title: Synthesis of 2,6-bridged piperazine-3-ones by N-acyliminium ion chemistry.
abstract: 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.
authors.affiliation: Laboratory of Organic Chemistry, Institute of Molecular Chemistry, University of Amsterdam, Nieuwe Achtergracht 129, The Netherlands.
authors.forename: Johan J N
authors.initials: JJ
authors.lastname: Veerman
authors.forename: Robin S
authors.initials: RS
authors.lastname: Bon
authors.forename: Bui T B
authors.initials: BT
authors.lastname: Hue
authors.forename: Daniel
authors.initials: D
authors.lastname: Girones
authors.forename: Floris P J T
authors.initials: FP
authors.lastname: Rutjes
authors.forename: Jan H
authors.initials: JH
authors.lastname: van Maarseveen
authors.forename: Henk
authors.initials: H
authors.lastname: Hiemstra