Photoinduced, Copper-Catalyzed Enantioconvergent Alkylations of Anilines by Racemic Tertiary Electrophiles: Synthesis and Mechanism

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(10), P. 4550 - 4558

Published: March 7, 2022

Transition-metal catalysis of substitution reactions alkyl electrophiles by nitrogen nucleophiles is beginning to emerge as a powerful strategy for synthesizing higher-order amines, well controlling their stereochemistry. Herein, we report that readily accessible chiral copper catalyst (commercially available components) can achieve the photoinduced, enantioconvergent coupling variety racemic tertiary with aniline generate new C–N bond good ee at fully substituted stereocenter product; whereas this copper-catalyzed proceeds −78 °C, in absence light and catalyst, virtually no formation observed even upon heating 80 °C. The mechanism catalytic process has been interrogated aid wide array tools, including independent synthesis proposed intermediates reactivity studies, spectroscopic investigations featuring photophysical EPR data, DFT calculations. These studies led identification three copper-based cycle, three-coordinate formally copper(II)–anilido (DFT analysis points its formulation copper(I)–anilidyl radical) complex serves persistent radical couples organic desired enantioselectivity.

Language: Английский

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Enantioselective propargylic amination and related tandem sequences to α-tertiary ethynylamines and azacycles

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(4), P. 521 - 532

Published: March 19, 2024

Language: Английский

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Remote copper-catalyzed enantioselective substitution of yne-thiophene carbonates

Science China Chemistry, Journal Year: 2024, Volume and Issue: 67(4), P. 1175 - 1180

Published: Feb. 29, 2024

Language: Английский

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Copper-Catalyzed Asymmetric Yne-Allylic Substitution Using Electron-Rich Arenes

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(4), P. 2746 - 2757

Published: Feb. 7, 2024

Remote stereocontrol in transition-metal catalysis is a challenging but interesting research topic. In this work, we achieved copper-catalyzed asymmetric yne-allylic substitution using electron-rich arenes and acyclic carbonates through remote enantioselectivity control. The reaction delivers variety of enantioenriched products that contain diverse set valuable moieties, such as conjugated enynes, indoles, indolizines, allenes, dihydrofurans, which are widely used organic synthesis act key units bioactive molecules natural products. synthetic value protocol has been demonstrated series further transformations, mechanistic studies have conducted to gain more insight into the reaction.

Language: Английский

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Remote Enantioselective [4 + 1] Annulation with Copper-Vinylvinylidene Intermediates

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(46), P. 21347 - 21355

Published: Nov. 11, 2022

The first copper-catalyzed enantioselective [4 + 1] annulation of yne-allylic esters with 1,3-dicarbonyl compounds was realized through an elegant remote stereocontrol strategy. very ε regioselective nucleophilic substitution developed by employing a novel chiral copper-vinylvinylidene species from the new C4 synthon esters. Thus, greatly diverse spirocycles were obtained ample scope and excellent levels chemo-, regio-, enantioselectivities. Moreover, detailed mechanistic studies suggest Conia-ene cascade pathway on stereochemical induction progress.

Language: Английский

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Investigation of the C–N Bond-Forming Step in a Photoinduced, Copper-Catalyzed Enantioconvergent N–Alkylation: Characterization and Application of a Stabilized Organic Radical as a Mechanistic Probe

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(9), P. 4114 - 4123

Published: Feb. 15, 2022

Whereas photoinduced, copper-catalyzed couplings of nitrogen nucleophiles with alkyl electrophiles have recently been shown to provide an attractive approach achieving a variety enantioselective C–N bond constructions, mechanistic studies these transformations lagged the advances in reaction development. Herein we insight into previously reported enantioconvergent coupling carbazole nucleophile racemic tertiary α-haloamide electrophile. Building on isolation copper(II) model complex whose EPR parameters serve as guide, independently synthesize two key intermediates proposed catalytic cycle, metalloradical (L*CuII(carb′)2) (L* = monodentate chiral phosphine ligand; carb′ carbazolide ligand), well α-amide organic radical (R·); generation and characterization R· was guided by DFT calculations, which suggested that it would be stable homocoupling. Continuous-wave (CW) pulse studies, along corresponding are among techniques used characterize reactive radicals. We establish radicals do indeed combine furnish product good yield significant enantiomeric excess (77% yield, 55% ee), thereby supporting chemical competence intermediates. calculations consistent initially binding via dative interaction from closed-shell carbonyl oxygen atom radical, positions α-carbon for direct copper(II)-bound N atom, generate enantioselectivity, without formation alkylcopper(III) intermediate.

Language: Английский

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Copper-catalysed convergent regio- and enantioselective alkynylallylic substitution

Nature Synthesis, Journal Year: 2022, Volume and Issue: 2(1), P. 37 - 48

Published: Oct. 24, 2022

Language: Английский

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Recent advances in copper-catalyzed decarboxylative reactions of propargylic cyclic carbonates/carbamates

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(49), P. 7483 - 7505

Published: Jan. 1, 2023

Copper-catalyzed decarboxylative reactions are powerful strategies for the construction of widely available skeletons such as allenes, ethynyl-containing heterocycles, and quaternary carbon centers.

Language: Английский

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Asymmetric Substitution by Alkynyl Copper Driven Dearomatization and Rearomatization

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(47)

Published: Oct. 16, 2023

Abstract Catalytic asymmetric transformations by dearomatization have developed into a widely applicable synthetic strategy, but heavily relied on the use of arenes bearing heteroatom. In this case, is facilitated involvement p ‐orbital electron Different from conventional substrate‐dependent model, here we demonstrate that activation d transition‐metal center can serve as driving force for dearomatization, and applied to development novel alkynyl copper remote substitution reaction. A newly modified PyBox chiral ligand enables construction valuable diarylmethyl triarylmethyl skeletons in high enantioselectivities. An unexpected tandem process involving sequential substitution/cyclization/1,5‐H shift leads formation enantioenriched C−N axis. gram‐scale reaction various downstream highlight robustness method potential products. Preliminary mechanistic studies reveal mononuclear Cu‐catalyzed process.

Language: Английский

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Asymmetric copper-catalyzed alkynylallylic monofluoroalkylations with fluorinated malonates

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(31), P. 4210 - 4213

Published: Jan. 1, 2024

The unprecedented copper-catalyzed asymmetric alkynylallylic monofluoroalkylation reaction is described

Language: Английский

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