Yadav Nagendra Nath, Ha Hyun-Joon
Department of Chemistry, North Eastern Regional Institute of Science and Technology.
Department of Chemistry, Hankuk University of Foreign Studies;
J Vis Exp. 2018 Aug 22(138):57572. doi: 10.3791/57572.
Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the aziridine ring. The utility of bicyclic aziridinium ions, specifically 1-azoniabicyclo[3.1.0]hexane and 1-azoniabicyclo[4.1.0]heptane tosylate highlighted in the aziridine ring openings by the nucleophile with the release of the ring strain to yield the corresponding ring-expanded azaheterocycles such as pyrrolidine, piperidine and azepane with diverse substituents on the ring in regio- and stereospecific manner. Herein, we report a simple and convenient method for the preparation of the stable 1-azabicyclo[4.1.0]heptane tosylate followed by selective ring opening via a nucleophilic attack either at the bridge or at the bridgehead carbon to yield piperidine and azepane rings, respectively. This synthetic strategy allowed us to prepare biologically active natural products containing piperidine and azepane motif including sedamine, allosedamine, fagomine and balanol in highly efficient manner.
双环氮丙啶离子是通过氮丙啶环中的氮原子进行分子内亲核进攻，去除合适的离去基团而产生的。双环氮丙啶离子，特别是1-氮杂双环[3.1.0]己烷和1-氮杂双环[4.1.0]庚烷对甲苯磺酸盐的效用，在亲核试剂引发的氮丙啶环开环反应中得到突出体现，反应通过释放环张力，以区域和立体专一的方式生成相应的扩环氮杂环，如在环上带有不同取代基的吡咯烷、哌啶和氮杂环庚烷。在此，我们报道了一种简单便捷的方法来制备稳定的1-氮杂双环[4.1.0]庚烷对甲苯磺酸盐，随后通过在桥碳或桥头碳处进行亲核进攻实现选择性开环，分别生成哌啶环和氮杂环庚烷环。这种合成策略使我们能够高效地制备含有哌啶和氮杂环庚烷结构单元的生物活性天然产物，包括景天胺、别景天胺、荞麦碱和巴拉诺醇。
