Organocatalytic activity of α,α-dipeptide derivatives of (S)-proline in the asymmetric aldol reaction in absence of solvent. Evidence for non-covalent π–π interactions in the transition state

Abstract

The trend in the magnitude of stereoselectivities observed in the asymmetric aldol reaction between cyclohexanone and aromatic aldehydes with varying electron densities, catalyzed by dipeptidic organocatalyst (S,S)-1d, which contains an aromatic naphthyl substituent in the acyclic amino acid residue, is in line with expectation based on π–π stacking interactions between the aromatic ring on the organocatalyst and the aromatic aldehydes. Such non-covalent interactions are apparently enhanced under solvent-free mechanochemical activation in a ball mill.