The Persistent Radical Effect in Organic Synthesis

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 59(1), P. 74 - 108

Published: May 22, 2019

Abstract Radical–radical couplings are mostly nearly diffusion‐controlled processes. Therefore, the selective cross‐coupling of two different radicals is challenging and not a synthetically valuable transformation. However, if have lifetimes they generated at equal rates, will become dominant process. This high cross‐selectivity based on kinetic phenomenon called persistent radical effect (PRE). In this Review, an explanation PRE supported by simulations simple model systems provided. Radical stabilities discussed within context their lifetimes, various examples PRE‐mediated radical–radical in synthesis summarized. It shown that restricted to coupling with transient radical. If one partner longer‐lived than other radical, operates achieved. important point expands scope chemistry. The Review divided into parts, namely 1) or organic 2) “radical–metal crossover reactions”; here, metal‐centered species more generally transition‐metal complexes able react discussed—a field has flourished recently.

Language: Английский

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Transition-Metal (Cu, Pd, Ni)-Catalyzed Difluoroalkylation via Cross-Coupling with Difluoroalkyl Halides

Accounts of Chemical Research, Journal Year: 2018, Volume and Issue: 51(9), P. 2264 - 2278

Published: Aug. 22, 2018

Difluoroalkylated compounds play a remarkably important role in life and materials sciences because of the unique characteristics difluoromethylene (CF2) group. In particular, precise introduction CF2 group at benzylic position can dramatically improve biological properties corresponding molecules. As consequence, difluoroalkylation aromatic has become powerful strategy modulating bioactivities organic However, efficient strategies to selectively synthesize difluoroalkylated arenes had been very limited before 2012. Traditional synthetic methods this regard suffer from either harsh reaction conditions or narrow substrate scope, significantly restricting their widespread applications, particularly for late-stage bioactive To overcome these limitations, straightforward route access valuable skeletons is direct (CF2R) onto rings through transition-metal-catalyzed cross-coupling. instability some metal species, which are prone protonation, dimerization, and/or generation other unknown byproducts, it difficult control catalytic cycle suppress side reactions. context, we proposed use low-cost widely available difluoroalkyl halides as fluoroalkyl sources reactions via Account, summarize our major efforts on copper-, palladium-, nickel-catalyzed difluoroalkylations aromatics with sources. Four modes reactions, including nucleophilic difluoroalkylation, electrophilic radical metal-difluorocarbene coupling (MeDiC), have demonstrated careful modulation systems. Among MeDiC represents new mode fluoroalkylation. These processes enable variety aryl arylboron reagents under mild conditions. A wide range halides, activated (Cl/BrCF2R, R = π system), unactivated (BrCF2R, alkyl, H), especially inert inexpensive industrial chemical chlorodifluoromethane (ClCF2H), applicable providing facile routes diverse (hetero)arenes. halide-based also be applied prepare alkenes, alkynes, alkanes feature impressive advantages over conventional synthesis terms efficiency, functional tolerance, structural diversity. molecules offers good opportunities development medicinal agents without need multistep de novo syntheses.

Language: Английский

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Transition Metal‐Catalyzed Dicarbofunctionalization of Unactivated Olefins

The Chemical Record, Journal Year: 2018, Volume and Issue: 18(9), P. 1314 - 1340

Published: March 8, 2018

Abstract Transition metal (TM)‐catalyzed difunctionalization of unactivated olefins with two carbon‐based entities is a powerful method to construct complex molecular architectures rapidly from simple and readily available feedstock chemicals. While dicarbofunctionalization has long history typically the use either carbon monoxide intercept C(sp 3 )‐[M] (alkyl‐TM) species or substrates lacking in β‐hydrogen (β‐Hs), development this class reaction still remains seriously limited due complications β‐H elimination arising situ‐generated intermediates. Over years, different approaches have been harnessed suppress elimination, which led various types olefin reactions even that generate intermediates bearing β‐Hs wide range electrophiles nucleophiles. In review, these developments will be discussed both through lens historical perspectives as well strategies scrutinized over years address issue elimination. However, review article by no means designed exhaustive field, merely presented provide readers an overview key developments.

Language: Английский

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Recent developments in nickel-catalyzed intermolecular dicarbofunctionalization of alkenes

Chemical Science, Journal Year: 2020, Volume and Issue: 11(17), P. 4287 - 4296

Published: Jan. 1, 2020

Nickel-catalyzed three-component alkene difunctionalization has rapidly emerged as a powerful tool for forging two C-C bonds in single reaction. Building upon the modes of bond construction traditional two-component cross-coupling, various research groups have demonstrated versatility nickel enabling catalytic 1,2-dicarbofunctionalization using wide range carbon-based electrophiles and nucleophiles fully intermolecular fashion. Though this area only recently, last few years witnessed proliferation publications on topic, underscoring potential strategy to develop into general platform that offers high regio- stereoselectivity. This minireview highlights recent progress alkenes via catalysis discusses lingering challenges within reactivity paradigm.

Language: Английский

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Nickel-Catalyzed Dicarbofunctionalization of Alkenes

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(15), P. 8542 - 8556

Published: July 2, 2020

1,2-Dicarbofunctionalization of alkenes has emerged as an efficient synthetic strategy for preparing substituted molecules by coupling readily available with electrophiles and/or nucleophiles. Nickel complexes serve effective catalysts owing to their tendency undergo facile oxidative addition and slow β-hydride elimination, capability access both two-electron radical pathways. Two-component alkene functionalization reactions have achieved high chemo-, regio-, stereoselectivities tethering one the partners substrate. Three-component reactions, however, often incorporate directing groups control selectivity. Only a few examples directing-group-free difunctionalizations unactivated been reported. Therefore, great opportunities exist development three-component difunctionalization broad substrate scopes tunable stereoselectivities.

Language: Английский

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Nickel-Catalyzed Reductive Dicarbofunctionalization of Alkenes

Journal of the American Chemical Society, Journal Year: 2017, Volume and Issue: 139(20), P. 6835 - 6838

Published: May 10, 2017

An intermolecular, three-component reductive dicarbofunctionalization of alkenes is presented here. The combination Ni catalysis with TDAE as final reductant enables the direct formation Csp3–Csp3 and Csp3–Csp2 bonds across a variety π-systems using two different electrophiles that are sequentially activated exquisite selectivity under mild reaction conditions.

Language: Английский

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Strategies toward Dicarbofunctionalization of Unactivated Olefins by Combined Heck Carbometalation and Cross-Coupling

The Journal of Organic Chemistry, Journal Year: 2018, Volume and Issue: 83(6), P. 3013 - 3022

Published: Feb. 26, 2018

The use of combined Heck carbometalation and cross-coupling remains one the most powerful ways for difunctionalization unactivated olefins with organometallic reagents organohalides. This synopsis will provide an overview this reaction developed in last three a half decades. Herein, both three-component two-component cyclization/cross-coupling processes be reviewed focus on strategies utilized to overcome complications β-hydride elimination from C(sp3)-[M] intermediates, which usually functions as major side reaction.

Language: Английский

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Ni-Catalyzed Enantioselective Reductive Diarylation of Activated Alkenes by Domino Cyclization/Cross-Coupling

Journal of the American Chemical Society, Journal Year: 2018, Volume and Issue: 140(39), P. 12364 - 12368

Published: Sept. 20, 2018

A Ni-catalyzed enantioselective reductive diarylation of activated alkenes by domino cyclizative/cross-coupling two aryl bromides is developed. This reaction proceeds under very mild conditions and shows broad substrate scope, without requiring the use preformed organometallic reagents. Moreover, this approach provides direct access to various bis-heterocycles bearing all-carbon quaternary centers in synthetically useful yields (up 81%) with excellent enantioselectivity (>30 examples, 90–99% ee).

Language: Английский

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Transition‐Metal‐Catalyzed Three‐Component Difunctionalizations of Alkenes

Chemistry - An Asian Journal, Journal Year: 2018, Volume and Issue: 13(17), P. 2277 - 2291

Published: June 13, 2018

Abstract Three‐component reactions can directly convert three reactants into the desired products in one pot and thus greatly shorten synthetic path. Recently, transition‐metal catalysis has been applied difunctionalization of alkenes remarkable progress achieved to facilitate construction a wide range functional molecules with high atom‐ step‐economic efficiency. This Focus Review highlights recent advances this field.

Language: Английский

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Enantioselective Three-Component Fluoroalkylarylation of Unactivated Olefins through Nickel-Catalyzed Cross-Electrophile Coupling

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(21), P. 9604 - 9611

Published: May 11, 2020

A nickel-catalyzed, enantioselective, three-component fluoroalkylarylation of unactivated alkenes with aryl halides and perfluoroalkyl iodides has been described. This cross-electrophile coupling protocol utilizes a chiral nickel/BiOx system as well pendant chelating group to facilitate the challenging three-component, asymmetric difunctionalization alkenes, providing direct access valuable β-fluoroalkyl arylalkanes high efficiency excellent enantioselectivity. The mild conditions allow for broad substrate scope good functional toleration.

Language: Английский

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