Synthetic Advantages of Defluorinative C−F Bond Functionalization

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(49)

Published: Aug. 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.

Language: Английский

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C−F bond activation enables synthesis of aryl difluoromethyl bicyclopentanes as benzophenone-type bioisosteres

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

Published: Jan. 10, 2024

Abstract Bioisosteric design has become an essential approach in the development of drug molecules. Recent advancements synthetic methodologies have enabled rapid adoption this strategy into discovery programs. Consequently, conceptionally innovative practices would be appreciated by medicinal chemistry community. Here we report expeditous method for synthesizing aryl difluoromethyl bicyclopentane (ADB) as a bioisostere benzophenone core. This involves merger light-driven C−F bond activation and strain-release under catalysis newly designed N -anionic-based organic photocatalyst. defluorinative coupling methodology enables direct conversion wide variety commercially available trifluoromethylaromatic bonds (more than 70 examples) corresponding bicyclo[1.1.1]pentanes (BCP) arenes/difluoromethyl BCP boronates single step. The can also applied to [3.1.1]and [4.1.1]propellane systems, providing access analogues with different geometries. Moreover, successfully used protocol rapidly prepare ADB-substituted bioactive molecule Adiporon. Biological testing shown that ADB scaffold potential enhance pharmacological properties benzophenone-type candidates.

Language: Английский

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Construction of C–X (X = S, O, Se) Bonds via Lewis Acid-Promoted Functionalization of Trifluoromethylarenes

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(11), P. 7339 - 7346

Published: May 16, 2023

The conversion of easily available trifluoromethylarenes through C–F bond activation provides an attractive pathway for rapid access to difluorobenzylic substructures in producing pharmaceuticals and agrochemicals. However, recent advances this area have been confined C–C(H) construction, thus limiting the diversity accessible motifs. In contrast, selective formation a carbon–heteroatom via functionalization, which enable fast convenient diverse fluorine-containing motifs with high chemical diversity, remains formidable synthetic challenge. Herein, we disclosed Lewis acid promoted photoredox-catalyzed strategy construction C–X (X = S, O or Se) bonds by single C(sp3)–F trifluoromethylarenes, direct synthesis medicinally interesting aryldifluoromethyl ether [ArCF2X– O, Se)] scaffolds. This method relies on readily reagents can tolerate range thiol, phenol, selenol nucleophiles. Its utility was exemplified late-stage modifications several pharmaceutical ingredients. Preliminary studies suggest two parallel pathways: photocatalytic electron-transfer (SET), electron donor–acceptor (EDA) process.

Language: Английский

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Recent Discovery, Development, and Synthetic Applications of Formic Acid Salts in Photochemistry

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(4)

Published: Oct. 9, 2023

The advancement of sustainable photoredox catalysis in synthetic organic chemistry has evolved immensely because the development versatile and cost-effective reagents. In recent years, a substantial effort been dedicated to exploring utility formic acid salts various photochemical reactions. this context, formates have demonstrated diverse capabilities, functioning as reductants, sources carbonyl groups, reagents for hydrogen atom transfer. Notably, CO

Language: Английский

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α‐Difluoroalkylation of Benzyl Amines with Trifluoromethylarenes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(40)

Published: Aug. 19, 2023

Abstract An α‐difluoroalkylation of benzyl amines with trifluoromethylarenes is disclosed herein. This protocol characterized by its operational simplicity, excellent chemoselectivity and broad scope—even advanced synthetic intermediates—, thus offering a new entry point to medicinally‐relevant α‐difluoroalkylated from simple, yet readily accessible, precursors.

Language: Английский

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Defluorinative Alkylboration of Alkenes Enabled by Dual Photoredox and Copper Catalysis

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

Published: Dec. 9, 2023

Abstract A regioselectivity reversed three‐component defluorinative alkylboration of alkenes with trifluoromethyls and bis(pinacolato)diboron via dual photoredox/copper catalysis is reported. The mild conditions are compatible a wide array nonactivated trifluoromethyl aromatics bearing electron‐donating or electron‐neutral substituents, trifluoroacetamides, various terminal internal alkenes, enabling straightforward access to synthetically valuable γ ‐ gem ‐difluoroalkyl boronates high efficiency. Furthermore, this protocol applicable alkene‐tethered furnish ‐difluoromethylene‐containing cyclic compounds. Synthetic applications preliminary mechanistic studies also presented.

Language: Английский

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Alkyl (Het)Arylsulfones from SuFEx Reagents via Photochemical S–F Bond Activation

Organic Letters, Journal Year: 2023, Volume and Issue: 25(12), P. 2084 - 2087

Published: March 20, 2023

A visible light-induced S-F bond activation of sulfur fluoride exchange (SuFEx) reagents to generate alkyl sulfones is described. The method free transition metals and relies on the use commercially available commodity chemicals. In addition, this demonstrates first photoredox functionalization SuFEx reagents. reaction has a diverse substrate scope, with applications in various aryl sulfonyl fluorides, both activated unactivated alkenes.

Language: Английский

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o-Phosphinodiarylamides as Reductive Photocatalysts for Dehalogenative and Deaminative Cross-Couplings

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(17), P. 11753 - 11761

Published: Aug. 22, 2023

The strong electron-donating ability in the photoactivated state and structural flexibility of organic anions have led to a growing interest utilizing photoexcited as reductive photocatalysts activate inert chemical bonds. Phenolate thiolate been extensively studied utilized catalysts wide range photocatalytic transformations. In contrast, employing nitrogen for radical generation received less attention despite vast possibilities designing adjusting catalyst properties. this work, we reported that diaryl amides possessing ortho-diphenylphosphaneyl substituents function visible-light photoredox activation aryl halides (chloride bromide) ammonium salts generate radicals phosphorylation, borylation, arylation, alkylation with corresponding interceptors. o-phosphinodiarylamide also trifluoromethyl groups trifluoromethylarene, trifluoroacetate, trifluoroacetamide defluoroalkylation alkenes. Notably, methods using o-phosphinodiarylamides are very efficient from large π-extended halides, spiro-conjugated poly indicating advantages anion-based approach application synthesizing conjugated molecules electronic materials interface modification without recourse transition-metal catalysis.

Language: Английский

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Light-induced aryldifluoromethyl-sulfonylation/thioetherification of alkenes using arenethiolates as a photoreductant and sulfur source

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(22), P. 9292 - 9300

Published: Jan. 1, 2023

A novel ATRA reaction was developed from simple and widely accessible alkenes, thiols, trifluoromethylarenes vis photo-induced EDA complex strategy. Several complicated bioactive molecules undergo smoothly the one-pot photosynthetic process.

Language: Английский

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Visible-light-mediated C–F bond cleavage for the synthesis of polyfluorinated compounds

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(13), P. 3341 - 3346

Published: Jan. 1, 2023

Herein, we describe a novel and efficient photo-redox catalytic difluorinated ester radical addition/defluoroalkylation coupling reaction between trifluoroacetic acid derivatives α-trifluoromethyl alkenes.

Language: Английский

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