Radical electrophilic aromatic substitution of electron-deficient aryl halides via aerobic ternary electron donor-acceptor photocatalysis DOI Creative Commons

Jiayi Gu,

Yingfen Meng,

Zhuo Cheng

et al.

Cell Reports Physical Science, Journal Year: 2024, Volume and Issue: 5(10), P. 102230 - 102230

Published: Oct. 1, 2024

Highlights•Ternary EDA exciplex induced alkyl aryl ether synthesis•Aerobic photocatalytic system•Good functional group compatibility and late-stage functionalization•Scalable synthesis of fine chemicalsSummaryThe direct use molecular oxygen as a clean, abundant, readily available reactant is one the green, sustainable, yet challenging methodologies for C–O bond construction to access diverse oxygenated compounds. Herein, we report ternary electron donor-acceptor complex system that utilizes O2 construct multiple bonds successively in single-step operation, enabling facile assembly ethers. Mechanistic investigation shows halide/2-tert-butyl-1,1,3,3-tetramethylguanidine/tetrahydrofuran generated situ plays an essential role, affording radical anion species captured by electrophilic form Meisenheimer-type intermediate, subsequently participates Williamson etherification process give products with good selectivity compatibility. This protocol not only enables rapid ethers but also allows chemicals, such proparacaine, decylparaben, sildenafil subunits, starting from halogenated compounds.Graphical abstract

Language: Английский

C−F bond activation enables synthesis of aryl difluoromethyl bicyclopentanes as benzophenone-type bioisosteres DOI Creative Commons
Mingshuo Chen,

Yuang Cui,

Xiaoping Chen

et al.

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

Citations

30
A review of frustrated Lewis pair enabled monoselective C–F bond activation DOI Creative Commons
Kenneth Lye, Rowan D. Young

Chemical Science, Journal Year: 2024, Volume and Issue: 15(8), P. 2712 - 2724

Published: Jan. 1, 2024

Frustrated Lewis pair (FLP) bond activation chemistry has greatly developed over the last two decades since seminal report of metal-free reversible hydrogen activation. Recently, FLP systems have been utilized to allow monoselective C-F (at equivalent sites) in polyfluoroalkanes. The problem 'over-defluorination' functionalization polyfluoroalkanes (where multiple fluoro-positions are uncontrollably functionalized) a long-standing chemical fluorocarbon for 80 years. mediated is complementary other solutions address and offers several advantages unique opportunities. This perspective highlights some these opportunities places development into context wider effort overcome 'over-defluorination'.

Language: Английский

Citations

20
Photoinduced copper-catalyzed C–N coupling with trifluoromethylated arenes DOI Creative Commons
Jun Huang, Qi Gao, Zhong Tao

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 14, 2023

Selective defluorinative functionalization of trifluoromethyl group (-CF3) is an attractive synthetic route to the pharmaceutically privileged fluorine-containing moiety. Herein, we report a strategy based on photoexcited copper catalysis activate C-F bond di- or trifluoromethylated arenes for divergent radical C-N coupling with carbazoles and aromatic amines. The use different ligands can tune reaction products diversity. A range substituted, structurally diverse α,α-difluoromethylamines be obtained from via carbazoles, while interesting double ready difluoromethylated arenes. Based this success, carbazole-centered PNP ligand designed optimal ligand, enabling copper-catalyzed construction imidoyl fluorides amines through functionalization. Interestingly, 1,2-difluoroalkylamination styrenes also developed, delivering γ,γ-difluoroalkylamines, bioisostere β-aminoketones, in synthetically useful yields. DFT studies reveal inner-sphere electron transfer mechanism Cu-catalyzed selective activation C(sp3)-F bonds.

Language: Английский

Citations

26
α‐Difluoroalkylation of Benzyl Amines with Trifluoromethylarenes DOI

Wen‐Jun Yue,

Rubén Martı́n

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

Citations

20
Defluorinative Alkylboration of Alkenes Enabled by Dual Photoredox and Copper Catalysis DOI Open Access

Yanmin Fan,

Zhonghou Huang,

Yi Lu

et al.

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

Citations

17
Visible-Light-Driven Iron-Catalyzed 1,2-Difluoroalkylthiolation of Alkenes DOI
Leifeng Yuan, Zemin Wang,

Wenli Zhuang

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(33), P. 7066 - 7071

Published: Aug. 12, 2024

The synthesis of medicinally interesting aryldifluoromethylated compounds has drawn significant research attention in recent years. Herein, we report an unprecedented iron-mediated process for the selective defluorination trifluoromethylarenes to achieve 1,2-difluoroalkylthiolation alkenes. Preliminary mechanistic studies revealed that thiolate anion, trifluoromethylarene, and iron cation could form electron donor-acceptor (EDA) complex, which induced then difunctionalization alkenes obtain products. generated make it difficult EDA complex again, thus avoiding excessive defluorination. This conversion concise ambient reaction conditions provides alternative solution obtaining difluorobenzylic intermediates.

Language: Английский

Citations

5
Light-induced aryldifluoromethyl-sulfonylation/thioetherification of alkenes using arenethiolates as a photoreductant and sulfur source DOI
Jiayu Li,

Zipeng Guo,

Xiaofeng Zhang

et al.

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

Citations

12
Nickel-catalysed chelation-assisted reductive defluorinative sulfenylation of trifluoropropionic acid derivatives DOI
Yu‐Qiu Guan,

Jia-Fan Qiao,

Yu‐Feng Liang

et al.

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

Citations

4
New Opportunities to Access Fluorinated Molecules Using Organophotoredox Catalysis via C(sp3)–F Bond Cleavage DOI Creative Commons
Sourav Roy, Tatiana Besset

JACS Au, Journal Year: 2025, Volume and Issue: 5(2), P. 466 - 485

Published: Feb. 7, 2025

Fluorinated molecules are of paramount importance because their unique properties. As a result, the search for innovative approaches to synthesis this class compounds has been relentless over years. Among these, combination photocatalysis and organofluorine chemistry turned out be an effective partnership access unattainable fluorinated molecules. This Perspective provides overview recent advances in synthesizing via organophotoredox-catalyzed defluorination process from trifluoromethylated compounds. It encompasses preparation difluoromethylated (hetero)arenes, amides, esters as well gem-difluoroalkene derivatives using C(sp3)–F bond activation or β-fragmentation. will highlight remaining challenges discuss future research opportunities.

Language: Английский

Citations

0
Selective Defluoroalkylation and Hydrodefluorination of Trifluoromethyl Groups Photocatalyzed by Dihydroacridine Derivatives DOI
Shiyu Li, Xinyu Yang,

Peng-Hui Shen

et al.

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

Citations

9