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 formal (3+3) cycloadditions of bicyclobutanes with aromatic azomethine imines: access to fused 2,3-diazabicyclo[3.1.1]heptanes

Chemical Science, Год журнала: 2024, Номер 15(46), С. 19488 - 19495

Опубликована: Янв. 1, 2024

We present the first enantioselective dearomative (3+3) cycloadditions of bicyclobutanes (BCBs) utilizing a chiral Lewis acid catalyst and bidentate chelating BCB substrates.

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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Pd-Catalyzed Cross-Coupling of Cyclopropanols with 2-Br-p-Quinone Methides/2-Br-Cinnamate Esters Followed by a 1,6- and 1,4-Conjugate Addition Reaction

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

A novel cascade Pd-catalyzed cross-coupling reaction of cyclopropyl alcohol-derived ketone homoenolate with 2-Br-p-quinone methides and 2-Br-cinnamate esters followed by a 1,6- 1,4-conjugate addition is disclosed. This protocol converts various alcohols into homoenolate, which undergoes C-C bond formation 2-Br p-quinone esters. The salient features this methodology include its operational simplicity, mild conditions, an environmentally benign protocol, high efficiency, good to excellent yields, wide substrate scope.

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

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 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.

Язык: Английский

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Conjugated 1,8 and 1,6 Addition of Bis-Trimethylsilylketene Acetal to Activated p-Quinone Methides via Trifluoromethanesulfonic Anhydride

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

In this work, we studied the conjugated additions of bis-trimethylsilylacetalketene acetals (bis-TMSKA) to para-quinone methides (p-QMs), which are one most explored molecules for study and gained significant attention in organic chemistry due their versatile reactivity, particularly Michael addition reactions. study, trifluoromethanesulfonic anhydride (Tf2O) was used as an activating agent p-QMs, aiming achieve 1,6-Michael products least reported 1,8-Michael with pyridine substituents. The reactivity p-QMs derived from demonstrated distinct reaction pathways, leading formation δ γ lactones. investigation also involved synthesizing a 1-indanone carboxylic acids obtained 1,6-addition.

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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Lewis Acid-Catalyzed 1,3-Dipolar Cycloaddition of Bicyclobutanes with Isatogens: Access to Indoxyl-Fused Bicyclo[3.1.1]heptanes

Опубликована: Сен. 2, 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 reactivity, offer a simple yet effective method synthesizing these bicyclic frameworks. Although (3+2) annulations involving BCBs have been extensively studied, 1,3-dipolar cycloaddi-tion leading to (3+3) annulation received limited attention. Herein, we report Lewis acid-catalyzed cycloaddition with isatogens allowing synthesis biologically relevant indoxyl-fused bicy-clo[3.1.1]heptanes. Moreover, reaction can be performed one-pot by in-situ generation 2-alkynylated nitrobenzenes. Additionally, preliminary mechanistic photophysical studies annulated prod-ucts, experiments towards asymmetric version this are also provided.

Язык: Английский

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