Exhaustive Hydrodefluorination or Deuterodefluorination of Trifluoromethylarenes via Metal-Free Photoredox Catalysis

Organic Letters, Journal Year: 2024, Volume and Issue: 26(4), P. 928 - 932

Published: Jan. 25, 2024

Perfluoroalkyl compounds are persistent environmental pollutants due to their chemical and thermal stability. Hydrodefluorination is one of the most promising strategies for disposal fluorine-containing compounds, which has attracted much attention from a broad spectrum scientific communities. Herein, we disclose metal-free, visible-light-promoted protocol exhaustive hydrodefluorination wide variety trifluoromethylarenes with up 95% yields. Moreover, methyl-d3 groups can be obtained via deuterium water D ratio 94%.

Language: Английский

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Cu-Electrocatalysis Enables Vicinal Bis(difluoromethylation) of Alkenes: Unraveling Dichotomous Role of Zn(CF₂H)₂(DMPU)₂ as Both Radical and Anion Source

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(32), P. 22498 - 22508

Published: July 30, 2024

The difluoromethyl group (CF2H) serves as an essential bioisostere in drug discovery campaigns according to Lipinski's Rule of 5 due its advantageous combination lipophilicity and hydrogen bonding ability, thereby improving the ADME properties. However, despite high prevalence importance vicinal bond donors pharmaceutical agents, a general synthetic method for doubly difluoromethylated compounds position is absent. Here we describe copper-electrocatalyzed strategy that enables bis(difluoromethylation) alkenes. By leveraging electrochemistry oxidize Zn(CF2H)2(DMPU)2-a conventionally utilized anionic transmetalating source, paved way utilize it CF2H radical source deliver terminal Mechanistic studies revealed interception resultant secondary by copper catalyst subsequent reductive elimination facilitated invoking Cu(III) intermediate, enabling second installation internal position. utility this electrocatalytic 1,2-bis(difluoromethylation) has been highlighted through late-stage bioisosteric replacement agents such sotalol dipivefrine.

Language: Английский

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A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

Beilstein Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 20, P. 2500 - 2566

Published: Oct. 9, 2024

With the resurgence of electrosynthesis in organic chemistry, there is a significant increase number routes available for late-stage functionalization (LSF) drugs. Electrosynthetic methods, which obviate need hazardous chemical oxidants or reductants, offer unprecedented control reactions through continuous variation applied potential and possibility combination with photochemical processes. This capability substantial advantage performing electrochemical photoelectrochemical LSF. Ultimately, these protocols are poised to become vital component medicinal chemist's toolkit. In this review, we discuss that have been demonstrated be applicable LSF pharmaceutical drugs, their derivatives, natural substrates. We present analyze representative examples illustrate electrochemistry photoelectrochemistry valuable molecular scaffolds.

Language: Английский

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Electrochemical nickel-catalysed defluoroalkylation ofgem-difluoroalkenes with alkyl halides

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(20), P. 7952 - 7958

Published: Jan. 1, 2023

Herein, a direct and efficient electrochemical method for the synthesis of monofluoroalkene products was promoted using gem -difluoroalkenes unactivated alkyl halides as starting materials with nickel catalyst.

Language: Английский

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Nickel-catalysed chelation-assisted reductive defluorinative sulfenylation of trifluoropropionic acid derivatives

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(17), P. 2405 - 2408

Published: Jan. 1, 2024

Nickel-catalysed chelation-assisted reductive cross-coupling of trifluoropropanamides/esters with disulfides to afford thioacrylamides/esters high E selectivity, involving triple C–F bond cleavage.

Language: Английский

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A selective and mild electrochemical defluorinative carboxylation for late-stage C(sp³)–F bond functionalization

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(22), P. 9075 - 9079

Published: Jan. 1, 2023

We report a protocol for the electrochemical defluorinative carboxylation of trifluoromethyl groups accessing their highly valuable α,α-difluorocarboxylic acid analogues.

Language: Английский

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Monodefluorinative Halogenation of Perfluoroalkyl Ketones via Organophosphorus-Mediated Selective C–F Activation

JACS Au, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Through the prosperity of organofluorine chemistry in modern organic synthesis, perfluorinated compounds are now abundant and widely available. Consequently, these substances become attractive starting materials for production complex, multifunctional fluorinated molecules. However, inherent challenges associated with activation discrimination C–F bonds typically lead to overdefluorination as well functional group incompatibility. To address problems, our utilized a rationally designed organophosphorus reagent that promoted mild selective manipulation single bond trifluoromethyl pentafluoroethyl ketones via an interrupted Perkow-type reaction, which allowed replacement fluorine more labile synthetically versatile congeners such chlorine, bromine, iodine. The resulting α-haloperfluoroketones have two reactive units orthogonal properties would be suitable subsequent structural diversification. DFT calculations identified favorable P–F interaction crucial factor from both thermodynamic kinetic viewpoints.

Language: Английский

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Electrochemical Access to Difluoromethyl Groups: An Overview of Scope, Mechanisms, and Challenges

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 6826 - 6851

Published: April 14, 2025

Language: Английский

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Selective Defluoroalkylation and Hydrodefluorination of Trifluoromethyl Groups Photocatalyzed by Dihydroacridine Derivatives

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(24), P. 17284 - 17296

Published: Dec. 6, 2023

The selective functionalization of trifluoromethyl groups through C-F cleavage poses a significant challenge due to the high bond energy C(sp3)-F bonds. Herein, we present dihydroacridine derivatives as photocatalysts that can functionalize with various alkenes under mild conditions. Mechanistic studies and DFT calculations revealed upon irradiation, exhibit reducibility function for reductive defluorination. This process involves sequential single-electron transfer mechanism. research provides valuable insights into properties photocatalysts, highlighting importance maintaining planar conformation large conjugated system optimal catalytic activity. These findings facilitate efficient reduction inert chemical

Language: Английский

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Recent Advance in the C−F Bond Functionalization of Trifluoromethyl Aromatic and Carbonyl Compounds

ChemCatChem, Journal Year: 2023, Volume and Issue: 16(8)

Published: Dec. 28, 2023

Abstract The selective C−F bonds functionalization in available trifluoromethyl compounds is an economic route for obtaining high‐value organic fluorine compounds. However, due to the high dissociation energy group, strength of bond decreases continuously during defluorination, posing a challenge modifying such molecules without over‐conversion. Over past few years, there has been significant progress developing efficient methods constructing difluoromethylene unit, using approaches as radical chemistry, photochemistry, electrochemistry, and organometallic chemistry. These involve difluorocarbon radicals, cations, anions, carbenes intermediates. In this review, we summarized recent five years research achievements field single cleavage aromatic carbonyl gain diverse difluoromethylene‐containing via different intermediate strategies.

Language: Английский

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