Asymmetric Michael additions of carbonyl compounds to N-substituted maleimides are
among the most convenient reactions to prepare optically pure succinimide building
blocks. Although a few β-amino acids were found to be highly efficient organocatalysts
in the addition of α-branched aldehydes, the effect of their structure on the results
of these reactions has not yet been investigated. In the present study, we disclose
several unexpected and interesting structural effects of aliphatic and cycloaliphatic
β-amino acids obtained in the enantioselective conjugate addition of isobutyraldehyde
to N-benzylmaleimide. The dependence of the sense of the enantioselectivity on the
bulkiness of the substituent on the β-carbon atom, the beneficial spatial arrangements
of the functional groups in cis isomers with cyclohexane scaffold and the inversion
of the enantioselectivity depending on the absence of a base additive observed with
some trans isomers are unprecedented findings. The minor influence of the nitrogen
substituent of the maleimide ring on both the reaction rate and the enantioselectivity
was also evidenced using alicyclic β-amino acid prepared from an easily available
terpene derivative.
