Access to Enantiopure 2-Azabicyclo[3.1.1]heptane Derivatives via Lewis Acid Catalysis DOI

Synfacts, Journal Year: 2024, Volume and Issue: 20(12), P. 1307 - 1307

Published: Nov. 21, 2024

Keywords bicyclo[1.1.0]butanes - cycloaddition azabicycloheptanes stereospecific

Language: Английский

Enantioselective Synthesis of Tetrahydro-1H-1,3-methanocarbazoles by Formal (3 + 3)-Cycloaddition Using Bicyclo[1.1.0]butanes DOI
Shubham Dutta, Constantin G. Daniliuc, Christian Mück‐Lichtenfeld

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

4
Ring Expansion toward Fused Diazabicyclo[3.1.1]heptanes through Lewis Acid Catalyzed Highly Selective C−C/C−N Bond Cross‐Exchange Reaction between Bicyclobutanes and Diaziridines DOI
Heng-Xian He, Feng Wu, Xu Zhang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Abstract The synthesis of bicyclic scaffolds has garnered considerable interest in drug discovery because their ability to mimic benzene bioisosteres. Herein, we introduce a new approach that utilizes Lewis acid (Sc(OTf) 3 )‐catalyzed σ‐bond cross‐exchange reaction between the C−C bond bicyclobutanes and C−N diaziridines produce multifunctionalized medicinally interesting azabicyclo[3.1.1]heptane derivatives. proceeds well with different broad range aryl‐ as alkenyl‐, but also alkyl‐substituted (up 98 % yield). Conducting scale‐up experiment exploring synthetic transformations cycloadducts emphasized practical application synthesis. Furthermore, zinc‐based chiral catalytic system was developed for enantioselective version this 96 ee ).

Language: Английский

Citations

11
Enantioselective [2π + 2σ] cycloaddition of bicyclobutanes with imines: An efficient approach to chiral 2-aza-bicyclo[2.1.1]hexanes DOI

Xuan-Ge Zhang,

Junjia Chen,

Zi-Yang Zhou

et al.

Chem Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 101295 - 101295

Published: March 1, 2025

Language: Английский

Citations

1
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

1
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 DOI
Jian Zhang,

Jia-Yi Su,

Hanliang Zheng

et al.

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

Citations

8
Enantioselective dearomative formal (3+3) cycloadditions of bicyclobutanes with aromatic azomethine imines: access to fused 2,3-diazabicyclo[3.1.1]heptanes DOI Creative Commons
Xue-Chun Yang, Feng Wu, Wen‐Biao Wu

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(46), P. 19488 - 19495

Published: Jan. 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.

Language: Английский

Citations

7
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

4
Lewis acid-catalyzed [2π+2σ] cycloaddition of dihydropyridines with bicyclobutanes DOI Creative Commons
Yujie Liang, Ronewa Nematswerani, Constantin G. Daniliuc

et al.

Chemical Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Herein we report a simple BF 3 -catalyzed cycloaddition of dihydropyridines with bicyclobutanes for the expedient synthesis novel three-dimensional azacycle-fused bicyclo[2.1.1]hexane scaffolds.

Language: Английский

Citations

0
Organic Reactions Catalyzed by Brønsted acid B(C6F5)3·H2O DOI
Tianwei Liu

Organic Chemistry Frontiers, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This article reviews the organic reactions catalyzed by Brønsted acid B(C 6 F 5 ) 3 ·H 2 O and their mechanisms, along with an outlook on its future catalytic prospects.

Language: Английский

Citations

0
Copper-Catalyzed Cross-Coupling of Bicyclobutanes with Triftosylhydrazone Leading to Skipped Dienes DOI
Xiaolong Zhang, Tian Tian, Xiwei Qi

et al.

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

Published: March 4, 2025

Here, we report a protocol for the synthesis of skipped dienes through cross-coupling bicyclo[1.1.0]butanes with trifluoromethyl triftosylhydrazones. The reaction is run using TpBr3Cu(NCMe) as catalyst to give access library trifluoromethylated (32 examples, ≤98% yield) excellent E/Z selectivity under mild and operationally safe conditions. presented methods proved be compatible various functionalized

Language: Английский

Citations

0