Synthesis of 3-Amino-β-lactams through Selective Imination of 3-Oxo-β-lactams

Abstract

3-Oxo-β-lactams are known to deliver different types of reaction products upon treatment with primary amines, predominantly governed by the nature of the C4 substituent. In this work, a C4 substituent-independent protocol for the conversion of 3-oxo-β-lactams to the corresponding 3-imino-β-lactams was developed. By using primary amine hydrochloric acid salts in combination with 2,4,6-collidine, or free primary amines in combination with acetic acid, the undesired ring opening of 4-aryl- and (S)-4-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)azetidine-2,3-diones toward ethanediamides and α-aminoamides, respectively, is avoided, enabling the smooth transformation of any 3-oxo-β-lactam into its imine counterpart. As demonstrated by the ensuing synthesis of 3-alkylamino-β-lactams, 3-imino-β-lactams serve as building blocks for the construction of functionalized 3-amino-β-lactams, with the latter being key motifs in drug discovery.