Expedite protocol for construction of chiral regioselectively N-protected monosubstituted piperazine, 1,4-diazepane, and 1,4-diazocane building blocks.
This paper describes the first study of solution-phase synthesis of chiral monosubstituted piperazine building blocks from nosylamide-activated aziridines. The protocol, involving aminolysis of the starting aziridines with omega-amino alcohols and subsequent Fukuyama-Mitsunobu cyclization, offers the advantage of mild conditions as well as short reaction times, and it leads to optically pure N-Boc- or N-Ns-protected piperazines. This four-step sequence, requiring only a single final chromatographic purification, was extended to include novel diazepane and diazocane derivatives.
Crestey
François
F
Department of Medicinal Chemistry, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark.
Witt
Matthias
M
Jaroszewski
Jerzy W
JW
Franzyk
Henrik
H
D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry; D001388:Aziridines / Q000737:chemistry; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
C545228:1,4-diazepane; D001381:Azepines; D001388:Aziridines; D010879:Piperazines; D000077489:Piperazine