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, Journal Year: 2024, Volume and Issue: unknown, P. 17837 - 17849

Published: Nov. 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.

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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Synthesis of 2,5-Dithia-bicyclo[4.1.1]octanes by Silver-Catalyzed Formal (4+3) Cycloadditions of Bicyclobutanes with Benzodithioloimines

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

Published: March 30, 2025

Cycloadditions of bicyclobutanes with two- or three-atom reaction partners have been widely exploited to access bicyclo[2.1.1]hexanes and bicyclo[3.1.1]heptanes. However, their application the synthesis bicyclo[4.1.1]octane derivatives has remained elusive. Herein, we report silver-catalyzed formal (4+3) cycloadditions between simple benzodithioloimines, establishing a new method for synthesizing previously inaccessible 2,5-dithia-bicyclo[4.1.1]octanes, which two sulfur atoms in frameworks. This mild tolerates bicyclobutane substrates wide range substituents. The synthetic utility this was demonstrated via various transformations products yield valuable sulfur-containing bridged bicyclic scaffolds.

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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Lewis Acid-Catalyzed 1,3-Dipolar Cycloaddition of Bicyclobutanes with Isatogens: Access to Tetracyclic 2-Oxa-3-azabicyclo[3.1.1]heptanes

JACS Au, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 19, 2024

The 'escape from flatland' concept has gained significant traction in modern drug discovery, emphasizing the importance of three-dimensional molecular architectures, which serve as saturated bioisosteres benzenoids. Bicyclo[1.1.0]butanes (BCBs), known for their high ring strain and numerous reactivities, offer a simple yet effective method synthesizing these bicyclic frameworks. Although (3 + 2) annulations involving BCBs have been extensively studied, 1,3-dipolar cycloaddition leading to 3) annulation received limited attention. Herein, we report Lewis acid-catalyzed with isatogens allowing synthesis biologically relevant tetracyclic 2-oxa-3-azabicyclo[3.1.1]heptanes. Moreover, reaction can be performed one-pot process by situ generation 2-alkynylated nitrobenzenes. Additionally, preliminary mechanistic photophysical studies annulated products experiments toward asymmetric version this are also provided.

Language: Английский

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