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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In(OTf)₃-Catalyzed (3 + 3) Dipolar Cyclization of Bicyclo[1.1.0]butanes with N-Nucleophilic 1,3-Dipoles: Access to 2,3-Diazabicyclo[3.1.1]heptanes, 2,3-Diazabicyclo[3.1.1]heptenes, and Enantiopure 2-Azabicyclo[3.1.1]heptanes

ACS Catalysis, Год журнала: 2024, Номер unknown, С. 17837 - 17849

Опубликована: Ноя. 18, 2024

The investigation into the synthesis of azabicyclo[3.1.1]heptanes (azaBCHeps) as bioisosteres to flat aza-aromatics has garnered increasing attention, while it encounters significant challenges. Herein, we have demonstrated In(OTf)3-catalyzed (3 + 3) dipolar cyclization bicyclo[1.1.0]butanes (BCBs) with hydrazones and π-allyl-iridium 1,3-dipoles, engendering a diverse array azaBCHeps. BCBs furnished densely substituted 2,3-diazabicyclo[3.1.1]heptanes 2,3-diazabicyclo[3.1.1]heptenes under nitrogen oxygen atmospheres, respectively. A combination experimental computational investigations lends robust support for proton-transfer-interposed sequential mechanism. More importantly, by integrating In(OTf)3/iridium relay catalysis, enantiopure 2-azabicyclo[3.1.1]heptanes were constructed through aza-π-allyl-iridium in situ generated from N-allyl carbonates. Both methodologies exhibit mild reaction conditions good tolerance various functional groups. Moreover, copious derivatization products highlights utility newly synthesized heterobicyclic motifs versatile building blocks synthetic chemistry.

Язык: 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, Год журнала: 2025, Номер unknown

Опубликована: Март 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.

Язык: Английский

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Conditions-Controlled Divergent Annulation of Bicyclo[1.1.0]butanes and Dioxopyrrolidines through Lewis Acid Catalysis

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 6025 - 6035

Опубликована: Март 28, 2025

Язык: 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, Год журнала: 2025, Номер unknown

Опубликована: Апрель 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.

Язык: Английский

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

Organic Letters, Год журнала: 2024, Номер unknown

Опубликована: Дек. 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.

Язык: Английский

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Palladium-catalyzed allylic amination of vinyl bicyclo[1.1.0]butanes: a strain release approach toward alkylidenecyclobutanes

Green Synthesis and Catalysis, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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Diastereoselective Dearomative 1,3-Dipolar Cycloaddition of Bicyclobutanes with Pyridinium Ylides: A Modular Approach to Multisubstituted Azabicyclo[3.1.1]heptanes

Опубликована: Авг. 1, 2024

We describe a formal 1,3-dipolar cycloaddition between bicyclobutanes and pyridinium ylides to form azabicycloheptanes via diastereoselective pyridine dearomatization. Microscale highthroughput experimentation led identification of conditions affording high yield stereoselectivity without the need for catalysis. These reactions proceed using as-received reagents solvents under ambient atmosphere. The resulting ring-fused azabicyclo[3.1.1]heptanes have diverse synthetic handles further transformations, making them potentially valuable scaffolds design Csp3-rich drug candidates. also demonstrate photochemical skeletal rearrangement give 1,1,3,3-tetrasubstitued cyclobutane.

Язык: Английский

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State-of-the-Art Strategies for Lewis Acid-Catalyzed Strain-Release Cycloadditions of Bicyclo[1.1.0]butanes (BCBs)

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(23), С. 6942 - 6957

Опубликована: Янв. 1, 2024

This review primarily focuses on the latest developments in Lewis acid-catalyzed strain-release cycloaddition reactions of BCBs.

Язык: Английский

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Cu(II)-Catalyzed Reaction of Ethynyl Methylene Cyclic Carbamates and Amines: Synthesis of Polysubstituted Pyrroles

Organic Letters, Год журнала: 2024, Номер 26(43), С. 9237 - 9243

Опубликована: Окт. 18, 2024

A copper-catalyzed efficient, operationally simple, general method for straightforward syntheses of polysubstituted pyrroles employing ethynyl methylene cyclic carbamates as precursors reacting with commercially available amines was first reported. wide variety were obtained in acceptable to good yields under mild conditions. This protocol features broad substrate scope, high functional group tolerance, and easy operation, therefore enabling late-stage functionalization rapid synthesis bioactive compounds, including structurally complex marketed drugs natural products. In addition, a scale-up experiment further highlighted the synthetic utility.

Язык: Английский

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