Enantioselective Alkyl–Acyl Radical Cross-Coupling Enabled by Metallaphotoredox Catalysis

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Radical-radical cross-coupling (RCC) offers a promising approach for carbon-carbon bond formation in organic synthesis, particularly creating complex, three-dimensional molecules. However, achieving both cross- and enantioselectivity RCC reactions has remained significant challenge. Here, we report novel metallaphotoredox platform that enables highly enantioselective decarboxylative coupling of carboxylic acid derivatives with aldehydes. Our strategy leverages independent control over radical generation subsequent through fine-tuning common photocatalyst simple chiral bis(oxazoline) nickel catalyst. This redox-neutral protocol requires no exogenous oxidants or reductants demonstrates broad substrate scope functional group compatibility the synthesis enantioenriched α-aryl α-amino ketones. The ketone products can be readily transformed into valuable β-amino alcohols, streamlining access to these important motifs. Furthermore, showcase potential this more challenging C(sp3)-C(sp3) alkyl-alkyl reactions. unified alkyl-acyl represents advance asymmetric catalysis underscores exploit new mechanisms solve long-standing synthetic problems.

Language: Английский

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Catalytic desymmetrization reactions to synthesize all-carbon quaternary stereocentres

Nature Synthesis, Journal Year: 2023, Volume and Issue: 2(11), P. 1020 - 1036

Published: Oct. 16, 2023

Language: Английский

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Emerging Trends in Copper-Promoted Radical-Involved C–O Bond Formations

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(32), P. 17527 - 17550

Published: Aug. 2, 2023

The C–O bond is ubiquitous in biologically active molecules, pharmaceutical agents, and functional materials, thereby making it an important group. Consequently, the development of bond-forming reactions using catalytic strategies has become increasingly research topic organic synthesis because more conventional methods involving strong base acid have many limitations. In contrast to ionic-pathway-based methods, copper-promoted radical-mediated formation experiencing a surge interest owing renaissance free-radical chemistry photoredox catalysis. This Perspective highlights appraises state-of-the-art techniques this burgeoning field. contents are organized according different reaction types working models.

Language: Английский

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Enantioselective Construction of Quaternary Stereocenters via Cooperative Photoredox/Fe/Chiral Primary Amine Triple Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9404 - 9412

Published: March 20, 2024

The catalytic and enantioselective construction of quaternary (all-carbon substituents) stereocenters poses a formidable challenge in organic synthesis due to the hindrance caused by steric factors. One conceptually viable potentially versatile approach is coupling C–C bond through an outer-sphere mechanism, accompanied realization enantiocontrol cooperative catalysis; however, examples such processes are yet be identified. Herein, we present method for creating different compounds with photoredox/Fe/chiral primary amine triple catalysis. This facilitates connection unactivated alkyl source tertiary moiety, which also rare. scalable process exhibits mild conditions, does not necessitate use base, possesses good functional-group tolerance. Preliminary investigations into underlying mechanisms have provided valuable insights reaction pathway.

Language: Английский

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Synthesis of a C₂-Symmetric Chiral Borinic Acid and Its Application in Catalytic Desymmetrization of 2,2-Disubstituted-1,3-Propanediols

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(15), P. 8338 - 8343

Published: April 10, 2023

Notwithstanding the common use of boronic acids in catalysis, design and synthesis efficient chiral remains a formidable challenge. Herein we disclose rational concise series novel C2-symmetric disubstituted acids, or borinic acids. Chiral have been found to be excellent agents that can achieve highly enantioselective desymmetrization 2,2-disubstituted-1,3-propanediols, providing diols with quaternary stereocenter, which has regarded recent years as challenging. A wide range substrates are tolerated this reaction, high enantioselectivity. The presence tetracoordinate borinate catalytic cycle proven by 11B NMR studies, stereocontrol model proposed.

Language: Английский

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Amino Acid-Derived Ionic Chiral Catalysts Enable Desymmetrizing Cross-Coupling to Remote Acyclic Quaternary Stereocenters

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(30), P. 16796 - 16811

Published: July 20, 2023

Synthetic application of asymmetric catalysis relies on strategic alignment bond construction to creation chirality a target molecule. Remote desymmetrization offers distinctive advantages spatial decoupling catalytic transformation and generation stereogenic element. However, such separation presents substantial difficulties for the chiral catalyst discriminate distant enantiotopic sites through reaction three or more bonds away from prochirality center. Here, we report strategy that establishes acyclic quaternary carbon stereocenters cross-coupling reactions at distal positions aryl substituents. The new class amino acid-derived ionic catalysts enables desymmetrizing (enantiotopic-group-selective) Suzuki-Miyaura reaction, Sonogashira Buchwald-Hartwig amination between diverse diarylmethane scaffolds aryl, alkynyl, coupling partners, providing rapid access enantioenriched molecules project substituents widely spaced in three-dimensional space. Experimental computational investigations reveal electrostatic steering substrates by C-terminus ligands interactions. Cooperative ion-dipole interactions catalyst's amide group potassium cation aid preorganization transmits asymmetry product. This study demonstrates it is practical achieve precise long-range stereocontrol engineering arrangements catalysts' substrate-recognizing groups metal centers.

Language: Английский

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Recent advances in the asymmetric catalytic construction of oxa-quaternary carbon centers

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(12), P. 3110 - 3129

Published: Jan. 1, 2023

This review focuses on the very recent advances (from 2020 to beginning of 2023) in enantioselective catalytic reactions for construction oxa-quaternary stereocenters.

Language: Английский

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Synthetic utility of functionalized alkylsilyl peroxides for Fe-catalyzed and visible-light-promoted radical transformation

Chemical Science, Journal Year: 2024, Volume and Issue: 15(13), P. 4757 - 4762

Published: Jan. 1, 2024

α-Keto-, β-acetoxy- and β-amidoalkylsilyl peroxides are prepared from various precursors utilized for Fe-catalyzed visible-light-promoted radical functionalization with coupling partners under mild conditions a broad substrate scope.

Language: Английский

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Asymmetric Total Synthesis of Alstrostine G Utilizing a Catalytic Asymmetric Desymmetrization Strategy

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(34)

Published: May 31, 2024

A highly effective enantioselective monobenzoylation of 1,3-diols has been developed for the synthesis 1,1-disubstituted tetrahydro-β-carbolines. The chemistry successfully applied to asymmetric total (+)-alstrostine G, which also features a cascade Heck/hemiamination reaction enabling facile construction pivotal pentacyclic core.

Language: Английский

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Desymmetrization strategy in natural product total synthesis

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This review provides a thorough overview of desymmetrization strategy in natural product total synthesis, highlighting its synthetic principle, advantages, current challenges and opportunities.

Language: Английский

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