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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Carbon–Carbon Bond Cleavage for Late-Stage Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(22), С. 12313 - 12370

Опубликована: Ноя. 9, 2023

Late-stage functionalization (LSF) introduces functional group or structural modification at the final stage of synthesis natural products, drugs, and complex compounds. It is anticipated that late-stage would improve drug discovery's effectiveness efficiency hasten creation various chemical libraries. Consequently, products a productive technique to produce product derivatives, which significantly impacts biology development. Carbon-carbon bonds make up fundamental framework organic molecules. Compared with carbon-carbon bond construction, activation can directly enable molecular editing (deletion, insertion, atoms groups atoms) provide more efficient accurate synthetic strategy. However, selective unstrained still one most challenging projects in synthesis. This review encompasses strategies employed recent years for cleavage by explicitly focusing on their applicability functionalization. expands current discourse reactions providing comprehensive overview types bonds. includes C-C(sp), C-C(sp2), C-C(sp3) single bonds; double triple bonds, focus catalysis transition metals organocatalysts. Additionally, specific topics, such as ring-opening processes involving three-, four-, five-, six-membered rings, are discussed, exemplar applications these techniques showcased context bioactive molecules discovery. aims shed light advancements field propose potential avenues future research realm

Язык: Английский

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A decarbonylative approach to alkylnickel intermediates and C(sp ³ )-C(sp ³ ) bond formation

Science, Год журнала: 2024, Номер 385(6715), С. 1331 - 1337

Опубликована: Сен. 19, 2024

The myriad nickel-catalyzed cross-coupling reactions rely on the formation of an organonickel intermediate, but limitations in forming monoalkylnickel species have limited options for C(sp 3 ) cross-coupling. monoalkylnickel(II) from abundant carboxylic acid esters would be valuable, derivatives are primarily decarboxylated to form alkyl radicals that lack correct reactivity. In this work, we disclose a facile oxidative addition and decarbonylation sequence forms intermediates through nonradical process. key ligand, bis(4-methylpyrazole)pyridine, accelerates decarbonylation, stabilizes alkylnickel(II) destabilizes off-cycle nickel(0) carbonyl species. utility new reactivity )-C(sp bond is demonstrated reaction challenging by purely radical methods—the selective primary with iodides.

Язык: Английский

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Mechanochemical Deoxyfluorination of Carboxylic Acids to Acyl Fluorides and Successive Mechanochemical Amide Bond Formation

ACS Sustainable Chemistry & Engineering, Год журнала: 2024, Номер 12(9), С. 3565 - 3574

Опубликована: Фев. 16, 2024

Diverse methods have been reported for the synthesis of acyl fluorides; however, an environmentally benign method fluorides remains underdeveloped. In this study, we developed solvent-free mechanochemical deoxyfluorination carboxylic acids to mediated by 1,1,2,2-tetrafluoroethyl-N,N-dimethylamine (TFEDMA) using a ball mill. This facilitated high product yields in short reaction times even sterically challenged acids. We also realized coupling and amines as well TFEDMA-mediated direct with via sequential one-pot deoxyfluorination/coupling pathway. Furthermore, protocol was expanded include peptide synthesis. The efficiency protocol, terms speed, characteristics, favorable E-factor, aligns requirements current environmental policies.

Язык: Английский

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Anthraquinone-based covalent organic framework as a recyclable direct hydrogen atom transfer photocatalyst for C–H functionalization

Chemical Science, Год журнала: 2024, Номер 15(13), С. 4920 - 4925

Опубликована: Янв. 1, 2024

A COF-based catalyst was synthesized to activate C–H bonds for C–C/C–N coupling via hydrogen atom transfer. The can be easily recycled, allowing downstream modification of the product realize C–N/C–S/C–O transformations.

Язык: Английский

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Pd-Catalyzed Divergent Site-Selective Difluoromethylation and Difluoromethylcarbonylation of Aryl Sulfonium Salts

ACS Catalysis, Год журнала: 2024, Номер 14(18), С. 13557 - 13566

Опубликована: Авг. 28, 2024

The incorporation of the difluoromethyl (CF2H) group into arenes has increasingly been recognized as important in drug discovery. Herein, we report a divergent cross-coupling method for constructing both aryl difluoromethanes and difluoroketones from thianthrenium salts. Site selectivity Negishi-type coupling C1 insertion reactions was achieved under palladium catalysis. Both transformations proceed with broad functional tolerance, enabling late-stage difluoromethylation difluoromethylcarbonylation complex molecules. synthetic utility this demonstrated by synthesizing four pharmaceutical analogues same precursor applying it downstream functionalization difluoroketones.

Язык: Английский

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Recent Advances in C–F Bond Activation of Acyl Fluorides Directed toward Catalytic Transformation by Transition Metals, N-Heterocyclic Carbenes, or Phosphines

Synthesis, Год журнала: 2022, Номер 54(17), С. 3667 - 3697

Опубликована: Май 6, 2022

Abstract Numerous studies on the activation of carbon–fluorine bonds have been reported in recent years. For example, acyl fluorides utilized as versatile reagents for acylation, arylation, and even fluorination. In this review, we focus compounds with bonds, highlight advances strategies their C–F via transition-metal catalysis, N-heterocyclic carbene (NHCs) organophosphine classical nucleophilic substitution reactions. 1 Introduction 2 Transition-Metal-Mediated Bond Activation 2.1 Acylation (Carbonyl-Retentive) Coupling Reactions 2.2 Decarbonylative 2.3 by Other Transition Metals 3 N-Heterocyclic Carbenes 3.1 NHC-Catalyzed Cycloaddition Acyl Fluorides 3.2 Radical Functionalization 3.3 Nucleophilic Fluorination (Hetero)aromatics 4 Phosphines 4.1 Phosphine-Catalyzed Direct 4.2 Indirect 5 Classical Substitution 6 Miscellaneous Examples 7 Summary Perspective

Язык: Английский

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Mechanism-Driven Development of Group 10 Metal-Catalyzed Decarbonylative Coupling Reactions

Accounts of Chemical Research, Год журнала: 2022, Номер 55(23), С. 3430 - 3444

Опубликована: Ноя. 16, 2022

ConspectusTransition-metal-catalyzed cross-coupling reactions are widely used in both academia and industry for the construction of carbon–carbon carbon–heteroatom bonds. The vast majority utilize aryl (pseudo)halides as electrophilic coupling partner. Carboxylic acid derivatives (RC(O)X) represent a complementary class electrophiles that can engage decarbonylative couplings to produce analogous products. This approach offers advantage RC(O)X abundant inexpensive. In addition, enables intramolecular (between R X carboxylic derivative) well intermolecular bond-forming (in which an exogeneous nucleophile is coupled with group derived from RC(O)X). these reactions, X-substituent on be tuned facilitate oxidative addition transmetalation, thus eliminating need base. Account details our group's development diverse variety base-free catalyzed by 10 metals. Furthermore, it highlights how catalyst design guided stoichiometric organometallic studies systems.Our early focused transform corresponding R–X extrusion CO. We first identified Pd Ni monodentate phosphine catalysts convert thioesters (ArC(O)SR) thioethers (ArSR). next expanded this reactivity fluoroalkyl thioesters, using readily available acids (RF) source. A Ni-phosphinoferrocene proved optimal, large bite angle bidentate ligand was necessary promote challenging RF–S reductive elimination step.We pursued aroyl halides. Palladium-based bearing dialkylbiaryl ligands (e.g., BrettPhos) were optimal converting chlorides (ArC(O)Cl) (ArCl). These selected based their ability key C–Cl step catalytic cycle. contrast, all attempts fluorides [ArC(O)F)] (ArF) unsuccessful either Pd- or Ni-based catalysts. Organometallic Ni-system show C(O)–F CO deinsertion proceed smoothly, but resulting nickel(II) fluoride intermediate fails undergo C–F elimination.In contrast its inertness elimination, highly reactive toward transmetalation. serves internal base, such no additional base required. leveraged "transmetalation active" achieve Ni-catalyzed between boron reagents access biaryl aryl-boronate ester By tuning electrophile, transmetalating reagent, catalyst, same also applicable fluoroalkylation difluoromethylacetyl arylboronate esters) amination phenol esters silyl amines).Moving forward, goal identify systems enable more bond constructions via manifold. inhibition remains major issue leading requirement high temperatures loadings. Identifying resistant binding and/or approaches remove under mild conditions will critical making practical scalable.

Язык: Английский

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A Difluoromethylation Reagent: Access to Difluoromethyl Arenes through Palladium Catalysis

Organic Letters, Год журнала: 2024, Номер 26(28), С. 6024 - 6029

Опубликована: Июль 10, 2024

A new radical difluoromethylation was developed by using inexpensive and readily available difluoroacetic anhydride

Язык: Английский

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Experimental Evidence for Zerovalent Pd(NHC) as a Competent Catalyst in C–N Cross-Coupling (NHC = DiMeIHept^Cl)

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(42), С. 29224 - 29236

Опубликована: Окт. 10, 2024

Use of the branched N-heterocyclic carbene (NHC) ligand 1,3-bis(2,6-bis(3-methyl-1-(2-methylpropyl)butyl)phenyl)-4,5-dichloro-1,3-dihydro-2

Язык: Английский

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