An Electrocatalytic Approach to the Radical Difunctionalization of Alkenes

ACS Catalysis, Год журнала: 2018, Номер 8(6), С. 5175 - 5187

Опубликована: Апрель 26, 2018

Given its many distinct characteristics, electrochemistry represents an attractive approach to meet the prevailing trends in organic synthesis. In particular, electrocatalysis—a process that integrates and small-molecule catalysis—has potential substantially improve scope of synthetic provide a wide range useful transformations. Recently, we have demonstrated new catalytic approaches combine redox-metal catalysis for oxidative difunctionalization alkenes access diverse array vicinally functionalized structures. This Perspective details our design principles underpinning development electrochemical diazidation, dichlorination, halotrifluoromethylation alkenes, which were built on foundational work by others areas electrochemistry, radical chemistry, transition-metal catalysis. The introduction redox-active Mn catalysts allows generation intermediates from readily available reagents at low potentials under mild conditions. These transition metals also impart selectivity control over alkene functionalization processes functioning as group transfer agents. As such, electrocatalytic reactions exhibit excellent chemoselectivity, broad substrate scope, high functional compatibility. Specifically, anodically coupled electrolysis, pairs two single-electron oxidation events parallel manner, enables regio- chemoselective heterodifunctionalization alkenes. products transformations describe this represent pertinent structures numerous medicinally relevant compounds. We anticipate parameters presented here are general will platform systems other challenging redox

Язык: Английский

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Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse

Chemical Reviews, Год журнала: 2017, Номер 117(8), С. 5619 - 5674

Опубликована: Янв. 20, 2017

Naturally produced halogenated compounds are ubiquitous across all domains of life where they perform a multitude biological functions and adopt diversity chemical structures. Accordingly, diverse collection enzyme catalysts to install remove halogens from organic scaffolds has evolved in nature. Accounting for the different properties four halogen atoms (fluorine, chlorine, bromine, iodine) reactivity their substrates, enzymes performing biosynthetic degradative halogenation chemistry utilize numerous mechanistic strategies involving oxidation, reduction, substitution. Biosynthetic reactions range simple aromatic substitutions stereoselective C–H functionalizations on remote carbon centers can initiate formation complex ring Dehalogenating enzymes, other hand, best known removing man-made organohalogens, yet also function naturally, albeit rarely, metabolic pathways. This review details scope mechanism nature's dehalogenation enzymatic strategies, highlights gaps our understanding, posits new advances field might arise near future.

Язык: Английский

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Electrocatalytic Radical Dichlorination of Alkenes with Nucleophilic Chlorine Sources

Journal of the American Chemical Society, Год журнала: 2017, Номер 139(43), С. 15548 - 15553

Опубликована: Окт. 8, 2017

We report a Mn-catalyzed electrochemical dichlorination of alkenes with MgCl2 as the chlorine source. This method provides operationally simple, sustainable, and efficient access to variety vicinally dichlorinated compounds. In particular, oxidatively labile functional groups, such alcohols, aldehydes, sulfides, amines, were transformed into desired vicinal dichlorides high chemoselectivity. Mechanistic data are consistent metal-mediated Cl atom transfer predominant pathway enabling dual C–Cl bond formation contradict an alternative involving evolution gas followed by Cl2-mediated electrophilic dichlorination.

Язык: Английский

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Anodically Coupled Electrolysis for the Heterodifunctionalization of Alkenes

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(7), С. 2438 - 2441

Опубликована: Фев. 6, 2018

The emergence of new catalytic strategies that cleverly adopt concepts and techniques frequently used in areas such as photochemistry electrochemistry has yielded a myriad organic reactions would be challenging to achieve using orthodox methods. Herein, we discuss the strategic use anodically coupled electrolysis, an electrochemical process combines two parallel oxidative events, complementary approach existing methods for redox transformations. Specifically, demonstrate electrolysis regio- chemoselective chlorotrifluoromethylation alkenes.

Язык: Английский

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Applications of Nonenzymatic Catalysts to the Alteration of Natural Products

Chemical Reviews, Год журнала: 2017, Номер 117(18), С. 11894 - 11951

Опубликована: Июнь 5, 2017

The application of small molecules as catalysts for the diversification natural product scaffolds is reviewed. Specifically, principles that relate to selectivity challenges intrinsic complex molecular are summarized. synthesis analogues products by this approach then described a quintessential "late-stage functionalization" exercise wherein serve lead scaffolds. Given historical enzymatic site-selective alteration molecules, focus Review on recent studies nonenzymatic catalysts. Reactions involving hydroxyl group derivatization with variety electrophilic reagents discussed. C–H bond functionalizations oxidations, aminations, and halogenations also presented. Several examples olefin C–C formations included. Numerous classes have been subjected these including polyketides, glycopeptides, terpenoids, macrolides, alkaloids, carbohydrates, others. What emerges platform chemical remodeling naturally occurring targets virtually all known functionalities microenvironments. However, design very broad catalysts, even broader demands (e.g., stereoselectivity, functional selectivity, site-selectivity) persist. Yet, significant spectrum powerful, catalytic alterations now exists such expansion scope seems inevitable. instances biological activity assays remodeled derivatives These reports may foreshadow further interdisciplinary impacts products, contributions SAR development, mode action studies, eventually medicinal chemistry.

Язык: Английский

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Merging shuttle reactions and paired electrolysis for reversible vicinal dihalogenations

Science, Год журнала: 2021, Номер 371(6528), С. 507 - 514

Опубликована: Янв. 28, 2021

Vicinal dibromides and dichlorides are important commodity chemicals indispensable synthetic intermediates in modern chemistry that traditionally synthesized using hazardous elemental chlorine bromine. Meanwhile, the environmental persistence of halogenated pollutants necessitates improved approaches to accelerate their remediation. Here, we introduce an electrochemically assisted shuttle (e-shuttle) paradigm for facile scalable interconversion alkenes vicinal dihalides, a class reactions can be used both synthesize useful dihalogenated molecules from simple recycle waste material through retro-dihalogenation. The reaction is demonstrated 1,2-dibromoethane, as well 1,1,1,2-tetrachloroethane or 1,2-dichloroethane, dibrominate dichlorinate, respectively, wide range setup with inexpensive graphite electrodes. Conversely, hexachlorinated persistent pollutant lindane could fully dechlorinated benzene soil samples alkene acceptors.

Язык: Английский

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Naturally Occurring Organohalogen Compounds—A Comprehensive Review

Fortschritte der Chemie Organischer Naturstoffe/Fortschritte der Chemie organischer Naturstoffe/Progress in the chemistry of organic natural products, Год журнала: 2023, Номер unknown, С. 1 - 546

Опубликована: Янв. 1, 2023

Язык: Английский

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Enhanced Three-Component Chloro-/Azido-Fluoroalkylation of Unactivated Alkenes via the Proximity Effect in a Heterogenous Metallaphotocatalyst

ACS Catalysis, Год журнала: 2025, Номер 15(3), С. 2180 - 2191

Опубликована: Янв. 22, 2025

Heterogeneous metallaphotocatalytic chemical transformations employing a recyclable catalyst are highly desirable for organic synthesis. However, the rational design and controlled preparation of well-defined, site-isolated metal/photo bifunctional heterogeneous catalysts to achieve this goal remain significant challenge. In study, we demonstrate covalent attachment homogeneous molecular MnSalen complex (where Salen = N,N′-bis(salicylidene)ethylenediamine) onto surface graphitic carbon nitride (CN) via an amide bond visible-light-driven chloro- azido-fluoroalkylation unactivated alkenes. The linkage between CN not only facilitates electron delocalization enhances light-harvesting capabilities photosensitizer but also exerts proximity effect that markedly ability Mn sites capture alkyl radical intermediates during reaction process. A diverse set alkenes could be efficiently azido-fluoroalkylated their corresponding difunctionalized products in moderate high yields with good functional group compatibility. Furthermore, practicability protocol is illustrated through late-stage diversification various bioactive compounds pharmaceuticals. Notably, integrated photocatalyst demonstrates stability can recycled at least 10 times without loss activity selectivity.

Язык: Английский

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Ti-Catalyzed Radical Alkylation of Secondary and Tertiary Alkyl Chlorides Using Michael Acceptors

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(44), С. 14836 - 14843

Опубликована: Окт. 10, 2018

Alkyl chlorides are common functional groups in synthetic organic chemistry. However, the engagement of unactivated alkyl chlorides, especially tertiary transition-metal-catalyzed C–C bond formation remains challenging. Herein, we describe development a TiIII-catalyzed radical addition 2° and 3° to electron-deficient alkenes. Mechanistic data consistent with inner-sphere activation C–Cl featuring TiIII-mediated Cl atom abstraction. Evidence suggests that active TiIII catalyst is generated from TiIV precursor Lewis-acid-assisted electron transfer process.

Язык: Английский

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Kinetically controlled E -selective catalytic olefin metathesis

Science, Год журнала: 2016, Номер 352(6285), С. 569 - 575

Опубликована: Апрель 28, 2016

A major shortcoming in olefin metathesis, a chemical process that is central to research several branches of chemistry, the lack efficient methods kinetically favor E isomers product distribution. Here we show E-selective cross-metathesis reactions may be designed generate thermodynamically disfavored alkenyl chlorides and fluorides high yield with exceptional stereoselectivity. With 1.0 5.0 mole % molybdenum-based catalyst, which delivered form air- moisture-stable paraffin pellets, typically proceed completion within 4 hours at ambient temperature. Many isomerically pure E-alkenyl chlorides, applicable catalytic cross-coupling transformations found biologically active entities, thus become easily directly accessible. Similarly, can synthesized from simpler compounds or more complex molecules.

Язык: Английский

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