Sequential C–F bond functionalizations of trifluoroacetamides and acetates via spin-center shifts

Science, Journal Year: 2021, Volume and Issue: 371(6535), P. 1232 - 1240

Published: March 5, 2021

Defluorinative functionalization of readily accessible trifluoromethyl groups constitutes an economical route to partially fluorinated molecules. However, the controllable replacement one or two fluorine atoms while maintaining high chemoselectivity remains a formidable challenge. Here we describe general strategy for sequential carbon-fluorine (C-F) bond functionalizations trifluoroacetamides and trifluoroacetates. The reaction begins with activation carbonyl oxygen atom by 4-dimethylaminopyridine-boryl radical, followed spin-center shift trigger C-F scission. A chemoselectivity-controllable two-stage process enables generation difluoro- monofluoroalkyl radicals, which are selectively functionalized different radical traps afford diverse products. mechanism origin were established experimental computational approaches.

Language: Английский

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Recent advance in the C–F bond functionalization of trifluoromethyl-containing compounds

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(14), P. 3915 - 3942

Published: Jan. 1, 2021

The C–F bond is the strongest single in organic compounds.

Language: Английский

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Recent Advances in the Synthesis of Difluorinated Architectures from Trifluoromethyl Groups

Advanced Synthesis & Catalysis, Journal Year: 2021, Volume and Issue: 364(2), P. 234 - 267

Published: Nov. 29, 2021

Abstract Fluorine‐containing moieties are widely used in the pharmaceutical, agrochemical, and material fields. Thus, these structures of immense interest fields organic synthesis medicinal chemistry. Among various fluorinated groups, difluoromethyl unit has drawn increasing attention due to its unique pharmaceutical properties. In recent years, several methods for difluoromethylated compounds have been rapidly developed. However, most treat aromatic with excess difluoromethylating reagents, which often contain organometallic compounds, so transformations generally less environmentally friendly atom‐economical. this review, we summarize development new motifs or difluoroalkenes from trifluoromethylated trifluoromethyl alkenes via single C( sp 3 )−F bond cleavage. magnified image

Language: Английский

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C-F bond activation under transition-metal-free conditions

Science China Chemistry, Journal Year: 2021, Volume and Issue: 64(10), P. 1630 - 1659

Published: Aug. 30, 2021

Abstract The unique properties of fluorine-containing organic compounds make fluorine substitution attractive for the development pharmaceuticals and various specialty materials, which have inspired evolution diverse C-F bond activation techniques. Although many advances been made in functionalizations activated bonds utilizing transition metal complexes, there are fewer approaches available nonactivated due to difficulty oxidative addition metals inert bonds. In this regard, using Lewis acid abstract fluoride light/radical initiator generate radical intermediate emerged as powerful tools activating those Meanwhile, these transition-metal-free processes greener, economical, pharmaceutical industry, without heavy residues. This review provides an overview recent activations under conditions. key mechanisms involved demonstrated discussed detail. Finally, a brief discussion on existing limitations field our perspective presented.

Language: Английский

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Lewis Base–Boryl Radicals Enabled Borylation Reactions and Selective Activation of Carbon–Heteroatom Bonds

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 56(2), P. 169 - 186

Published: Dec. 26, 2022

ConspectusThe past decades have witnessed tremendous progress on radical reactions. However, in comparison with carbon, nitrogen, oxygen, and other main group element centered radicals, the synthetic chemistry of boron radicals was less studied, mainly due to high electron-deficiency instability such 3-center-5-electron species. In 1980s, Roberts co-workers found that coordination a Lewis base (amines or phosphines) center could form 4-center-7-electron boryl (Lewis base-boryl LBRs) are be more stable. only limited applications were developed. 2008, Curran achieved breakthrough discovery N-heterocyclic carbene (NHC) which enable range reduction polymerization Despite these exciting findings, powerful valuable LBRs would expected, given structures reactivities easily modulated, provide ample opportunities discover new this Account, summary our key contributions LBR-enabled borylation reactions selective activation inert carbon-heteroatom bonds will presented.Organoboron compounds shown versatile chemical society, their syntheses rely principally ionic The development mechanistically different allows synthesizing products inaccessible by traditional methods. For purpose, we progressively developed series NHC-boryl mediated chemo-, regio-, stereoselective alkenes alkynes, wide variety structurally diverse organoboron molecules successfully prepared. utility borylated also demonstrated. Furthermore, disclosed photoredox protocol for oxidative generation enabled useful defluoroborylation arylboration reactions.Selective bond is an ideal way convert simple starting materials value-added products, while cleavage bonds, particular chemoselectivity control when multiple identical present similar environments, remains long-standing challenge. We envisaged finely tuning properties might solution address Recently, 4-dimethylaminopyridine (DMAP)-boryl promoted sequential C-F functionalization trifluoroacetic acid derivatives, α-C-F selectively snipped via spin-center shift mechanism. This strategy enables facile conversion abundantly available highly mono- difluorinated molecules. Encouraged finding, further three-step sequence construct all-carbon quaternary centers from trichloromethyl groups, where three C-Cl cleaved rational choice suitable precursors each step. dehydroxylative alkylation α-hydroxy carboxylic derivatives achieved, allowing efficient some biomass platform value products.

Language: Английский

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Radical-Polar Crossover Enabled Triple Cleavage of CF₂Br₂: A Multicomponent Tandem Cyclization to 3-Fluoropyrazoles

Organic Letters, Journal Year: 2023, Volume and Issue: 25(32), P. 6062 - 6066

Published: Aug. 8, 2023

The elaboration of step-economy and catalytic approaches for accessing diverse fluorinated heterocyclics is highly desirable. Described herein a radical-polar crossover enabled three-component cyclization to polysubstituted fluoropyrazoles by using CF2Br2 as novel C1F1 synthon. Mechanistic experiments revealed that the in situ generation reactive intermediate gem-difluorovinylimine ion key this transformation. This protocol unlocks reactivity adds significant synthetic values fluorine chemistry.

Language: Английский

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Unconventional Transformations of Difluorocarbene with Amines and Ethers

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(5), P. 592 - 607

Published: Feb. 9, 2023

ConspectusFluorine-containing compounds are extensively involved in various fields originating from intriguing and unique characteristics of fluorine atom; notably, pharmaceuticals, the involvement a atom or fluorine-containing group is chief technique for improving pesticide effect developing new drugs. Difluorocarbene, one most important powerful reagents, widely employed studied many areas mainly to assemble gem-difluoromethyl molecules, including but not limited abundant reactions between difluorocarbene with nucleophilic substrates, Wittig reaction ketones aldehydes, cascade both nucleophile an electrophile, [2+1] cycloaddition alkenes alkynes. However, its unconventional protocols beyond as difluoromethyl synthon have rarely been studied, thus, it highly desired given abundance, inexpensiveness peculiar properties. In this Account, we discuss our discovery transformations difluorocarbene, instead sole source (different other dihalocarbene), actually can serve electron acceptor activate C-X bonds (X = N O) thus promote myriad fascinating assembly versatile valuable products aza-compounds (primary/secondary/tertiary amines well NH3 NaNH2 so on) aliphatic ethers absence transition metals expensive ligands. Inspired by electron-deficient first found that isocyanides could be readily formed situ when unoccupied orbital meets lone-pair primary amines; basic condition, defluorination cyclizations afford plethora N-containing heterocycles. Meanwhile, disclosed cyano anion accessible were mixed up suitable conditions, series aryl nitrile obtained presence Pd catalysis ArI. Interestingly, encountered secondary amines, formamides rendered under mild reactions. Of note, concomitant functionalizations C moieties via cleavage unstrained C(sp3)-N bond metal oxidant sparce, which indeed significantly add versatility diversity products. Gratifyingly, uitilizing cyclic tertiary achieved difluorocarbene-mediated deconstructive time, showing successive scission simultaneous functionalization atoms would introduced into oxidants. This method provides brand-new while very universal synthetic pathway selectively cleave inert unactivated Csp3-N bonds, halodifluoromethyl reagents act C1 halo (Cl, Br, I) sources. Fascinatingly, nitrogen ylides generated approach deaminative arylation alkenylation was time appropriate represents mode lead formal transition-metal free Suzuki cross coupling. Besides, also proceed novel recombination render meaningful 2-fluoroindoles 3-(2,2-difluoroethyl)-2-fluoroindoles ortho-vinylanilines, 3-fluorined oxindoles 2-aminoarylketones, acts F1 simultaneously. Last least, recently lone-pair-electron oxygen trap form oxonium ylide, eventually leads C-O formation ethers.

Language: Английский

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Synthetic Advantages of Defluorinative C−F Bond Functionalization

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(49)

Published: Aug. 22, 2023

Abstract Much progress has been made in the development of methods to both create compounds that contain C−F bonds and functionalize bonds. As such, are becoming common versatile synthetic functional handles. This review summarizes advantages defluorinative functionalization reactions for small molecule synthesis. The coverage is organized by type carbon framework fluorine attached mono‐ polyfluorinated motifs. main challenges, opportunities advances discussed each class organofluorine. Most text focuses on case studies illustrate how defluorofunctionalization can improve routes targets or properties enable unique mechanisms reactions. broader goal showcase incorporating exploiting design routes, improvement specific advent new methods.

Language: Английский

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A Traceless Heterocyclic Amine Mediator in Regioselectivity−Switchable Formal [1 + 2 + 2] Cycloaddition Reaction to 1,3,4- and 1,4,5-Trisubstituted Pyrazoles

Organic Letters, Journal Year: 2023, Volume and Issue: 25(3), P. 512 - 516

Published: Jan. 12, 2023

Switchable multicomponent reactions have been attractive tools for the construction of compound libraries with skeleton diversity and complexity by slightly changing reaction conditions. Described herein is a regioselectivity-switchable formal [1 + 2 2] cycloaddition from difluoroalkyl compounds, enaminones, RNHNH2, ultimately using 1-methylindazol-3-amine as traceless mediator to switch inherent regioselectivity 1,3,4-trisubstituted pyrazole formation 1,4,5-trisubstituted pyrazoles. Remarkable features this work include mild conditions, simple operation, broad scopes.

Language: Английский

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Recent advances in N-heterocyclic carbene (NHC)-catalyzed fluorination and fluoroalkylation

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(7), P. 2112 - 2133

Published: Jan. 1, 2024

Organofluorine compounds are of high value. NHC-catalyzed fluorination and fluoroalkylation have served as powerful versatile vehicles for accessing the related organofluorines. This review focuses on recent developments in this area.

Language: Английский

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