Green Synthesis of α,β- and β,β-Dipeptides under Solvent-Free Conditions

The reactivity of N-tert-butyloxycarbonyl-N-carboxyanhydrides derived from β-alanine, (S)-β3-homophenylglycine, and (S)-β3-carboxyhomoglycine with different α- and β-amino ester hydrochlorides was examined under ball-milling activation. In particular, good to excellent yields of several relevant α,β- and β,β-dipeptides were obtained. An illustrative application of this methodology consisted in the high-yield synthesis of the mammalian α,β-dipeptide N-Boc-l-carnosine-OMe.