1.9 Trifluoromethoxylation and Other Fluoroalkoxylation Reactions DOI
Damian E. Yerien, Sebastián Barata‐Vallejo, Al Postigo

et al.

Published: Jan. 1, 2024

Abstract In this review, methods to achieve the direct fluoroalkoxylation of a variety substrates are dis-cussed, including transformations arenes/hetarenes and compounds with carbon–carbon multiple bonds, reactions at C(sp3) carbon centers. These involve introduction fluoroalkoxy groups, CF3O, CHF2O, (CF3)2CFO, into organic molecules. Several types methodology discussed for achieving these transformations, thermal radical processes, electron-transfer mechanisms, photocatalysis, electrochemical approaches, redox-neutral pathways. The employ either fluoroalkoxylating reagents or nucleophilic sources fluorinated group.

Language: Английский

Continuous Flow Decarboxylative Monofluoroalkylation Enabled by Photoredox Catalysis DOI Creative Commons

F Pasca,

Yuri Gelato,

Michael Andresini

et al.

JACS Au, Journal Year: 2025, Volume and Issue: 5(2), P. 684 - 692

Published: Feb. 2, 2025

Herein, we report a scalable and mild strategy for the monofluoroalkylation of wide array Giese acceptors via visible-light-mediated photoredox catalysis in continuous flow. The use flow technology significantly enhances productivity scalability, whereas mildness conditions functional group tolerance are ensured by leveraging 4CzIPN, transition-metal-free organic photocatalyst. Structurally diverse secondary tertiary monofluoroalkyl radicals can thus be accessed from readily available α-monofluorocarboxylic acids. Given reaction conditions, this protocol is also amenable to late-stage functionalization biologically relevant molecules such as menthol, amantadine, bepotastine, estrone derivatives, rendering it suitable application drug discovery programs, which introduction fluorinated fragments highly sought after. This method was extended enable reductive multicomponent radical-polar crossover transformation rapidly increase complexity assembled architectures single synthetic operation.

Language: Английский

Citations

3
Introduction of the difluoromethyl group at the meta- or para-position of pyridines through regioselectivity switch DOI Creative Commons
Pengwei Xu, Zhe Wang, Shu‐Min Guo

et al.

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

Published: May 15, 2024

Abstract Difluoromethyl pyridines have gained significant attention in medicinal and agricultural chemistry. The direct C−H-difluoromethylation of represents a highly efficient economic way to access these azines. However, the meta-difluoromethylation has remained elusive methods for site-switchable regioselective meta- para-difluoromethylation are unknown. Here, we demonstrate meta-C−H-difluoromethylation through radical process by using oxazino pyridine intermediates, which easily accessed from pyridines. selectivity can be readily switched para situ transformation pyridinium salts upon acid treatment. preparation various para-difluoromethylated this approach is presented. mild conditions used also allow late-stage or containing drugs. Sequential double functionalization presented, further underlines value work.

Language: Английский

Citations

12
Divergent functionalization of alkenes enabled by photoredox activation of CDFA and α-halo carboxylic acids DOI Creative Commons
Rahul Giri, Egor S. Zhilin, Dmitry Katayev

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(27), P. 10659 - 10667

Published: Jan. 1, 2024

The direct activation of α-halo carboxylic acids using visible-light-mediated photoredox catalysis facilitates the formation bifunctional radical intermediates, allowing reactivity toward olefins to be fine-tuned by varying solvent system.

Language: Английский

Citations

5
Iron(II) triflate as a photocatalyst for trifluoromethylation of functionalized arenes under blue LED light: Access to bioactive compounds DOI
Sandeep Kumawat, Kishore Natte

Journal of Catalysis, Journal Year: 2024, Volume and Issue: 434, P. 115506 - 115506

Published: April 20, 2024

Language: Английский

Citations

4
Radical trifluoromethoxylation of fluorinated alkenes for accessing difluoro(trifluoromethoxy)methyl groups DOI Creative Commons

Koki Kawai,

Mai Usui,

Sota Ikawa

et al.

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

In this study, we explore the potential of difluoro(trifluoromethoxy)methyl group, CF 2 –O–CF 3 , an underexplored but promising structural analog trifluoromethoxy group (OCF ).

Language: Английский

Citations

0
Unified Hydrogen Atom Transfer Approach To Construct Vicinal Functionality DOI
Jeffrey Chang,

Munnu Kumar,

Masakuni Okamoto

et al.

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

Published: Feb. 6, 2025

Due to their prevalence in pharmaceuticals and natural products, vicinally functionalized motifs are highly sought-after. Traditionally, these fragments synthesized from alkene precursors via oxidation reactions. However, complementary syntheses a C–C bond-forming approach underexplored. Herein, we disclose unified for accessing by acetal reagents made affordable, prefunctionalized starting materials. We have demonstrated the wide applicability of this methodology variety molecularly complex substrates. Additionally, coupled products can be employed one-pot cyclizations synthesize lactones.

Language: Английский

Citations

0
Discovery of a Distinctive Reagent for Divergent Arene Trifluoromethylsulfinylation DOI Creative Commons
Liuqing Yang, Yu Lu, Lulu Liu

et al.

JACS Au, Journal Year: 2025, Volume and Issue: 5(3), P. 1448 - 1459

Published: Feb. 19, 2025

Simple and direct arene trifluoromethylsulfinylation is highly desirable in drug design but remains a major challenge. Herein, we report modular, mild, innate C–H of wide variety arenes via distinctive trifluoromethylsulfinylating reagent N-hydroxyphthalimide-O-trifluoromethanesulfinate following divergent efficient pathways. This can be conducted redox-neutral manner at room temperature with light-, metal-, photocatalyst-free mild conditions. Mechanistic studies density functional theory (DFT) calculations revealed that the success this approach hinges upon an activated trifluoromethanesulfite ester proceeds homolytic cleavage very low bond dissociation energy to generate dummy aminoxyl radical (PINO) active CF3S(O) radical, which could accidentally transformed into trifluoromethanesulfonic anhydride, CF3S(O)OS(O)CF3, for transfer S(O)CF3 group exemplary set strong EDG-substituted arenes. DFT computation corroborates novel by TfOH heterolytic produce CF3S(O)OTf, responsible electrophilic challenging weak substrates through addition–elimination mechanism. Such functionalization using affords innovative strategy marked improvement over previously developed reagents. Notably, simple conditions, broad reactivities, good compatibility, reaction modes (homolysis heterolysis), as well late-stage (LST) complex biologically molecules these reactions underline great potential preparation functionalized drug-like molecules.

Language: Английский

Citations

0
Visible-light-induced C2-selective trifluoromethylation of indoles catalyzed by copper-containing covalent organic frameworks DOI
Zhicheng Chen,

Mengqi Zou,

Xianghui Zhu

et al.

Journal of Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 116077 - 116077

Published: March 1, 2025

Language: Английский

Citations

0
Visible‐Light‐Induced C−H Amidation of (Hetero)arenes with Hypervalent Iodine(III) Reagents DOI Open Access
Xiaojuan Wang, He Wang, Zhenkun Ma

et al.

Asian Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Abstract A visible‐light‐promoted C−H amidation of (hetero)arenes with hypervalent iodine reagents has been successfully achieved good yields. The high efficiency, broad substrate range and functional group compatibility demonstrated the utility method. Moreover, this protocol was suitable for late‐stage functionalization natural products. Mechanistic studies have shown that N‐centred saccharin radical mediates arenes.

Language: Английский

Citations

0
Nitrogen-Based Organofluorine Functional Molecules: Synthesis and Applications DOI
Shuai Liu, Jun Zhou, Lu Yu

et al.

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Fluorine and nitrogen form a successful partnership in organic synthesis, medicinal chemistry, material sciences. Although fluorine-nitrogen chemistry has long rich history, this field received increasing interest made remarkable progress over the past two decades, driven by recent advancements transition metal organocatalysis photochemistry. This review, emphasizing contributions from 2015 to 2023, aims update state of art synthesis applications nitrogen-based organofluorine functional molecules chemistry. In dedicated sections, we first focus on fluorine-containing reagents organized according type groups attached nitrogen, including N-F, N-RF, N-SRF, N-ORF. review also covers nitrogen-linked building blocks, catalysts, pharmaceuticals, agrochemicals, underlining these components' broad applicability growing importance modern

Language: Английский

Citations

0