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Updated: Dec 3, 2025

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Practical and scalable synthesis of orthogonally protected-2-substituted chiral piperazines
Srinivas Chamakuri1, Manuj M Shah, David C H Yang
1Department of Pharmacology and Chemical Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. Damian.Young@bcm.edu Srinivas.Chamakuri@bcm.edu.
Abstract:
A synthetic route to orthogonally protected, enantiomerically pure 2-substituted piperazines is described. Starting from α-amino acids, within four steps chiral 2-substituted piperazines are obtained. The key transformation involves an aza-Michael addition between an orthogonally bis-protected chiral 1,2-diamine and the in situ generated vinyl diphenyl sulfonium salt derived from 2-bromoethyl-diphenylsulfonium triflate. Further validation using different protecting groups as well as synthesis on multigram scale was performed. The method was also applied to the construction of chiral 1,4-diazepanes and 1,4-diazocanes. Additionally, the method was utilized in a formal synthesis of chiral mirtazapine.
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