Complete regioselective addition of grignard reagents to pyrazine N-oxides, toward an efficient enantioselective synthesis of substituted piperazines.
A conceptually new one-pot strategy for the synthesis of protected substituted piperazines via the addition of Grignard reagents to pyrazine N-oxides is presented. This strategy is high yielding (33-91% over three steps), step-efficient, and fast. The synthesized N,N-diprotected piperazines are convenient to handle and allow for orthogonal deprotection at either nitrogen for selective transformations. In addition, this is a synthetic route to enantiomerically enriched piperazines by using a combination of phenyl magnesium chloride and (-)-sparteine, which resulted in enantiomeric excesses up to 83%.
Andersson
Hans
H
Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.
Banchelin
Thomas Sainte-Luce
TS
Das
Sajal
S
Gustafsson
Magnus
M
Olsson
Roger
R
Almqvist
Fredrik
F
D007202:Indicators and Reagents / Q000737:chemistry; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D011719:Pyrazines / Q000737:chemistry*; D013237:Stereoisomerism
D007202:Indicators and Reagents; D009942:Organometallic Compounds; D010087:Oxides; D010879:Piperazines; D011719:Pyrazines