Metal-Free Photochemical Imino-Alkylation of Alkenes with Bifunctional Oxime Esters

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(34), С. 15871 - 15878

Опубликована: Авг. 19, 2022

The concurrent installation of C-C and C-N bonds across alkene frameworks represents a powerful tool to prepare motifs that are ubiquitous in pharmaceuticals bioactive compounds. To construct such prevalent bonds, most difunctionalization methods demand the use precious metals or activated alkenes. We report metal-free, photochemically mediated imino-alkylation electronically diverse alkenes install both alkyl iminyl groups highly efficient manner. exceptionally mild reaction conditions, broad substrate scope, excellent functional group tolerance, facile one-pot protocol highlight utility this method privileged from readily available acid feedstocks. One key striking feature transformation is an electrophilic trifluoromethyl radical equally with electron-deficient electron-rich Additionally, dispersion-corrected density theory (DFT) empirical investigations provide detailed mechanistic insight into reaction.

Язык: Английский

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Photoinduced, Copper-Catalyzed Enantioconvergent Alkylations of Anilines by Racemic Tertiary Electrophiles: Synthesis and Mechanism

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(10), С. 4550 - 4558

Опубликована: Март 7, 2022

Transition-metal catalysis of substitution reactions alkyl electrophiles by nitrogen nucleophiles is beginning to emerge as a powerful strategy for synthesizing higher-order amines, well controlling their stereochemistry. Herein, we report that readily accessible chiral copper catalyst (commercially available components) can achieve the photoinduced, enantioconvergent coupling variety racemic tertiary with aniline generate new C–N bond good ee at fully substituted stereocenter product; whereas this copper-catalyzed proceeds −78 °C, in absence light and catalyst, virtually no formation observed even upon heating 80 °C. The mechanism catalytic process has been interrogated aid wide array tools, including independent synthesis proposed intermediates reactivity studies, spectroscopic investigations featuring photophysical EPR data, DFT calculations. These studies led identification three copper-based cycle, three-coordinate formally copper(II)–anilido (DFT analysis points its formulation copper(I)–anilidyl radical) complex serves persistent radical couples organic desired enantioselectivity.

Язык: Английский

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Merging Halogen-Atom Transfer (XAT) and Copper Catalysis for the Modular Suzuki–Miyaura-Type Cross-Coupling of Alkyl Iodides and Organoborons

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(4), С. 1986 - 1992

Опубликована: Янв. 21, 2022

We report here a mechanistically distinct approach to achieve Suzuki-Miyaura-type cross-couplings between alkyl iodides and aryl organoborons. This process requires copper catalyst but, in contrast with previous approaches based on palladium nickel systems, does not utilizes the metal for activation of electrophile. Instead, this strategy exploits halogen-atom-transfer ability α-aminoalkyl radicals convert secondary into corresponding that then are coupled aryl, vinyl, alkynyl, benzyl, allyl boronate species. These novel coupling reactions feature simple setup conditions (1 h at room temperature) facilitate access privileged motifs targeted by pharmaceutical sector.

Язык: Английский

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Metal-Free Amino(hetero)arylation and Aminosulfonylation of Alkenes Enabled by Photoinduced Energy Transfer

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(30), С. 16630 - 16641

Опубликована: Июль 24, 2023

β-(Hetero)arylethylamines are privileged structural motifs found in many high-value organic molecules, including pharmaceuticals and natural products. To construct these important molecular skeletons, previous methods mainly achieved by amino(hetero)arylation reaction with the aid of transition metals preactivated substrates. Herein, we report a metal-free photoinduced intermolecular for single-step installation both (hetero)aryl iminyl groups across alkenes an efficient regioselective manner. This method shows broad scope (up to 124 examples) excellent tolerance various olefins─from simplest ethylene complex multisubstituted can all participate reaction. Furthermore, aminosulfonylation be also conducted presence sodium bisulfite as SO2 source.

Язык: Английский

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Metallaphotoredox-enabled aminocarboxylation of alkenes with CO2

Nature Catalysis, Год журнала: 2023, Номер 6(10), С. 959 - 968

Опубликована: Сен. 21, 2023

Язык: Английский

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The Merger of Aryl Radical-Mediated Halogen-Atom Transfer (XAT) and Copper Catalysis for the Modular Cross-Coupling-Type Functionalization of Alkyl Iodides

ACS Catalysis, Год журнала: 2023, Номер 13(7), С. 4985 - 4991

Опубликована: Март 28, 2023

Here, we report a toolbox strategy to cross-couple unactivated secondary alkyl iodides with various N-, O-, and C-based nucleophiles. This harnesses the ability of photoredox-generated phenyl radicals mediate halogen-atom transfer (XAT) convert into corresponding radicals. These species engage in second catalytic cycle, mediated by copper, which enables C–N/O/C bond formation

Язык: Английский

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General and Modular Route to (Halo)alkyl BCP-Heteroaryls Enabled by α-Aminoalkyl Radical-Mediated Halogen-Atom Transfer

ACS Catalysis, Год журнала: 2023, Номер 14(2), С. 619 - 627

Опубликована: Дек. 28, 2023

Synthesis of bicyclo[1.1.1]pentane (BCP) heteroaryls continues to be a part the most important tasks in organic synthesis because they are significant class bioisosteres with universal applications drug discovery. However, substrate scope current multicomponent reactions is limited tertiary alkyl radicals and prefunctionalized (het)arenes due their intrinsic mechanisms, resulting decrease application value. Herein, we report straightforward alternative for (halo)alkyl BCP-heteroaryls from [1.1.1]propellane enabled by α-aminoalkyl radical-mediated halogen-atom transfer (XAT). Carbon derived commonly available precursors such as primary, secondary, halides polyhalides perform additions onto give BCP radicals, which then engage C–H/C–C couplings different heteroarenes. A wide range easily constructed moderate-to-good yields. Late-stage functionalization performed on approved derivatives proceeds good efficiency produce corresponding BCP-heteroaryls. The control experiments density functional theory (DFT) calculations reveal radical nature reaction. This approach not only verifies (XAT) strategy but also provides practical efficient route multifunctionalized BCPs, significantly expands BCP-heteroaryl-type development.

Язык: Английский

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N-glycoside synthesis through combined copper- and photoredox-catalysed N-glycosylation of N-nucleophiles

Nature Synthesis, Год журнала: 2024, Номер 3(5), С. 623 - 632

Опубликована: Март 1, 2024

Язык: Английский

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A Radical Strategy for the Alkylation of Amides with Alkyl Halides by Merging Boryl Radical-Mediated Halogen-Atom Transfer and Copper Catalysis

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(32), С. 22424 - 22430

Опубликована: Авг. 1, 2024

Amide alkylation is a fundamental process in organic chemistry. However, the low nucleophilicity of amides means that divergent coupling with alkyl electrophiles often not achievable. To circumvent this reactivity challenge, individual amine synthesis followed by amidation standard agents generally required. Herein, we demonstrate radical solution to challenge using an amine–borane complex and copper catalysis under oxidative conditions. While borohydride reagents are used as reducing ionic chemistry, their conversion into amine-ligated boryl radicals diverts toward halogen-atom transfer. This enables halides corresponding for amide functionalization via catalysis. The applicable N-alkylation primary employing unactivated iodides bromides, it was also showcased late-state both amide- halide-containing drugs.

Язык: Английский

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Dehydroxylative radical N-glycosylation of heterocycles with 1-hydroxycarbohydrates enabled by copper metallaphotoredox catalysis

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 22, 2024

Abstract N-Glycosylated heterocycles play important roles in biological systems and drug development. The synthesis of these compounds heavily relies on ionic N-glycosylation, which is usually constrained by factors such as labile glycosyl donors, precious metal catalysts, stringent conditions. Herein, we report a dehydroxylative radical method for synthesizing N -glycosides leveraging copper metallaphotoredox catalysis, stable readily available 1-hydroxy carbohydrates are activated direct N-glycosylation. Our employs inexpensive photo- copper- catalysts can tolerate some extent water. reaction exhibits broad substrate scope, encompassing 76 examples, demonstrates high stereoselectivity, favoring 1,2- trans selectivity furanoses α-selectivity pyranoses. It also site-selectivity substrates containing multiple N-atoms. synthetic utility showcased through the late-stage functionalization bioactive pharmaceuticals like Olaparib, Axitinib, Metaxalone. Mechanistic studies prove presence radicals importance catalysis.

Язык: Английский

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