HFIP in Organic Synthesis

Chemical Reviews, Год журнала: 2022, Номер 122(15), С. 12544 - 12747

Опубликована: Июль 17, 2022

1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) is a polar, strongly hydrogen bond-donating solvent that has found numerous uses in organic synthesis due to its ability stabilize ionic species, transfer protons, and engage range of other intermolecular interactions. The use this exponentially increased the past decade become choice some areas, such as C–H functionalization chemistry. In review, following brief history HFIP an overview physical properties, literature examples reactions using or additive are presented, emphasizing effect each reaction.

Язык: Английский

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Halogen-atom and group transfer reactivity enabled by hydrogen tunneling

Science, Год журнала: 2022, Номер 377(6612), С. 1323 - 1328

Опубликована: Сен. 15, 2022

The generation of carbon radicals by halogen-atom and group transfer reactions is generally achieved using tin silicon reagents that maximize the interplay enthalpic (thermodynamic) polar (kinetic) effects. In this work, we demonstrate a distinct reactivity mode enabled quantum mechanical tunneling uses cyclohexadiene derivative γ-terpinene as abstractor under mild photochemical conditions. This protocol activates alkyl aryl halides well several alcohol thiol derivatives. Experimental computational studies unveiled noncanonical pathway whereby cyclohexadienyl radical undergoes concerted aromatization or abstraction through an effective H atom. activation mechanism seemingly thermodynamically kinetically unfavorable but rendered feasible tunneling.

Язык: Английский

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Catalytic Electrophilic Halogenation of Arenes with Electron-Withdrawing Substituents

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(29), С. 13415 - 13425

Опубликована: Июль 15, 2022

The electrophilic halogenation of arenes is perhaps the simplest method to prepare aryl halides, which are important structural motifs in agrochemicals, materials, and pharmaceuticals. However, nucleophilicity weakened by electron-withdrawing substituents, whose reactions usually require harsh conditions lead limited substrate scopes applications. Therefore, containing groups (EWGs) complex bioactive compounds under mild has been a long-standing challenge. Herein, we describe Brønsted acid-catalyzed with substituents conditions, providing an efficient protocol for halides. hydrogen bonding acid protic solvent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) enables this transformation thus solves problem.

Язык: Английский

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Electrophilic Halospirocyclization of N-Benzylacrylamides to Access 4-Halomethyl-2-azaspiro[4.5]decanes

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(19), С. 13610 - 13621

Опубликована: Сен. 11, 2023

An electrophilic spirocyclization of N-benzylacrylamides with N-halosuccinimides (NXS) as the halogenating reagents has been developed. This reaction is carried out at room temperature under simple conditions without relying on metal reagents, photochemistry, or electrochemistry, providing a fast and efficient route to synthesize wide variety 4-halomethyl-2-azaspiro[4.5]decanes satisfactory yields. The approach further highlighted through gram-scale synthesis diverse transformations spiro products.

Язык: Английский

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Fluorinated Alcohols: Magic Reaction Medium and Promoters for Organic Synthesis

The Chemical Record, Год журнала: 2019, Номер 20(2), С. 142 - 161

Опубликована: Июль 2, 2019

Abstract Fluorinated alcohols have been widely used in the synthetic organic chemistry over past decades. The unique properties such as strong hydrogen‐bonding donor ability and low nucleophilicity allow them to promote reactions absence of any catalyst. These approaches distinct advantages terms operational simplicity, practicability environmental friendliness. Reactions promoted by fluorinated alcohols, including nucleophilic substitution reactions, annulation electrophilic dearomatization functionalization multiple bond, epoxidation miscellaneous summarized this account.

Язык: Английский

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Enantioselective, Lewis Base-Catalyzed Sulfenocyclization of Polyenes

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(10), С. 3569 - 3573

Опубликована: Март 6, 2018

A sulfenium-ion-initiated, catalytic, enantioselective polyene cyclization is described. Homogeranylarenes and ortho-geranylphenols undergo polycyclization in good yield, diastereoselectivity, enantioselectivity. The stereodetermining step the generation of an enantiomerically enriched thiiranium ion from a terminal alkene sulfenylating agent presence chiral Lewis basic catalyst. use hexafluoroisopropyl alcohol as solvent crucial to obtain yields. thioether moiety resulting reaction can be subsequently transformed into diverse oxygen carbon functionality postcyclization. utility this method demonstrated by syntheses (+)-ferruginol (+)-hinokiol.

Язык: Английский

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Redox-triggered cascade dearomative cyclizations enabled by hexafluoroisopropanol

Chemical Science, Год журнала: 2018, Номер 9(43), С. 8253 - 8259

Опубликована: Янв. 1, 2018

Aromatization as the driving force to initiate hydride transfer addressed drawbacks of transfer-involved reactions.

Язык: Английский

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Catalytic Enantioselective Dihalogenation in Total Synthesis

Accounts of Chemical Research, Год журнала: 2018, Номер 51(5), С. 1260 - 1271

Опубликована: Апрель 17, 2018

ConspectusTo date, more than 5000 biogenic halogenated molecules have been characterized. This number continues to increase as chemists explore chloride- and bromide-rich marine environments in search of novel bioactive natural products. Naturally occurring organohalogens span nearly all biosynthetic structural classes, exhibit a range unique biological activities, the subject numerous investigations. Despite abundance interest molecules, enantioselective methods capable forging carbon–halogen bonds synthetically relevant contexts remain scarce. Accordingly, syntheses often rely on multistep functional group interconversions establish stereocenters. Our has developed an dihalogenation reaction utilized it only reported examples catalytic halogenation product synthesis. In this Account, we describe our laboratory's development method for catalytic, application synthesis both mono- polyhalogenated first part, initial discovery TADDOL-mediated dibromination cinnamyl alcohols. Extension second-generation system selective bromochlorination, dichlorination, is then detailed. controlling enantioselectivity dihalide formation, chemoselectivity polyolefinic substrates, regioselectivity case bromochlorination. The ability exert control over halide delivery permits electronically nonbiased olefins required total synthesis.In second demonstrate how described provided efficient access host structurally diverse most direct methodology naturally vicinal dihalides. Chiral bromochlorides represent class >175 products; five members class, including its flagship member, (+)-halomon, accomplished through use Likewise, dichlorination two chlorosulfolipids, linear, acyclic polychlorides. Synthesis chiral monohalides achieved solvolysis enantioenriched bromochlorides; approach resulted bromocyclohexane-containing products enantiospecific bromopolyene cyclization. reviewing these syntheses, framework mediated by emerged.The highly enabling detail encourage further useful methodologies.

Язык: Английский

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Triptycenyl Sulfide: A Practical and Active Catalyst for Electrophilic Aromatic Halogenation Using N-Halosuccinimides

Journal of the American Chemical Society, Год журнала: 2019, Номер 142(3), С. 1621 - 1629

Опубликована: Дек. 23, 2019

A Lewis base catalyst Trip-SMe (Trip = triptycenyl) for electrophilic aromatic halogenation using N-halosuccinimides (NXS) is introduced. In the presence of an appropriate activator (as a noncoordinating-anion source), series unactivated compounds were halogenated at ambient temperature NXS. This catalytic system was applicable to transformations that are currently unachievable except use Br2 or Cl2: e.g., multihalogenation naphthalene, regioselective bromination BINOL, etc. Controlled experiments revealed triptycenyl substituent exerts crucial role activity, and kinetic implied occurrence sulfonium salt [Trip-S(Me)Br][SbF6] as active species. Compared simple dialkyl sulfides, exhibited significant charge-separated ion pair character within halonium complex whose structural information obtained by single-crystal X-ray analysis. preliminary computational study disclosed π functionality key motif consolidate enhancement electrophilicity.

Язык: Английский

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Electrochemical Vicinal Difluorination of Alkenes: Scalable and Amenable to Electron‐Rich Substrates

Angewandte Chemie International Edition, Год журнала: 2019, Номер 59(3), С. 1155 - 1160

Опубликована: Ноя. 7, 2019

Fluorinated alkyl groups are important motifs in bioactive compounds, positively influencing pharmacokinetics, potency and conformation. The oxidative difluorination of alkenes represents an strategy for their preparation, yet current methods limited alkene-types tolerance electron-rich, readily oxidized functionalities, as well safety scalability. Herein, we report a method the number unactivated that is tolerant electron-rich functionality, giving products otherwise unattainable. Key to success electrochemical generation hypervalent iodine mediator using "ex-cell" approach, which avoids substrate decomposition. more sustainable conditions give good excellent yields up decagram scales.

Язык: Английский

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