Unconventional Transformations of Difluorocarbene with Amines and Ethers

Accounts of Chemical Research, Год журнала: 2023, Номер 56(5), С. 592 - 607

Опубликована: Фев. 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.

Язык: Английский

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Synthetic Advantages of Defluorinative C−F Bond Functionalization

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(49)

Опубликована: Авг. 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.

Язык: 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, Год журнала: 2023, Номер 25(3), С. 512 - 516

Опубликована: Янв. 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.

Язык: Английский

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Copper-catalysed difluorocarbene transfer enables modular synthesis

Nature Chemistry, Год журнала: 2023, Номер 15(8), С. 1064 - 1073

Опубликована: Июнь 12, 2023

Язык: Английский

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

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(7), С. 2112 - 2133

Опубликована: Янв. 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.

Язык: Английский

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A Journey of the Development of Privileged Difluorocarbene Reagents TMSCF₂X (X = Br, F, Cl) for Organic Synthesis

Accounts of Chemical Research, Год журнала: 2024, Номер 57(5), С. 693 - 713

Опубликована: Фев. 14, 2024

ConspectusAs fluorine has played an increasingly important role in modulating the physical, chemical, and biological properties of organic molecules, selective introduction atom(s) or fluorinated moieties into target molecules become a powerful tool development new pharmaceuticals, agrochemicals, functional materials. In this context, difluoromethylene (CF2) difluoromethyl (CF2H) groups are special interest because their ability to serve as bioisosteres ethereal oxygen atoms hydroxyl (OH) thiol (SH) groups, respectively. Difluorocarbene is one most versatile reactive intermediates incorporate CF2 CF2H groups; however, before 2006, previously known difluorocarbene reagents suffered from several drawbacks such using ozone-depleting substances (ODSs), difficult-to-handle reagents, harsh reaction conditions having narrow substrate scope and/or low yields. Moreover, reactivity generated different precursors (reagents) was often unpredictable, since generation (activation modes) various different, these may mismatch those required for subsequent difluorocarbene-involved transformations. Therefore, environmentally friendly well investigation mechanistic insights reactions, been highly desirable.In Account, we summarize our contributions applications synthesis 2006. We have developed seven including 2-chloro-2,2-difluoroacetophenone (1), chlorodifluoromethyl phenyl sulfone (2), S-difluoromethyl-S-phenyl-N-tosylsulfoximine (3), difluoromethyltri(n-butyl)ammonium chloride (4), (chlorodifluoromethyl)trimethylsilane (TMSCF2Cl, 5), (bromodifluoromethyl)trimethylsilane (TMSCF2Br, 6), (trifluoromethyl)trimethylsilane (TMSCF3, 7). journey, realized key factor ideal reagent that can be used broad range is, should allow activation modes species, under basic/acidic/neutral conditions, at wide temperatures, solvents, which compatible with Among all silanes TMSCF2X (X = Br, F, Cl) stood out privileged ones, paves avenue further developing chemistry. particular, TMSCF2Br recognized "all-rounder": applied almost common more importantly, also enables many other novel transformations cannot achieve, thanks its unique structure rich releasing conditions. It expected commercial availability now, chemistry will accelerated years come.

Язык: Английский

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Oxygen Migration–Defluorination Strategy Enables the Aminocarbonylation of Enaminones with o-Aminobenzamides and CF₂Br₂

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

The development of different concept approaches and user-friendly carbonyl surrogates for aminocarbonylation is highly desirable. Herein, we report the photocatalytic enaminones with easily available o-aminobenzamides CF2Br2 through an oxygen migration-defluorination strategy. reaction features switchable transformation construction carbamoyl-substituted enol products allows expedient synthesis fully substituted maleimides under mild conditions.

Язык: Английский

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Promising reagents for difluoroalkylation

Organic Chemistry Frontiers, Год журнала: 2020, Номер 7(17), С. 2538 - 2575

Опубликована: Янв. 1, 2020

This review describes recent advances in difluoroalkylation reactions using different substrates.

Язык: Английский

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Copper-Catalyzed Asymmetric Radical 1,2-Carboalkynylation of Alkenes with Alkyl Halides and Terminal Alkynes

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(20), С. 9501 - 9509

Опубликована: Апрель 25, 2020

A copper-catalyzed intermolecular three-component asymmetric radical 1,2-carboalkynylation of alkenes has been developed, providing straightforward access to diverse chiral alkynes from readily available alkyl halides and terminal alkynes. The utilization a cinchona alkaloid-derived multidentate N,N,P-ligand is crucial for the efficient generation mildly oxidative precursors by copper effective inhibition undesired Glaser coupling side reaction. substrate scope broad, covering (hetero)aryl-, alkynyl-, aminocarbonyl-substituted alkenes, (hetero)aryl as well silyl alkynes, tertiary primary with excellent functional group compatibility. Facile transformations obtained have also demonstrated, highlighting complementarity this protocol direct 1,2-dicarbofunctionalization reactions C(sp2/sp3)-based reagents.

Язык: Английский

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Selective Defluoroallylation of Trifluoromethylarenes

Journal of the American Chemical Society, Год журнала: 2019, Номер 141(36), С. 14120 - 14125

Опубликована: Авг. 22, 2019

We report a fluoride-initiated coupling reaction between trifluoromethylarenes and allylsilanes to access allylated α,α-difluorobenzylic compounds. This method's utility is demonstrated through 30 mmol scale reaction, sequential allylation/derivatization protocol multiple examples of site-selective trifluoromethylarene allylation. Initial mechanistic studies suggest base-induced single electron transfer pathway responsible for the high efficiency selectivity this novel C–F substitution process.

Язык: Английский

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