Catalytic Asymmetric Construction of Chiral Polysubstituted 3-Azabicyclo[3.1.1]heptanes by Copper-Catalyzed Stereoselective Formal [4π+2σ] Cycloaddition

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(30), С. 21069 - 21077

Опубликована: Июль 16, 2024

The direct construction of bioisosteric compounds enriched in C

Язык: Английский

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Reaction Paradigms that Leverage Cycloaddition and Ring Strain to Construction Bicyclic Aryl Bioisosteres from Bicyclo[1.1.0]butanes

Asian Journal of Organic Chemistry, Год журнала: 2024, Номер 13(5)

Опубликована: Фев. 21, 2024

Abstract Within a medicinal chemist's toolbox, one of the most effective strategies to improve overall properties biologically active compound is bioisosteric replacement. Ever since first example replacing benzene with bicyclo[1.1.1]pentane (BCP) group was published in late 1990s, [1] chemistry community has continually been expanding scope such phenyl replacements. Recent interest from academia focused on novel synthetic access C( sp 3 )‐rich bicyclic hydrocarbons expanded ring sizes. Herein, we summarize some these transformations and reveal that rely strain releasing cycloadditions bicyclo[1.1.0]butane (BCB) bicyclo[2.1.0]pentane (housane). We have organized this review based mechanism release strategies, namely, carbene cycloadditions, energy transfer photocatalyzed electron catalyzed polar cycloadditions.

Язык: Английский

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Bicyclo[1.1.0]butyl Radical Cations: Synthesis and Application to [2π + 2σ] Cycloaddition Reactions

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(23), С. 16237 - 16247

Опубликована: Май 29, 2024

As the chemistry that surrounds field of strained hydrocarbons, such as bicyclo[1.1.0]butane, continues to expand, it becomes increasingly advantageous develop alternative reactivity modes harness their unique properties access new regions chemical space. Herein, we report use photoredox catalysis promote single-electron oxidation bicyclo[1.1.0]butanes. The synthetic utility resulting radical cations is highlighted by ability undergo highly regio- and diastereoselective [2π + 2σ] cycloaddition reactions. most notable feature this transformation breadth alkene classes can be employed, including nonactivated alkenes, which have so far been elusive for previous strategies. A rigorous mechanistic investigation, in conjunction with DFT computation, was undertaken order better understand physical nature bicyclo[1.1.0]butyl thus provides a platform from further studies into applications these intermediates built upon.

Язык: Английский

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Synthesis of Borylated Carbocycles by [2 + 2]-Cycloadditions and Photo-Ene Reactions

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(14), С. 10142 - 10149

Опубликована: Март 27, 2024

Saturated bicyclic compounds make up a valuable class of building blocks in the development agrochemicals and pharmaceuticals. Here, we present synthesis borylated bicyclo[2.1.1]hexanes via crossed [2 + 2]-cycloaddition. Due to presence C–B bond, variety structures can be easily prepared that are not accessible by other methods. Moreover, rare photo-ene reaction is also disclosed, allowing for diastereoselective trisubstituted cyclopentanes.

Язык: Английский

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Lewis Acid Catalyzed Cycloaddition of Bicyclobutanes with Ynamides for the Synthesis of Polysubstituted 2‐Amino‐bicyclo[2.1.1]hexenes

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(32)

Опубликована: Май 24, 2024

Abstract Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf) 3 ‐catalyzed [3+2] cycloaddition bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding diverse array polysubstituted 2‐amino‐bicyclo[2.1.1]hexenes good excellent yields. These products offer valuable starting materials for the construction novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that reaction involves nucleophilic addition ynamides bicyclo[1.1.0]butanes, followed by an intramolecular cyclization situ generated enolate keteniminium ion. We expect these findings will encourage utilization complex bioisosteres foster further investigation into BCB‐based chemistry.

Язык: Английский

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Strain-release transformations of bicyclo[1.1.0]butanes and [1.1.1]propellanes

Tetrahedron Chem, Год журнала: 2024, Номер 9, С. 100070 - 100070

Опубликована: Фев. 28, 2024

Bicyclo[1.1.0]butanes (BCBs) and [1.1.1]propellanes (tricyclo[1.1.1.01,3]pentanes, TCPs) are structurally unique compounds with different chemical properties. Strain-release driven reactions have emerged as an atom- step-economic strategy for the organic synthesis. Using this strategy, a variety of functional ring molecules been efficiently synthesized, including various cyclobutane molecules, bicyclo[2.1.1]hexanes, bicyclo[1.1.1]pentanes, others. More specifically, these strain release-driven include aspects nucleophilic addition, radical electrophilic or transition metal catalysis. This review will discuss recent developments in strain-release transformations bicyclo[1.1.0]butanes [1.1.1]propellanes.

Язык: Английский

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B(C₆F₅)₃-Catalyzed Formal (n + 3) (n = 5 and 6) Cycloaddition of Bicyclo[1.1.0]butanes to Medium Bicyclo[n.1.1]alkanes

Organic Letters, Год журнала: 2024, Номер 26(19), С. 4104 - 4110

Опубликована: Май 3, 2024

Herein, a B(C6F5)3-catalyzed formal (n + 3) = 5 and 6) cycloaddition of bicyclo[1.1.0]butanes (BCBs) with imidazolidines/hexahydropyrimidines is described. The reaction provides modular, atom-economical, efficient strategy to two libraries synthetically challenging medium-bridged rings, 2,5-diazabicyclo[5.1.1]nonanes 2,6-diazabicyclo[6.1.1]decanes, in moderate excellent yields. This also features simple operation, mild conditions, broad substrate scope. A scale-up experiment various synthetic transformations products further highlight the utility.

Язык: Английский

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Lewis acid catalyzed [4+2] annulation of bicyclobutanes with dienol ethers for the synthesis of bicyclo[4.1.1]octanes

Chemical Science, Год журнала: 2024, Номер 15(28), С. 10823 - 10829

Опубликована: Янв. 1, 2024

Bicyclo[4.1.1]octanes (BCOs) were synthesized in up to quantitative yields through the formal [4+2] cycloaddition of aryl and alkyl bicyclobutane (BCB) ketones with dienol silyl ethers using Al(OTf) 3 as a Lewis acid catalyst.

Язык: Английский

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Palladium-catalyzed decarboxylative (4 + 3) cycloadditions of bicyclobutanes with 2-alkylidenetrimethylene carbonates for the synthesis of 2-oxabicyclo[4.1.1]octanes

Chemical Science, Год журнала: 2024, Номер 15(34), С. 13942 - 13948

Опубликована: Янв. 1, 2024

While cycloaddition reactions of bicyclobutanes (BCBs) have emerged as a potent method for synthesizing (hetero-)bicyclo[

Язык: Английский

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Titanium catalyzed [2σ + 2π] cycloaddition of bicyclo[1.1.0]-butanes with 1,3-dienes for efficient synthesis of stilbene bioisosteres

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 23, 2024

Abstract Natural stilbenes have shown significant potential in the prevention and treatment of diseases due to their diverse pharmacological activities. Here we present a mild effective Ti-catalyzed intermolecular radical-relay [2σ + 2π] cycloaddition bicyclo[1.1.0]-butanes 1,3-dienes. This transformation enables synthesis bicyclo[2.1.1]hexane (BCH) scaffolds containing aryl vinyl groups with excellent regio- trans -selectivity broad functional group tolerance, thus offering rapid access structurally stilbene bioisosteres.

Язык: Английский

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