CuH-Catalyzed Olefin Functionalization: From Hydroamination to Carbonyl Addition

Accounts of Chemical Research, Год журнала: 2020, Номер 53(6), С. 1229 - 1243

Опубликована: Май 13, 2020

ConspectusIn organic synthesis, ligand-modified copper(I) hydride (CuH) complexes have become well-known reagents and catalysts for selective reduction, particularly toward Michael acceptors carbonyl compounds. Recently, our group others found that these undergo migratory insertion (hydrocupration) with relatively unactivated electronically unpolarized olefins, producing alkylcopper intermediates can be leveraged to forge a variety of useful bonds. The resulting formal hydrofunctionalization reactions formed the basis resurgence research in CuH catalysis. This Account chronicles development this concept group, highlighting its origin context asymmetric hydroamination, evolution more general C–X bond-forming reactions, applications addition olefin-derived nucleophiles derivatives.Hydroamination, an olefin into N–H bond amine, is process significant academic industrial interest, due potential transform widely available alkenes alkynes valuable complex amines. We developed polarity-reversed strategy catalytic enantioselective hydroamination relying on reaction olefins generate chiral organocopper intermediates, which are intercepted by electrophilic amine reagents. By engineering auxiliary ligand, electrophile, conditions, scope method has since been extended include many types including challenging internal olefins. Further, expanded enable synthesis primary, secondary, tertiary amines as well amides, N-alkylated heterocycles, anilines. All exhibit high regio- stereoselectivity and, mild conditions required, excellent tolerance heterocycles polar functional groups.Though generation species from was originally devised means solve problem, we soon could react efficiently unexpectedly broad range electrophiles, alkyl halides, silicon reagents, arylpalladium species, derivatives. ability function precursors nucleophilic proved advantageous because it overcomes disadvantages associated traditional organometallic removing need pregeneration nucleophile separate operation, CuH-catalyzed feature improved step economy, enhanced tolerance, catalyst control over stereoselectivity. Following paradigm, feedstock such allene, butadiene, styrene employed alkylation ketones, imines, aldehydes.

Язык: Английский

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Catalytic reductive aminations using molecular hydrogen for synthesis of different kinds of amines

Chemical Society Reviews, Год журнала: 2020, Номер 49(17), С. 6273 - 6328

Опубликована: Янв. 1, 2020

Reductive aminations constitute an important class of reactions widely applied in research laboratories and industries for the synthesis amines as well pharmaceuticals, agrochemicals biomolecules. In particular, catalytic reductive using molecular hydrogen are highly valued essential cost-effective sustainable production different kinds their functionalization. These couple easily accessible carbonyl compounds (aldehydes or ketones) with ammonia, nitro presence suitable catalysts that enable preparation linear branched primary, secondary tertiary including N-methylamines molecules used life science applications. general, represent valuable fine bulk chemicals, which serve key precursors central intermediates advanced molecules, dyes polymers. Noteworthily, amine functionalities present a large number biomolecules, play vital roles function these active compounds. challenging processes, especially syntheses primary amines, often non-selective suffer from over-alkylation reduction to corresponding alcohols. Hence, development perform efficient selective manner is crucial continues be attracts scientific interest. this regard, both homogeneous heterogeneous have successfully been developed access various amines. There need comprehensive review on discuss potential applicability methodology commercial, industrial medicinal importance. Consequently, we applications functionalized structurally diverse benzylic, heterocyclic aliphatic more complex drug targets. addition, mechanisms formation desired products possible side emphasized. This aims at communities working fields organic synthesis, catalysis, biological chemistry.

Язык: Английский

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Recent Advances in the Enantioselective Synthesis of Chiral Amines via Transition Metal-Catalyzed Asymmetric Hydrogenation

Chemical Reviews, Год журнала: 2021, Номер 122(1), С. 269 - 339

Опубликована: Окт. 22, 2021

Chiral amines are key structural motifs present in a wide variety of natural products, drugs, and other biologically active compounds. During the past decade, significant advances have been made with respect to enantioselective synthesis chiral amines, many them based on catalytic asymmetric hydrogenation (AH). The review covers use AH bearing stereogenic center either α, β, or γ position nitrogen atom, reported from 2010 2020. Therefore, we provide an overview recent imines, enamides, enamines, allyl N-heteroaromatic

Язык: Английский

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Single Electron Transfer-Induced Redox Processes Involving N-(Acyloxy)phthalimides

ACS Catalysis, Год журнала: 2021, Номер 11(3), С. 1640 - 1683

Опубликована: Янв. 20, 2021

The past decade has witnessed the emergence of N-(acyloxy)phthalimides (NHPI esters) and its derivatives at forefront synthetic methods facilitating construction diverse molecular frameworks from readily available carboxylic acid feedstock. NHPI esters are predisposed to undergo reductive fragmentation via a single electron transfer (SET) process under thermal, photochemical, or electrochemical conditions generate corresponding carbon- nitrogen-centered radicals that participate in multitude transformations forge carbon–carbon carbon–heteroatom bonds. chemistry involving received broad applicability not only well-designed cascade annulations but also medicinal natural product synthesis. This comprehensive Review, broadly categorized according nature bond formation, details progress made this field since initial discovery by providing representative examples with mechanistic details, an emphasis on challenges future directions.

Язык: Английский

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Strategic evolution in transition metal-catalyzed directed C–H bond activation and future directions

Coordination Chemistry Reviews, Год журнала: 2020, Номер 431, С. 213683 - 213683

Опубликована: Дек. 9, 2020

Язык: Английский

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Site-Selective Defluorinative sp³ C–H Alkylation of Secondary Amides

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(17), С. 6395 - 6400

Опубликована: Апрель 27, 2021

A site-selective defluorinative sp3 C–H alkylation of secondary amides that rapidly and reliably incorporates gem-difluoroalkene motifs into previously unfunctionalized sites is disclosed. This protocol distinguished by its mild conditions, wide scope, exquisite site-selectivity, thus unlocking a new platform to introduce carbonyl isosteres at saturated hydrocarbon sites.

Язык: Английский

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Chiral Alkyl Amine Synthesis via Catalytic Enantioselective Hydroalkylation of Enecarbamates

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(4), С. 1959 - 1967

Опубликована: Янв. 22, 2021

Chiral alkyl amines are omnipresent as bioactive molecules and synthetic intermediates. The catalytic enantioselective synthesis of from readily accessible precursors is challenging. Here we develop a nickel-catalyzed hydroalkylation method to assemble wide range chiral enecarbamates (N-Cbz-protected enamines) halides with high regio- enantioselectivity. works for both nonactivated activated able produce enantiomerically enriched two minimally differentiated α-alkyl substituents. mild conditions lead functional group tolerance, which demonstrated in the postproduct functionalization many natural products drug molecules, well building blocks key intermediates compounds.

Язык: Английский

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Catalytic asymmetric reductive hydroalkylation of enamides and enecarbamates to chiral aliphatic amines

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Фев. 26, 2021

Abstract To increase the reliability and success rate of drug discovery, efforts have been made to C( sp 3 ) fraction avoid flat molecules. -Rich enantiopure amines are most frequently encountered as chiral auxiliaries, synthetic intermediates for pharmaceutical agents bioactive natural products. Streamlined construction aliphatic has long regarded a paramount challenge. Mainstream approaches, including hydrogenation enamines imines, C–H amination, alkylation were applied synthesis with circumscribed skeleton structures; typically, carbon centre was adjacent an auxiliary aryl or ester group. Herein, we report mild general nickel-catalysed asymmetric reductive hydroalkylation effectively convert enamides enecarbamates into drug-like α-branched derivatives. This reaction involves regio- stereoselective hydrometallation enamide enecarbamate generate catalytic amount enantioenriched alkylnickel intermediate, followed by C–C bond formation via alkyl electrophiles.

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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Copper-catalysed amination of alkyl iodides enabled by halogen-atom transfer

Nature Catalysis, Год журнала: 2021, Номер 4(7), С. 623 - 630

Опубликована: Июль 12, 2021

Язык: Английский

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