Asymmetric Construction of α,α‐Disubstituted Piperazinones Enabled by Benzilic Amide Rearrangement

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(18)

Опубликована: Март 4, 2023

An unprecedent asymmetric catalytic benzilic amide rearrangement for the synthesis of α,α-disubstituted piperazinones is reported. The reaction proceeds via a domino [4+1] imidazolidination/formal 1,2-nitrogen shift/1,2-aryl or alkyl migration sequence, employing readily available vicinal tricarbonyl compounds and 1,2-diamines as starting materials. This approach provides an efficient access to chiral C3-disubsituted piperazin-2-ones with high enantiocontrol, which are exceedingly difficult from existing synthetic methodologies. observed enantioselectivity was proposed be controlled by dynamic kinetic resolution in 1,2-aryl/alkyl step. resulting densely functionalized products versatile building blocks bioactive natural products, drug molecules their analogues.

Язык: Английский

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Tropos Diphenylmethane-Based Phosphine–Phosphoramidite Ligands: Design, Synthesis, and Application in Catalytic Asymmetric Hydrogenation

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

A series of chiral hybrid diphosphorus ligands incorporating a conformationally flexible tropos diphenylmethane-based phosphoramidite unit have been developed and evaluated in the Rh-catalyzed asymmetric hydrogenation 2-(1-arylvinyl)anilides α-enamides, leading to up >99% yield 99% enantiomeric excess. Preliminary results from comparative studies showcased extraordinary catalytic performance these phosphine–phosphoramidite ligands, with competency essentially superior those well-established regular rigid backbone.

Язык: Английский

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Asymmetric one-carbon ring expansion of diverse N-heterocycles via copper-catalyzed diyne cyclization

Science Advances, Год журнала: 2024, Номер 10(41)

Опубликована: Окт. 9, 2024

One-carbon ring expansion reaction of N-heterocycles has gained particular attention in the past decade because this method allows for conversion readily available into potentially useful complex ring-expanded N-heterocycles, which are inaccessible by traditional methods. However, catalytic asymmetric variant been rarely reported to date. Herein, we disclose an enantioselective one-carbon through chiral copper-catalyzed diyne cyclization, leading practical, atom-economic and divergent assembly array valuable bearing a quaternary stereocenter generally good excellent yields with enantioselectivities (up >99% ee). This protocol represents first example based on alkynes.

Язык: Английский

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Kinetic Resolution to Simultaneously Access Both Primary and Secondary NH-Unprotected Chiral Amines via Ir-Catalyzed Asymmetric Reductive Amination

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

This report describes a new kinetic resolution-asymmetric reductive amination strategy to collectively gain access both primary and secondary chiral NH-unprotected amines. Catalyzed by the complex of iridium bulky tunable phosphoramidite ligands, various ketones racemic amines could be smoothly converted two different types amine products. Bronsted acids as additives play triple roles, decreasing inhibitory effect, promoting formation imine intermediates, guiding reaction proceed through "outer-sphere" H-addition along with ligand.

Язык: Английский

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Cobalt-Catalyzed Enantioselective Reductive Amination of Ketones with Hydrazides

Organic Letters, Год журнала: 2023, Номер 26(4), С. 769 - 774

Опубликована: Дек. 4, 2023

An efficient cobalt-catalyzed asymmetric reductive amination of ketones with hydrazides has been realized, directly producing valuable chiral hydrazines in high yields and enantioselectivities (up to 98% enantiomeric excess).

Язык: Английский

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Asymmetric Construction of α,α‐Disubstituted Piperazinones Enabled by Benzilic Amide Rearrangement

Angewandte Chemie, Год журнала: 2023, Номер 135(18)

Опубликована: Март 4, 2023

Abstract An unprecedent asymmetric catalytic benzilic amide rearrangement for the synthesis of α,α‐disubstituted piperazinones is reported. The reaction proceeds via a domino [4+1] imidazolidination/formal 1,2‐nitrogen shift/1,2‐aryl or alkyl migration sequence, employing readily available vicinal tricarbonyl compounds and 1,2‐diamines as starting materials. This approach provides an efficient access to chiral C3‐disubsituted piperazin‐2‐ones with high enantiocontrol, which are exceedingly difficult from existing synthetic methodologies. observed enantioselectivity was proposed be controlled by dynamic kinetic resolution in 1,2‐aryl/alkyl step. resulting densely functionalized products versatile building blocks bioactive natural products, drug molecules their analogues.

Язык: Английский

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Penta- versus hexa-coordinated iridium catalysts control the reactivity of the direct reductive amination between aliphatic amines and aliphatic ketones: a DFT-guided mechanism

Catalysis Science & Technology, Год журнала: 2024, Номер 14(14), С. 3984 - 3995

Опубликована: Янв. 1, 2024

The mechanism of the iridium-catalysed direct reductive amination between aliphatic partners was studied by DFT calculations leading to important changes in rate-determining step depending on nature ligand coordinating iridium.

Язык: Английский

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Facile access to C-substituted piperazin-2-ones and mianserin derivative enabled by chemoselective carbene insertion and cyclization cascade

Chemical Communications, Год журнала: 2024, Номер 60(44), С. 5691 - 5694

Опубликована: Янв. 1, 2024

A simple method to synthesize carbon-substituted piperazinones achieved from donor–acceptor diazo compounds and 1,2-diamine derivatives under Cu-catalyzed conditions.

Язык: Английский

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Ketone Scope and Their Limitations in Transition Metal Catalyzed Direct Asymmetric Hydrogenative Aminations

ChemistrySelect, Год журнала: 2024, Номер 9(26)

Опубликована: Июль 10, 2024

Abstract Chiral amines are valuable building blocks in the manufacture of agrochemicals, pharmaceuticals, natural products, fine chemicals, functional materials among others. Compared to asymmetric hydrogenation imines/enamides and biocatalytic/organocatalytic reductive amination, transition metal catalyzed direct hydrogenative amination reactions (DAHA) using molecular dihydrogen as reductant highly economical, atom and/or step‐efficient thus attractive for researchers from both industry academia. In previous reviews, catalysts/methods development, applications synthesis pharmaceuticals [N] source were summarized discussed. this review, we summarize discuss ketone substrates scope upon utilizing state‐of‐the‐art catalysts. The substrate limitations, potential key mechanisms also critically concluded.

Язык: Английский

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Ir/XuPhos-Catalyzed Direct Asymmetric Reductive Amination of Ketones with Secondary Amines

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(23), С. 6735 - 6741

Опубликована: Янв. 1, 2024

We herein report a novel iridium catalyst with XuPhos as chiral monodentate phosphine ligand for the direct asymmetric reductive amination of ketones secondary amines, providing series tertiary amines efficiently.

Язык: Английский

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