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

Accounts of Chemical Research, Год журнала: 2018, Номер 51(9), С. 2264 - 2278

Опубликована: Авг. 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.

Язык: Английский

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Transition Metal‐Catalyzed Dicarbofunctionalization of Unactivated Olefins

The Chemical Record, Год журнала: 2018, Номер 18(9), С. 1314 - 1340

Опубликована: Март 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.

Язык: Английский

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Recent developments in nickel-catalyzed intermolecular dicarbofunctionalization of alkenes

Chemical Science, Год журнала: 2020, Номер 11(17), С. 4287 - 4296

Опубликована: Янв. 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.

Язык: Английский

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Nickel-Catalyzed Dicarbofunctionalization of Alkenes

ACS Catalysis, Год журнала: 2020, Номер 10(15), С. 8542 - 8556

Опубликована: Июль 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.

Язык: Английский

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

The Journal of Organic Chemistry, Год журнала: 2018, Номер 83(6), С. 3013 - 3022

Опубликована: Фев. 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.

Язык: Английский

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Difunctionalization of Alkenes Involving Metal Migration

Angewandte Chemie International Edition, Год журнала: 2019, Номер 59(21), С. 7990 - 8003

Опубликована: Дек. 4, 2019

The direct difunctionalization of alkenes, a cheap and abundant feedstock, represents one the most attractive strategies for increasing molecular complexity in synthetic organic chemistry. In contrast with 1,2-difunctionalization recent advances showcase alkene 1,n-difunctionalizations (n≠2) involving metal migration is an emerging rapidly growing area research. This promising strategy not only opens novel avenue future development transformations, but also significantly expands upon bond disconnections available modern synthesis. Minireview summarizes progress migratory emphasis on driving force migration.

Язык: Английский

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

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(39), С. 12364 - 12368

Опубликована: Сен. 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).

Язык: Английский

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Transition‐Metal‐Catalyzed Three‐Component Difunctionalizations of Alkenes

Chemistry - An Asian Journal, Год журнала: 2018, Номер 13(17), С. 2277 - 2291

Опубликована: Июнь 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.

Язык: Английский

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Asymmetric Ni-Catalyzed Radical Relayed Reductive Coupling

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(31), С. 13515 - 13522

Опубликована: Июнь 29, 2020

Alkene dicarbofunctionalizations enable the streamlined construction of aliphatic structures and have thus been subject intense research efforts. Despite significant progress, catalytic asymmetric variants remain scarce. Inspired by advantages reductive cross-coupling approaches, we present here a highly efficient intermolecular Ni-catalyzed dicarbofunctionalization alkenes. Two distinct readily available electrophiles, namely, Csp2- Csp3-halides, are added simultaneously across variety olefins (vinyl amides, vinyl boranes, phosphonates) at room temperature in regio- enantioselective manner. The reaction, devoid sensitive organometallic reagents, takes advantage an situ generated chiral alkyl Ni(III)-intermediate to ensure stereodefined outcome Csp3–Csp2 bond-forming reaction. An (l)-(+)-isoleucine bisoxazoline ligand presence coordinating sites on alkene key for successful these "asymmetric radical relayed couplings" (ARRRCs). Further, multiple transformations amides obtained this process showcase potential new methodology straightforward assembly building blocks such as primary secondary amines oxazolines, highlighting its synthetic utility.

Язык: Английский

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Transition Metal (Ni, Cu, Pd)-Catalyzed Alkene Dicarbofunctionalization Reactions

Accounts of Chemical Research, Год журнала: 2021, Номер 54(17), С. 3415 - 3437

Опубликована: Авг. 12, 2021

ConspectusRecently, alkene dicarbofunctionalization, i.e., the powerful organic synthesis method of difunctionalization with two carbon sources, emerged as a formidable reaction immense promise to synthesize complex molecules expeditiously from simple chemicals. This is generally achieved transition metals (TMs) through interception by sources an alkylmetal [β-H–C(sp3)–[M]] species, key intermediate prone undergo rapid β-H elimination. Related prior reports, since Paolo Chiusoli and Catellani's work in 1982 [ Tetrahedron Lett. 1982, 23, 4517], have used bicyclic disubstituted terminal alkenes, wherein elimination avoided geometric restriction or complete lack β-H's. With reasoning that β-H–C(sp3)–[M] intermediates could be rendered amenable use first row late TMs formation coordination-assisted transient metallacycles, these strategies were implemented address problem dicarbofunctionalization reactions.Because catalyze C(sp3)–C(sp3) coupling, Cu Ni anticipated impart sufficient stability intermediates, generated catalytically upon carbometalation, for their subsequent electrophiles/nucleophiles three-component reactions. Additionally, such innate property enable coupling partners entropically driven cyclization/coupling The cyclometalation concept stabilize intractable was hypothesized when reactions performed. idea curtail founded Whitesides's J. Am. Chem. Soc. 1976, 98, 6521] observation metallacycles much slower than acyclic alkylmetals.In this Account, examples demonstrate catalysts alkenylzinc reagents, alkyl halides, aryl halides afford carbo- heterocycles. In addition, forming nickellacycles enabled regioselective performance various alkenyl compounds. situ [M]-H alkenes after induced unprecedented metallacycle contraction process, which six-membered metal-containing rings shrank five-membered cycles, allowing creation new carbon–carbon bonds at allylic (1,3) positions. Applications are discussed.

Язык: Английский

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