Asymmetric synthesis of 2-arylpiperazines

Satoshi Yokoshima; Kazutoshi Watanabe; Fumiaki Uehara; Yoshihiro Usui; Hiroshi Tanaka

doi:10.1016/j.bmcl.2014.10.047

Asymmetric synthesis of 2-arylpiperazines

Bioorg Med Chem Lett. 2014 Dec 15;24(24):5749-5751. doi: 10.1016/j.bmcl.2014.10.047. Epub 2014 Oct 22.

Authors

Satoshi Yokoshima¹, Kazutoshi Watanabe², Fumiaki Uehara³, Yoshihiro Usui³, Hiroshi Tanaka³

Affiliations

¹ Research Division, Mitsubishi Tanabe Pharma Corporation, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. Electronic address: yokosima@ps.nagoya-u.ac.jp.
² Research Division, Mitsubishi Tanabe Pharma Corporation, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. Electronic address: Watanabe.Kazutoshi@mb.mt-pharma.co.jp.
³ Research Division, Mitsubishi Tanabe Pharma Corporation, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.

PMID: 25453813
DOI: 10.1016/j.bmcl.2014.10.047

Abstract

An asymmetric synthesis of 2-arylpiperazines starting from phenacyl bromides, a variety of which are easily available, has been established. The synthesis features a CBS reduction of phenacyl bromide to provide optically enriched compounds, an SN2 reaction of 1,2,3-oxathiazolidine 2-oxides with an azide anion with invert of configuration, and construction of the piperazine ring via reduction of piperazine-2,3-diones.

Keywords: Asymmetric synthesis; Heterocycles; Piperazines.

MeSH terms

Acetophenones / chemistry
Diketopiperazines / chemistry
Isomerism
Oxidation-Reduction
Piperazines / chemical synthesis
Piperazines / chemistry*

Substances

Acetophenones
Diketopiperazines
Piperazines
phenacyl bromide