Palladium-Catalyzed Ligand-Controlled Switchable Hetero-(5 + 3)/Enantioselective [2σ+2σ] Cycloadditions of Bicyclobutanes with Vinyl Oxiranes

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(29), С. 19621 - 19628

Опубликована: Май 13, 2024

For nearly 60 years, significant research efforts have been focused on developing strategies for the cycloaddition of bicyclobutanes (BCBs). However, higher-order and catalytic asymmetric BCBs long-standing formidable challenges. Here, we report Pd-catalyzed ligand-controlled, tunable cycloadditions divergent synthesis bridged bicyclic frameworks. The dppb ligand facilitates formal (5+3) vinyl oxiranes, yielding valuable eight-membered ethers with scaffolds in 100% regioselectivity. Cy-DPEphos promotes selective hetero-[2σ+2σ] to access pharmacologically important 2-oxabicyclo[3.1.1]heptane (O-BCHeps). Furthermore, corresponding O-BCHeps 94–99% ee has achieved using chiral (S)-DTBM-Segphos, representing first cross-dimerization two strained rings. obtained are promising bioisosteres ortho-substituted benzenes.

Язык: Английский

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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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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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Zinc‐Catalyzed Enantioselective Formal (3+2) Cycloadditions of Bicyclobutanes with Imines: Catalytic Asymmetric Synthesis of Azabicyclo[2.1.1]hexanes

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(48)

Опубликована: Сен. 2, 2024

Abstract The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp 3 )‐rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is scarcity of catalytic asymmetric cycloadditions BCBs to fulfill the need enantioenriched saturated bicycles in drug design development. In this study, an synthesis valuable azabicyclo[2.1.1]hexanes (aza‐BCHs) by enantioselective zinc‐catalyzed (3+2) with imines reported. proceeds effectively novel type BCB that incorporates 2‐acyl imidazole group diverse array alkynyl‐ aryl‐substituted imines. target aza‐BCHs, consist α‐chiral amine fragments two quaternary carbon centers, are efficiently synthesized up 94 % 96.5:3.5 er under mild conditions. Experimental computational studies reveal follows concerted nucleophilic ring‐opening mechanism This distinct from previous on Lewis acid‐catalyzed BCBs.

Язык: Английский

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Enantioselective formal (3 + 3) cycloaddition of bicyclobutanes with nitrones enabled by asymmetric Lewis acid catalysis

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

Опубликована: Сен. 12, 2024

Язык: Английский

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Divergent Synthesis of Sulfur‐Containing Bridged Cyclobutanes by Lewis Acid Catalyzed Formal Cycloadditions of Pyridinium 1,4‐Zwitterionic Thiolates and Bicyclobutanes

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Май 31, 2024

Bridged cyclobutanes and sulfur heterocycles are currently under intense investigation as building blocks for pharmaceutical drug design. Two formal cycloaddition modes involving bicyclobutanes (BCBs) pyridinium 1,4-zwitterionic thiolate derivatives were described to rapidly expand the chemical space of sulfur-containing bridged cyclobutanes. By using Ni(ClO

Язык: Английский

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Enantioselective synthesis of 2-substituted bicyclo[1.1.1]pentanes via sequential asymmetric imine addition of bicyclo[1.1.0]butanes and skeletal editing

Nature Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Язык: Английский

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Palladium-catalyzed enantioselective [2σ + 2π] cycloadditions of vinyl-carbonyl-bicyclo[1.1.0]butanes with arylidenemalononitriles

Chinese Chemical Letters, Год журнала: 2025, Номер unknown, С. 111072 - 111072

Опубликована: Март 1, 2025

Язык: Английский

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