Recent Progress in Transition-Metal-Catalyzed Asymmetric Reductive Amination

ACS Catalysis, Год журнала: 2021, Номер 11(22), С. 13809 - 13837

Опубликована: Окт. 29, 2021

Asymmetric reductive amination (ARA) of a prochiral carbonyl compound with an amine using H2/hydrogen surrogate is concise and operationally simple method for the synthesis chiral amines. ARA proceeds via condensation group amine/ammonia followed by enantioselective reduction generated intermediate. The activation reductant stereoselective transfer hydrogen to intermediate imine/enamine often mediated transition metal catalyst. Considering wide applications enantiopure amines in pharmaceuticals, agrochemicals, materials, development effective catalysts has been intensively pursued last two decades. Since first report Blaser 1999, this key research area grown significantly recent years, as reflected advances catalyst design, diversifying substrate scope better mechanistic understanding. Several highly efficient general methodologies applicable challenging partners have demonstrated, providing ready access variety In Review, we present progress featuring diverse employing metal-catalysts. This Review provides organized critical discussion on engineering evolution, expanding susbstrate insights. To conclude, remaining challenges opportunities are also highlighted.

Язык: Английский

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Enantioselective Synthesis of α-Trifluoromethyl Amines via Biocatalytic N–H Bond Insertion with Acceptor-Acceptor Carbene Donors

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(6), С. 2590 - 2602

Опубликована: Фев. 2, 2022

The biocatalytic toolbox has recently been expanded to include enzyme-catalyzed carbene transfer reactions not occurring in Nature. Herein, we report the development of a strategy for synthesis enantioenriched α-trifluoromethyl amines through an asymmetric N-H insertion reaction catalyzed by engineered variants cytochrome c552 from Hydrogenobacter thermophilus. Using combination protein and substrate engineering, this metalloprotein scaffold was redesigned enable chiral amino esters with up >99% yield 95:5 er using benzyl 2-diazotrifluoropropanoate as donor. When diazo reagent varied, enantioselectivity enzyme could be inverted produce opposite enantiomers these products 99.5:0.5 er. This methodology is applicable broad range aryl amine substrates, it can leveraged obtain chemoenzymatic access β-trifluoromethyl-β-amino alcohols halides. Computational analyses provide insights into interplay protein- reagent-mediated control on reaction. work introduces first example carbenoid acceptor-acceptor donor, offers solution enantioselective α-trifluoromethylated valuable synthons medicinal chemistry bioactive molecules.

Язык: Английский

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Nickel-Catalyzed anti-Markovnikov Hydroalkylation of Trifluoromethylalkenes

ACS Catalysis, Год журнала: 2022, Номер 12(15), С. 9410 - 9417

Опубликована: Июль 18, 2022

Transition-metal-catalyzed difunctionalization of olefins constitutes a fertile synthetic platform for rapid access to complex molecules from bulk chemicals. However, substrates featuring fluoroalkyl substituents are rarely employed because facile β-fluoride elimination pathways. Herein, we report hydroalkylation trifluoromethylalkenes with alkyl halides under nickel catalysis that enables the construction 1,1,1-trifluoropropane derivatives. The common pathway is suppressed by identifying competent proton donor favors protonolysis process. Also, unactivated alkenes could be readily as when using Ni/hydrosilane catalytic system.

Язык: Английский

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Enantioselective Cobalt-Catalyzed Hydroboration of Fluoroalkyl-Substituted Alkenes to Access Chiral Fluoroalkylboronates

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(33), С. 15333 - 15338

Опубликована: Авг. 11, 2022

Selective defluoroborylation and asymmetric hydroboration reactions of fluoroalkyl-substituted terminal alkenes with pinacolborane (HBpin) have been developed cobalt catalysts generated from Co(acac)2 bisphosphine ligands. A variety undergo this enantioselective hydroboration, affording the corresponding chiral alkylboronates containing stereogenic carbon centers high enantioselectivity (up to 98% ee). This provides a versatile foundation for synthesis organofluorine compounds centers.

Язык: Английский

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Enantioselective Zn-Catalyzed Hydrophosphinylation of Nitrones: An Efficient Approach for Constructing Chiral α-Hydroxyamino-Phosphine Oxides

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Although enantioselective hydrofunctionalizations of nitrones are established for synthesis various types chiral hydroxylamines, the asymmetric catalytic hydrophosphinylation remains highly challenging. Herein, an efficient of...

Язык: Английский

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Electrochemical‐Induced Hydroxysulfonylation of α‐CF₃ Alkenes to Access Tertiary β‐Hydroxysulfones

Advanced Synthesis & Catalysis, Год журнала: 2022, Номер 364(5), С. 1016 - 1022

Опубликована: Янв. 25, 2022

Abstract An electrochemical hydroxysulfonylation of α‐CF 3 alkenes was accomplished in this work. By using easily available sodium sulfinates as the sulfonylating agents, a series valuable α‐trifluoromethyl tertiary alcohols were synthesized under mild and environmentally friendly electrolysis conditions moderate to good yields. The preliminary mechanistic investigation indicates that difunctional reaction involves radical process via sulfonyl radical. Gram‐scale synthesis shows significant potential application protocol. magnified image

Язык: Английский

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Transition-Metal-Catalyzed Asymmetric Couplings of α-Aminoalkyl Fragments to Access Chiral Alkylamines

ACS Catalysis, Год журнала: 2021, Номер 11(11), С. 6560 - 6577

Опубликована: Май 19, 2021

Enantiomerically pure alkylamines are pivotal structural elements in a broad range of pharmaceuticals, agrochemicals, natural products, and chemical building blocks. The development useful methodologies for the preparation these alkyamines is one central long-standing challenges facing synthetic chemistry. In recent years, transition-metal-catalyzed enantioselective coupling reactions α-aminoalkyl species have emerged as appealing C–C bond-forming approaches construction chiral alkylamines. This technique remarkable its substantial advantages functional group compatibility, substrate scope, molecular complexity, practicality, which provides complementarity orthogonality to traditional metal-catalyzed amine synthesis. Review underscores advances asymmetric alkylamine bond forming organized by type key intermediates, including (1) couplings α-aminoalkyl-metal species, (2) radicals, (3) imines with carbon electrophiles, (4) enamines mediated M–H species. addition, practicalities such tools also been highlighted total syntheses selected biologically interesting molecules stereoselective assembly challenging target compounds.

Язык: Английский

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Fe-Catalyzed Alkylazidation of α-Trifluoromethylalkenes: An Access to Quaternary Stereocenters Containing CF₃ and N₃ Groups

Organic Letters, Год журнала: 2023, Номер 25(8), С. 1336 - 1341

Опубликована: Фев. 23, 2023

A concise Fe-catalyzed alkylazidation of α-trifluoromethylalkenes via a C–C bond cleavage/radical addition/azidation cascade is described. This protocol features broad substrate scope, excellent functional group compatibility, and the ability to be performed on gram scale, thus offering practical step-economic approach synthetically useful tertiary α-trifluoromethyl azides.

Язык: Английский

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Electrochemical heterodifunctionalization of α-CF₃alkenes to access α-trifluoromethyl-β-sulfonyl tertiary alcohols

Chemical Communications, Год журнала: 2021, Номер 57(71), С. 8969 - 8972

Опубликована: Янв. 1, 2021

An unprecedented electrochemical heterodifunctionalization of α-CF3 alkenes with benzenesulfonyl hydrazides was accomplished in this work, wherein a β-sulfonyl and α-hydroxyl group were simultaneously incorporated across the olefinic double bond single operation. Consequently, series potentially medicinally valuable densely functionalized α-trifluoromethyl-β-sulfonyl tertiary alcohols assembled under mild conditions. Electrochemically-driven oxidative 1,2-difunctionlization electron-deficient well obviates need for oxidizing reagents, thus rendering protocol more eco-friendly.

Язык: Английский

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Nickel-catalyzed regio- and enantio-selective Markovnikov hydromonofluoroalkylation of 1,3-dienes

Chemical Science, Год журнала: 2022, Номер 13(42), С. 12519 - 12526

Опубликована: Янв. 1, 2022

We report a highly enantio- and regio-selective Markovnikov hydromonofluoro(methyl)alkylation of 1,3-dienes using chiral Ni catalysis, allowing access to allylic compounds bearing CH 2 F, CD F or monofluoroalkyl group at the stereocenter.

Язык: Английский

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