Simple, highly enantioselective access to quaternary 1,3,4,4- tetrasubstituted β-lactams from amino acids: A solid-phase approach

Abstract

An operationally simple four-step procedure for the solid-phase synthesis of chiral (3S,4S)-1,3,4,4-tetrasubstituted β-lactams is described. The key step for the four-membered ring formation consisted in the enantioselective phosphazene base-assisted cyclization of resin-bound N-(alkyl)-N-[(S)-2- chloropropionyl]amino acid derivatives. A low-epimerization process during the incorporation of the 2S-chloropropionyl moiety into the N-alkylamino acid resins was crucial for the final stereochemical outcome, since the 3,4-stereochemistry was exclusively dictated by the configuration of this moiety. To evaluate the scope of this procedure a small library of quaternary, highly functionalized β-lactams has been generated. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.