Issue 43, 2020

Practical and scalable synthesis of orthogonally protected-2-substituted chiral piperazines

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.

Graphical abstract: Practical and scalable synthesis of orthogonally protected-2-substituted chiral piperazines

Supplementary files

Article information

Article type
Communication
Submitted
18 Aug 2020
Accepted
20 Oct 2020
First published
28 Oct 2020

Org. Biomol. Chem., 2020,18, 8844-8849

Practical and scalable synthesis of orthogonally protected-2-substituted chiral piperazines

S. Chamakuri, M. M. Shah, D. C. H. Yang, C. Santini and D. W. Young, Org. Biomol. Chem., 2020, 18, 8844 DOI: 10.1039/D0OB01713B

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