Enantioselective Synthesis of N−N Bisindole Atropisomers

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(44)

Published: Sept. 15, 2022

N-N Atropisomers are a common motif in natural products and represent significant dimension for exploration modern pharmaceutical medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective bisindole atropisomers is unprecedented. Herein, first via palladium-catalyzed de novo construction one indole skeleton presented. A wide variety axially chiral bisindoles were generated good yields with excellent enantioselectivities cascade condensation/N-arylation reaction. Structurally diverse indole-pyrrole, indole-carbazole, non-biaryl-indole possessing axis accessed using this protocol. Moreover, investigations density functional theory (DFT) calculations provided insight into reaction mechanism enantiocontrol.

Language: Английский

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Design and catalytic atroposelective synthesis of axially chiral isochromenone-indoles

Science China Chemistry, Journal Year: 2022, Volume and Issue: 65(10), P. 1929 - 1937

Published: Sept. 13, 2022

Language: Английский

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Enantioselective Synthesis of N‐N Atropisomers by Palladium‐Catalyzed C−H Functionalization of Pyrroles

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(21)

Published: March 21, 2023

The catalytic asymmetric construction of N-N atropisomeric biaryls remains a formidable challenge. Studies them lag far behind studies the more classical carbon-carbon biaryl atropisomers, hampering meaningful development. Herein, first palladium-catalyzed enantioselective C-H activation pyrroles for synthesis atropisomers is presented. Structurally diverse indole-pyrrole possessing chiral axis were produced with good yields and high enantioselectivities by alkenylation, alkynylation, allylation, or arylation reactions. Furthermore, kinetic resolution trisubstituted heterobiaryls sterically demanding substituents was also achieved. Importantly, this versatile functionalization strategy enables iterative exquisite selectivity, expediting formation valuable, complex, atropisomers.

Language: Английский

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Pd-Catalyzed Asymmetric Larock Indole Synthesis to Access Axially Chiral N-Arylindoles

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5493 - 5501

Published: Feb. 13, 2024

Larock indole synthesis is one of the most straightforward and efficient methods for indoles; however, there has been no asymmetric version yet construction indole-based axially chiral N-arylindoles since its initial report in 1991. Herein we first example an by employing a sulfinamide phosphine (SadPhos) ligand (Ming-Phos) with palladium. It allows rapid wide range N-arylindole compounds good yields up to 98:2 er. The application this unique scaffold as organocatalyst promising. Furthermore, kinetic study revealed that alkyne migratory insertion rate-determining step, which proven density functional theory (DFT) calculations. Additionally, DFT studies also suggest N–C dihedral difference caused steric hindrance contributes enantioselectivity control.

Language: Английский

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Atroposelective catalysis

Nature Reviews Chemistry, Journal Year: 2024, Volume and Issue: 8(7), P. 497 - 517

Published: June 18, 2024

Language: Английский

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Rhodium-Catalyzed Atroposelective C–H Alkylation of 1-Aryl Isoquinoline Derivatives with Cyclopropanols

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 4017 - 4024

Published: Feb. 20, 2025

Language: Английский

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Oxygen‐Linked Cyclopentadienyl Rhodium(III) Complexes‐Catalyzed Asymmetric C−H Arylation of Benzo[h]quinolines with 1‐Diazonaphthoquinones

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(28), P. 15510 - 15516

Published: April 16, 2021

Abstract Chiral cyclopentadienyl rhodium (CpRh) complex‐catalyzed asymmetric C−H functionalization reactions have witnessed a significant progress in organic synthesis. In sharp contrast, the reported chiral Cp ligands are limited to C‐linked and often synthetically challenging. To address these issues, we developed novel class of tunable bearing oxygen linkers, which were efficient catalysts for arylation benzo[ h ]quinolines with 1‐diazonaphthoquinones, affording axially heterobiaryls excellent yields enantioselectivity (up 99 % yield, 98.5:1.5 er). Mechanistic studies suggest that reaction is likely proceed by electrophilic activation, followed coupling cyclometalated rhodium(III) complex 1‐diazonaphthoquinones.

Language: Английский

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Rhodium‐Catalyzed Atroposelective Access to Axially Chiral Olefins via C−H Bond Activation and Directing Group Migration

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(1)

Published: Oct. 22, 2021

Axially chiral open-chain olefins represent an underexplored class of platform. In this report, two classes tetrasubstituted axially acyclic have been accessed in excellent enantioselectivity and regioselectivity via C-H activation (hetero)arenes assisted by a migratable directing group en route to coupling with sterically hindered alkynes. The indoles bearing N-aminocarbonyl afforded C-N acrylamides the assistance racemic zinc carboxylate additive. DFT studies suggest β-nitrogen elimination-reinsertion pathway for migration. Meanwhile, employment N-phenoxycarboxamide delivered C-C enamides migration oxidizing group. Experiments that both cases (hetero)arene substrate adopts well-defined orientation during activation, which turn determines disposition alkyne migratory insertion. Synthetic applications representative are demonstrated.

Language: Английский

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Enantioselective Synthesis of Atropisomeric Biaryls by Pd‐Catalyzed Asymmetric Buchwald–Hartwig Amination

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(40), P. 21718 - 21722

Published: Aug. 10, 2021

Abstract N−C Biaryl atropisomers are prevalent in natural products and bioactive drug molecules. However, the enantioselective synthesis of such molecules has not developed significantly. Particularly, biaryl by stereoselective metal‐catalyzed aryl amination remains unprecedented. Herein, a Pd‐catalyzed cross‐coupling strategy is presented for axially chiral A broad spectrum compounds was obtained with excellent enantioselectivities (up to 99 % ee) good yields 98 %). The practicality this reaction validated useful biological

Language: Английский

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Enantioselective and Diastereoselective C–H Alkylation of Benzamides: Synergized Axial and Central Chirality via a Single Stereodetermining Step

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(15), P. 9151 - 9158

Published: July 9, 2021

In this report, distally disposed axial and central chirality has been installed in a synergistic fashion via rhodium-catalyzed C–H alkylation of benzamides using N-arylmaleimide as the alkylating reagent, which enantio- diastereo-determining steps are merged into single one. The coupling system features mild reaction conditions, broad substrate scope, excellent diastereoselectivity. chiral induction enabled by judicious choice rhodium cyclopentadienyl catalyst that serves to control both orientation olefin unit prochiral C–N bond.

Language: Английский

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