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

Lewis Acid-Catalyzed 1,3-Dipolar Cycloaddition of Bicyclobutanes with Isatogens: Access to Tetracyclic 2-Oxa-3-azabicyclo[3.1.1]heptanes DOI Creative Commons

Shiksha Deswal,

Rohan Chandra Das,

Deeptanu Sarkar

et al.

JACS Au, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 19, 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 reactivities, offer a simple yet effective method synthesizing these bicyclic frameworks. Although (3 + 2) annulations involving BCBs have been extensively studied, 1,3-dipolar cycloaddition leading to 3) annulation received limited attention. Herein, we report Lewis acid-catalyzed with isatogens allowing synthesis biologically relevant tetracyclic 2-oxa-3-azabicyclo[3.1.1]heptanes. Moreover, reaction can be performed one-pot process by situ generation 2-alkynylated nitrobenzenes. Additionally, preliminary mechanistic photophysical studies annulated products experiments toward asymmetric version this are also provided.

Language: Английский

Citations

2
Lewis Acid Catalyzed Cycloaddition Reaction of Bicyclo[1.1.0]butanes DOI
Hui Yang, Jie Chen, Ling Zhou

et al.

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

Published: Oct. 29, 2024

Abstract In recent years, formal cycloaddition reactions involving bicyclo[1.1.0]butanes (BCBs) have furnished an array of innovative methodologies and strategies for the efficient synthesis bicyclo[2.1.1]hexanes (BCHs). Most methods can be broadly classified into two main modes: radical pathway two-electron pathway. This Synpacts article will summarize advancements in Lewis acid catalyzed BCBs with alkenes, dipolar molecules, alkynes, spanning period from 2022 to 2024. Additionally, we introduce reaction ynamides, by Sc(OTf)3, which has been recently developed our group. approach offers a novel method polysubstituted 2-amino-bicyclo[2.1.1]hexenes. 1 Introduction 2 Acid Catalyzed Formal Cycloaddition Alkenes Dipoles 3 Alkynes 4 Conclusion

Language: Английский

Citations

1
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

Citations

0