Toolbox for Distal C–H Bond Functionalizations in Organic Molecules

Chemical Reviews, Journal Year: 2021, Volume and Issue: 122(6), P. 5682 - 5841

Published: Oct. 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.

Language: Английский

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Copper-catalyzed radical relay in C(sp³)–H functionalization

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(5), P. 1640 - 1658

Published: Jan. 1, 2022

Radical-involved transition metal (TM) catalysis has greatly enabled new reactivities in recent decades. Copper-catalyzed radical relay offers enormous potential C(sp3)-H functionalization which combines the unique regioselectivity of hydrogen atom transfer (HAT) and versatility copper-catalyzed cross-coupling. More importantly, significant progress been achieved asymmetric C-H through judicious ligand design. This tutorial review will highlight advances this rapidly growing area, we hope survey inspire future strategic developments for selective functionalization.

Language: Английский

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Organoselenium Compounds: Chemistry and Applications in Organic Synthesis

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(52)

Published: June 28, 2023

Abstract Selenium, originally described as a toxin, turns out to be crucial trace element for life that appears selenocysteine and its dimer, selenocystine. From the point of view drug developments, selenium‐containing drugs are isosteres sulfur oxygen with advantage presence selenium atom confers antioxidant properties high lipophilicity, which would increase cell membrane permeation leading better oral bioavailability. In this article, we have focused on relevant features atom, above all, corresponding synthetic approaches access variety organoselenium molecules along proposed reaction mechanisms. The preparation biological selenosugars, including selenoglycosides, selenonucleosides, selenopeptides, other compounds will treated. We attempted condense most important aspects interesting examples chemistry into single article.

Language: Английский

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

Chemistry - An Asian Journal, Journal Year: 2020, Volume and Issue: 15(6), P. 651 - 672

Published: Feb. 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.

Language: Английский

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Radical‐Promoted Distal C−H Functionalization of C(sp³) Centers with Fluorinated Moieties

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(22), P. 12170 - 12191

Published: Sept. 17, 2020

Due to their unique properties, fluorinated scaffolds are pivotal compounds in pharmaceuticals, agrochemicals, and materials science. Over the last years, development of versatile strategies for selective synthesis molecules by direct C-H bond functionalization has attracted a lot attention. In particular, design novel transformations based on radical process was bottleneck distal reactions, offering synthetic solutions introduction groups. This Minireview highlights major contributions this blossoming field. The new methodologies remote aliphatic derivatives with various groups 1,5-hydrogen atom transfer β-fragmentation reaction will be showcased discussed.

Language: Английский

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Copper-Catalyzed, Chloroamide-Directed Benzylic C–H Difluoromethylation

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(50), P. 19941 - 19949

Published: Nov. 22, 2019

We report herein the first catalytic strategy to harness amidyl radicals derived from N-chloroamides for C–C bond formation, allowing discovery of benzylic C–H difluoromethylation. Under copper-catalyzed conditions, a wide variety N-chlorocarboxamides and N-chlorocarbamates direct selective difluoromethylation with nucleophilic difluoromethyl source at room temperature. This scalable protocol exhibits broad substrate scope functional group tolerance, enabling late-stage bioactive molecules. copper-catalyzed, chloroamide-directed has also been extended pentafluoroethylation trifluoromethylation. Mechanistic studies on reactions support that involve formation via intramolecular activation, followed by copper-mediated transfer groups radicals.

Language: Английский

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Alkene versus alkyne reactivity in unactivated 1,6-enynes: regio- and chemoselective radical cyclization with chalcogens under metal- and oxidant-free conditions

Green Chemistry, Journal Year: 2020, Volume and Issue: 22(7), P. 2288 - 2300

Published: Jan. 1, 2020

Substituted pyrrolidine derivatives are obtained via regio- and chemoselective 5-exo-dig radical cyclization of unactivated 1,6-enynes with chalcogens under metal- oxidant-free conditions.

Language: Английский

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

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(15)

Published: Feb. 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.

Language: 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, Journal Year: 2021, Volume and Issue: 144(1), P. 339 - 348

Published: Dec. 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.

Language: Английский

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Photocatalytic C–H Trifluoromethylthiolation by the Decatungstate Anion

Organic Letters, Journal Year: 2021, Volume and Issue: 23(15), P. 5729 - 5733

Published: July 14, 2021

A broadly applicable method for the trifluoromethylthiolation of methylene C(sp3)–H, methine α-oxygen and formyl C(sp2)–H bonds is presented using decatungstate anion as sole catalyst. By adjusting substrate ratio reaction concentration, this was applied to 40 examples in good regioselectivities, including derivatization natural products. Furthermore, SCF3–drug analogues were synthesized by subsequent functionalization SCF3 products, highlighting importance photocatalyzed C–H functionalization.

Language: Английский

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