Synthesis of Fluorine-Containing Multisubstituted Oxa-Spiro[4,5]cyclohexadienones via a Fluorinated Alcohol-Catalyzed One-Pot Sequential Cascade Strategy

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(5), С. 2847 - 2857

Опубликована: Фев. 16, 2024

In recent years, the application of fluorinated alcohols as solvents, cosolvents, or additives has become important in modern organic synthesis. However, their potential efficient catalysts synthesis not been well-explored. this article, we report on development a one-pot sequential cascade reaction p-quinone methides with difluoroenoxysilanes using hexafluoroisopropanol catalyst. This allows for preparation multisubstituted oxa-spiro[4,5]cyclohexadienones. By 50 mol % 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP), proceeds smoothly to yield 1,6-conjugated products, which are then subjected oxidative dearomatization/hemiacetalization PhI(OAc)2. The overall process affords moderate high yields and excellent diastereoselectivities.

Язык: Английский

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B(C₆F₅)₃/Chiral Phosphoric Acid Promoted Asymmetric C-3 gem-Difluoroalkylation of Quinoxalin-2-ones with Difluoroenoxysilanes

Organic Letters, Год журнала: 2024, Номер 26(31), С. 6551 - 6555

Опубликована: Июль 30, 2024

The asymmetric Mannich-type reaction of quinoxalin-2-ones with difluoroenoxysilanes has been developed for the synthesis chiral gem-difluoroalkylated quinoxalin-2-ones. worked in presence phosphoric acid CPA 1 and B(C6F5)3 THF at room temperature. exhibited a good substrate scope furnishing products yields (up to 97%) up 96% ee.

Язык: Английский

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Base-Dependent Divergent Carbodifluoroalkylation and Halodifluoroalkylation of Alkenes under Visible-Light Irradiation

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(18), С. 13457 - 13471

Опубликована: Сен. 3, 2024

Organic molecules containing a difluoroalkyl group are valuable and versatile chemicals because of their unique physicochemical biological properties. Accordingly, the development efficient practical difluoroalkylation for preparation these compounds is important attractive. Herein, we demonstrate photoredox-catalyzed base-dependent selective carbodifluoroalkylation halodifluoroalkylation alkenes using readily available 2-(allyloxy)arylaldehydes [or 2-(allylamino)arylaldehydes] XCF

Язык: Английский

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Hexafluoroisopropanol (HFIP)-Promoted Hydrodifluoroalkylation of Furans and Vinyl Ethers Using Difluorinated Silyl Enol Ethers for the Synthesis of gem-Difluorinated Ethers

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 18, 2025

A hexafluoroisopropanol (HFIP)-promoted hydrodifluoroalkylation of furans and vinyl ethers with difluorinated silyl enol has been developed. Because the inherent electron richer nature poor nucleophilicity ethers, employment simple as substrates for nucleophilic dearomatization without a metal or stoichiometric chemical oxidizing reagent is challenging, especially considering rearomatization driving force ring fragmentation furan system. This protocol exploits formation oxocarbenium intermediate from using HFIP proton source to allow addition which provides an efficient synthetic strategy install gem-difluorinated group into heterocycles.

Язык: Английский

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(3+2) Annulation of Donor–Acceptor Cyclopropanes with Difluoroenoxysilanes: Syntheses of gem-Difluorocyclopentenes via α,α-Difluoroketone Scaffolds

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Herein, we present an acid- and base-mediated approach for ring opening of donor-acceptor cyclopropanes (DACs) followed by (3+2) annulation, yielding biologically relevant gem-difluorinated cyclopentenes via α,α-difluoroketone scaffolds. Fluorinated rings are essential building blocks in drug discovery materials research. This methodology has a broad substrate scope, is scalable, provides practical synthetic route to obtain value-added fluorinated compounds.

Язык: Английский

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N-Aryl/-Alkenyl difluoroketenimines: transient intermediates for the general synthesis of difluoroalkylated heterocycles

Green Synthesis and Catalysis, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Ball‐Milling‐Promoted Copper‐Catalyzed Solid‐State Radical C–H Difluoroalkylation Reactions

ChemistryEurope, Год журнала: 2025, Номер unknown

Опубликована: Апрель 17, 2025

A mechanochemical strategy for promoting copper‐catalyzed solid‐state radical C–H difluoroalkylation reactions has been devised. Compared to traditional solution‐based methods, this mechanoredox approach offers enhanced ease of handling, greater cleanliness, and improved sustainability the synthesis difluoroalkylated indoles, which constitute crucial structural motifs in contemporary drug discovery. The underlying reaction mechanism is investigated through meticulous step‐by‐step control experiments that highlighted substantial influence conditions. versatility protocol demonstrated by its applications complex natural products derivatives.

Язык: Английский

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gem-Difluoroalkylation of Cyclic Ethers Enabled by Cobalt-Catalyzed C(sp³)–H Oxidation under Mild Conditions

Organic Letters, Год журнала: 2024, Номер 26(31), С. 6742 - 6747

Опубликована: Июль 26, 2024

Fluorinated rings have emerged as privileged structural modules in the fields of drug discovery and materials research. The incorporation fluorine atoms into aromatic or heterocycles can lead to significant improvements physicochemical biological properties small molecules, making them valuable components design new drugs functional materials. Herein, we presented a cobalt-catalyzed C–H oxidation/gem-difluorination cascade reaction readily available cyclic ethers with difluoroenoxysilanes, affording series gem-difluorinated analogues moderate high yields. obtained products versatile fluoroalkyl building blocks were showcased through divergent-oriented transformations.

Язык: Английский

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Synthesis of Fluoro 3(2H)-Furanones via a TFA-Catalyzed Dehydrofluorinative Cyclization of 2,2-Difluoro-3-hydroxy-1,4-diketones

Organic Letters, Год журнала: 2023, Номер 25(38), С. 7057 - 7061

Опубликована: Сен. 13, 2023

A TFA-catalyzed dehydrofluorinative cyclization of 2,2-difluoro-3-hydroxy-1,4-diketones has been developed in the presence amines under mild conditions which difluorinated substrates are readily prepared according to our reported literature. This protocol provides a rapid construction fluoro 3(2H)-furanones good excellent yields with functional group tolerance. Easy scale-up synthesis also shows practical advantage.

Язык: Английский

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Electrochemical Giese Reaction of α-Trifluoromethylstyrenes with Disulfides: Efficient Access to β-Trifluoromethylated Thioethers

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(20), С. 14940 - 14950

Опубликована: Окт. 9, 2024

An electrochemical Giese-type hydrothiolation of α-trifluoromethylstyrenes with disulfides is disclosed for the first time under metal-free and mild conditions. This approach provides a facile methodology β-trifluoromethylated thioethers in moderate to good yields high functional group tolerance starting from readily available substrates. Additionally, late-stage modification drug molecules gram-scale synthesis show practical advantages. The radical pathway this reaction has been revealed by control experiments cyclic voltammetry measurements.

Язык: Английский

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