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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Photocatalytic Hydrogen Atom Transfer-Induced Arbuzov-Type α-C(sp³)–H Phosphonylation of Aliphatic Amines

ACS Catalysis, Год журнала: 2023, Номер 13(24), С. 16105 - 16113

Опубликована: Дек. 5, 2023

Despite remarkable progress in photocatalytic hydrogen atom transfer (HAT)-induced C(sp3)–H functionalization, achieving to C(sp3)–P transformation by the HAT process remains highly challenging due P-reagents' compatibility issues. α-Aminophosphonic acids have shown great potential medicinal chemistry, yet their synthesis is hindered limited substrate scopes, poor functional group tolerance, and reliance on prefunctionalized substrates, restricting broad applications. Herein, we report HAT-induced α-C(sp3)–H phosphonylation of aliphatic amines, providing rapid access structurally diverse α-aminophosphonates from abundant amines. Leveraging intramolecular HAT, radical polar crossover, an Arbuzov-type cascade, challenges associated with were overcome. This protocol features base-free, redox-neutral, mild conditions employing amines as limiting reagents, allows for late-stage complex drug molecules possessing amine moieties.

Язык: Английский

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Blue Light Irradiated Metal-, Oxidant-, and Base-Free Cross-Dehydrogenative Coupling of C(sp²)–H and N–H Bonds: Amination of Naphthoquinones with Amines

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(11), С. 7401 - 7424

Опубликована: Май 12, 2023

Herein, we report a blue-light-driven amination of C(sp2)-H bond naphthoquinones and quinones with the N-H primary secondary amines for synthesis 2-amino-naphthoquinones 2-amino-quinones. The coupling wide array aliphatic, aromatic, chiral, primary, having electron donating (-CH3, -OCH3, -SCH3), withdrawing (-F, -Cl, -Br, -I), CO2H, -OH, -NH2 groups acidic protons selectively occurred to afford C-N coupled in 60-99% yields hydrogen gas as byproduct methanol solvent without using any additional reagents, additives, oxidant under blue light irradiation. Mechanistic insight by DFT computation, controlled experiments, kinetic isotopic effect, substitution effect substrates suggest that reaction proceeds radical pathway which naphthoquinone forms highly oxidizing naphthoquinonyl biradical upon irradiation (457 nm). Consequently, transfer from electron-rich amine an leads anion aminyl cation, followed proton delocalization leading carbon-centered radical. cross-coupling nitrogen radicals bond, subsequent elimination (which was also confirmed GC-TCD), affording 2-amino-1,4-naphthoquinone metal-, reagent-, base-, oxidant-free conditions.

Язык: Английский

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Nickel‐Catalyzed Site‐Selective Intermolecular C(sp³)−H Amidation

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(50)

Опубликована: Окт. 18, 2022

A nickel-catalyzed site-selective intermolecular amidation of saturated C(sp3 )-H bonds is reported. This mild protocol exhibits a predictable reactivity pattern to incorporate amide functions at sites adjacent nitrogen and oxygen atoms in either cyclic or acyclic frameworks, thus offering complementary profile existing oxidative-type processes metal-catalyzed )-N bond-forming reactions operating via two-electron manifolds.

Язык: Английский

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Amidative β-Scission of Alcohols Enabled by Dual Catalysis of Photoredox Proton-Coupled Electron Transfer and Inner-Sphere Ni-Nitrenoid Transfer

Journal of the American Chemical Society, Год журнала: 2023, Номер 146(1), С. 1001 - 1008

Опубликована: Дек. 18, 2023

The photoredox/Ni dual catalysis is an appealing strategy to enable unconventional C-heteroatom bond formation. While significant advances have been achieved using this system, intermolecular C(sp

Язык: Английский

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γ-Amino C(sp³)–H Functionalization of Aliphatic Amines through a Light-Driven Triple Catalysis

ACS Catalysis, Год журнала: 2024, Номер 14(10), С. 8005 - 8012

Опубликована: Май 9, 2024

We report intra- and intermolecular γ-amino C(sp3)–H functionalization of aliphatic amines using a vinylsulfone-based HAT (hydrogen atom transfer) auxiliary triple catalysis, which is composed photoredox, cobalt, Brønsted acid catalysts under visible light irradiation. The process accomplishes four elementary steps: (i) electrophilic carbon-centered radical formation on the via MHAT (metal hydride hydrogen reaction, (ii) generation through 1,6-HAT (iii) single-electron oxidation to carbocation equivalents, (iv) nucleophilic substitution with internal or external nucleophiles. As result, this afforded γ-amino-functionalized products, such as azetidines, 1,3-diamine, 1,3-aminoalcohol derivatives.

Язык: Английский

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Electrochemical direct α-amidation and α-pyrazolation of N-alkoxy- and N-aryloxycarbonyl pyrrolidines

Green Chemistry, Год журнала: 2024, Номер 26(12), С. 7419 - 7423

Опубликована: Янв. 1, 2024

We have developed a straightforward electrochemical protocol for direct α-amidation and α-pyrazolation of N -alkoxy- -aryloxycarbonyl pyrrolidines with amides or pyrazoles.

Язык: Английский

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A Voltage-Controlled Strategy for Modular Shono-Type Amination

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(42), С. 28663 - 28668

Опубликована: Окт. 14, 2024

Shono-type oxidation to generate functionalized heterocycles is a powerful method for late-stage diversification of relevant pharmacophores; however, development beyond oxygen-based nucleophiles remains underdeveloped. The limited scope can often be ascribed constant current electrolysis resulting in potential drifts that oxidize desired nucleophilic partner. Herein, we report voltage-controlled strategy selectively broad substrates, enabling modular C-N bond formation from protected amine nucleophiles. We implement an electroanalytically guided workflow using cyclic voltammetry (CV) and differential pulse (DPV) identify potentials across range heterocyclic substrates. Controlled (CPE) generates α-functionalized products moderate good yields carbamate-, sulfonamide-, benzamide-derived importance voltage control further exemplified through systematic study comparing our developed CPE (CCE) protocols. Voltage-guided CCE traditionally optimized reveal the maintaining high selectivity over scope; case with morpholine-derived substrate illustrates negative impact drifting under CCE. Sulfonamide drugs, which have significant overlap model are rendered competent CPE. Lastly, sequential C-O functionalization difunctionalized pyrrolidines broadening utility this reaction.

Язык: Английский

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Alicyclic‐Amine‐Derived Imine‐BF₃ Complexes: Easy‐to‐Make Building Blocks for the Synthesis of Valuable α‐Functionalized Azacycles

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(1)

Опубликована: Ноя. 1, 2023

A new strategy to access α-functionalized alicyclic amines via their corresponding imine-BF

Язык: Английский

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Photocatalytic Oxidative C(sp³)-H/N–H Cross-Dehydrogenative Coupling of Tertiary Anilines with Amides/Imides: Synthesis of N-Mannich Bases

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 30, 2025

A photocatalytic method for the synthesis of N-Mannich bases has been developed through C(sp3)-H/N-H cross-dehydrogenative coupling N,N-dimethylanilines with amides/imides. This process utilizes 2,4,6-triphenylpyrylium tetrafluoroborate (TPT) as photocatalyst and is conducted at ambient temperature atmospheric air. Various aromatic, heteroaromatic aliphatic (cyclic) amides, well imides were successfully employed, yielding moderate to good results. Preliminary mechanistic isotope-labeling studies indicate that reaction likely proceeds via a single electron transfer pathway involves an α-aminoalkyl radical intermediate.

Язык: Английский

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