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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Palladium-Catalyzed Alkoxycarbonylation of Alcohols for the Synthesis of Cyclobutanecarboxylates with α-Quaternary Carbon Centers

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

Published: Jan. 27, 2025

A palladium-catalyzed alkoxycarbonylation with two different alcohols for the synthesis of cyclobutanecarboxylates bearing an α-quaternary carbon center is presented. The reaction utilizes readily accessible starting materials, tolerates a broad scope functional groups, and provides straightforward efficient approach diverse array carbon. Meanwhile, this strategy effectively prevents transition-metal-catalyzed ring-opening cyclobutanols, preserves cyclobutane framework, affords 1,1-disubstituted in high yields excellent regioisomeric ratios.

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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Ag(I)-Catalyzed Tandem Cyclization–Cycloaddition–Isomerization Reaction of 2-Alkynylbenzaldoxime with Bicyclobutane: A Route to Multiply Substituted Cyclobutanols

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

Published: April 1, 2025

Multiply substituted cyclobutanols are pivotal synthetic intermediates for constructing complex molecular architectures via ring-opening strategies. The development of efficient methods these valuable building blocks has garnered significant interest in the chemical community. In this work, we have described a novel silver(I)-catalyzed tandem cyclization–cycloaddition–isomerization sequence with bicyclobutanes and 2-alkynylbenzaldoximes, which offered an effective route to multiply cyclobutanols. This protocol features mild conditions, remarkable stereospecificity, broad substrate scope, excellent functional group tolerance. addition, application potential reaction was readily proven by its high efficiency reactants bearing biological moieties scale-up experiments.

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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Lewis Acid-Catalyzed Enantioselective (4 + 3)/Thia-(3 + 2) Cycloadditions of Bicyclobutanes and Enaminothiones: Catalyst-Directed Divergent Synthesis of Bridged Sulfur Heterocycles

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 7877 - 7890

Published: April 28, 2025

Language: Английский

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Recent Advances in Catalytic Asymmetric Transformations of Bicyclobutane: A Versatile Building Block for Enantiopure Bioisosteric Molecules

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 8078 - 8093

Published: April 30, 2025

Language: Английский

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

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 6025 - 6035

Published: March 28, 2025

Language: Английский

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Substrate-Regulated Divergent Addition of N-Sulfonyl Ketimines to Bicyclo[1.1.0]butanes Enabled by Photoinduced Energy Transfer

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

Published: April 3, 2025

A substrate-regulated divergent addition of N-sulfonyl ketimines to bicyclo[1.1.0]butanes (BCBs) was developed using a photoinduced energy transfer strategy. The [2π+2σ] cycloaddition BCBs with saccharin-derived cyclic yields benzosultam-fused aza-BCHs good and excellent diastereoselectivity. In contrast, reactions chain produce 1,3-fully substituted cyclobutanes via energy-transfer-induced N-S bond homolysis. ease large-scale synthesis derivatizations products highlight their application potentials.

Language: Английский

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Recent Advances in Photochemical Strain-Release Reactions of Bicyclo[1.1.0]butanes

Chemical Communications, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Bicyclo[1.1.0]butanes (BCBs) are attractive compounds for their beautiful "butterfly" conformations, distinctive properties, and novel reactivities. As soon as the first example had been synthesized, a wide range of strain-release reactions were explored preparation cyclobutanes bicyclic systems in ground state or excited state. In particular, with demand construction rigid three-dimensional aliphatic skeletons to "escape from flatland" drug discovery programs, numerous efforts have devoted this area expanding boundaries reactivities broadening chemical space bioisosteric products. recent years, great resurgence dramatic evolution photochemistry, photochemical generally relying on single electron transfer (SET) energy (EnT) strategies can provide much more opportunities capability innovative transformations BCBs. review, we summarize highlight advances (year > 2016) topic hope that it will inspire wonderful chemistry

Language: Английский

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