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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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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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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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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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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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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Lewis Acid-Catalyzed Asymmetric [2σ + 2π] Cycloaddition Reactions of Bicyclo[1.1.0]butanes and Vinyl Azido/Diazo Compounds

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 4634 - 4643

Опубликована: Март 4, 2025

Язык: Английский

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Stereoselective Alder-Ene Reactions of Bicyclo[1.1.0]butanes: Facile Synthesis of Cyclopropyl- and Aryl-Substituted Cyclobutenes

Journal of the American Chemical Society, Год журнала: 2023, Номер 146(1), С. 1196 - 1203

Опубликована: Дек. 29, 2023

Bicyclo[1.1.0]butanes (BCBs), strained carbocycles comprising two fused cyclopropane rings, have become well-established building blocks in organic synthesis, medicinal chemistry, and chemical biology due to their diverse reactivity profile with radicals, nucleophiles, cations, carbenes. The constraints of the bicyclic ring system confer high p-character on interbridgehead C–C bond, leading this broad reaction profile; however, use BCBs pericyclic processes has date been largely overlooked favor such stepwise, non-concerted additions. Here, we describe as substrates for ene-like reactions alkenes alkynes, which give rise cyclobutenes decorated highly substituted cyclopropanes arenes. former products are obtained from stereoselective cyclopropenes, generated situ vinyl diazoacetates under blue light irradiation (440 nm). Cyclobutenes featuring a quaternary aryl-bearing carbon atom prepared equivalent arynes, proceed yields mild conditions. Mechanistic studies highlight importance electronic effects while computational investigations support concerted pathway rationalize excellent stereoselectivity cyclopropenes.

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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