文献类型：期刊文献

英文题名：Eu(OTf)3-Catalyzed Formal Dipolar [4π+2σ] Cycloaddition of Bicyclo-[1.1.0]butanes with Nitrones: Access to Polysubstituted 2-Oxa-3-azabicyclo[3.1.1]heptanes

作者：Zhang, Jian[1];Su, Jia-Yi[2];Zheng, Hanliang[1];Li, Hao[2];Deng, Wei-Ping[1]

机构：[1]Zhejiang Normal Univ, Coll Chem & Mat Sci, Key Lab, Minist Educ Adv Catalysis Mat, 688 Yingbin Rd, Jinhua 321004, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2024

卷号：63

期号：13

外文期刊名：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

收录：;EI(收录号：20240815587880);WOS:【SCI-EXPANDED(收录号:WOS:001165457900001)，CCR-EXPANDED(收录号:WOS:001165457900001)】；

基金：This work was supported by the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang (No. 2022R01007), National Key Research and Development Program of China (2021YFA0804900), and the Start-up Research Grant from Zhejiang Normal University.

语种：英文

外文关键词：Bicyclic Compounds; Bioisosteres; Dipolar Cycloaddition; Bicyclo[1.1.0]butanes; Strained Molecules

摘要：Herein, we have synthesized multifunctionalized 2-oxa-3-azabicyclo[3.1.1]heptanes, which are considered potential bioisosteres for meta-substituted arenes, through Eu(OTf)3-catalyzed formal dipolar [4 pi+2 sigma] cycloaddition of bicyclo[1.1.0]butanes with nitrones. This methodology represents the initial instance of fabricating bicyclo[3.1.1]heptanes adorned with multiple heteroatoms. The protocol exhibits both mild reaction conditions and a good tolerance for various functional groups. Computational density functional theory calculations support that the reaction mechanism likely involves a nucleophilic addition of nitrones to bicyclo[1.1.0]butanes, succeeded by an intramolecular cyclization. The synthetic utility of this novel protocol has been demonstrated in the concise synthesis of the analogue of Rupatadine.