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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Asymmetric Cross-Coupling of Aldehydes with Diverse Carbonyl or Iminyl Compounds by Photoredox-Mediated Cobalt Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(15), P. 10857 - 10867

Published: April 8, 2024

The asymmetric cross-coupling of unsaturated bonds, hampered by their comparable polarity and reactivity, as well the scarcity efficient catalytic systems capable diastereo- enantiocontrol, presents a significant hurdle in organic synthesis. In this study, we introduce highly adaptable photochemical cobalt catalysis framework that facilitates chemo- stereoselective reductive cross-couplings between common aldehydes with broad array carbonyl iminyl compounds, including N-acylhydrazones, aryl ketones, aldehydes, α-keto esters. Our methodology hinges on synergistic mechanism driven photoredox-induced single-electron reduction subsequent radical–radical coupling, all precisely guided chiral catalyst. Various optically enriched β-amino alcohols unsymmetrical 1,2-diol derivatives (80 examples) have been synthesized good yields (up to 90% yield) high stereoselectivities >20:1 dr, 99% ee). Of particular note, approach accomplishes unattainable transformations disparate partners without reliance any external photosensitizer, thereby further emphasizing its versatility cost-efficiency.

Language: Английский

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Catalytic Asymmetric Redox‐Neutral [3+2] Photocycloadditions of Cyclopropyl Ketones with Vinylazaarenes Enabled by Consecutive Photoinduced Electron Transfer

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(30)

Published: April 30, 2024

Abstract Consecutive photoinduced electron transfer (ConPET) is a powerful and atom‐economical protocol to overcome the limitations of intrinsic redox potential visible light‐absorbing photosensitizers, thereby considerably improving substrate reaction types. Likely because such an exothermic single‐electron (SET) process usually does not require aid chiral catalysts, resulting in inevitable racemic background reaction, notably, no enantioselective manifolds have been reported. Herein, we report on viability cooperative ConPET hydrogen‐bonding catalysis for [3+2] photocycloaddition cyclopropyl ketones with vinylazaarenes. In addition enabling first use olefins that preferentially interact this platform paves way efficient synthesis pharmaceutically synthetically important cyclopentyl functionalized by azaarenes high yields, ees dr. The robust capacity method can be further highlighted low loading catalyst (1.0 mol %), good compatibility both 2‐azaarene 3‐pyridine‐based olefins, successful concurrent construction three stereocenters cyclopentane rings involving elusive but all‐carbon quaternary.

Language: Английский

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Radical Cross Coupling and Enantioselective Protonation through Asymmetric Photoredox Catalysis

Advanced Science, Journal Year: 2024, Volume and Issue: 11(12)

Published: Jan. 17, 2024

Abstract An unprecedented enantioselective protonation reaction enabled by photoredox catalytic radical coupling is developed. Under cooperative dicynopyrazine‐derived chromophore (DPZ) as a photosensitizer and chiral phosphoric acid catalyst, Hantzsch ester sacrificial reductant, the transformations between α‐substituted enones cyanoazaarenes or 2‐(chloromethyl)azaaren‐1‐iums can proceed tandem reduction, coupling, process efficiently. Two classes of pharmaceutically important enantioenriched azaarene variants, which contain synthetically versatile ketone‐substituted tertiary carbon stereocenter at β ‐ γ ‐position azaarenes, are synthesized with high yields ees.

Language: Английский

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Asymmetric Photoredox Catalytic Minisci-Type Reactions of α-Bromide Amides

Organic Letters, Journal Year: 2025, Volume and Issue: 27(5), P. 1244 - 1249

Published: Jan. 23, 2025

An asymmetric photoredox catalytic Minisci-type reaction between α-bromide amides and imine-containing azaarenes has been successfully developed. This catalyst system employs a chiral phosphoric acid alongside 3DPAFIPN as photosensitizer. The produces diverse array of valuable amides, featuring azaarene-substituted tertiary carbon stereocenters at the β-position, in high yields (up to 85%) good excellent enantioselectivities >99% enantiomeric excess (ee)). Importantly, this work marks first example radical addition simple utilizing radicals functionalized with electron-withdrawing carbonyl groups, which are conventionally considered unfavorable for such transformations, especially an enantioselective manner.

Language: Английский

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Chiral Primary Amine-Catalyzed Asymmetric Photochemical Reactions of Pyridotriazoles with Boronic Acids to Access Triarylmethanes

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

Published: Jan. 29, 2025

Imine-containing azaarene-based triarylmethanes are vital molecular motifs that prevalent in a wide array of bioactive compounds. Recognizing the limitations current synthetic methodologies─marked by scarcity examples and difficulties flexible functional group modulation─we have developed an efficient modular asymmetric photochemical strategy employing pyridotriazoles boronic acids as substrates. Utilizing novel chiral diamine-derived pyrroles primary amines catalysts, we successfully synthesized diverse range with high yields excellent enantioselectivities. This method not only exhibits broad substrate scope outstanding tolerance but also enables precise synthesis deuterated derivatives using inexpensive D2O deuterium source. Mechanistic studies reveal unusual 1,4-boron shift is critical step generating boronated enamine intermediate, while shedding light on potential enantiocontrol mechanisms facilitated catalyst.

Language: Английский

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Recent advances in catalytic asymmetric synthesis

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 12

Published: May 9, 2024

Asymmetric catalysis stands at the forefront of modern chemistry, serving as a cornerstone for efficient creation enantiopure chiral molecules characterized by their high selectivity. In this review, we delve into realm asymmetric catalytic reactions, which spans various methodologies, each contributing to broader landscape enantioselective synthesis molecules. Transition metals play central role catalysts wide range transformations with ligands such phosphines, N -heterocyclic carbenes (NHCs), etc., facilitating formation C-C and C-X bonds, enabling precise control over stereochemistry. Enantioselective photocatalytic reactions leverage power light driving force electrocatalysis has emerged sustainable approach, being both atom-efficient environmentally friendly, while offering versatile toolkit reductions oxidations. Biocatalysis relies on nature’s most catalysts, i.e., enzymes, provide exquisite selectivity, well tolerance diverse functional groups under mild conditions. Thus, enzymatic optical resolution, kinetic resolution dynamic have revolutionized production compounds. organocatalysis uses metal-free organocatalysts, consisting modular phosphorus, sulfur nitrogen components, remarkably transformations. Additionally, unlocking traditionally unreactive C-H bonds through selective functionalization expanded arsenal synthesis, atom-economical construction Incorporating flow chemistry been transformative, continuous systems reaction conditions, enhancing efficiency optimization. Researchers are increasingly adopting hybrid approaches that combine multiple strategies synergistically tackle complex synthetic challenges. This convergence holds great promise, propelling field forward in form. As these methodologies evolve complement one another, they push boundaries what can be accomplished leading discovery novel, highly may lead groundbreaking applications across industries.

Language: Английский

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Catalytic asymmetric [4 + 2] dearomative photocycloadditions of anthracene and its derivatives with alkenylazaarenes

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 29, 2024

Abstract Photocatalysis through energy transfer has been investigated for the facilitation of [4 + 2] cycloaddition reactions. However, high reactivity radical species poses a challenging obstacle to achieving enantiocontrol with chiral catalysts, as no enantioselective examples have reported thus far. Here, we present development catalytic asymmetric dearomative photocycloaddition involving anthracene and its derivatives alkenylazaarenes. This accomplishment is achieved by utilizing cooperative photosensitizer Brønsted acid catalysis platform. Importantly, this process enables activation substrates from triplet DPZ, thereby initiating precise stereoselective sequential transformation. The significance our work highlighted synthesis diverse range pharmaceutical valuable cycloadducts incorporating attractive azaarenes, all obtained yields, ees, drs. broad substrate scope further underscored successful construction all-carbon quaternary stereocenters adjacent stereocenters.

Language: Английский

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Chiral phosphoric acid-catalyzed asymmetric epoxidation of alkenyl aza-heteroarenes using hydrogen peroxide

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 20, 2024

The synthesis of chiral α-azaheteroaryl oxiranes via enantioselective catalysis is a formidable challenge due to the required complex stereoselectivity and diverse N-heterocyclic structures. These compounds play crucial role in developing bioactive molecules, where precise chirality significantly influences biological activity. Here we show that using phosphoric acid as catalyst, our method efficiently addresses these challenges. This technique not only achieves high enantio- diastereoselectivity but also demonstrates superior chemo- stereocontrol during epoxidation alkenyl aza-heteroarenes. Our approach leverages synergistic blend electrostatic hydrogen-bonding interactions, enabling effective activation both substrates hydrogen peroxide. resulting exhibit enhanced diversity functionality, aiding construction azaaryl with contiguous stereocenters. Kinetic density functional theory studies elucidate mechanism, highlighting acid's pivotal this intricate process.

Language: Английский

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From Radical Coupling to Enantioselective Controlled Protonation: Advancing Precise Construction of Stereocenters

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

Published: Jan. 23, 2025

Recent advancements in green and sustainable platforms, particularly visible light-driven photocatalysis, have spurred significant progress radical chemistry, enabling the efficient synthesis of important molecules from simple readily available feedstocks under mild conditions. However, rapid orbital flipping high reactivity radicals pose substantial challenges for achieving precise enantiocontrol stereocenter formation via coupling. In this study, we present a generic strategy that modulates elusive approach, facilitating enantiocontrollable protonation through 1,3-boron migration. We successfully developed two previously photocatalytic asymmetric transformations: de Mayo reaction utilizing energy transfer three-component reactions cyanoazaarenes initiated by single-electron transfer. Moreover, incorporation cost-effective D2O as deuterium source enhances synthetic pharmaceutical significance method, offering valuable tool future applications.

Language: Английский

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