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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Electrochemical Late-Stage Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(19), С. 11269 - 11335

Опубликована: Сен. 26, 2023

Late-stage functionalization (LSF) constitutes a powerful strategy for the assembly or diversification of novel molecular entities with improved physicochemical biological activities. LSF can thus greatly accelerate development medicinally relevant compounds, crop protecting agents, and functional materials. Electrochemical synthesis has emerged as an environmentally friendly platform transformation organic compounds. Over past decade, electrochemical late-stage (eLSF) gained major momentum, which is summarized herein up to February 2023.

Язык: Английский

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Carbon–Carbon Bond Cleavage for Late-Stage Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(22), С. 12313 - 12370

Опубликована: Ноя. 9, 2023

Late-stage functionalization (LSF) introduces functional group or structural modification at the final stage of synthesis natural products, drugs, and complex compounds. It is anticipated that late-stage would improve drug discovery's effectiveness efficiency hasten creation various chemical libraries. Consequently, products a productive technique to produce product derivatives, which significantly impacts biology development. Carbon-carbon bonds make up fundamental framework organic molecules. Compared with carbon-carbon bond construction, activation can directly enable molecular editing (deletion, insertion, atoms groups atoms) provide more efficient accurate synthetic strategy. However, selective unstrained still one most challenging projects in synthesis. This review encompasses strategies employed recent years for cleavage by explicitly focusing on their applicability functionalization. expands current discourse reactions providing comprehensive overview types bonds. includes C-C(sp), C-C(sp2), C-C(sp3) single bonds; double triple bonds, focus catalysis transition metals organocatalysts. Additionally, specific topics, such as ring-opening processes involving three-, four-, five-, six-membered rings, are discussed, exemplar applications these techniques showcased context bioactive molecules discovery. aims shed light advancements field propose potential avenues future research realm

Язык: Английский

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Enroute sustainability: metal free C–H bond functionalisation

Chemical Society Reviews, Год журнала: 2023, Номер 52(7), С. 2391 - 2479

Опубликована: Янв. 1, 2023

The metal-free C–H functionalisation is providing environmentally benign, cost-effective, sustainable catalytic systems. Comprehensive developments of various reactions are the focal point this review.

Язык: Английский

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Electrochemical Desaturative β‐Acylation of Cyclic N‐Aryl Amines

Angewandte Chemie International Edition, Год журнала: 2021, Номер 61(6)

Опубликована: Дек. 8, 2021

Abstract Herein, we disclose a straightforward, robust, and simple route to access β‐substituted desaturated cyclic amines via an electrochemically driven desaturative β‐functionalization of amines. This transformation is based on multiple single‐electron oxidation processes using catalytic amounts ferrocene. The reaction proceeds in the absence stoichiometric electrolyte under mild conditions, affording desired products with high chemo‐ regioselectivity. was tolerant broad range substrates also enables late‐stage β‐C(sp 3 )−H acylation potentially valuable products. Preliminary mechanistic studies voltammetry reveal key role ferrocene as redox mediator reaction.

Язык: Английский

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Diradical Generation via Relayed Proton-Coupled Electron Transfer

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(7), С. 3137 - 3145

Опубликована: Фев. 8, 2022

Diradical generation followed by radical–radical cross-coupling is a powerful synthetic tool, but its detailed mechanism has yet to be established. Herein, we proposed and confirmed new model named relayed proton-coupled electron transfer (relayed-PCET) for diradical generation, which could open door reactions. Quantum mechanics calculations were performed on selected carbene-mediated reaction designed model, the exact electronic structural changes during radical processes have been observed first time.

Язык: Английский

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Multiple-fold C–F bond functionalization for the synthesis of (hetero)cyclic compounds: fluorine as a detachable chemical handle

Organic Chemistry Frontiers, Год журнала: 2022, Номер 9(7), С. 2013 - 2055

Опубликована: Янв. 1, 2022

We highlighted the recent advances in field of multiple-fold C–F bond functionalization for synthesis (hetero)cyclic compounds.

Язык: Английский

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Enabling late-stage drug diversification by high-throughput experimentation with geometric deep learning

Nature Chemistry, Год журнала: 2023, Номер 16(2), С. 239 - 248

Опубликована: Ноя. 23, 2023

Abstract Late-stage functionalization is an economical approach to optimize the properties of drug candidates. However, chemical complexity molecules often makes late-stage diversification challenging. To address this problem, a platform based on geometric deep learning and high-throughput reaction screening was developed. Considering borylation as critical step in functionalization, computational model predicted yields for diverse conditions with mean absolute error margin 4–5%, while reactivity novel reactions known unknown substrates classified balanced accuracy 92% 67%, respectively. The regioselectivity major products accurately captured classifier F -score 67%. When applied 23 commercial molecules, successfully identified numerous opportunities structural diversification. influence steric electronic information performance quantified, comprehensive simple user-friendly format introduced that proved be key enabler seamlessly integrating experimentation functionalization.

Язык: Английский

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Triarylamines as catalytic donors in light-mediated electron donor–acceptor complexes

Chemical Science, Год журнала: 2023, Номер 14(13), С. 3470 - 3481

Опубликована: Янв. 1, 2023

Recently, photochemistry of Electron Donor-Acceptor (EDA) complexes employing catalytic amounts electron donors have become interest as a new methodology in the catalysis field, allowing for decoupling transfer (ET) from bond-forming event. However, examples practical EDA systems regime remain scarce, and their mechanism is not yet well-understood. Herein, we report discovery an complex between triarylamines α-perfluorosulfonylpropiophenone reagents, catalyzing C-H perfluoroalkylation arenes heteroarenes under visible light irradiation pH- redox-neutral conditions. We elucidate this reaction using detailed photophysical characterization complex, resulting triarylamine radical cation, its turnover

Язык: Английский

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Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

Acta Pharmaceutica Sinica B, Год журнала: 2023, Номер 14(3), С. 1030 - 1076

Опубликована: Ноя. 18, 2023

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, "the most fruitful basis for the discovery of a new is start with old drug"

Язык: Английский

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