Stereocontrolled Disruption of the Ugi Reaction toward the Production of Chiral Piperazinones: Substrate Scope and Process Development

The
factors determining diastereoselectivity observed in the multicomponent
conversion of amino acids, aziridine aldehyde dimers, and isocyanides
into chiral piperazinones have been investigated. Amino acid-dependent
selectivity for either trans- or cis-substituted piperazinone products has been achieved. An experimentally
determined diastereoselectivity model for the three-component reaction
driven by aziridine aldehyde dimers has predictive value for different
substrate classes. Moreover, this model is useful in reconciling the
previously reported observations in multicomponent reactions between
isocyanides, α-amino acids, and monofunctional aldehydes.