Toolbox for Distal C–H Bond Functionalizations in Organic Molecules

Chemical Reviews, Год журнала: 2021, Номер 122(6), С. 5682 - 5841

Опубликована: Окт. 18, 2021

Transition-metal-catalyzed C–H activation has developed a contemporary approach to the omnipresent area of retrosynthetic disconnection. Scientific researchers have been tempted take help this methodology plan their synthetic discourses. This paradigm shift helped in development industrial units as well, making synthesis natural products and pharmaceutical drugs step-economical. In vast zone bond activation, functionalization proximal bonds gained utmost popularity. Unlike bonds, distal is more strenuous requires distinctly specialized techniques. review, we compiled various methods adopted functionalize mechanistic insights within each these procedures, scope methodology. With give complete overview expeditious progress made field organic chemistry while also highlighting its pitfalls, thus leaving open for further modifications.

Язык: Английский

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Piperidine Derivatives: Recent Advances in Synthesis and Pharmacological Applications

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2937 - 2937

Опубликована: Фев. 2, 2023

Piperidines are among the most important synthetic fragments for designing drugs and play a significant role in pharmaceutical industry. Their derivatives present more than twenty classes of pharmaceuticals, as well alkaloids. The current review summarizes recent scientific literature on intra- intermolecular reactions leading to formation various piperidine derivatives: substituted piperidines, spiropiperidines, condensed piperidinones. Moreover, applications natural piperidines were covered, latest advances discovery biological evaluation potential containing moiety. This is designed help both novice researchers taking their first steps this field experienced scientists looking suitable substrates synthesis biologically active piperidines.

Язык: Английский

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Copper-Catalyzed, N-Directed Csp³–H Trifluoromethylthiolation (−SCF₃) and Trifluoromethylselenation (−SeCF₃)

Journal of the American Chemical Society, Год журнала: 2019, Номер 141(46), С. 18405 - 18410

Опубликована: Ноя. 7, 2019

A direct and versatile copper-catalyzed trifluoromethylthiolation trifluoromethylselenation of primary, secondary, tertiary aliphatic C-H bonds was developed. The reaction provides access to molecules containing these emerging moieties in the presence a wide range common functional groups complex molecular environments.

Язык: Английский

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N‐Centered Radical Directed Remote C−H Bond Functionalization via Hydrogen Atom Transfer

Chemistry - An Asian Journal, Год журнала: 2020, Номер 15(6), С. 651 - 672

Опубликована: Фев. 3, 2020

The N-centered radical directed remote C-H bond functionalization via hydrogen-atom-transfer at distant sites has developed as an enormous potential tool for the organic synthetic chemists. Unactivated and secondary tertiary, well selected primary bonds, can be utilized by following these methodologies. synthesis of heterocyclic scaffolds provides them extra attention modern days' developments in this field unactivated bonds functionalizations.

Язык: Английский

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Enantioselective Radical Construction of 5-Membered Cyclic Sulfonamides by Metalloradical C–H Amination

Journal of the American Chemical Society, Год журнала: 2019, Номер 141(45), С. 18160 - 18169

Опубликована: Окт. 17, 2019

Both arylsulfonyl and alkylsulfonyl azides can be effectively activated by the cobalt(II) complexes of D2-symmetric chiral amidoporphyrins for enantioselective radical 1,5-C–H amination to stereoselectively construct 5-membered cyclic sulfonamides. In addition C–H bonds with varied electronic properties, Co(II)-based metalloradical system features chemoselective allylic is compatible heteroaryl groups, producing functionalized sulfonamides in high yields enantioselectivities. The unique profile reactivity selectivity Co(II)-catalyzed attributed its underlying stepwise mechanism, which supported several lines experimental evidence.

Язык: Английский

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Reactivity-Controlling Factors in Carboxylate-Assisted C–H Activation under 4d and 3d Transition Metal Catalysis

ACS Catalysis, Год журнала: 2020, Номер 10(18), С. 10551 - 10558

Опубликована: Авг. 17, 2020

Detailed density functional theory calculations provide valuable insight into reactivity-controlling factors in transition metal-catalyzed C–H activation by carboxylate assistance. The chelation-assisted of a variety arenes 3d and 4d metal complexes was analyzed means bond order analysis through (DFT) as well energy decomposition DLPNO–CCSD(T) calculations, thereby providing in-depth information on distinct electronic influences the key state demonstrating preferred base-assisted internal electrophilic substitution (BIES) rather than concerted metalation-deprotonation (CMD) pathway.

Язык: Английский

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Enantioconvergent Amination of Racemic Tertiary C–H Bonds

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(49), С. 20902 - 20911

Опубликована: Ноя. 30, 2020

Racemization is considered to be an intrinsic stereochemical feature of free radical chemistry as can seen in traditional halogenation reactions optically active tertiary C-H bonds. If the facile process racemization could effectively combined with ensuing step bond formation enantioselective fashion, then it would give rise deracemizative functionalization racemic bonds for stereoselective construction chiral molecules bearing quaternary stereocenters. As a demonstration this unique potential chemistry, we herein report that metalloradical catalysis successfully applied devise Co(II)-based catalytic system enantioconvergent amination C(sp3)-H The key success development catalyst fitting steric, electronic, and environments D2-symmetric amidoporphyrin supporting ligand. existence optimal reaction temperature recognized important factor realization process. Supported by optimized ligand, catalyze 1,6-amination at temperature, affording α-tertiary amines excellent yields high enantiocontrol newly created Systematic studies, including experiments utilizing deuterium-labeled substrates model system, shed light on underlying mechanistic details new amination. remarkable power create stereocenters multiple functionalities from ubiquitous bonds, showcased bicyclic N-heterocycles, opens door future synthetic applications technology.

Язык: Английский

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Remote C(sp³)−H Acylation of Amides and Cascade Cyclization via N‐Heterocyclic Carbene Organocatalysis

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(15)

Опубликована: Фев. 3, 2022

Abstract The direct functionalization of inert C(sp 3 )−H bonds under environmentally benign catalytic conditions remains a challenging task in synthetic chemistry. Here, we report an organocatalytic remote acylation amides and cascade cyclization through radical‐mediated 1,5‐hydrogen atom transfer mechanism using N‐heterocyclic carbene as the catalyst. Notably, diversity nitrogen‐containing substrates, including simple linear aliphatic carbamates ortho ‐alkyl benzamides, can be successfully applied to this system. With established protocol, over 120 examples functionalized δ‐amino ketones isoquinolinones with diverse substituents were easily synthesized up 99 % yield mild conditions. robustness generality strategy further highlighted by successful unactivated late‐stage modification pharmaceutical molecules. Then, asymmetric control radical reaction was attempted proven feasible newly designed chiral thiazolium catalyst, moderate enantioselectivity obtained at current stage. Preliminary mechanistic investigations several reactions, KIE experiments, computational studies shed light on mechanism.

Язык: Английский

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Intermolecular 1,2-Difunctionalization of Alkenes Enabled by Fluoroamide-Directed Remote Benzyl C(sp³)–H Functionalization

Journal of the American Chemical Society, Год журнала: 2021, Номер 144(1), С. 339 - 348

Опубликована: Дек. 22, 2021

A copper-catalyzed remote benzylic C-H functionalization strategy enabling 1,2-difunctionalization of alkenes with 2-methylbenzeneamides and nucleophiles, including alcohols, indoles, pyrroles, the intrinsic amino groups, is reported, which characterized by its redox-neutral conditions, exquisite site-selectivity, broad substrate scope, wide utilizations late-stage modifying bioactive molecules. This reaction proceeds through nitrogen-centered radical generation, hydrogen atom transfer, addition across alkenes, single-electron oxidation, carbocation electrophilic course cascades. While using external nucleophiles manipulates three-component alkene alkylalkoxylation alkyl-heteroarylation to access dialkyl ethers, 3-alkylindoles, 3-alkylpyrroles, omitting results in two-component alkylamidation ([5+2] annulation) benzo-[f][1,2]thiazepine 1,1-dioxides.

Язык: Английский

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Copper-Mediated Radical Fluorine-Atom Transfer to Sulfonyl Radical: A Dramatic 4-Methoxypyridine 1-Oxide Ligand Effect

ACS Catalysis, Год журнала: 2024, Номер 14(5), С. 3115 - 3127

Опубликована: Фев. 13, 2024

Although the transition metal-catalyzed radical fluorine atom transfer (FAT) strategy has emerged as a powerful tool for construction of C–F bonds, to our knowledge, this approach rarely been applied formation S–F bonds. Here, we report that 4-methoxypyridine 1-oxide can serve an inexpensive and simple yet effective ligand thus promote transformation copper-mediated challengeable FAT sulfonyl radicals, paving way assembly FSO2 group. Based on concept, three Cu(I)-catalyzed protocols involving site-selective intra- intermolecular fluorosulfonylation inert C(sp3)–H bonds 1,2-aminofluorosulfonylation inactivated alkenes have developed, enabling preparation C(sp3)-rich aliphatic fluorides cannot be easily synthesized by known methods. These practical operationally methods result in high functional group tolerance under mild conditions modification bioactive derivatives highly valued molecules. Detailed mechanistic studies indicate unique role facilitating such rare FATs via outer-sphere pathway.

Язык: Английский

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