Multicomponent Synthesis of α-Branched Amines via a Zinc-Mediated Carbonyl Alkylative Amination Reaction

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(13), С. 9045 - 9062

Опубликована: Март 15, 2024

Methods for the synthesis of α-branched alkylamines are important due to their ubiquity in biologically active molecules. Despite development many methods amine preparation, C(sp3)-rich nitrogen-containing compounds continue pose challenges synthesis. While carbonyl reductive amination (CRA) between ketones and is cornerstone method alkylamine synthesis, it sometimes limited by sterically demanding condensation step dialkyl amines more restricted availability compared aldehydes. We recently reported a "higher-order" variant this transformation, alkylative (CAA), which utilized halogen atom transfer (XAT)-mediated radical mechanism, enabling streamlined complex alkylamines. efficacy visible-light-driven approach, displayed scalability issues, competitive was problem certain substrate classes, limiting applicability. Here, we report change reaction regime that expands CAA platform through realization an extremely broad zinc-mediated reaction. This new strategy enabled elimination CRA, simplified purification, improved scope. Furthermore, harnessed carboxylic acid derivatives as alkyl donors facilitated α-trialkyl tertiary amines, cannot be accessed via CRA. Zn-mediated can carried out at variety scales, from 10 μmol setup microtiter plates high-throughput experimentation, gram-scale medicinally-relevant compounds. believe transformation enables robust, efficient, economical access provides viable alternative current benchmark methods.

Язык: Английский

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Enantioselective alkylation of α-amino C(sp3)−H bonds via photoredox and nickel catalysis

Nature Catalysis, Год журнала: 2024, Номер 7(8), С. 889 - 899

Опубликована: Июль 4, 2024

Язык: Английский

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Visible Light-Induced C–H Alkylation of Azauracils with N-Hydroxyphthalimide Esters via Catalytic EDA Complex

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

Herein, we report sodium iodide (NaI)-catalyzed decarboxylative C–H alkylation of azauracils with N-hydroxyphthalimide (NHPI) esters facilitated by visible light activation catalytic electron donor–acceptor (EDA) complexes. Control experiments and density functional theory calculations suggest that the coupling reaction proceeds via a transiently assembled EDA complex between NHPI ester NaI in N,N-dimethylacetamide solvent. This synthetic method efficiently applies to primary, secondary, tertiary under mild, photocatalyst-free, redox-neutral conditions, achieving high yields desired alkylated azauracils.

Язык: Английский

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Enantioselective Alkyl–Acyl Radical Cross-Coupling Enabled by Metallaphotoredox Catalysis

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Radical-radical cross-coupling (RCC) offers a promising approach for carbon-carbon bond formation in organic synthesis, particularly creating complex, three-dimensional molecules. However, achieving both cross- and enantioselectivity RCC reactions has remained significant challenge. Here, we report novel metallaphotoredox platform that enables highly enantioselective decarboxylative coupling of carboxylic acid derivatives with aldehydes. Our strategy leverages independent control over radical generation subsequent through fine-tuning common photocatalyst simple chiral bis(oxazoline) nickel catalyst. This redox-neutral protocol requires no exogenous oxidants or reductants demonstrates broad substrate scope functional group compatibility the synthesis enantioenriched α-aryl α-amino ketones. The ketone products can be readily transformed into valuable β-amino alcohols, streamlining access to these important motifs. Furthermore, showcase potential this more challenging C(sp3)-C(sp3) alkyl-alkyl reactions. unified alkyl-acyl represents advance asymmetric catalysis underscores exploit new mechanisms solve long-standing synthetic problems.

Язык: Английский

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Utilization of C(sp³)‐Carboxylic Acids and Their Redox‐Active Esters in Decarboxylative Carbon−Carbon Bond Formation

Advanced Synthesis & Catalysis, Год журнала: 2021, Номер 363(15), С. 3693 - 3736

Опубликована: Май 11, 2021

Abstract Over the last several years, radical‐mediated decarboxylative cross‐coupling reactions employing alkyl carboxylic acids have emerged as a powerful tool for regiospecific construction of carbon−carbon bonds. Under thermal or photocatalytic conditions, wide variety C( sp 3 )‐carboxylic and their redox‐active esters undergo C−C bond formation with suitable reactant partners, leading to complex chemical scaffolds wide‐ranging applications. This synthetic strategy has advantages over more conventional organometallic reagents, including abundant starting material availability high functional group tolerance associated mild reaction conditions. review article highlights recent developments in functionalization α‐heteroatom‐substituted well challenging unactivated acids, representative examples discussed against backdrop insightful comments on mechanisms. In addition, synthesis natural products, drug molecules, late‐stage modification bioactive molecules this non‐traditional are included. been categorized into three main sections that organized around type being forged: )−C( 2 ), ). Further, separately each section. magnified image

Язык: Английский

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Decarboxylation‐Initiated Intermolecular Carbon‐Heteroatom Bond Formation

Advanced Synthesis & Catalysis, Год журнала: 2021, Номер 363(11), С. 2678 - 2722

Опубликована: Март 31, 2021

Abstract Carboxylic acids are among the most used feedstock chemicals due to their great structural diversity and easy handling. The use of carboxylic derivatives in decarboxylative couplings has proven be a valuable tool for construction C−C C‐heteroatom bonds. This synthetic strategy provides complementary bond disconnection traditional cross‐coupling methods. In this review, we provide comprehensive overview decarboxylation‐initiated intermolecular formation, outlining several main mechanistic concepts combined with early examples highlighting achievements made past decade until January 2021. these reactions, undergo initial decarboxylation then react other heteroatom electrophiles nucleophiles, thus replacing carboxylate group prevalent functionality. magnified image

Язык: Английский

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Three-component 1,2-dicarbofunctionalization of alkenes involving alkyl radicals

Chemical Communications, Год журнала: 2021, Номер 58(6), С. 730 - 746

Опубликована: Дек. 8, 2021

This article provides a comprehensive perspective on three-component 1,2-dicarbofunctionalization of alkenes involving alkyl radicals, which generated from structurally diverse electrophilic and nucleophilic precursors under mild conditions.

Язык: Английский

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Asymmetric 1,4-functionalization of 1,3-enynes via dual photoredox and chromium catalysis

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 26, 2022

Abstract The merger of photoredox and transition-metal catalysis has evolved as a robust platform in organic synthesis over the past decade. stereoselective 1,4-functionalization 1,3-enynes, prevalent synthon synthetic chemistry, could afford valuable chiral allene derivatives. However, tremendous efforts have been focused on ionic reaction pathway. radical-involved asymmetric 1,3-enynes remains prominent challenge. Herein, we describe three-component 1,4-dialkylation via dual chromium to provide allenols. This method features readily available starting materials, broad substrate scope, good functional group compatibility, high regioselectivity, simultaneous control axial central chiralities. Mechanistic studies suggest that this proceeds through redox-neutral

Язык: Английский

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Copper-Catalyzed Intermolecular Functionalization of Unactivated C(sp³)–H Bonds and Aliphatic Carboxylic Acids

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(36), С. 14667 - 14675

Опубликована: Авг. 31, 2021

Intermolecular functionalization of C(sp3)-H bonds and aliphatic carboxylic acids enables the efficient synthesis high value-added organic compounds from readily available starting materials. Although methods involving hydrogen atom transfer have been developed for such functionalization, these either work only activated or bring in a narrow set functional groups. Here we describe Cu-catalyzed process diverse both unactivated acids. The is enabled by trapping alkyl radicals generated through abstraction arylsulfonyl-based SOMO-philes, which introduces large array C, N, S, Se, halide-based chemoselectivity can be switched C-H to decarboxylative matching bond dissociation energy reagent with that target O-H bond.

Язык: Английский

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Regioselective Access to Vicinal Diamines by Metal‐Free Photosensitized Amidylimination of Alkenes with Oxime Esters

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(44)

Опубликована: Сен. 9, 2022

A metal-free photosensitized protocol for regioselective diamination of alkene feedstocks over a single step was developed based on the rationally designed bifunctional reagent, thus affording range differentially protected 1,2-diamines in moderate to high yields. Mechanistic studies reveal that reaction is initiated with triplet-triplet energy transfer between thioxanthone catalyst and followed by fragmentation simultaneously generate long-lived iminyl radical transient amidyl radical. The excellent regioselectivity presumably stems from large reactivity difference two different N-centered species. This characterized regioselectivity, broad functional group tolerance, mild conditions, which would enrich diversity versatility facilitate diversity-oriented synthesis 1,2-diamine-containing complex molecule scaffolds.

Язык: Английский

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