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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Silver(I)/Dirhodium(II) Catalytic Platform for Asymmetric N–H Insertion Reaction of Heteroaromatics

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 146(1), P. 733 - 741

Published: Dec. 27, 2023

Transition-metal-catalyzed enantioselective N–H insertion reactions of carbene species offer a powerful and straightforward strategy to produce chiral nitrogen-containing compounds. Developing highly selective using indole variants can meet synthetic demand. Herein we present an asymmetric reaction into bonds the aromatic heterocycles donor/acceptor-substituted diazo compounds based on heteronuclear catalytic platform. Although previously developed catalysis comprising silver catalyst or dirhodium(II,II) paddlewheel complexes with without phosphoric acid showed modest performance, unique combination widely available Rh2(OAc)4 silver(I) phosphate dimer [(S)-TRIP-Ag]2 enabled (up 98% ee). Moreover, Ag/Rh system facilitated regioselective C–H functionalization protic indoles. Mechanistic investigation density functional theory indicated that in situ-generated Ag–Rh trimetallic enolate is protonated environment.

Language: Английский

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Enantioselective Synthesis of N-Substituted Indoles with α,β-Stereocenters via Sequential Aza-Piancatelli/Cyclization Reactions

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

A sequence of catalytic asymmetric aza-Piancatelli rearrangement and Pd-catalyzed cyclization has been developed to construct chiral N-substituted indoles featuring α,β-consecutive stereocenters. This indole framework, bearing α,β-chiral centers, is a prevalent structural motif in natural products biologically active molecules, yet enantioselective methods for its preparation remain scarce. protocol offers efficient access diverse array derivatives with stereocenters, achieving high yields excellent enantioselectivities.

Language: Английский

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Enantioselective N–H Bond Insertion Reaction of Anilines Enabled by Ruthenium and Chiral Phosphoric Acid Cooperative Catalysis

Organic Letters, Journal Year: 2024, Volume and Issue: 26(29), P. 6214 - 6219

Published: July 17, 2024

The enantioselective carbene insertion into N-H bonds of anilines has been realized by cooperative catalysis ruthenium complexes and chiral phosphoric acids, providing the expected α-aryl glycines in moderate to good yields with high enantioselectivity. Typically, slightly modifying reaction conditions, this approach allows bond be effective for both α-alkyl diazoacetates first time enantioselectivity (up 96% 95% ee, respectively).

Language: Английский

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Enantioselective insertion of vinyl diazoacetates into O–H bonds of carboxylic acids

New Journal of Chemistry, Journal Year: 2024, Volume and Issue: 48(12), P. 5092 - 5096

Published: Jan. 1, 2024

A rhodium and phosphoric acid-catalyzed regio- enantioselective vinyl carbene insertion into the O–H bonds of carboxylic acids has been achieved.

Language: Английский

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Cycloaddition and Skeleton Rearrangement of Heterocyclic Ketene Aminals (HKAs) with 1-Diazonaphthalen-2(1H)-ones for the Synthesis of Functionalized 1,2,3-Triazoles

Organic Letters, Journal Year: 2024, Volume and Issue: 26(32), P. 6866 - 6871

Published: Aug. 2, 2024

We developed a protocol for the synthesis of highly functionalized 5,6-dihydro-imidazo[1,2-

Language: Английский

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Iron(II) Phthalocyanine-Catalyzed Homodimerization and Tandem Diamination of Diazo Compounds with Primary Amines: Access to Construct Substituted 2,3-Diaminosuccinonitriles in One-Pot

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(11), P. 7718 - 7726

Published: May 24, 2024

We herein first report the homodimerization and tandem diamination of diazo compounds with primary amines catalyzed by iron(II) phthalocyanine (PcFe(II)), which can construct one C-C bond two C-N bonds within 20 min in one-pot. Compared to traditional metal-catalyzed N-H insertion reaction between reagents, developed almost does not generate product, but homodimerization/tandem product. The proposed mechanism studies indicate that play a crucial role homocoupling via dimerization iron(III)-acetonitrile radical generated from diazoacetonitrile PcFe(II) coordinated bis(amines); β-hydride elimination is involved, then, attack toward carbon atoms on formed followed. Moreover, this novel be used effectively prepare substituted 2,3-diaminosuccinonitriles high yields even up >99:1 d.r., encouragingly these products contain both 1,2-diamines succinonitrile motifs, are classes important organic significant applications many yields. This also suitable for gram-scale preparation 2,3-bis(phenylamino)succinonitrile (

Language: Английский

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Palladium-Catalyzed Reaction of Indolines with Dihydropyrroles: Access to N-Alkylated Indoles

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(14), P. 9990 - 10003

Published: July 3, 2024

Palladium-catalyzed reaction of indolines with 1-acyl-2,3-dihydro-1

Language: Английский

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Enantioselective Synthesis of Aminals Via Nickel-Catalyzed Hydroamination of 2-Azadienes with Indoles and N-Heterocycles

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(45), P. 30947 - 30957

Published: Oct. 30, 2024

New methods for the enantioselective synthesis of N-alkylated indoles and their derivatives are great interest because pivotal structural elements in biologically active molecules natural products. They also versatile intermediates organic synthesis. Among well-established asymmetric hydroamination methods, with indole-based substrates is a formidable challenge. This observation likely due to reduced nucleophilicity indole nitrogen. Herein, unique nickel-catalyzed enantio- branched-selective 2-azadienes structurally related N-heterocycles reported generation enantioenriched

Language: Английский

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Rhodium-catalyzed atropodivergent hydroamination of alkynes by leveraging two potential enantiodetermining steps

Science Advances, Journal Year: 2024, Volume and Issue: 10(48)

Published: Nov. 27, 2024

A pair of enantiomers is known to have different biological activities. Two catalysts with opposite chirality are nearly always required deliver both enantiomeric products. In this work, chiral rhodium(III) cyclopentadienyl complexes repurposed as efficient for enantiodivergent and atroposelective hydroamination sterically hindered alkynes. Products been obtained using the same or closely analogous catalyst in good efficiency excellent enantioselectivity, enantiodivergence was mainly enabled by an achiral carboxylic acid its silver salt. Mechanistic studies revealed origin ascribable switch enantiodetermining step (alkyne insertion versus protonolysis) under control, which constitutes a previously unidentified working mode leveraging two elementary steps.

Language: Английский

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