Work

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

Year: 2024

Type: article

Abstract: 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 of benzenoids. Bicyclo[1.1.0]butanes (BCBs), known for their high ring strain and numerous reactivities, offer a simple yet effective method for synthesizing these bicyclic frameworks. Although (3 + 2) annulations involving BCBs have been extensively studied, the 1,3-dipolar cycloaddition of BCBs leading to (3 + 3) annulation has received limited attention. Herein, we report the Lewis acid-catalyzed 1,3-dipolar cycloaddition of BCBs with isatogens allowing the synthesis of biologically relevant tetracyclic 2-oxa-3-azabicyclo[3.1.1]heptanes. Moreover, the reaction can be performed in a one-pot process by the in situ generation of isatogens from 2-alkynylated nitrobenzenes. Additionally, preliminary mechanistic and photophysical studies of the (3 + 3) annulated products and experiments toward the asymmetric version of this reaction are also provided.

Source: JACS Au

DOI: 10.1021/jacsau.4c00839

Authors: Shiksha Deswal, Rohan Chandra Das, Deeptanu Sarkar, Akkattu T. Biju

Institution: Indian Institute of Science Bangalore

Language: English

Topic: Organic Chemistry Cycloaddition Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $3,500

Funders: Indian Institute of Science, Ministry of Education, India, Science and Engineering Research Board