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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Synthetic Advantages of Defluorinative C−F Bond Functionalization

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(49)

Опубликована: Авг. 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.

Язык: Английский

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Recent advances in radical enabled selective C_sp³–F bond activation of multifluorinated compounds

Chemical Communications, Год журнала: 2021, Номер 58(8), С. 1066 - 1077

Опубликована: Дек. 24, 2021

Fluorine-containing molecules have found broad applications in pharmaceutical and agrochemical industries as introducing fluorine into a molecule could significantly tune the biological activities of parent molecules. Thus, synthesis fluorine-containing has received substantial attention over past few decades. As complementary strategy for fluorinated compounds through new Csp3-F bonds formation, selective cleavage inert from easily-available cost-effective multifluorinated molecules, such fluoroalkylaromatics, α-trifluoromethyl alkenes α-multifluorinated carbonyl compounds, been emerging an attractive alternative to access Moreover, inherent nature radical reactions offers opportunity functionalizations occur under mild conditions. In this regard, development photoredox catalysis, transition-metal or electrochemistry enable species generation via gained progress made recent years. This highlight summerizes advances single-electron-transfer enabled pathways.

Язык: Английский

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Photocatalytic gem‐Difluoroolefination Reactions by a Formal C−C Coupling/Defluorination Reaction with Diazoacetates

Angewandte Chemie International Edition, Год журнала: 2021, Номер 61(4)

Опубликована: Окт. 30, 2021

The photolysis of diazoalkanes to conduct singlet carbene transfer reactions colored has recently attracted significant interest in organic synthesis. Herein, we describe a photocatalytic approach that allows the access triplet intermediates via energy highly efficient gem-difluoroolefination with α-trifluoromethyl styrenes. use tertiary amines proved pivotal unlock this unusual reaction pathway and prevent undesired cyclopropanation pathways. amine further facilitates ultimate abstraction fluoride yield gem-difluoroolefins (43 examples, up 88 % yield), which is supported by experimental theoretical mechanistic studies. We explored synthesis method broad substrate scope, ranging from simple olefins heterocyclic towards decoration pharmaceutically relevant building blocks.

Язык: Английский

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Reductive quenching-initiated catalyst-controlled divergent alkylation of α-CF3-olefins

Chem Catalysis, Год журнала: 2022, Номер 2(6), С. 1380 - 1393

Опубликована: Апрель 21, 2022

Gem-difluoroalkenes and trifluoromethyl alkanes are pervasive in biologically active molecules. Photo-catalyzed alkylation of α-CF3-olefins provides a straightforward approach to access these scaffolds; however, such strategy is often hampered, gem-difluoroalkenes usually formed instead under reductive quenching-initiated photoredox conditions. It both mechanistically synthetically appealing if simple change the catalyst can chemo-selectively lead either type products. Here, we show visible-light-induced photo-catalyst for preparing from α-CF3-olefins. The chemo-selectivity reactions arises judicious choice rather than modification substrate structures. A wide variety substrates bearing an assortment functional groups (62 examples) compatible with this strategy. use HFIP as additive promotes formation probably via facilitation hydrogen atom transfer step O-H but not α-C-H bond.

Язык: Английский

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Ni-Catalyzed Radical-Promoted Defluoroalkylborylation of Trifluoromethyl Alkenes To Access gem-Difluorohomoallylic Boronates

Organic Letters, Год журнала: 2022, Номер 24(12), С. 2446 - 2451

Опубликована: Март 21, 2022

gem-Difluoroalkenyl boronates are attractive synthons for constructing diverse gem-difluoroalkenes and organoboron compounds. However, the strategies construction of gem-difluorohomoallyl has scarcely been described. Herein, we develop an efficient protocol gem-difluorohomoallylic through a Ni-catalyzed radical-promoted defluoroalkylborylation α-trifluoromethyl alkenes with α-haloboronates under mild conditions. This reaction features broad substrate scope good functional group tolerance transformations.

Язык: Английский

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Enantioselective nickel-catalyzed dicarbofunctionalization of 3,3,3-trifluoropropene

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

Опубликована: Сен. 21, 2022

Despite paramount applications of chiral trifluoromethylated compounds in medicinal chemistry and materials science, limited strategies have been developed for catalytic asymmetric synthesis such valuable fluorinated structures. Here, we report a nickel catalyzed enantioselective dicarbofunctionalization inexpensive industrial chemical 3,3,3-trifluoropropene (TFP) with readily available tertiary alkyl aryl iodides. The reaction overcomes the β-F elimination side TFP, proceeds efficiently under mild conditions. protocol possesses advantages, as synthetic convenience, high enantioselectivity, excellent functional group tolerance, providing rapid straightforward access to interest.

Язык: Английский

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Precise electro-reduction of alkyl halides for radical defluorinative alkylation

Science China Chemistry, Год журнала: 2022, Номер 65(4), С. 762 - 770

Опубликована: Март 10, 2022

Язык: Английский

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Nickel-Catalyzed anti-Markovnikov Hydroalkylation of Trifluoromethylalkenes

ACS Catalysis, Год журнала: 2022, Номер 12(15), С. 9410 - 9417

Опубликована: Июль 18, 2022

Transition-metal-catalyzed difunctionalization of olefins constitutes a fertile synthetic platform for rapid access to complex molecules from bulk chemicals. However, substrates featuring fluoroalkyl substituents are rarely employed because facile β-fluoride elimination pathways. Herein, we report hydroalkylation trifluoromethylalkenes with alkyl halides under nickel catalysis that enables the construction 1,1,1-trifluoropropane derivatives. The common pathway is suppressed by identifying competent proton donor favors protonolysis process. Also, unactivated alkenes could be readily as when using Ni/hydrosilane catalytic system.

Язык: Английский

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Photoredox-Catalyzed Allylic Defluorinative Alkoxycarbonylation of Trifluoromethyl Alkenes through Intermolecular Alkoxycarbonyl Radical Addition

Organic Letters, Год журнала: 2022, Номер 24(7), С. 1471 - 1475

Опубликована: Фев. 15, 2022

The gem-difluoroalkene moiety is an ideal carbonyl bioisostere in medicinal chemistry, but efficient synthesis of β-gem-difluoroalkene esters remains challenging so far. Herein, we disclose a photoredox-catalyzed allylic defluorinative alkoxycarbonylation trifluoromethyl alkenes enabled by intermolecular alkoxycarbonyl radical addition. A wide variety alcohol oxalate derivatives were amenable, affording various with excellent functional group tolerance. Notably, the potential synthetic value this method highlighted successful late-stage modification for bioactive molecules.

Язык: Английский

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