Photocatalytic Late-Stage C–H Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(8), С. 4237 - 4352

Опубликована: Янв. 24, 2023

The emergence of modern photocatalysis, characterized by mildness and selectivity, has significantly spurred innovative late-stage C–H functionalization approaches that make use low energy photons as a controllable source. Compared to traditional strategies, photocatalysis paves the way toward complementary and/or previously unattainable regio- chemoselectivities. Merging compelling benefits with workflow offers potentially unmatched arsenal tackle drug development campaigns beyond. This Review highlights photocatalytic strategies small-molecule drugs, agrochemicals, natural products, classified according targeted bond newly formed one. Emphasis is devoted identifying, describing, comparing main mechanistic scenarios. draws critical comparison between established ionic chemistry photocatalyzed radical-based manifolds. aims establish current state-of-the-art illustrate key unsolved challenges be addressed in future. authors aim introduce general readership functionalization, specialist practitioners evaluation methodologies, potential for improvement, future uncharted directions.

Язык: Английский

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N–O Bond Activation by Energy Transfer Photocatalysis

Accounts of Chemical Research, Год журнала: 2022, Номер 55(17), С. 2526 - 2541

Опубликована: Авг. 20, 2022

ConspectusA radical shift toward energy transfer photocatalysis from electron under visible-light photoirradiation is often due to the greener prospects of atom and process economy. Recent advances in embrace unique strategies for direct small-molecule activation sometimes extraordinary chemical bond formation absence additional/sacrificial reagents. Selective requires careful selection substrates photocatalysts a perfect match with respect their triplet energies while having incompatible redox potentials prevent competitive pathways. Substrates containing labile N–O bonds are potential targets generating reactive key intermediates via access variety functionalized molecules. Typically, differential densities N O heteroatoms have been exploited generation either N- or O-centered by pathway. However, latest developments involve homolysis generate both radicals subsequent utilization diverse organic transformations, also sacrificial In this Account, we highlight our contributions field intermediates, coverage useful mechanistic insights. More specifically, well-designed bond-containing such as 1,2,4-oxadiazolines, oxime esters, N-indolyl carbonates, N-enoxybenzotriazoles were successfully utilized versatile transformations involving selective over high state energy. Direct N-, O-, C-centered (if decarboxylation follows) was achieved cross-couplings rearrangement processes. particular, open-shell nitrogen including N(sp2) N(sp3) nitrenes, utilized. Notably, diversified identical through control reaction conditions. 1,2,4-Oxadiazolines converted into spiro-azolactams iminyl presence 1O2, benzimidazoles, sulfoximines external sulfoxide reagent nitrene inert Besides, esters underwent intramolecular C(sp3)–N radical–radical coupling intermolecular combined transfer–hydrogen strategy. Furthermore, series electrochemical photophysical experiments well computational studies performed substantiate proposed energy-transfer-driven We hope that Account will serve guide rational design processes further bonds.

Язык: Английский

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Lewis Base–Boryl Radicals Enabled Borylation Reactions and Selective Activation of Carbon–Heteroatom Bonds

Accounts of Chemical Research, Год журнала: 2022, Номер 56(2), С. 169 - 186

Опубликована: Дек. 26, 2022

ConspectusThe past decades have witnessed tremendous progress on radical reactions. However, in comparison with carbon, nitrogen, oxygen, and other main group element centered radicals, the synthetic chemistry of boron radicals was less studied, mainly due to high electron-deficiency instability such 3-center-5-electron species. In 1980s, Roberts co-workers found that coordination a Lewis base (amines or phosphines) center could form 4-center-7-electron boryl (Lewis base-boryl LBRs) are be more stable. only limited applications were developed. 2008, Curran achieved breakthrough discovery N-heterocyclic carbene (NHC) which enable range reduction polymerization Despite these exciting findings, powerful valuable LBRs would expected, given structures reactivities easily modulated, provide ample opportunities discover new this Account, summary our key contributions LBR-enabled borylation reactions selective activation inert carbon-heteroatom bonds will presented.Organoboron compounds shown versatile chemical society, their syntheses rely principally ionic The development mechanistically different allows synthesizing products inaccessible by traditional methods. For purpose, we progressively developed series NHC-boryl mediated chemo-, regio-, stereoselective alkenes alkynes, wide variety structurally diverse organoboron molecules successfully prepared. utility borylated also demonstrated. Furthermore, disclosed photoredox protocol for oxidative generation enabled useful defluoroborylation arylboration reactions.Selective bond is an ideal way convert simple starting materials value-added products, while cleavage bonds, particular chemoselectivity control when multiple identical present similar environments, remains long-standing challenge. We envisaged finely tuning properties might solution address Recently, 4-dimethylaminopyridine (DMAP)-boryl promoted sequential C-F functionalization trifluoroacetic acid derivatives, α-C-F selectively snipped via spin-center shift mechanism. This strategy enables facile conversion abundantly available highly mono- difluorinated molecules. Encouraged finding, further three-step sequence construct all-carbon quaternary centers from trichloromethyl groups, where three C-Cl cleaved rational choice suitable precursors each step. dehydroxylative alkylation α-hydroxy carboxylic derivatives achieved, allowing efficient some biomass platform value products.

Язык: Английский

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From Stable Radicals to Thermally Robust High-Spin Diradicals and Triradicals

Chemical Reviews, Год журнала: 2023, Номер 123(20), С. 11954 - 12003

Опубликована: Окт. 13, 2023

Stable radicals and thermally robust high-spin di- triradicals have emerged as important organic materials due to their promising applications in diverse fields. New fundamental properties, such SOMO/HOMO inversion of orbital energies, are explored for the design new stable radicals, including highly luminescent ones with good photostability. A relation singlet–triplet energy gap corresponding diradicals is proposed. Thermally triradicals, gaps that comparable or greater than a thermal at room temperature, more challenging synthesize but rewarding. We summarize number based on nitronyl nitroxides provide between experimental pairwise exchange coupling constant J/k species vs hyperfine constants monoradicals. This allows us identify outliers, which may correspond where not measured sufficient accuracy. Double helical diradicals, spin density delocalized over chiral π-system, been barely explored, sole example diradical possessing alternant π-system Kekulé resonance form. Finally, we discuss electrical conductivity derivatives triangulene diradicals.

Язык: Английский

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Photoenzymatic enantioselective intermolecular radical hydroamination

Nature Catalysis, Год журнала: 2023, Номер 6(8), С. 687 - 694

Опубликована: Июль 31, 2023

Язык: Английский

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Radical Polarity

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Окт. 3, 2024

The polarity of a radical intermediate profoundly impacts its reactivity and selectivity. To quantify this influence predict effects, the electrophilicity/nucleophilicity >500 radicals has been calculated. This database open-shell species entails frequently encountered synthetic intermediates, including centered at sp

Язык: Английский

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Remote site-selective arene C–H functionalization enabled by N-heterocyclic carbene organocatalysis

Nature Catalysis, Год журнала: 2024, Номер 7(8), С. 900 - 911

Опубликована: Июль 11, 2024

Язык: Английский

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Site-selective arene C–H amination with iron-aminyl radical

Nature Catalysis, Год журнала: 2024, Номер 7(6), С. 636 - 645

Опубликована: Апрель 1, 2024

Язык: Английский

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The advent of electrophilic hydroxylamine-derived reagents for the direct preparation of unprotected amines

Chemical Communications, Год журнала: 2022, Номер 58(72), С. 9991 - 10003

Опубликована: Янв. 1, 2022

Electrophilic aminating reagents have seen a renaissance in recent years as effective nitrogen sources for the synthesis of unprotected amino functionalities.

Язык: Английский

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Diastereoselective Radical Aminoacylation of Olefins through N-Heterocyclic Carbene Catalysis

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(49), С. 22767 - 22777

Опубликована: Ноя. 24, 2022

There have been significant advancements in radical-mediated reactions through covalent-based organocatalysis. Here, we present the generation of iminyl and amidyl radicals via N-heterocyclic carbene (NHC) catalysis, enabling diastereoselective aminoacylation trisubstituted alkenes. Different from photoredox single electron transfer deprotonated Breslow intermediate to O-aryl hydroxylamine generates an NHC-bound ketyl radical, which undergoes diastereocontrolled cross-coupling with prochiral C-centered radical. This operationally simple method provides a straightforward access variety pyrroline oxazolidinone heterocycles vicinal stereocenters (77 examples, up >19:1 d.r.). Electrochemical studies acyl thiazolium salts support our reaction design highlight reducing ability Breslow-type derivatives. A detailed computational analysis this organocatalytic system suggests that radical–radical coupling is rate-determining step, π–π stacking interaction between radical intermediates subtly controls diastereoselectivity.

Язык: Английский

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