Scalable Annulation Approach to Functionalized 1-Azabicycloalkanes
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Updated: Oct 31, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Semen S Bondarenko1,2, Oksana V Livitska1,2, Anatolii M Fedorchenko1
1Enamine Ltd, 78 Winston Churchill Street, 02094Kyiv, Ukraine.
Abstract:
A unified, scalable annulation strategy toward functionalized 1-azabicycloalkanes is presented, enabling the efficient preparation of 1-azabicyclo[3.2.0]heptane, pyrrolizidine, indolizidine, and quinolizidine cores. The approach relies on a reproducible and scalable α-alkylation of cyclic α-amino esters enabled by TMEDA-assisted lithium amide control, followed by intramolecular cyclization. Some key structure-reactivity relationships governing annulation efficiency are identified, and the resulting bicyclic amines are shown to be compatible with standard medicinal chemistry workflows, providing practical access to underrepresented three-dimensional chemical space.
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