Switching between the [2π+2σ] and Hetero‐[4π+2σ] Cycloaddition Reactivity of Bicyclobutanes with Lewis Acid Catalysts Enables the Synthesis of Spirocycles and Bridged Heterocycles

• Published in: Angewandte Chemie International Edition Vol. 63; no. 29; pp. e202405222 - n/a
• Main Authors: Wang, Ji‐Jie, Tang, Lei, Xiao, Yuanjiu, Wu, Wen‐Biao, Wang, Guoqiang, Feng, Jian‐Jun
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 15.07.2024; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkanes; Alkenes; Benzene; Bicyclic compounds; Catalysts; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Cycloaddition; Heterocycles; Hexanes; Lewis acid; Octanes; Physical Sciences; Science & Technology; Spirooxindoles; Stereoselectivity; Strained molecules; Substrates; Spirooxindoles; Heterocycles; Cycloaddition; Strained molecules; STRAIN-RELEASE; ANNULATION; COMPLEXITY; Bicyclic compounds; CHEMISTRY; DIVERSITY
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202405222

The exploration of the complex chemical diversity of bicyclo[n.1.1]alkanes and their use as benzene bioisosteres has garnered significant attention over the past two decades. Regiodivergent syntheses of thiabicyclo[4.1.1]octanes (S‐BCOs) and highly substituted bicyclo[2.1.1]hexanes (BCHs) using a Lewis acid‐catalyzed formal cycloaddition of bicyclobutanes (BCBs) and 3‐benzylideneindoline‐2‐thione derivatives have been established. The first hetero‐(4+3) cycloaddition of BCBs, catalyzed by Zn(OTf)2, was achieved with a broad substrate scope under mild conditions. In contrast, the less electrophilic BCB ester undergoes a Sc(OTf)3‐catalyzed [2π+2σ] reaction with 1,1,2‐trisubstituted alkenes, yielding BCHs with a spirocyclic quaternary carbon center. Control experiments and preliminary theoretical calculations suggest that the diastereoselective [2π+2σ] product formation may involve a concerted cycloaddition between a zwitterionic intermediate and E‐1,1,2‐trisubstituted alkenes. Additionally, the hetero‐(4+3) cycloaddition may involve a concerted nucleophilic ring‐opening mechanism. Regiodivergent syntheses of thiabicyclo[4.1.1]octanes (S‐BCOs) and highly substituted bicyclo[2.1.1]hexanes have been achieved through a Lewis acid‐catalyzed cycloaddition of bicyclobutanes (BCBs) and 3‐benzylideneindoline‐2‐thione derivatives. Moreover, rapid access of S‐BCOs, which were not readily accessible by known methods, has been realized through Zn(OTf)2‐catalyzed uncommon [4π+2σ] cycloadditions of BCBs.