Catalytic atroposelective synthesis

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(5), P. 483 - 498

Published: April 30, 2024

Language: Английский

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Cobalt‐Catalyzed Asymmetric Aza‐Nozaki–Hiyama–Kishi (NHK) Reaction of α‐Imino Esters with Alkenyl Halides

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(7)

Published: Jan. 2, 2024

Chromium-catalyzed enantioselective Nozaki-Hiyama-Kishi (NHK) reaction represents one of the most powerful approaches for formation chiral carbon-heteroatom bond. However, construction sterically encumbered tetrasubstituted stereocenter through NHK still posts a significant challenge. Herein, we disclose cobalt-catalyzed aza-NHK ketimine with alkenyl halide to provide convenient synthetic approach manufacture enantioenriched α-vinylic amino acid. This protocol exhibits excellent functional group tolerance 99 % ee in cases. Additionally, this asymmetric reductive method is also applicable aldimine access trisubstituted stereogenic centers.

Language: Английский

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Recent Advances in Asymmetric Organometallic Electrochemical Synthesis (AOES)

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

ConspectusIn recent years, our research group has dedicated significant effort to the field of asymmetric organometallic electrochemical synthesis (AOES), which integrates electrochemistry with transition metal catalysis. On one hand, we have rationalized that compounds can serve as molecular electrocatalysts (mediators) reduce overpotentials and enhance both reactivity selectivity reactions. other conditions for catalysis be substantially improved through electrochemistry, enabling precise modulation metal's oxidation state by controlling potentials regulating electron transfer rate via current adjustments. This synergistic approach addresses key challenges inherent in traditional catalysis, particularly those related use redox-active chemical reagents. Furthermore, redox conveniently tuned modifying their ligands, thereby governing reaction regioselectivity stereoselectivity. As a result, AOES emerged powerful promising tool chiral compounds.In this Account, summarize contextualize efforts AOES. Our primary strategy involves leveraging controllability potential regulate organometallics, facilitating desired An efficient platform was established under mild conditions, significantly reducing reliance on been systematically categorized into three sections based distinct electrolysis modes: combined anodic oxidation, cathodic reduction, paired electrolysis. In each section, highlight innovative discoveries tailored unique characteristics respective modes.In many transformations, metal-catalyzed reactions involving reagents utilizing exhibit similar reactivities. However, also observed notable differences certain cases. These findings include following: (1) Enhanced efficiency synthesis: instance, Rh-catalyzed enantioselective functionalization C–H bonds demonstrates superior efficiency. (2) Expanded scope transformations: previously challenging achieved due tunability potentials. A example is reductive coupling aryl chlorides, expands range accessible transformations. Additionally, mechanistic studies explore techniques intrinsic such controlled experiments, impact electrode materials catalyst performance, cyclic voltammetry studies. investigations provide more intuitive understanding behavior catalysts study mechanisms, guide design new catalytic systems.The advancements offer robust environmentally friendly sustainable selective By integrating developed versatile organic not only enhances but reduces environmental impact. We anticipate Account will stimulate further innovation realm AOES, leading discovery systems development synthetic methodologies.

Language: Английский

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A Dynamic Kinetic Resolution Approach to Axially Chiral Diaryl Ethers by Catalytic Atroposelective Transfer Hydrogenation

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(7)

Published: Dec. 20, 2022

Diaryl ethers are widespread in biologically active compounds, ligands and catalysts. It is known that the diaryl ether skeleton may exhibit atropisomerism when both aryl rings unsymmetrically substituted with bulky groups. Despite recent advances, only very few catalytic asymmetric methods have been developed to construct such axially chiral compounds. We describe herein a dynamic kinetic resolution approach via Brønsted acid catalyzed atroposelective transfer hydrogenation (ATH) reaction of dicarbaldehydes anilines. The desired could be obtained moderate good chemical yields (up 79 %) high enantioselectivities 95 % ee) under standard conditions. Such structural motifs interesting precursors for further transformations potential applications synthesis or

Language: Английский

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Data-driven design of new chiral carboxylic acid for construction of indoles with C-central and C–N axial chirality via cobalt catalysis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 31, 2023

Challenging enantio- and diastereoselective cobalt-catalyzed C-H alkylation has been realized by an innovative data-driven knowledge transfer strategy. Harnessing the statistics of a related transformation as source, designed machine learning (ML) model took advantage delta enabled accurate extrapolative enantioselectivity predictions. Powered model, virtual screening broad scope 360 chiral carboxylic acids led to discovery new catalyst featuring intriguing furyl moiety. Further experiments verified that predicted acid can achieve excellent stereochemical control for target alkylation, which supported expedient synthesis large library substituted indoles with C-central C-N axial chirality. The reported approach provides powerful data engine accelerate molecular catalysis harnessing hidden value available structure-performance statistics.

Language: Английский

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Electrophilic Selenium-Catalyzed Desymmetrizing Cyclization to Access P-Stereogenic Heterocycles

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(20), P. 13301 - 13309

Published: Oct. 2, 2023

The construction of phosphorus stereocenters under metal-free conditions remains a formidable challenge. Herein, we report mechanistically distinct chiral electrophilic selenium catalysis-enabled desymmetrizing cyclization to access valuable phosphorus-stereogenic heterocycles with high efficiency. This ambient temperature method affords broad range compounds that bear phenolic hydroxyl group as useful synthetic handle and, thus, enriches the toolbox for rapid generation molecular complexity. control experiments and DFT calculations indicate dual-hydrogen-bonding bridge formed between substrate TfO– anion plays crucial role in determining enantioselectivity transformation.

Language: Английский

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Cobalt-Catalyzed Enantioselective Cross-Electrophile Couplings: Stereoselective Syntheses of 5–7-Membered Azacycles

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(30), P. 16464 - 16473

Published: July 21, 2023

Cobalt complexes of chiral pyrox ligands catalyzed enantioselective reductive couplings nonconjugated iododienes with aryl iodides or alkenyl bromides. The reaction enabled stereoselective syntheses 5-7-membered azacycles carrying quaternary stereocenters. Mechanistically, cross-electrophile selectivity originated from selective coupling alkylcobalt(I) generated after cyclization iodides.

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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Cobalt‐Catalyzed Enantioselective Reductive α‐Chloro‐Carbonyl Addition of Ketimine to Construct the β‐Tertiary Amino Acid Analogues

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(25)

Published: Jan. 22, 2024

β-Tertiary amino acid derivatives constitute one of the most frequently occurring units in natural products and bioactive molecules. However, efficient asymmetric synthesis this motif still remains a significant challenge. Herein, we disclose cobalt-catalyzed enantioselective reductive addition reaction ketimine using α-chloro carbonyl compound as radical precursor, providing expedient access to diverse array enantioenriched β-quaternary analogues. This protocol exhibits outstanding enantioselectivity broad substrate scope with excellent functional group tolerance. Preliminary mechanism studies rule out possibility Reformatsky-type confirm involvement species stereoselective process. The synthetic utility has been demonstrated through rapid assembly iterative oligopeptide, showcasing its versatile platform for late-stage modification drug candidates.

Language: Английский

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Cobalt-Catalyzed Asymmetric Reductive Alkenylation and Arylation of Heterobiaryl Tosylates: Kinetic Resolution or Dynamic Kinetic Resolution?

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(49), P. 26747 - 26755

Published: Nov. 29, 2023

Herein, we report a cobalt-catalyzed atroposelective reductive cross-coupling of racemic heterobiaryl tosylates with C(sp2)–X type electrophile. Both aryl and alkenyl halides are competent precursors for this reaction, providing variety heterobiaryls as the products in highly enantioselective manner high functionality tolerance. The related asymmetric arylation alkenylation discovered to proceed divergent mechanisms. reaction pathway changes from kinetic resolution (KR) when bromides iodides bearing strong electron-withdrawing substitution on para-position employed starting materials an enantioconvergent transformation via dynamic KR configurationally labile cobaltacycles relatively electron-rich used. change mechanisms turns out arise relative rates two competing elementary steps, which epimerization cyclic Co(I) intermediates their trapping by coupling electrophiles C(sp2)-type oxidative addition.

Language: Английский

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