Synthesis of 2,6-bridged piperazine-3-ones by N-acyliminium ion chemistry.
Several 2-substituted and 2,5-disubstituted piperazine-3,6-diones were synthesized starting from readily available alpha-amino acids. After activation of a lactam carbonyl via introduction of a methoxycarbonyl group onto nitrogen, this carbonyl was selectively reduced. Treatment of the resulting urethane with protic acid generated the corresponding N-acyliminium ion, which was trapped by a nucleophilic C2-side chain to provide 2,6-bridged piperazine-3-ones. Several aromatic, heteroaromatic, and nonaromatic side chains were used as pi-nucleophiles. In addition, the effect of the presence of a C5-methyl group on the stereochemical outcome of the cyclization was examined.
Veerman
Johan J N
JJ
Laboratory of Organic Chemistry, Institute of Molecular Chemistry, University of Amsterdam, Nieuwe Achtergracht 129, The Netherlands.
Bon
Robin S
RS
Hue
Bui T B
BT
Girones
Daniel
D
Rutjes
Floris P J T
FP
van Maarseveen
Jan H
JH
Hiemstra
Henk
H