Enantioselective [2+2]-cycloadditions with triplet photoenzymes

Nature, Journal Year: 2022, Volume and Issue: 611(7937), P. 715 - 720

Published: Sept. 21, 2022

Language: Английский

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Modular Access to Chiral α-(Hetero)aryl Amines via Ni/Photoredox-Catalyzed Enantioselective Cross-Coupling

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(19), P. 8797 - 8806

Published: May 3, 2022

Chiral α-aryl N-heterocycles are commonly found in natural products, pharmaceutical agents, and chiral catalysts but remain challenging to access via asymmetric catalysis. Herein, we report a general modular approach for the direct enantioselective α-arylation of saturated azacycles acyclic N-alkyl benzamides nickel/photoredox dual This process exploits hydrogen atom transfer ability photoeliminated chlorine radicals convert corresponding α-amino alkyl that then coupled with ubiquitous inexpensive (hetero)aryl chlorides. These coupling reactions require no oxidants or organometallic reagents, feature feedstock starting materials, broad substrate scope, high enantioselectivities, applicable late-stage diversification medicinally relevant complex molecules. Mechanistic studies suggest nickel catalyst uncommonly plays multiple roles, accomplishing radical generation, capture, cross-coupling, induction.

Language: Английский

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Enantioselective [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes with Vinylazaarenes through Asymmetric Photoredox Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(12), P. 8372 - 8380

Published: March 18, 2024

Here we present a highly enantioselective [2π + 2σ] photocycloaddition of bicyclo[1.1.0]butanes (BCBs). The reaction uses variety vinylazaarenes as partners and is catalyzed by polycyclic aromatic hydrocarbon (PAH)-containing chiral phosphoric acid bifunctional photosensitizer. A wide array pharmaceutically important bicyclo[2.1.1]hexane (BCH) derivatives have been synthesized with high yields, enantioselectivity, diastereoselectivity. In addition to the diverse 1-ketocarbonyl-3-substituted BCBs, α/β-substituted are compatible such an unprecedented photoredox catalytic pathway, resulting in successful assembly all-carbon quaternary stereocenter or two adjacent tertiary stereocenters on product.

Language: Английский

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Site- and enantioselective cross-coupling of saturated N-heterocycles with carboxylic acids by cooperative Ni/photoredox catalysis

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

Published: Jan. 9, 2023

Abstract Site- and enantioselective cross-coupling of saturated N -heterocycles carboxylic acids—two the most abundant versatile functionalities—to form pharmaceutically relevant α-acylated amine derivatives remains a major challenge in organic synthesis. Here, we report general strategy for highly site- α-acylation with situ-activated acids. This modular approach exploits hydrogen-atom-transfer reactivity photocatalytically generated chlorine radicals combination asymmetric nickel catalysis to selectively functionalize cyclic α-amino C−H bonds presence benzylic, allylic, acyclic α-amino, α-oxy methylene groups. The mild scalable protocol requires no organometallic reagents, displays excellent chemo-, enantioselectivity, is amenable late-stage diversification, including synthesis previously inaccessible Taxol derivatives. Mechanistic studies highlight exceptional versatility chiral catalyst orchestrating (i) catalytic elimination, (ii) alkyl radical capture, (iii) cross-coupling, (iv) induction.

Language: Английский

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Double Strain-Release [2π+2σ]-Photocycloaddition

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5232 - 5241

Published: Feb. 13, 2024

In pursuit of potent pharmaceutical candidates and to further improve their chemical traits, small ring systems can serve as a potential starting point. Small units have the additional merit loaded strain at core, making them suitable reactants they capitalize on this intrinsic driving force. With introduction cyclobutenone strained precursor ketene, photocycloaddition with another unit, bicyclo[1.1.0]butane (BCB), enables reactivity both π-units in transient ketene. This double strain-release driven [2π+2σ]-photocycloaddition promotes synthesis diverse heterobicyclo[2.1.1]hexane units, pharmaceutically relevant bioisostere. The effective under catalyst-free conditions high functional group tolerance defines its synthetic utility. Experimental mechanistic studies density theory (DFT) calculations suggest that takes place via triplet mechanism.

Language: Английский

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Catalytic asymmetric photocycloaddition reactions mediated by enantioselective radical approaches

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

Published: Jan. 1, 2025

The use of olefins in the construction cyclic compounds represents a powerful strategy for advancing pharmaceutical industry.

Language: Английский

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Catalytic Asymmetric Hydrogen Atom Transfer: Enantioselective Hydroamination of Alkenes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(29), P. 16118 - 16129

Published: July 11, 2023

We report a highly enantioselective radical-based hydroamination of enol esters with sulfonamides jointly catalyzed by an Ir photocatalyst, Brønsted base, and tetrapeptide thiol. This method is demonstrated for the formation 23 protected β-amino-alcohol products, achieving selectivities up to 97:3 er. The stereochemistry product set through selective hydrogen atom transfer from chiral thiol catalyst prochiral C-centered radical. Structure–selectivity relationships derived structural variation both peptide olefin substrate provide key insights into development optimal catalyst. Experimental computational mechanistic studies indicate that hydrogen-bonding, π–π stacking, London dispersion interactions are contributing factors recognition enantioinduction. These findings further asymmetric catalysis contribute understanding noncovalent relevant such transformations.

Language: Английский

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Highly Enantioselective Radical Cation [2 + 2] and [4 + 2] Cycloadditions by Chiral Iron(III) Photoredox Catalysis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(28), P. 15054 - 15060

Published: July 5, 2023

Radical cations show a unique reactivity that is fundamentally different from of conventional and have thus attracted considerable attention as alternative cationic intermediates for novel types organic reactions. However, asymmetric catalysis to promote enantioselective radical cation reactions remains major challenge in contemporary synthesis. Here, we report the judicious design an ion pair consisting chiral counteranion induces excellent level enantioselectivity. This strategy was applied enantio-, diastereo-, regioselective [2 + 2] cycloadditions, well [4 by using iron(III) photoredox catalysis. We anticipate this has potential expand use several mature anions develop numerous unprecedented

Language: Английский

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Asymmetric Transfer Hydrogenation of Cyclobutenediones

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(7), P. 4942 - 4957

Published: Feb. 7, 2024

Four-membered carbocycles are fundamental substructures in bioactive molecules and approved drugs serve as irreplaceable building blocks organic synthesis. However, developing efficient protocols furnishing diversified four-membered ring compounds a highly regio-, diastereo-, enantioselective fashion remains challenging but very desirable. Here, we report the unprecedented asymmetric transfer hydrogenation of cyclobutenediones. The reaction can selectively afford three types products high yields with stereoselectivities, functionalized enable series further transformations to form more compounds. Asymmetric synthesis di-, tri-, tetrasubstituted has also been achieved. Systematic mechanistic studies theoretical calculations have revealed origin regioselectivity, key transition state models, sequence double triple processes. work provides new choice for catalytic cyclobutanes related structures demonstrates robustness accurate selectivity control substrates.

Language: Английский

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Extending Photocatalyst Activity through Choice of Electron Donor

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(10), P. 6445 - 6453

Published: Jan. 11, 2023

Sacrificial additives are commonly employed in photoredox catalysis as a convenient source of electrons, but what occurs after electron transfer is often overlooked. Tertiary alkylamines initially form radical cations following transfer, which readily deprotonate to strongly reducing, neutral α-amino radicals. Similarly, the oxalate anion (C2O4•-) rapidly decomposes CO2•- (E0 ≈ -2.2 V vs SCE). We show that not only these reactive intermediates formed under conditions, they can also impact desired photochemistry, both positively and negatively. Photoredox systems using an donor able engage substrates with greater energy demands, extending reactivity past limits single multiphoton transition metal catalysts. Furthermore, offers better chemoselectivity than triethylamine when reducing moderate requirements.

Language: Английский

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