Sequential C–F bond functionalizations of trifluoroacetamides and acetates via spin-center shifts

Science, Journal Year: 2021, Volume and Issue: 371(6535), P. 1232 - 1240

Published: March 5, 2021

Defluorinative functionalization of readily accessible trifluoromethyl groups constitutes an economical route to partially fluorinated molecules. However, the controllable replacement one or two fluorine atoms while maintaining high chemoselectivity remains a formidable challenge. Here we describe general strategy for sequential carbon-fluorine (C-F) bond functionalizations trifluoroacetamides and trifluoroacetates. The reaction begins with activation carbonyl oxygen atom by 4-dimethylaminopyridine-boryl radical, followed spin-center shift trigger C-F scission. A chemoselectivity-controllable two-stage process enables generation difluoro- monofluoroalkyl radicals, which are selectively functionalized different radical traps afford diverse products. mechanism origin were established experimental computational approaches.

Language: Английский

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Recent progress on selective deconstructive modes of halodifluoromethyl and trifluoromethyl-containing reagents

Chemical Society Reviews, Journal Year: 2020, Volume and Issue: 49(24), P. 9197 - 9219

Published: Jan. 1, 2020

Halodifluoromethyl and trifluoromethyl-containing compounds can act various rolesviaselective cleavage modes to access more valuable fluorinated or nonfluorinated molecules.

Language: Английский

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Recent advance in the C–F bond functionalization of trifluoromethyl-containing compounds

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(14), P. 3915 - 3942

Published: Jan. 1, 2021

The C–F bond is the strongest single in organic compounds.

Language: Английский

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Frustrated Lewis-Pair-Meditated Selective Single Fluoride Substitution in Trifluoromethyl Groups

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(5), P. 2572 - 2578

Published: Jan. 14, 2020

Single fluoride substitution in trifluoromethylarenes is an ongoing synthetic challenge that often leads to "over-reaction", where multiple fluorides are replaced. Development of this reaction would allow simple access a vast range difluoromethyl derivatives current interest pharmaceutical, agrochemistry, and materials sciences. Using catalytic frustrated Lewis pair approach, we have developed generic protocol allows single one trifluoromethyl groups with neutral phosphine pyridine bases. The resulting phosphonium pyridinium salts can be further functionalized via nucleophilic substitution, photoredox coupling, electrophilic transfer reactions allowing the generation array products.

Language: Английский

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Photochemical C–F Activation Enables Defluorinative Alkylation of Trifluoroacetates and -Acetamides

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(47), P. 19648 - 19654

Published: Nov. 18, 2021

The installation of gem-difluoromethylene groups into organic structures remains a daunting synthetic challenge despite their attractive structural, physical, and biochemical properties. A very efficient retrosynthetic approach would be the functionalization single C–F bond from trifluoromethyl group. Recent advances in this line attack have enabled activation trifluoromethylarenes, but limit accessible motifs to only benzylic gem-difluorinated scaffolds. In contrast, trifluoroacetates enable use as bifunctional synthon. Herein, we report photochemically mediated method for defluorinative alkylation commodity feedstock: ethyl trifluoroacetate. novel mechanistic was identified using our previously developed diaryl ketone HAT catalyst hydroalkylation diverse suite alkenes. Furthermore, electrochemical studies revealed that more challenging radical precursors, namely trifluoroacetamides, could also functionalized via synergistic Lewis acid/photochemical activation. Finally, concise gem-difluoro analogs FDA-approved pharmaceutical compounds.

Language: Английский

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Visible-Light-Induced Palladium-Catalyzed Selective Defluoroarylation of Trifluoromethylarenes with Arylboronic Acids

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(34), P. 13971 - 13979

Published: Aug. 19, 2021

Selective functionalization of inactive C(sp3)-F bonds to prepare medicinally interesting aryldifluoromethylated compounds remains challenging. One promising route is the transition-metal-catalyzed cross-coupling through oxidative addition bond in trifluoromethylarenes (ArCF3), which are ideal precursors for this process due their ready availability and low cost. Here, we report an unprecedented excited-state palladium catalysis strategy selective defluoroarylation with arylboronic acids. This visible-light-induced palladium-catalyzed proceeds under mild reaction conditions allows transformation a variety acids ArCF3. Preliminary mechanistic studies reveal that ArCF3 palladium(0) via single electron transfer pathway responsible activation.

Language: Английский

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Recent Advances in the Synthesis of Difluorinated Architectures from Trifluoromethyl Groups

Advanced Synthesis & Catalysis, Journal Year: 2021, Volume and Issue: 364(2), P. 234 - 267

Published: Nov. 29, 2021

Abstract Fluorine‐containing moieties are widely used in the pharmaceutical, agrochemical, and material fields. Thus, these structures of immense interest fields organic synthesis medicinal chemistry. Among various fluorinated groups, difluoromethyl unit has drawn increasing attention due to its unique pharmaceutical properties. In recent years, several methods for difluoromethylated compounds have been rapidly developed. However, most treat aromatic with excess difluoromethylating reagents, which often contain organometallic compounds, so transformations generally less environmentally friendly atom‐economical. this review, we summarize development new motifs or difluoroalkenes from trifluoromethylated trifluoromethyl alkenes via single C( sp 3 )−F bond cleavage. magnified image

Language: Английский

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C-F bond activation under transition-metal-free conditions

Science China Chemistry, Journal Year: 2021, Volume and Issue: 64(10), P. 1630 - 1659

Published: Aug. 30, 2021

Abstract The unique properties of fluorine-containing organic compounds make fluorine substitution attractive for the development pharmaceuticals and various specialty materials, which have inspired evolution diverse C-F bond activation techniques. Although many advances been made in functionalizations activated bonds utilizing transition metal complexes, there are fewer approaches available nonactivated due to difficulty oxidative addition metals inert bonds. In this regard, using Lewis acid abstract fluoride light/radical initiator generate radical intermediate emerged as powerful tools activating those Meanwhile, these transition-metal-free processes greener, economical, pharmaceutical industry, without heavy residues. This review provides an overview recent activations under conditions. key mechanisms involved demonstrated discussed detail. Finally, a brief discussion on existing limitations field our perspective presented.

Language: Английский

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Arenethiolate as a Dual Function Catalyst for Photocatalytic Defluoroalkylation and Hydrodefluorination of Trifluoromethyls

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(7), P. 4103 - 4109

Published: March 18, 2022

Thiol is known to act as a hydrogen atom transfer catalyst working in synergy with photocatalyst photoredox catalysis, but we report herein that an arene thiolate appropriate substituent can be photoactivated under visible light function both strongly reducing electron-donating redox and HAT enable catalytic C–F activation of trifluoromethyl substrates for selective hydrodefluorination coupling various alkenes the presence formate salts. These reactions demonstrate promising utility arenethiolates dual photocatalysts. The synthetic this method demonstrated by broad scope amenable substrates, including trifluoromethylated (hetero)arenes, trifluoroacetates, trifluoroacetamides, which exhibited high levels chemoselectivity. reaction efficacy allows site-selective late-stage functionalization multitrifluoromethylated bioactive compounds pharmaceuticals

Language: Английский

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Photoredox‐Catalyzed Defluorinative Functionalizations of Polyfluorinated Aliphatic Amides and Esters

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(9)

Published: Dec. 10, 2021

Abstract Selective C−F bond functionalization of perfluoalkyl units has huge potential towards accessing functionalized organofluorinated compounds, but remains challenging due to the high strength and inherent selectivity challenges. We report a new catalytic approach selective strong bonds in polyfluorinated aliphatic esters amides. This simple reaction proceeds mild operational fashion with divergent conversions, including hydrodefluorination, defluoroalkylation, defluoroalkenylation, affording diverse array important partially fluorinated motifs. Straightforward downstream chemistry alcohols, amines drug derivatives highlights protocol.

Language: Английский

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