Late-stage difluoromethylation: concepts, developments and perspective

Chemical Society Reviews, Год журнала: 2021, Номер 50(14), С. 8214 - 8247

Опубликована: Янв. 1, 2021

This review describes the conceptual advances that have led to multiple difluoromethylation processes making use of well-defined CF₂H sources.

Язык: Английский

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

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(47), С. 19648 - 19654

Опубликована: Ноя. 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.

Язык: Английский

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Visible-light photoredox-catalyzed selective carboxylation of C(sp3)−F bonds with CO2

Chem, Год журнала: 2021, Номер 7(11), С. 3099 - 3113

Опубликована: Авг. 27, 2021

Язык: Английский

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Chemoselective Electrosynthesis Using Rapid Alternating Polarity

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(40), С. 16580 - 16588

Опубликована: Окт. 1, 2021

Challenges in the selective manipulation of functional groups (chemoselectivity) organic synthesis have historically been overcome either by using reagents/catalysts that tunably interact with a substrate or through modification to shield undesired sites reactivity (protecting groups). Although electrochemistry offers precise redox control achieve unique chemoselectivity, this approach often becomes challenging presence multiple redox-active functionalities. Historically, electrosynthesis has performed almost solely direct current (DC). In contrast, applying alternating (AC) known change reaction outcomes considerably on an analytical scale but rarely strategically exploited for use complex preparative synthesis. Here we show how square waveform employed deliver electric current—rapid polarity (rAP)—enables over chemoselective reduction carbonyl compounds, one most widely used manifolds. The observed cannot be recapitulated DC electrolysis chemical reagents. synthetic value brought new method controlling chemoselectivity is vividly demonstrated context classical problems such as chiral auxiliary removal and cutting-edge medicinal chemistry topics PROTACs.

Язык: Английский

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Selective [2σ + 2σ] Cycloaddition Enabled by Boronyl Radical Catalysis: Synthesis of Highly Substituted Bicyclo[3.1.1]heptanes

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(7), С. 4304 - 4310

Опубликована: Фев. 10, 2023

In contrast to the traditional and widely-used cycloaddition reactions involving at least a π bond component, [2σ + 2σ] radical between bicyclo[1.1.0]butanes (BCBs) cyclopropyl ketones has been developed provide modular, concise, atom-economical synthetic route substituted bicyclo[3.1.1]heptane (BCH) derivatives that are 3D bioisosteres of benzenes core skeleton number terpene natural products. The reaction was catalyzed by combination simple tetraalkoxydiboron(4) compound B2pin2 3-pentyl isonicotinate. broad substrate scope demonstrated synthesizing series new highly functionalized BCHs with up six substituents on 99% isolated yield. Computational mechanistic investigations supported pyridine-assisted boronyl catalytic cycle.

Язык: Английский

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Recent Advances in the Synthesis of Difluorinated Architectures from Trifluoromethyl Groups

Advanced Synthesis & Catalysis, Год журнала: 2021, Номер 364(2), С. 234 - 267

Опубликована: Ноя. 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

Язык: Английский

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

Science China Chemistry, Год журнала: 2021, Номер 64(10), С. 1630 - 1659

Опубликована: Авг. 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.

Язык: Английский

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Photochemical and electrochemical strategies in C–F bond activation and functionalization

Organic Chemistry Frontiers, Год журнала: 2021, Номер 9(3), С. 853 - 873

Опубликована: Дек. 7, 2021

The recent advances in photochemical or electrochemical C–F bond activation and functionalization have been summarized discussed.

Язык: Английский

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

ACS Catalysis, Год журнала: 2022, Номер 12(7), С. 4103 - 4109

Опубликована: Март 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

Язык: Английский

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Photocatalytic defluoroalkylation and hydrodefluorination of trifluoromethyls using o-phosphinophenolate

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Янв. 17, 2022

Under visible light irradiation, o-phosphinophenolate functions as an easily accessible photoredox catalyst to activate trifluoromethyl groups in trifluoroacetamides, trifluoroacetates, and (hetero)arenes deliver corresponding difluoromethyl radicals. It works relay with a thiol hydrogen atom transfer (HAT) enable selective defluoroalkylation hydrodefluorination. The reaction allows for the facile synthesis of broad scope difluoromethylene-incorporated carbonyl (hetero)aromatic compounds, which are valuable fluorinated intermediates interest pharmaceutical industry. ortho-diphenylphosphino substituent, is believed facilitate photoinduced electron transfer, plays essential role redox reactivity phenolate. In addition groups, pentafluoroethyl could also be selectively defluoroalkylated.

Язык: Английский

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