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

Palladium-catalyzed decarboxylative (4 + 3) cycloadditions of bicyclobutanes with 2-alkylidenetrimethylene carbonates for the synthesis of 2-oxabicyclo[4.1.1]octanes DOI Creative Commons

X. N. Gao,

Lei Tang, Xu Zhang

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(34), P. 13942 - 13948

Published: Jan. 1, 2024

While cycloaddition reactions of bicyclobutanes (BCBs) have emerged as a potent method for synthesizing (hetero-)bicyclo[

Language: Английский

Citations

24
Enantioselective formal (3 + 3) cycloaddition of bicyclobutanes with nitrones enabled by asymmetric Lewis acid catalysis DOI Creative Commons
Wen‐Biao Wu, Bing Xu, Xue-Chun Yang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 12, 2024

Language: Английский

Citations

24
Facile access to bicyclo[2.1.1]hexanes by Lewis acid-catalyzed formal cycloaddition between silyl enol ethers and bicyclo[1.1.0]butanes DOI Creative Commons

Sai Hu,

Yuming Pan,

Dongshun Ni

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 20, 2024

Abstract Saturated three-dimensional carbocycles have gained increasing prominence in synthetic and medicinal chemistry. In particular, bicyclo[2.1.1]hexanes (BCHs) been identified as the molecular replacement for benzenes. Here, we present facile access to a variety of BCHs via stepwise two-electron formal (3 + 2) cycloaddition between silyl enol ethers bicyclo[1.1.0]butanes (BCBs) under Lewis acid catalysis. The reaction features wide functional group tolerance ethers, allowing efficient construction two vicinal quaternary carbon centers silyl-protected tertiary alcohol unit streamlined fashion. Interestingly, with conjugated dienol can provide bicyclo[4.1.1]octanes (BCOs) equipped that facilitate further transformation. utilities this methodology are demonstrated by late-stage modification natural products, transformations units on bicyclo[2.1.1]hexane frameworks, derivatization bicyclo[4.1.1]octanes, delivering functionalized bicycles traditionally inaccessible.

Language: Английский

Citations

19
Lewis Acid-Catalyzed Asymmetric [2σ + 2π] Cycloaddition Reactions of Bicyclo[1.1.0]butanes and Vinyl Azido/Diazo Compounds DOI

Haosong Ren,

Zhongren Lin,

Tianxiang Li

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 4634 - 4643

Published: March 4, 2025

Language: Английский

Citations

3
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 International Edition, Journal Year: 2024, Volume and Issue: 63(48)

Published: Aug. 22, 2024

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)

Language: Английский

Citations

12
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

2
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

9
Recent Progress in (3+3) Cycloadditions of Bicyclobutanes to Access Bicyclo[3.1.1]heptane Derivatives DOI
Jian‐Jun Feng

Synlett, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Abstract The synthesis of bicyclo[3.1.1]heptane (BCHeps) derivatives, which serve as three-dimensional (3D) bioisosteres benzenes and are the core skeleton several terpene natural products, is garnering growing interest. (3+3) cycloadditions bicyclobutanes (BCBs) represent an attractive method for efficiently accessing (hetero)BCHep skeletons with 100% atom economy. Herein, we give a brief summary recent achievements in this approach diverse BCHep emphasizing our progress initial palladium-catalyzed vinyl oxiranes. 1 Introduction 2 Radical Cycloaddition Reaction 3 Polar 4 Palladium-Catalyzed Enantioselective 5 Conclusion

Language: Английский

Citations

8
Synthesis of fluorine-containing bicyclo[4.1.1]octenes via photocatalyzed defluorinative (4+3) annulation of bicyclo[1.1.0]butanes with gem-difluoroalkenes DOI Creative Commons
Kuan Zhang,

Zhengyang Gao,

Yan Xia

et al.

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

Published: Dec. 13, 2024

This manuscript presents a photoredox-catalyzed defluorinative (4 + 3) annulation of bicyclo[1.1.0]butanes with gem -difluoroalkenes, providing practical and straightforward access to the fluorine-containing bicyclo[4.1.1]octenes.

Language: Английский

Citations

6
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

4