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

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-

SUBMITTER: Deswal S 

PROVIDER: S-EPMC11775695 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature