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

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(12), С. 8372 - 8380

Опубликована: Март 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.

Язык: Английский

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Multiplicative enhancement of stereoenrichment by a single catalyst for deracemization of alcohols

Science, Год журнала: 2023, Номер 382(6669), С. 458 - 464

Опубликована: Окт. 26, 2023

Stereochemical enrichment of a racemic mixture by deracemization must overcome unfavorable entropic effects as well the principle microscopic reversibility; recently, photochemical reaction pathways unveiled energetic input light have led to innovations toward this end, most often ablation stereogenic C(sp3)-H bond. We report photochemically driven protocol in which single chiral catalyst two mechanistically different steps, C-C bond cleavage and formation, achieve multiplicative enhancement stereoinduction, leads high levels stereoselectivity. Ligand-to-metal charge transfer excitation titanium coordinated phosphoric acid or bisoxazoline efficiently enriches alcohols that feature adjacent fully substituted centers enantiomeric ratios up 99:1. Mechanistic investigations support pathway sequential radical-mediated scission formation through common prochiral intermediate reveal that, although overall stereoenrichment is high, selectivity each individual step moderate.

Язык: Английский

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Catalytic Deracemization Reactions

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(20), С. 10917 - 10929

Опубликована: Май 13, 2023

Deracemization, which converts a racemate into its single enantiomer without separation of the intermediate, has gained renewed interest in asymmetric synthesis with inherent atomic economy and high efficiency. However, this ideal process requires selective energy input delicate reaction design to surmount thermodynamical kinetical constraints. With rapid development catalysis, many catalytic strategies concert exogenous have been exploited facilitate nonspontaneous enantioenrichment. In perspective, we will discuss basic ideas accomplish deracemization, categorized by three major sources including chemical (redox)-, photo- mechanical from attrition. Emphasis be given features underlying deracemization mechanism together perspectives on future development.

Язык: Английский

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Catalytic Photochemical Deracemization via Short‐Lived Intermediates

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(50)

Опубликована: Июль 10, 2023

Upon irradiation in the presence of a suitable chiral catalyst, racemic compound mixtures can be converted into enantiomerically pure compounds with same constitution. The process is called photochemical deracemization and involves formation short-lived intermediates. By opening different reaction channels for forward to intermediate re-constitution molecule, entropically disfavored becomes feasible. Since discovery first 2018, field has been growing rapidly. This review comprehensively covers research performed area discusses current developments. It subdivided according mode action respective substrate classes. focus this on scope individual reactions discussion mechanistic details underlying presented reaction.

Язык: Английский

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Enantioselective [2 + 2] Photocycloreversion Enables De Novo Deracemization Synthesis of Cyclobutanes

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(32), С. 22840 - 22849

Опубликована: Авг. 2, 2024

While photochemical deracemization significantly enhances atom economy by eliminating the necessity for additional oxidants or reductants, laborious presynthesis of substrates from feedstock chemicals is often required, thereby compromising practicality this method. In study, we propose a novel approach known as de novo synthesis, which involves direct utilization simple undergoing both transformation and reversible transformation. The efficient enantiocontrol chiral catalysts in latter process establishes an effective platform deracemization. This alternative practical to address challenges asymmetric photocatalysis has been successfully demonstrated photosensitized synthesis azaarene-functionalized cyclobutanes featuring three stereocenters, including all-carbon quaternary center. By exclusively employing suitable catalyst enable kinetically controlled [2 + 2] photocycloreversion, pave creative path toward achieving more cost-effective

Язык: Английский

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

Organic Letters, Год журнала: 2025, Номер 27(5), С. 1244 - 1249

Опубликована: Янв. 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.

Язык: Английский

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Catalytic asymmetric photocycloaddition reactions mediated by enantioselective radical approaches

Chemical Society Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

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

Язык: 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, Год журнала: 2025, Номер unknown

Опубликована: Янв. 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.

Язык: Английский

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Asymmetric Olefin Isomerization via Photoredox Catalytic Hydrogen Atom Transfer and Enantioselective Protonation

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(33), С. 18307 - 18315

Опубликована: Авг. 8, 2023

Asymmetric olefin isomerization can be appreciated as an ideal synthetic approach to access valuable enantioenriched C═C-containing molecules due the excellent atom economy. Nonetheless, its occurrence usually requires a thermodynamic advantage, namely, higher stability of product substrate. It has thus led rather limited examples success. Herein, we report photoredox catalytic hydrogen transfer (HAT) and enantioselective protonation strategy for challenging asymmetric isomerization. As paradigm, by establishing dual catalyst system involving visible light photosensitizer DPZ chiral phosphoric acid, with assistance N-hydroxyimide perform HAT, wide array allylic azaarene derivatives, featuring α-tertiary carbon stereocenters β-C═C bonds, was synthesized high yields, ees, E/Z ratios starting from conjugated α-substituted alkenylazaarene E/Z-mixtures. The good compatibility assembling deuterium on using inexpensive D2O source further underscores broad applicability promising utility this strategy. Moreover, mechanistic studies have provided clear insights into challenges in terms reactivity enantioselectivity. exploration will robustly inspire development thermodynamically unfavorable isomerizations.

Язык: Английский

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Visible‐Light‐Mediated Photocatalytic Deracemization

Chemistry - A European Journal, Год журнала: 2023, Номер 29(29)

Опубликована: Март 28, 2023

Abstract Asymmetric catalysis has long been recognized as a powerful tool for the synthesis of enantioenriched molecules. In addition to precise enantiocontrol, high‐atom economy, which is crucial practicality, always pursued by chemists in development methodologies. Consequently, deracemization, direct conversion racemic compound one its enantiomers, and thus characterized 100 % atom efficiency, attracted increasing interest. Recently, visible‐light‐driven photocatalysis demonstrated be promising platform deracemization. Central success ability efficiently overcome prevailing kinetic issues chemical transformations intrinsic thermodynamic challenges, typically require use additional stoichiometric reagents, undermining original advantages. this review, advances attractive area are systematically summarized discussed, with examples organized according different modalities energy transfer single‐electron photocatalysis.

Язык: Английский

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