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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Skeletal Editing: Interconversion of Arenes and Heteroarenes

Helvetica Chimica Acta, Год журнала: 2023, Номер 106(3)

Опубликована: Янв. 13, 2023

Abstract Skeletal editing involves making specific point‐changes to the core of a molecule through selective insertion, deletion or exchange atoms. It thus represents potentially powerful strategy for step‐economic modification complex substrates and is perfect complement methods such as C−H functionalization that target molecular periphery. Given their ubiquity in biologically active compounds, ability perform skeletal on – therefore interconvert between aromatic heterocycles especially valuable. This review summarizes both recent key historical examples applied interconversion rings; we anticipate it will serve highlight not only innovative enabling nature current methods, but also tremendous opportunities still exist field.

Язык: Английский

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“Magic Chloro”: Profound Effects of the Chlorine Atom in Drug Discovery

Journal of Medicinal Chemistry, Год журнала: 2023, Номер 66(8), С. 5305 - 5331

Опубликована: Апрель 4, 2023

Chlorine is one of the most common atoms present in small-molecule drugs beyond carbon, hydrogen, nitrogen, and oxygen. There are currently more than 250 FDA-approved chlorine-containing drugs, yet beneficial effect chloro substituent has not been reviewed. The seemingly simple substitution a hydrogen atom (R = H) with chlorine Cl) can result remarkable improvements potency up to 100,000-fold lead profound effects on pharmacokinetic parameters including clearance, half-life, drug exposure vivo. Following literature terminology "magic methyl effect" term coined herein. Although reports 500-fold or 1000-fold often serendipitous discoveries that be considered "magical" rather planned, hypotheses made explain magic lessons accelerate cycle discovery.

Язык: Английский

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Late-Stage C(sp³)–H Methylation of Drug Molecules

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(5), С. 2787 - 2793

Опубликована: Янв. 25, 2023

Methyl groups are well understood to play a critical role in pharmaceutical molecules, especially those bearing saturated heterocyclic cores. Accordingly, methods that install methyl onto complex molecules highly coveted. Late-stage C-H functionalization is particularly attractive approach, allowing chemists bypass lengthy syntheses and facilitating the expedited synthesis of drug analogues. Herein, we disclose direct introduction via C(sp3)-H broad array heterocycles, enabled by merger decatungstate photocatalysis unique nickel-mediated SH2 bond formation. To further demonstrate its synthetic utility as tool for late-stage functionalization, this method was applied range en route an methylated

Язык: Английский

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Paired Oxidative and Reductive Catalysis: Breaking the Potential Barrier of Electrochemical C(sp³)−H Alkenylation**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(24)

Опубликована: Апрель 1, 2023

Due to the intrinsic inertness of alkanes, strong oxidative conditions are typically required enable their C(sp3 )-H functionalization. Herein, a paired electrocatalysis strategy was developed by integrating catalysis with reductive in one cell without interference, which earth-abundant iron and nickel employed as anodic cathodic catalysts, respectively. This approach lowers previously high oxidation potential for alkane activation, enabling electrochemical functionalization at ultra-low ≈0.25 V vs. Ag/AgCl under mild conditions. Structurally diverse alkenes, including challenging all-carbon tetrasubstituted olefins, can be accessed using readily available alkenyl electrophiles.

Язык: Английский

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Organo‐Mediator Enabled Electrochemical Deuteration of Styrenes

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(45)

Опубликована: Сен. 12, 2023

Despite widespread use of the deuterium isotope effect, selective labeling chemical molecules remains a major challenge. Herein, facile and general electrochemically driven, organic mediator enabled deuteration styrenes with oxide (D2 O) as economical source was reported. Importantly, this transformation could be suitable for various electron rich mediated by triphenylphosphine (TPP). The reaction proceeded under mild conditions without transition-metal catalysts, affording desired products in good yields excellent D-incorporation (D-inc, up to >99 %). Mechanistic investigations means experiments cyclic voltammetry tests provided sufficient support transformation. Notably, method proved powerful tool late-stage biorelevant compounds.

Язык: Английский

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Photodriven Methane Conversion on Transition Metal Oxide Catalyst: Recent Progress and Prospects

Advanced Science, Год журнала: 2023, Номер 11(8)

Опубликована: Окт. 26, 2023

Methane as the main component in natural gas is a promising chemical raw material for synthesizing value-added chemicals, but its harsh conversion process often causes severe energy and environment concerns. Photocatalysis provides an attractive path to active convert methane into various products under mild conditions with clean sustainable solar energy, although many challenges remain at present. In this review, recent advances photocatalytic are systematically summarized. As basis of conversion, activation first elucidated from structural molecules. The study committed categorizing elucidating research progress laws intricate reactions according target products, including partial oxidation, reforming, coupling, combustion, functionalization. Advanced reactor designs also designed enrich options reliability performance evaluation. prospects discussed, which turn offers guidelines methane-conversion-related photocatalyst exploration, reaction mechanism investigation, advanced photoreactor design.

Язык: Английский

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Overview of Recent Scale-Ups in Organic Electrosynthesis (2000–2023)

Organic Process Research & Development, Год журнала: 2024, Номер 28(2), С. 338 - 366

Опубликована: Янв. 18, 2024

This review summarizes examples of organic electrosynthesis from the peer-reviewed literature 2000 to 2023 that have been conducted on scales 20 g or above. A significant portion these were a ≤100 scale, while detailed reports kilogram-scale remain scarce in pharmaceutical industry. In addition chemical transformation, this also highlights type reactor used and projected productivity metric as ways compare different reports. The selected scale-ups described herein illustrate remaining challenges currently preventing routine use large-scale

Язык: Английский

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Alcohol-alcohol cross-coupling enabled by S _H 2 radical sorting

Science, Год журнала: 2024, Номер 383(6689), С. 1350 - 1357

Опубликована: Март 21, 2024

Alcohols represent a functional group class with unparalleled abundance and structural diversity. In an era of chemical synthesis that prioritizes reducing time to target maximizing exploration space, harnessing these building blocks for carbon-carbon bond-forming reactions is key goal in organic chemistry. particular, leveraging single activation mode form new C(sp

Язык: Английский

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Enantioselective alkylation of α-amino C(sp3)−H bonds via photoredox and nickel catalysis

Nature Catalysis, Год журнала: 2024, Номер 7(8), С. 889 - 899

Опубликована: Июль 4, 2024

Язык: Английский

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