Switching between the [2π+2σ] and Hetero‐[4π+2σ] Cycloaddition Reactivity of Bicyclobutanes with Lewis Acid Catalysts Enables the Synthesis of Spirocycles and Bridged Heterocycles

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(29)

Опубликована: Май 11, 2024

Abstract The exploration of the complex chemical diversity bicyclo[n.1.1]alkanes and their use as benzene bioisosteres has garnered significant attention over past two decades. Regiodivergent syntheses thiabicyclo[4.1.1]octanes (S‐BCOs) highly substituted bicyclo[2.1.1]hexanes (BCHs) using a Lewis acid‐catalyzed formal cycloaddition bicyclobutanes (BCBs) 3‐benzylideneindoline‐2‐thione derivatives have been established. first hetero‐(4+3) BCBs, catalyzed by Zn(OTf) 2 , was achieved with broad substrate scope under mild conditions. In contrast, less electrophilic BCB ester undergoes Sc(OTf) 3 ‐catalyzed [2π+2σ] reaction 1,1,2‐trisubstituted alkenes, yielding BCHs spirocyclic quaternary carbon center. Control experiments preliminary theoretical calculations suggest that diastereoselective product formation may involve concerted between zwitterionic intermediate E ‐1,1,2‐trisubstituted alkenes. Additionally, nucleophilic ring‐opening mechanism.

Язык: Английский

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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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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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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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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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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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Enantioselective Synthesis of Tetrahydro-1H-1,3-methanocarbazoles by Formal (3 + 3)-Cycloaddition Using Bicyclo[1.1.0]butanes

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Asymmetric synthesis presents many challenges, with the selective formation of chiral bridged polyheterocycles being a notable example. Cycloadditions using bicyclo[1.1.0]butanes (BCB) offer promising solution along those lines, yet, despite significant advances in that emerging area, asymmetric control has remained limited thus far. Here, we describe an organocatalytic, enantioselective formal (3 + 3)-cycloaddition BCBs 1H-indol-3-yl((hetero)aryl)methanol derivatives. This approach enables rapid and efficient tetrahydro-1H-1,3-methanocarbazole derivatives (34 examples) from readily available starting materials, very good stereochemical (up to 98:2 er). Successful scale-up experiments product modification demonstrated potential this methodology. Control DFT calculations provide insights into mechanistic pathway.

Язык: Английский

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Access to spiro-bicyclo[2.1.1]hexanes via BF₃·Et₂O-catalyzed formal [2π + 2σ] cycloaddition of bicyclo[1.1.0]butanes with benzofuran-derived oxa(aza)dienes

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(16), С. 4539 - 4545

Опубликована: Янв. 1, 2024

Rapid access to diverse spiro[benzofuran-2,2′-bicyclo[2.1.1]hexanes] via BF 3 ·Et 2 O-catalyzed [2π + 2σ] cycloaddition of bicyclo[1.1.0]butanes with readily available benzofuran-derived oxa(aza)dienes.

Язык: Английский

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Palladium-catalysed [2σ + 2π] cycloaddition reactions of bicyclo[1.1.0]butanes with aldehydes

Nature Synthesis, Год журнала: 2024, Номер unknown

Опубликована: Сен. 27, 2024

Язык: Английский

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Divergent Enantioselective Access to Diverse Chiral Compounds from Bicyclo[1.1.0]butanes and α,β-Unsaturated Ketones under Catalyst Control

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Сен. 30, 2024

Achieving structural and stereogenic diversity from the same starting materials remains a fundamental challenge in organic synthesis, requiring precise control over selectivity. Here, we report divergent catalytic methods that selectively yield either cycloaddition or addition/elimination products bicyclo[1.1.0]butanes α,β-unsaturated ketones. By employing chiral Lewis acid Brønsted catalysts, achieved excellent regio-, diastereo-, enantioselectivity across all three distinct transformations, affording diverse array of synthetically valuable bicyclo[2.1.1]hexanes cyclobutenes. The outcomes are controlled by differential activation substrates specific catalyst with reaction conditions dictating pathway This strategy demonstrates power catalysis creating molecular complexity diversity, offering tool for synthesis enantioenriched building blocks.

Язык: Английский

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