Native Amides as Enabling Vehicles for Forging sp³–sp³ Architectures via Interrupted Deaminative Ni-Catalyzed Chain-Walking

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 3869 - 3874

Published: Feb. 8, 2023

Herein, we disclose an interrupted deaminative Ni-catalyzed chain-walking strategy that forges sp3-sp3 architectures at remote, yet previously unfunctionalized, methylene sp3 C-H sites enabled by the presence of native amides. This protocol is characterized its mild conditions and wide scope, including challenging substrate combinations. Site-selectivity can be dictated a judicious choice ligand, thus offering opportunity to enable bond formations are otherwise inaccessible in conventional events.

Language: Английский

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Kinetically-Controlled Ni-Catalyzed Direct Carboxylation of Unactivated Secondary Alkyl Bromides without Chain Walking

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(3), P. 1753 - 1759

Published: Jan. 9, 2024

Herein, we report the direct carboxylation of unactivated secondary alkyl bromides enabled by merger photoredox and nickel catalysis, a previously inaccessible endeavor in arena. Site-selectivity is dictated kinetically controlled insertion CO2 at initial C(sp3)–Br site rapid formation Ni(I)–alkyl species, thus avoiding undesired β-hydride elimination chain-walking processes. Preliminary mechanistic experiments reveal subtleties stereoelectronic effects for guiding reactivity site-selectivity.

Language: Английский

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Catalyst‐Controlled Regiodivergent and Enantioselective Formal Hydroamination of N,N‐Disubstituted Acrylamides to α‐Tertiary‐α‐Aminolactam and β‐Aminoamide Derivatives

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(22)

Published: March 30, 2023

Enantioenriched α-tertiary-α-aminoacid and α-chiral-β-aminoacid derivatives play an important role in biological science pharmaceutical chemistry. Thus, the development of methods for their synthesis is highly valuable yet remains challenging. Herein, unprecedented catalyst-controlled regiodivergent enantioselective formal hydroamination N,N-disubstituted acrylamides with aminating agents has been developed, accessing enantioenriched α-tertiary-α-aminolactam α-chiral-β-aminoamide derivatives. Sterically-disfavored electronically-disfavored electron-deficient alkenes have successfully tuned using different transition metals chiral ligands. Notably, extremely hindered aliphatic were synthesized by Cu-H catalyzed asymmetric C-N bond forming tertiary alkyl species. accessed Ni-H anti-Markovnikov-selective hydroaminations alkenes. This set reactions tolerates a wide range functional groups to deliver diverse good yields high levels enantioselectivity.

Language: Английский

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Electrochemical NiH‐Catalyzed C(sp³)−C(sp³) Coupling of Alkyl Halides and Alkyl Alkenes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(44)

Published: Sept. 14, 2023

Herein, an electrochemically driven NiH-catalyzed reductive coupling of alkyl halides and alkenes for the construction Csp3 -Csp3 bonds is firstly reported. Notably, serve dual function as substrates hydrogen sources to generate NiH species under electrochemical conditions. The tunable nature this reaction realized by introducing intramolecular coordinating group substrate, where product can be easily adjusted give desired branched products. method proceeds mild conditions, exhibits a broad substrate scope, affords moderate excellent yields with over 70 examples, including late-stage modification natural products drug derivatives. Mechanistic insights offer evidence process. sp3 -carbon-halogen activated through single electron transfer (SET) nickel catalyst in its low valence state, generated cathodic reduction, generation from pivotal transformation.

Language: Английский

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Palladium‐Catalyzed Inward Isomerization Hydroaminocarbonylation of Alkenes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(26)

Published: April 15, 2024

In contrast to the kinetically favored outward isomerization-hydrocarbonylation of alkenes, disfavored inward alkenes remains an important challenge. Herein, we have developed a novel and effective palladium-catalyzed isomerization-hydroaminocarbonylation unactivated aniline hydrochlorides for formation synthetically valuable α-aryl carboxylic amides in high yields site-selectivities. The efficiency reaction is attributed relay catalysis strategy, which Markovnikov-favored [PdH]-P

Language: Английский

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Enantioselective synthesis of chiral α,α-dialkyl indoles and related azoles by cobalt-catalyzed hydroalkylation and regioselectivity switch

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 6, 2024

Abstract General, catalytic and enantioselective construction of chiral α,α -dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed anti- Markovnikov alkene hydroalkylation via the remote stereocontrol for synthesis other N -heterocycles. This asymmetric C(sp 3 )−C(sp ) coupling features high flexibility in introducing diverse set alkyl groups at α -position The utility this methodology has been demonstrated by late-stage functionalization drug molecules, bioactive natural products functional materials, identification class molecules exhibiting anti-apoptosis activities UVB-irradiated HaCaT cells. Ligands play vital role controlling reaction regioselectivity. Changing ligand from bi-dentate L6 tridentate L12 enables CoH-catalyzed hydroalkylation. Mechanistic studies disclose that involves migratory insertion process while MHAT process.

Language: Английский

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Enantioselective Ni-Catalyzed 1,2-Borylalkynylation of Unactivated Alkenes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(25), P. 17140 - 17149

Published: June 12, 2024

Enantioselective three-component difunctionalization of alkenes with boron reagents represents an attractive strategy for assembling three-dimensional chiral organoboron compounds. However, regio- and enantiocontrol comprise the pivot challenges in these transformations, which predominantly require use activated conjugated alkenes. Herein, by utilizing various carbonyl directing groups, including amides, sulfinamides, ketones, esters, we succeed realizing a nickel-catalyzed 1,2-borylalkynylation unactivated to enable simultaneous incorporation entity sp-fragment across double bond. The products contain boryl, alkynyl, functional groups orthogonal synthetic reactivities, offering three handles further derivatization access valuable intermediates. utility this ligand-enabled asymmetric protocol has been highlighted through late-stage decoration drug-relevant molecules.

Language: Английский

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Remote Stereocenter through Amide-Directed, Rhodium-Catalyzed Enantioselective Hydroboration of Unactivated Internal Alkenes

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(29), P. 13071 - 13078

Published: July 13, 2022

Despite the frequent occurrence of γ-branched amines in bioactive molecules, direct catalytic asymmetric synthesis this structural motif containing a remote stereocenter remains an important synthetic challenge. Here, we report amide-directed, rhodium-catalyzed highly diastereo- and enantioselective hydroboration unactivated internal alkenes. This method provided facile access to enantioenriched β,γ-vicinal stereocenters. The application strategy molecules was demonstrated. Computational studies indicated that migratory insertion alkene into rhodium hydride controls enantioselectivity.

Language: Английский

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Nickel-Catalyzed Remote C(sp³)–N/O Bond Formation of Alkenes with Unactivated Amines and Alcohols

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(7), P. 4409 - 4420

Published: March 17, 2023

Transition metal-catalyzed remote hydrofunctionalization of alkenes is an efficient method to realize C(sp3)–H functionalization. However, with unactivated amines and alcohols has not been successfully developed date. Herein, we report nickel-catalyzed hydroamination hydroetherification alcohols, accessing a series gem-diamine N,O-acetal derivatives in good high yields (up 93%) exclusive regioselectivities. The mechanistic investigations DFT computations indicated that the use 2-iodo-2-methylpropane (tBuI) as both mild hydride source radical precursor was essential afford functionalized products. This research work provides install amino or alkoxyl group at position far from double bond alkenes.

Language: Английский

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Ligand-Controlled NiH-Catalyzed Regiodivergent and Enantioselective Hydroamination of Alkenyl Amides

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(15), P. 10041 - 10047

Published: July 18, 2023

Transition-metal-catalyzed remote hydrofunctionalization of alkenes remains an efficient but challenging protocol in chemical synthesis. Herein, we reported a ligand-controlled, directing-group-assisted strategy to promote NiH-catalyzed site-selective (α, β, or γ) hydroamination unactivated with weakly coordinating amide groups. The key success lies the employment proper yet commercially available bidentate nitrogen-containing ligands, which enables delivery 1,1-, 1,2-, and 1,3-diamines good-to-excellent regioselectivity starting from same substrates. A broad range O-benzoylhydroxylamine electrophiles different functional groups can be installed via Ni migration nonmigration. Moreover, these predicable positionally selective protocols provide method for enantioselective synthesis highly valued 1,2-diamines (via aliphatic C–H amination) 1,3-diamines.

Language: Английский

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