This paper describes an original methodology for peptide bond synthesis avoiding toxic solvents and reactants. Ball-milling stoichiometric amounts of Boc-protected α-amino acid N-carboxyanhydrides (Boc-AA-NCA) or Boc-protected α-amino acid N-hydroxysuccinimide esters (Boc-AA-OSu) with α-amino acid alkyl ester salts in the presence of NaHCO₃ and a minimal quantity of EtOAc led to the production of di- to pentapeptides in an efficient and environmentally benign manner. This approach was successfully applied to the synthesis of Leu-enkephalin.

The synthesis of various amides has been realised avoiding the use of any organic solvent from activation of carboxylic acids with CDI to isolation of the amides. Mechanochemistry was the key point of the process allowing rapid formation of the amide bond and efficient water-based purification of the final products.

This tutorial review focuses on the rearrangement of β-amino alcohols via aziridinium intermediates. It covers the literature from 1947 to January 2009 (55 references). The rearrangement of β-amino alcohols can be performed by activation of the hydroxy group followed by the addition of nucleophiles (Nu). In most examples, an aziridinium intermediate is involved in the rearrangement. The ratio of amines resulting from the attack of nucleophiles at either the C-1 or C-2 position of the aziridinium intermediate, depends on the nature of the nucleophiles and the R² substituent. In some cases, solvent as well as temperature can influence the ratio of amines.