Enantioselective Synthesis of N−N Bisindole Atropisomers

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

Опубликована: Сен. 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.

Язык: Английский

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Design and catalytic atroposelective synthesis of axially chiral isochromenone-indoles

Science China Chemistry, Год журнала: 2022, Номер 65(10), С. 1929 - 1937

Опубликована: Сен. 13, 2022

Язык: Английский

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

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(21)

Опубликована: Март 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.

Язык: Английский

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

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(8), С. 5493 - 5501

Опубликована: Фев. 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.

Язык: Английский

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Atroposelective catalysis

Nature Reviews Chemistry, Год журнала: 2024, Номер 8(7), С. 497 - 517

Опубликована: Июнь 18, 2024

Язык: 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, Год журнала: 2021, Номер 60(28), С. 15510 - 15516

Опубликована: Апрель 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.

Язык: 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, Год журнала: 2021, Номер 61(1)

Опубликована: Окт. 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.

Язык: Английский

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

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(40), С. 21718 - 21722

Опубликована: Авг. 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

Язык: 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, Год журнала: 2021, Номер 11(15), С. 9151 - 9158

Опубликована: Июль 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.

Язык: Английский

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Design and synthesis of axially chiral aryl-pyrroloindoles via the strategy of organocatalytic asymmetric (2 + 3) cyclization

Fundamental Research, Год журнала: 2022, Номер 3(2), С. 237 - 248

Опубликована: Янв. 21, 2022

The catalytic asymmetric construction of axially chiral indole-based frameworks is an important area research due to the unique characteristics such frameworks. Nevertheless, in this still its infancy and has some challenges, as designing constructing new classes scaffolds developing their applications catalysts, ligands, etc. To overcome these we present herein design atroposelective synthesis aryl-pyrroloindoles a class via strategy organocatalytic (2 + 3) cyclization between 3-arylindoles propargylic alcohols. More importantly, was derived into phosphines, which served efficient ligands palladium-catalyzed reactions. Moreover, theoretical calculations provided in-depth understanding reaction mechanism. This work offers for scaffolds, are promising finding more catalysis.

Язык: Английский

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