Enantioselective formal [4π+2σ] cycloaddition of bicyclobutanes with nitrones enabled by asymmetric Lewis acid catalysis DOI Creative Commons
Jian‐Jun Feng, Wen‐Biao Wu, Xue-Chun Yang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 18, 2024

Abstract The absence of catalytic asymmetric methods for synthesizing chiral (hetero)bicyclo[n.1.1]alkanes has hindered their application in new drug discovery. Here we demonstrate the achievability an polar cycloaddition BCB using a Lewis acid catalyst and bidentate chelating substrate, as exemplified by current enantioselective formal [4π+2σ] BCBs with nitrones. In addition to diverse incorporating acyl imidazole group or pyrazole moiety, wide array nitrones are compatible this catalysis, successfully assembling two congested quaternary carbon centers aza-trisubstituted center pharmaceutically important hetero-bicyclo[3.1.1]heptane product up 99% yield >99% ee.

Language: Английский

Enantioselective Dearomative [2π + 2σ] Photocycloaddition of Naphthalene Derivatives with Bicyclo[1.1.0]butanes Enabled by Gd(III) Catalysis DOI
Wenjie Shen, Xiaoqin Zou, Muzi Li

et al.

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

Citations

0
Conditions-Controlled Divergent Annulation of Bicyclo[1.1.0]butanes and Dioxopyrrolidines through Lewis Acid Catalysis DOI
Jun‐Long Li, Chuan Xie, Rong Zeng

et al.

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

Published: March 28, 2025

Language: Английский

Citations

0
Synthesis of 2,5-Dithia-bicyclo[4.1.1]octanes by Silver-Catalyzed Formal (4+3) Cycloadditions of Bicyclobutanes with Benzodithioloimines DOI

Xuechen Zhou,

Jianyang Dong,

Huijuan Liao

et al.

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

Citations

0
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 DOI

Shijie Zhu,

Jiaojiao Lei,

Shengwen Yang

et al.

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

Citations

0
Lewis Acid‐Catalyzed Unusual (4+3) Annulation of para‐Quinone Methides with Bicyclobutanes: Access to Oxabicyclo[4.1.1] octanes DOI

Shiksha Deswal,

Avishek Guin, Akkattu T. Biju

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(48)

Published: Aug. 22, 2024

Abstract Over the past few years, there has been a surge of interest in chemistry bicyclobutanes (BCBs). Although BCBs have used to synthesize bicyclo[2.1.1]hexanes and bicyclo[3.1.1]heptanes, synthesis bicyclo[4.1.1]octanes remained elusive. Herein, we report first Lewis acid‐catalyzed unexpected (4+3) annulation para ‐quinonemethides ( p ‐QMs) with allowing oxabicyclo[4.1.1]octanes proceeding under mild conditions. With 5 mol % Bi(OTf) 3 , reaction afforded annulated product high regioselectivity good functional group compatibility via simultaneous acid activation ‐QMs. The is likely initiated by 1,6‐addition activated ‐QMs followed C2‐selective intramolecular addition phenol moiety generated cyclobutyl cation intermediate. Moreover, detailed mechanistic studies provided insight into mechanism reaction.

Language: Английский

Citations

3
Palladium-Catalyzed Strain-Enabled [2π + 2σ] Cycloadditions of Vinyl Bicyclo[1.1.0]butanes with Methyleneindolinones DOI

Lan Zheng,

Yumin Yang, Zhiping Liu

et al.

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

Citations

3
Palladium-catalyzed allylic amination of vinyl bicyclo[1.1.0]butanes: a strain release approach toward alkylidenecyclobutanes DOI Creative Commons
Huan Zhang, Wenjie Liang, Jun‐An Xiao

et al.

Green Synthesis and Catalysis, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

2
Modular Synthesis of Azidobicyclo[2.1.1]hexanes via (3 + 2) Annulation of α-Substituted Vinyl Azides and Bicyclo[1.1.0]butanes DOI

Sai Hu,

Yuhong Gao,

Yuming Pan

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(20), P. 15151 - 15157

Published: Sept. 27, 2024

Here, we present a mild and rapid method to access azidobicyclo[2.1.1]hexanes via formal (3 + 2) cycloaddition of α-substituted vinyl azides bicyclo[1.1.0]butanes under Lewis acid catalysis. A wide range were tolerated conditions. Notably, the resulting cycloadducts could be transformed into structurally attractive 3-azabicyclo[3.1.1]heptenes through microwave-promoted rearrangement. The utilities highlighted by copper(I)-catalyzed Huisgen 1,3-dipolar tertiary alkyl azide further transformation ketone groups.

Language: Английский

Citations

2
State-of-the-Art Strategies for Lewis Acid-Catalyzed Strain-Release Cycloadditions of Bicyclo[1.1.0]butanes (BCBs) DOI
Xiang Liu, Jiawei He, Keyu Lin

et al.

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(23), P. 6942 - 6957

Published: Jan. 1, 2024

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

Language: Английский

Citations

2
Stereocontrolled Synthesis of Cyclobutylamines Enabled by Lewis Acid-Catalyzed (3 + 2 + 2) Cycloaddition/Ring-Opening Strategy of Bicyclo[1.1.0]butanes with Triazinanes DOI

Yijun Duan,

Feng Chen,

Ye Guo

et al.

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

Published: Dec. 2, 2024

Herein, we develop a modular and efficient "cycloaddition/ring-opening" strategy of bicyclo[1.1.0]butanes (BCBs) with triazinanes to provide series syn-diastereoselective cyclobutylamines via 2,4-diazabicyclo[4.1.1]octanes (aza-BCOs). The reaction features simple operation, mild conditions, broad substrate scope. Mechanistic studies suggest that the cycloaddition follows stepwise (3 + 2 2) rather than (4 3) cycloaddition, involving an SN2 nucleophilic addition formaldimine Lewis acid-activated BCB species. A scale-up experiment various synthetic transformations product further highlight utility. We expect our findings will encourage exploration chemistry access more synthetically challenging cyclobutane frameworks.

Language: Английский

Citations

2