文献类型：期刊文献

英文题名：Synthesis of Azabicyclo[3.1.1]heptenes Enabled by Catalyst-Controlled Annulations of Bicyclo[1.1.0]butanes with Vinyl Azides

作者：Lin, Zhongren[1,2];Ren, Haosong[1,2];Lin, Xinbo[1,2];Yu, Xinhong[1,2];Zheng, Jun[1,2]

机构：[1]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Minist Educ, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2024

卷号：146

期号：27

起止页码：18565

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20242716616258);WOS:【SCI-EXPANDED(收录号:WOS:001258179400001)】；

基金：This work was supported by National Natural Science Foundation of China (22301075), Shanghai Scientific and Technological Innovation Projects (23ZR1417400), East China University of Science and Technology for startup funding, the Program of Introducing Talents of Discipline to Universities, and The 111 Project (BP0719034).

语种：英文

外文关键词：Butane - Catalysis - Scaffolds

摘要：Bridged bicyclic scaffolds are emerging bioisosteres of planar aromatic rings under the concept of "escape from flatland". However, adopting this concept into the exploration of bioisosteres of pyridines remains elusive due to the challenge of incorporating a N atom into such bridged bicyclic structures. Herein, we report practical routes for the divergent synthesis of 2- and 3-azabicyclo[3.1.1]heptenes (aza-BCHepes) as potential bioisosteres of pyridines from the readily accessible vinyl azides and bicyclo[1.1.0]butanes (BCBs) via two distinct catalytic annulations. The reactivity of vinyl azides tailored with BCBs is the key to achieving divergent transformations. Ti-III-catalyzed single-electron reductive generation of C-radicals from BCBs allows a concise (3 + 3) annulation with vinyl azides, affording novel 2-aza-BCHepe scaffolds. In contrast, scandium catalysis enables an efficient dipolar (3 + 2) annulation with vinyl azides to generate 2-azidobicyclo[2.1.1]hexanes, which subsequently undergo a chemoselective rearrangement to construct 3-aza-BCHepes. Both approaches efficiently deliver unique azabicyclo[3.1.1]heptene scaffolds with a high functional group tolerance. The synthetic utility has been further demonstrated by scale-up reactions and diverse postcatalytic transformations, providing valuable azabicyclics including 2- and 3-azabicyclo[3.1.1]heptanes and rigid bicyclic amino esters. In addition, the related sp(2)-hybridized nitrogen atom and the similar geometric property between pyridines and corresponding aza-BCHepes indicate that they are promising bioisosteres of pyridines.