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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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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Formal [2σ + 2σ]-Cycloaddition of Aziridines with Bicyclo[1.1.0]butanes: Access to Enantiopure 2-Azabicyclo[3.1.1]heptane Derivatives

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

Опубликована: Сен. 19, 2024

Saturated nitrogen heterocycles are among the most significant structural components in small-molecule pharmaceuticals. Herein, a protocol for construction of enantiopure 2-azabicyclo[3.1.1]heptane derivatives by stereospecific intermolecular formal cycloaddition aziridines with bicyclo[1.1.0]butanes is described. The reaction run using B(C

Язык: Английский

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Copper-Catalyzed Enantioselective [4π + 2σ] Cycloaddition of Bicyclobutanes with Nitrones

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

Опубликована: Сен. 25, 2024

The selective construction of bridged bicyclic scaffolds has garnered increasing attention because their extensive use as saturated bioisosteres arene in pharmaceutical industry. However, sharp contrast to racemic counterparts, assembling chiral structures an enantioselective and regioselective manner remains challenging. Herein, we describe our protocol for constructing 2-oxa-3-azabicyclo[3.1.1]heptanes (BCHeps) by [4π + 2σ] cycloadditions bicyclo[1.1.0]butanes (BCBs) nitrones taking advantage a copper(II) complex Lewis acid catalyst. This method features mild conditions, good functional group tolerance, high yield (up 99%), excellent enantioselectivity 99% ee). Density theory (DFT) calculation elucidates the origin reaction's mechanism BCB activation Cu(II) complex.

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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