2023, Номер 13(2), С. 1103 - 1124

Опубликована: Янв. 3, 2023

Transition-metal-catalyzed direct C–N bond formation via metal nitrenoid (metal imido/nitrene complexes) transfer reactions such as C–H amination/amidation and alkene aziridination is a versatile synthetic strategy for the preparation of nitrogen-containing compounds. In this area development, iron catalysts are appealing in context cost, biocompatibility, environmental sustainability, iron-catalyzed amination have become complementary approach organic compounds with complexity. Reactive species been widely proposed reaction intermediates C═C bonds. However, their short lifetimes solution make study these difficult. comparison iron, ruthenium nitrenoids considerably more stable but yet reactive enough reactions, leading to reliable surrogates understanding mechanism. Perspective, developments complexes supported by macrocyclic or polydentate ligands catalytic that occur summarized, well mechanisms involved highlights on intermediates. Current limitations, challenges, potential opportunities future also discussed.

Язык: Английский

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O-Allylhydroxyamine: A Bifunctional Olefin for Construction of Axially and Centrally Chiral Amino Alcohols via Asymmetric Carboamidation

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(14), С. 8150 - 8162

Опубликована: Апрель 4, 2023

Difunctionalization of olefins offers an attractive approach to access complex chiral structures. Reported herein is the design N-protected O-allylhydroxyamines as bifunctional that undergo catalytic asymmetric 1,2-carboamidation with three classes (hetero)arenes afford amino alcohols via C-H activation. The C═C bond in O-allylhydroxyamine activated by intramolecular electrophilic amidating moiety well a migrating directing group. carboamidation reaction pattern depends on nature (hetero)arene reagent. Simple achiral reacted give centrally β-amino excellent enantioselectivity. employment axially prochiral or racemic heteroarenes afforded both axial and central chirality enantio- diastereoselectivity. In case heteroarenes, coupling follows kinetic resolution s-factor up >600. A nitrene-based mechanism has been suggested based experimental studies, unique mode induction diastereoselectivity proposed. Applications alcohol products have demonstrated.

Язык: Английский

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Intermolecular Enantioselective Benzylic C(sp³)−H Amination by Cationic Copper Catalysis**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(24)

Опубликована: Апрель 14, 2023

Chiral benzylic amines are privileged motifs in pharmacologically active molecules. Intramolecular enantioselective radical C(sp3 )-H functionalization by hydrogen-atom transfer has emerged as a straightforward, powerful tool for the synthesis of chiral amines, but methods intermolecular amination remain elusive. Herein, we report cationic copper catalytic system with peroxide an oxidant. This mild, straightforward method can be used to transform array feedstock alkylarenes and amides into high enantioselectivities, it good functional group tolerance broad substrate scope. More importantly, synthesize bioactive molecules, including drugs. Preliminary mechanistic studies indicate that reaction involves radicals generated transfer.

Язык: Английский

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