Photoredox-catalysed amidyl radical insertion to bicyclo[1.1.0]butanes

Nature Catalysis, Год журнала: 2024, Номер 7(11), С. 1232 - 1242

Опубликована: Окт. 22, 2024

Abstract Replacing planar aromatic rings in drug molecules with C( sp 3 )-rich isosteric mimetics, such as bicyclo[ n .1.1]alkanes, can significantly alter their physicochemical and pharmacokinetic properties, often leading to higher clinical success rates. However, unlike a benzene ring, the structurally rigid mimetics of heteroaromatic are rare. Heterobicyclo[ .1.1]alkanes promising this regard, but lack modular synthetic methods has currently hindered exploration. We envisioned that strategic selective insertion different heteroatomic units bicyclo[1.1.0]butanes could offer highly platform access diverse heterobicyclo[ .1.1]alkanes. Herein we report photoredox-catalysed regioselective chemoselective amidyl radicals bicyclo[1.1.0]butanes, providing direct 2-oxa-4-azabicyclo[3.1.1]hept-3-enes. The exit vector analysis shows geometric resemblance these heterobicyclic motifs pyridine pyrimidine derivatives, suggesting potential medicinally important heterocycles. Additionally, various downstream transformations demonstrate utility versatile building blocks chemistry.

Язык: Английский

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Combining Multiple Photosensitizer Modules into One Supramolecular System for Synergetic Enhanced Photodynamic Therapy

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(11)

Опубликована: Янв. 9, 2024

Photodynamic therapy (PDT), as an emerging cancer treatment, requires the development of highly desirable photosensitizers (PSs) with integrated functional groups to achieve enhanced therapeutic efficacy. Coordination-driven self-assembly (CDSA) would provide alternative approach for combining multiple PSs synergistically. Here, we demonstrate a simple yet powerful strategy conventional chromophores (tetraphenylethylene, porphyrin, or Zn-porphyrin) pyridinium salt together through condensation reactions, followed by CDSA construct series novel metallo-supramolecular (S1-S3). The generation reactive oxygen species (ROS) is dramatically direct combination two different PSs, and further reinforced in subsequent ensembles. Among all ensembles, S2 porphyrin cores shows highest ROS efficiency, specific interactions lysosome, strong emission probing cells. Moreover, cellular living experiments confirm that has excellent PDT efficacy, biocompatibility, biosafety. As such, this study will enable more efficient potential clinical applications.

Язык: Английский

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Photocatalytic Unsymmetrical Diamination of Styrenes, Indoles, and Benzofurans Facilitated by Benzotriazolyl and Iminyl Radicals

Organic Letters, Год журнала: 2024, Номер 26(2), С. 559 - 564

Опубликована: Янв. 9, 2024

Utilizing energy transfer catalysis, this research employed the bifunctional reagents benzotriazole carboxylic acid oxime esters to simultaneously generate and imine radicals. The synthesis of two distinct C–N bonds in a single conversion is showcased through radical addition radical–radical cross-coupling processes between ester olefins. This process facilitates intermolecular two-component unsymmetrical diamination reaction Using approach, more than 40 benzotriazole-containing molecules were successfully synthesized using styrene, indole, benzofuran as acceptors, with yields ranging from moderate excellent.

Язык: Английский

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Regiodivergent Alkylation of Pyridines: Alkyllithium Clusters Direct Chemical Reactivity

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Regiodivergent C-C bond-forming reactions are a powerful tool for constructing diverse molecular architectures from common precursors. While transition metal catalysis has dominated regioselective transformations, achieving similar precision with transition-metal-free methods remains an unmet challenge, particularly when using identical starting materials. In this work, we report transition-metal-free, regiodivergent direct alkylation of electronically unbiased pyridines 1,1-diborylalkanes as the sole alkylating agent. The key to controlling regioselectivity lies in choice alkyllithium activator 1,1-diborylalkanes: methyllithium directs predominantly C4 position, while sec-butyllithium promotes C2-alkylation. Mechanistic studies reveal that structural dynamics clusters dictate regioselectivity, tetrameric favoring C4-alkylation and dimeric preferring This method demonstrates broad substrate scope, enables late-stage functionalization complex molecules, allows sequential installation two distinct alkyl groups onto pyridine scaffold. Our approach provides versatile site-selective functionalization, offering new possibilities synthesizing alkylated pharmaceutical materials research.

Язык: Английский

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Site‐Selective Pyridine C−H Alkylation with Alcohols and Thiols via Single‐Electron Transfer of Frustrated Lewis Pairs

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(51)

Опубликована: Окт. 31, 2022

A unified strategy for the deoxygenative or desulfurative pyridylation of various alcohols and thiols has been developed through a single-electron transfer (SET) process frustrated Lewis pairs (FLPs) derived from pyridinium salts PtBu3 . Mechanistic studies revealed that N-amidopyridinium serve as effective acids formation FLPs with , generated phosphine radical cation ionically couples in situ xanthate, eventually affording alkyl facile β-scission under photocatalyst-free conditions. The reaction efficiency was further accelerated by visible-light irradiation. This method is conceptually appealing using encounter complexes FLP chemistry to promote SET, which provides previously unrecognized opportunity selective heteroarylation diverse range functional groups, even complex settings mild

Язык: Английский

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Unlocking the Potential of β-Fragmentation of Aminophosphoranyl Radicals for Sulfonyl Radical Reactions

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(26), С. 14510 - 14518

Опубликована: Июнь 20, 2023

Exploiting β-scission in aminophosphoranyl radicals for radical-mediated transformations has been a longstanding challenge. In this study, we investigated the untapped potential of β-fragmentation by leveraging unique properties P-N bond and substituents P(III) reagents. Our approach carefully considers factors such as cone angle electronic phosphine employs density functional theory (DFT) calculations to probe structural molecular orbital influence. We successfully induced through N-S cleavage under visible light mild conditions, generating range sulfonyl derived from pyridinium salts via photochemical activity electron donor-acceptor (EDA) complexes. This innovative synthetic strategy exhibits broad applicability, including late-stage functionalization, paves way valuable reactions, alkene hydrosulfonylation, difunctionalization, pyridylic C-H sulfonylation.

Язык: Английский

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C-4 Regioselective Alkylation of Pyridines Driven by Mechanochemically Activated Magnesium Metal

Organic Letters, Год журнала: 2023, Номер 25(14), С. 2531 - 2536

Опубликована: Апрель 5, 2023

Mechanochemically activated magnesium(0) metal as a highly active mediator driving direct C-4–H alkylation of pyridines with alkyl halides has been developed. Excellent regioselectivity and substrate scope, including those containing reducible functionalities, free amines, alcohols, well biologically relevant molecules were achieved to access 4-alkylpyridine products. Preliminary mechanistic studies suggested radical–radical coupling pathway.

Язык: Английский

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Modular and Practical 1,2‐Aryl(Alkenyl) Heteroatom Functionalization of Alkenes through Iron/Photoredox Dual Catalysis**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(44)

Опубликована: Сен. 13, 2023

Abstract Efficient methods for synthesizing 1,2‐aryl(alkenyl) heteroatomic cores, encompassing heteroatoms such as nitrogen, oxygen, sulfur, and halogens, are of significant importance in medicinal chemistry pharmaceutical research. In this study, we present a mild, versatile practical photoredox/iron dual catalytic system that enables access to highly privileged pharmacophores with exceptional efficiency site selectivity. Our approach exhibits an extensive scope, allowing the direct utilization wide range commodity or commercially available (hetero)arenes well activated unactivated alkenes diverse functional groups, drug scaffolds, natural product motifs substrates. By merging iron catalysis photoredox cycle, vast array alkene functionalization products incorporate neighboring azido, amino, halo, thiocyano nitrooxy group were secured. The scalability ability rapid synthesize numerous bioactive small molecules from readily starting materials highlight utility protocol.

Язык: Английский

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Photoinduced Remote C(sp³)–H Imination Enabled by Vinyl Radical-Mediated 1,5-Hydrogen Atom Transfer

Organic Letters, Год журнала: 2023, Номер 25(9), С. 1595 - 1599

Опубликована: Фев. 24, 2023

A vinyl radical-mediated 1,5-hydrogen atom transfer strategy for remote C(sp3)-H imination under visible-light-induced photochemical metal-free conditions afforded diverse γ-imino alkenes with excellent stereoselectivity. Oxime ester-based bifunctional reagents provided not only nucleophilic alkyl radicals radical addition reactions electron-deficient alkynes but also long-lived steady-state imine trapping following the intramolecular migration of unstable olefin radicals.

Язык: Английский

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Visible light catalyzed arylsilylation of alkenes to construct silicon-containing 1,1-diaryl moieties

Green Chemistry, Год журнала: 2024, Номер 26(8), С. 4785 - 4791

Опубликована: Янв. 1, 2024

We have developed an efficient photocatalyzed arylsilylation of alkenes, utilizing silylboranes and (hetero)aryl nitriles in the presence base photocatalyst.

Язык: Английский

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