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

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 111072 - 111072

Published: March 1, 2025

Language: Английский

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Lewis acid-catalyzed [2π+2σ] cycloaddition of dihydropyridines with bicyclobutanes

Chemical Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Herein we report a simple BF 3 -catalyzed cycloaddition of dihydropyridines with bicyclobutanes for the expedient synthesis novel three-dimensional azacycle-fused bicyclo[2.1.1]hexane scaffolds.

Language: Английский

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Enantioselective [2π + 2σ] cycloaddition of bicyclobutanes with imines: An efficient approach to chiral 2-aza-bicyclo[2.1.1]hexanes

Chem Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 101295 - 101295

Published: March 1, 2025

Language: Английский

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Enantioselective Dearomative [2π + 2σ] Photocycloaddition of Naphthalene Derivatives with Bicyclo[1.1.0]butanes Enabled by Gd(III) Catalysis

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

The cycloaddition reactions of bicyclo[1.1.0]butanes with alkenes, imines, nitrones, or aziridines have served as an efficient platform to create conformationally restricted saturated bicyclic scaffolds. However, the use readily available aromatics in such reactions, especially asymmetric manner, remains underexplored. Herein, we report a highly regio- and enantioselective dearomative [2π + 2σ] photocycloaddition reaction between naphthalene derivatives bicyclo[1.1.0]butanes, enabled by Gd(III) catalysis. Bicyclo[1.1.0]butanes naphthalenes adorned diverse array functional groups are well-tolerated under mild conditions, affording enantioenriched pharmaceutically important bicyclo[2.1.1]hexanes 30–96% yields 81–93% ee 12:1 → >20:1 rr. synthetic versatility this is further demonstrated facile removal directing group derivatizations dearomatized product. UV–vis absorption spectroscopy studies suggest involvement excited species process.

Language: Английский

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FeCl₃-Catalyzed Intermolecular Formal [8π+2σ] Cycloaddition of Azaheptafulvene with Bicyclo[1.1.0]butanes for the Synthesis of Cycloheptatriene-Fused 2-Azabicyclo[3.1.1]heptanes

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Higher-order cycloadditions are a simple and effective strategy for constructing significant medium-sized architectures. Azaheptafulvenes reacting with readily accessible bicyclo[1.1.0]butanes (BCBs) through FeCl3-promoted intermolecular formal [8π+2σ] cycloaddition reactions to access cycloheptatriene-fused 2-azabicyclo[3.1.1]heptanes have been developed. This new reaction tolerated wide range of azaheptafulvenes BCBs. Furthermore, the amplification experiment synthetic transformations adducts, including modifications marketed drugs, further highlighted their practicalities. Control experiments DFT calculations suggest that diastereoselective product formation may involve stepwise pathway.

Language: Английский

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Regio- and Diastereoselective Cascade Reactions of Bicyclo[1.1.0]butanes: Access to gem-Difluorinated Carbocyclic Rings

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

gem-Difluorinated carbocyclic rings are attractive motifs in drug development. Herein, we report the transition-metal free cascade reaction of bicyclo[1.1.0]butanes (BCBs) with gem-difluorocyclopropenes for synthesis gem-difluorinated excellent regio- and diastereoselectivity. This method was successfully applied to provide a broad range cyclopentenes cyclopropanes, which could undergo variety difluoromethylene (CF2) retaining transformations.

Language: Английский

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Catalyst-Controlled Regiodivergent Synthesis of Bicyclo[2.1.1]hexanes via Photochemical Strain-Release Cycloadditions

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Bicyclo[2.1.1]hexane is an emerging scaffold in various pharmaceutical settings, but the scarcity of approaches to target different regioisomers from a common starting material prevents targeting broader range chemical space. Herein, we demonstrate new design for photocatalyst-controlled regiodivergent synthesis this scaffold. Of particular interest that two distinct substitution patterns was achieved under photochemical conditions with catalyst control. This possible due activating group, N-methylimidazole, not only playing important role guiding divergent pathways also enabling transformation functional groups. Transient absorption spectroscopy discerned between mechanisms, as assignable bands consistent electron transfer and energy processes were distinctively observed, depending on identity photocatalyst.

Language: Английский

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Zwitterionic π-Allyl-Pd Species Enabled [2σ+2π] Cycloaddition Reactions of Vinylbicyclo[1.1.0]butanes (VBCBs) with Alkenes, Carbonyls, and Imines

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(24), P. 18799 - 18809

Published: Dec. 11, 2024

Transition-metal-catalyzed cycloaddition reactions of strained small-ring compounds are powerful methods for constructing carbo- and heterocyclic structures medicinal interest. However, the application this strategy to bicyclo[1.1.0]butanes (BCBs), which among most carbocycles known, remains underdeveloped. Herein, we report vinylbicyclo[1.1.0]butane (VBCB) as a platform synthon palladium-catalyzed formal [2σ+2π] with various 2π-components, enabling synthesis BCHs, oxa-BCHs, aza-BCHs under identical reaction conditions. The zwitterionic π-allyl-Pd species generated through activation VBCBs is key circumventing potential carbene reactivity serves common intermediate cycloadditions diverse 2π-systems, including alkenes, aldehydes, ketones, imines. Notably, by utilizing Pd2(dba)3 an anthracene-derived Trost ligand, wide array BCHs bearing two vicinal chiral centers has been prepared in highly diastereo-, enantioselective manner. generality practicality method have demonstrated broad substrate scope, scale-up reactions, versatile transformation multiple functional groups into BCH scaffolds. Preliminary mechanistic studies support formation species.

Language: Английский

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Palladium-Catalyzed Strain-Enabled [2π + 2σ] Cycloadditions of Vinyl Bicyclo[1.1.0]butanes with Methyleneindolinones

Organic Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

A palladium-catalyzed [2π + 2σ] cycloaddition of vinyl bicyclo[1.1.0]butanes with methyleneindolinones has been developed. The reaction enables the construction spirobicyclo[2.1.1]hexanes bearing an all-carbon quaternary center in moderate to good yields excellent diastereoselectivities. This method features a broad substrate scope functional group compatibility. practical utility this protocol was further demonstrated by gram-scale synthesis and postsynthetic transformations desired product.

Language: Английский

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Theoretical Studies on the Reaction Mechanism for the Cycloaddition of Zwitterionic π-Allenyl Palladium Species: Substrate-Controlled Isomerization

Molecules, Journal Year: 2024, Volume and Issue: 30(1), P. 103 - 103

Published: Dec. 30, 2024

Zwitterionic π-allenyl palladium species are newly developed intermediates. A substrate-controlled step existed in the cycloaddition of zwitterionic with tropsulfimides or tropones. With assistance previously experimental studies, allenyl/propargyl was provenly found by HRMS. Further DFT calculation studies show that generated through oxidative addition Pd(0), which can be promoted Lewis acid like Yb(OTf)3, and more likely undergoes an outer sphere nucleophilic attack. The isomerization is caused difference dissociation energy between intermediation tropones, forming specificity.

Language: Английский

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