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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Contemporary Approaches for Amide Bond Formation

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(24), P. 4359 - 4391

Published: Nov. 7, 2023

Abstract Amide bond construction has garnered significant interest in recent decades due to amides being one of the most prevalent functional groups among bioactive molecules. Out thirty‐seven new drugs approved by FDA 2022, eleven are small molecules containing at least amide bond. Additionally, there nineteen large as drugs, some which have peptide structures, and therefore, also bear bonds. In years, multiple teams embraced challenge developing more efficient methods for formation. This dedication led numerous publications appearing monthly prestigious journals, showcasing advancements this field. The primary goal review is present viable strategies constructing It crucial differentiate between formation synthesis; hence, focus on describing specific forming C(O)−N particular, concentrates developed within last six years. There a particular emphasis approaches that consider thought process when selecting starting materials groups. approach ensures coverage all common chemical transformations yield

Language: 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, Journal Year: 2024, Volume and Issue: 57(5), P. 693 - 713

Published: Feb. 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.

Language: Английский

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

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

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Controllable Single and Double Difluoromethylene Insertions into C–Cu Bonds: Copper-Mediated Tetrafluoroethylation and Hexafluoropropylation of Aryl Iodides with TMSCF₂H and TMSCF₂Br

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(27), P. 12202 - 12211

Published: July 5, 2022

The selective difluoromethylene insertion into a C–Cu bond is challenging task and currently limited to either single CF2 CuCF3 or double insertions CuC6F5 (or (Z)-CF3CF = CFCu). Achieving both the same even more difficult. Herein, highly controllable CuCF2H species with TMSCF2Br reagent have been described, affording two previously unknown fluoroalkylcopper "Cu(CF2)nCF2H" (n 1 2) independently under different reaction conditions. This work represents first example of in manner. synthetic value obtained demonstrated by their reactions aryl iodides, halogenation agents, cinnamyl chloride, which enables direct transfer HCF2CF2 HCF2CF2CF2 moieties organic molecules. key fluorocarbon chain elongation from C1 C2 C3 presumably attributed reactivities 0, 1, 2 3) loading reagent.

Language: Английский

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Controllable Fluorocarbon Chain Elongation: TMSCF₂Br-Enabled Trifluorovinylation and Pentafluorocyclopropylation of Aldehydes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(3), P. 1806 - 1812

Published: Jan. 9, 2024

Controllable fluorocarbon chain elongation (CFCE) is a promising yet underdeveloped strategy for the well-defined synthesis of structurally novel polyfluorinated compounds. Herein, direct and efficient trifluorovinylation pentafluorocyclopropylation aldehydes are described by using TMSCF

Language: Английский

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Difluorocarbene-induced [1,2]- and [2,3]-Stevens rearrangement of tertiary amines

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 5, 2024

The [1,2]- and [2,3]-Stevens rearrangements are one of the most fascinating chemical bond reorganization strategies in organic chemistry, they have been demonstrated a wide range applications, representing fundamental reaction tactic for synthesis nitrogen compounds community. However, their applicabilities limited by scarcity efficient, general, straightforward methods generating ammonium ylides. Herein, we report general difluorocarbene-induced tertiary amine-involved stemmed from situ generated difluoromethyl ylides, which allows versatile amines bearing either allyl, benzyl, or propargyl groups, resulting corresponding products under same conditions with way. Broad substrate scope, simple operation, mild late-stage modification natural highlight advantages this strategy, meanwhile, rearrangement is believed to bring opportunities transformations ylides assembly valuable amino acids. This will further enrich repertoire difluorocarbene species, facilitate development reactions involving salts, provide an avenue type reactions.

Language: Английский

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Deaminative Arylation and Alkenyaltion of Aliphatic Tertiary Amines with Aryl and Alkenylboronic Acids via Nitrogen Ylides

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(52)

Published: Oct. 31, 2022

Transition-metal-catalyzed Suzuki-Miyaura coupling has significantly advanced C-C bond formation and been well recognized in organic synthesis, pharmaceuticals, materials science other fields. In this rapid development, cross without transition metal catalyst is a big challenge field, using widely existing tertiary amines as electrophiles to directly couple with boronic acids great hurdles yet significant application prospects. Herein, we report an efficient general deaminative arylation alkenylation of (propargyl amines, allyl 1H-indol-3-yl methane amines) ary alkenylboronic enabled by difluorocarbene under transition-metal-free conditions. Preliminary mechanism experiments suggest that situ formed difluoromethyl quaternary amine salt, nitrogen ylide tetracoordinate boron species are the key intermediates, subsequent 1,2-metallate shift protodeboronation complete new reaction.

Language: Английский

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One‐Carbon Ring Expansion of Indoles and Pyrroles: A Straightforward Access to 3‐Fluorinated Quinolines and Pyridines

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(5)

Published: Dec. 12, 2023

Abstract 3‐Fluorinated quinolines and pyridines are prevalent pharmacophores, yet their synthesis is often challenging. Herein, we demonstrate that dibromofluoromethane as bromofluorocarbene source enables the one‐carbon ring expansion of readily available indoles pyrroles to structurally diverse 3‐fluorinated pyridines. This straightforward protocol requires only a short reaction time ten minutes can be performed under air atmosphere. Preliminary investigations reveal this strategy also applied other valuable azines by using different 1,1‐dibromoalkanes bromocarbene sources.

Language: Английский

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Transition‐Metal‐Free Controllable Single and Double Difluoromethylene Formal Insertions into C−H Bonds of Aldehydes with TMSCF₂Br

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(7)

Published: Dec. 15, 2022

We have developed a new strategy for controllable single and double difluoromethylene (CF2 ) formal insertions into C-H bonds of aldehydes with nearly full selectivity under transition-metal-free conditions. The key to the success CF2 lies in well-defined formation 2,2-difluoroenolsilyl ether 2,2,3,3-tetrafluorocyclopropanolsilyl intermediates using difluorocarbene reagent TMSCF2 Br (TMS=trimethylsilyl). These two can react various electrophiles including proton sources halogenation reagents, allowing access diverse arrays ketones containing tetrafluoroethylene units. first synthesis relatively stable ethers has been achieved, which offers platform explore other unknown chemical space.

Language: Английский

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